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The impact of FDA Patient-Focused Drug Development (PFDD) on US drug development strategies: a survey of views from pharmaceutical product companies

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The impact of FDA Patient-Focused Drug Development (PFDD) on US drug development strategies: a survey of views from pharmaceutical product companies

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Content THE IMPACT OF FDA PATIENT-FOCUSED DRUG DEVELOPMENT (PFDD)
ON US DRUG DEVELOPMENT STRATEGIES:
A SURVEY OF VIEWS FROM PHARMACEUTICAL PRODUCT COMPANIES
by
Mladen Karlo Bozic
A Dissertation Presented to the
FACULTY OF THE USC MANN SCHOOL OF PHARMACY AND
PHARMACEUTICAL SCIENCES
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF REGULATORY SCIENCE
May 2024
Copyright 2024 Mladen Karlo Bozic

ii
Dedication
I dedicate this research to my mother, Ana (b. Friedrich) Bozic, who has been my neverending life inspiration and biggest supporter. She taught me the meaning of resilience,
persistence, and what it truly means to keep going despite life's hurdles. To all aspiring to begin
an academic journey later in life: do it! No corporate success measures against this achievement.

iii
Acknowledgments
First, I would like to acknowledge my appreciation and gratitude to my advisor, Dr.
Eunjoo Pacifici. Words can hardly depict the amount of time, patience, support, and academic
rigor Dr. Pacifici has poured into guiding me toward the finish line over the last five or so years.
Among many things, from her, I have learned a whole new meaning of the word “iterative” and
the value of revisiting my writing. This entire journey would not have been possible without her
insistence on excellence. Second, I would like to thank Dr. Frances Richmond, whose wisdom
I’ve attempted to harvest from the moment I met her. Thank you for your dedication and
commitment to the evolution of the regulatory science field. Throughout my journey, I have
frequently relied on your advice and guidance. To the rest of the regulatory science department,
thank you for your support, timely communication, and follow-ups. To my fellow 2018 cohort –
thank you for everything! I am happy I can call you friends and fellow doctoral students. We did
it! You have all inspired me to keep going. We had so much fun as a group. I will never forget
our cohort’s trip to Asia and countless memories from China, Japan, South Korea, and Taiwan.
Lastly, and most importantly, embarking on an academic journey and successfully completing it
this late in life does not happen without those with whom we share our lives. It takes a village.
To Jim who was with me on day one. Without you, I couldn’t have done it. To Doug, whose
support was unwavering. To my family, especially my mother Ana, late father Mladen, sister
Mima, and brothers Nenad and Goran, and niece Maja, thank you for supporting me. I remain
grateful for all the words of encouragement and for believing in me until the end.

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Table of Contents
Dedication....................................................................................................................................... ii
Acknowledgments.......................................................................................................................... iii
List of Tables ................................................................................................................................ vii
List of Figures.............................................................................................................................. viii
Abstract.......................................................................................................................................... xi
Chapter 1. Overview ........................................................................................................................1
1.1 Introduction................................................................................................................. 1
1.2 Statement of the Problem............................................................................................ 3
1.3 Purpose of the Study ................................................................................................... 4
1.4 Importance of the Study.............................................................................................. 5
1.5 Limitations, Delimitations, Assumptions.................................................................... 5
1.6 Organization of Qualifying Materials......................................................................... 6
Chapter 2. Literature Review...........................................................................................................8
2.1 Early History of Drug Development........................................................................... 8
2.2 Rise of the Modern Pharmaceutical Industry............................................................ 10
2.2.1 Labeling Mandate Under 1906 Pure Food and Drug Act............................ 12
2.2.2 Safety Mandate Under 1938 Food, Drug, and Cosmetic Act ...................... 13
2.2.3 Efficacy Mandate Under 1962 Kefauver-Harris Amendments and
Emergence of Benefit-Risk Considerations ................................................ 15
2.3 Growing Influence of Patients in the Drug Development Process............................ 17
2.3.1 The Orphan Drug Act of 1983 and Grass-Roots Rare Disease
Advocacy..................................................................................................... 18
2.3.2 Patients Confront the FDA: HIV and AIDS Crisis...................................... 19
2.3.3 Building a New Regulatory Framework: The Role of Patients in
Policy Making ............................................................................................. 21
2.3.3.1 Parent-Patient Muscular Dystrophy................................................ 22
2.3.3.2 Noah’s Hope ................................................................................... 23
2.4 Legislative Actions to Advance the Role of Patients: Prescription Drug User
Fee Act (PDUFA) V, 21st Century Cures Act, PDUFA VI and PDUFA VII............ 24
2.4.1 Prescription Drug User Fee Act V – Food and Drug Administration
Safety and Innovation Act (FDASIA): Listening to Patient
Perspectives................................................................................................. 26
2.4.2 The 21st Century Cures Act: Mandating the Implementation of PFDD ...... 30
2.4.3 Prescription Drug User Fee Act (PDUFA) VI – Food and Drug
Administration Reauthorization Act (FDARA): Providing Guidance
to Implement PFDD .................................................................................... 31

v
2.4.3.1 Guidance 1. Patient-Focused Drug Development: Collecting
Comprehensive and Representative Input ...................................... 31
2.4.3.2 Guidance 2. Patient-Focused Drug Development: Methods to
Identify What is Important to Patients............................................ 33
2.4.3.3 Guidance 3. Patient-Focused Drug Development: Selecting,
Developing or Modifying Fit-for-Purpose Clinical Outcomes
Assessments.................................................................................... 33
2.4.3.4 Guidance 4: Patient-Focused Drug Development:
Incorporating Clinical Outcome Assessments into Endpoints
for Regulatory Decision Making .................................................... 34
2.4.4 Prescription Drug User Fee Act (PDUFA) VII: FDA Advances
Patient Focused Drug Development............................................................ 35
2.5 Industry’s Response to Patient-Focused Drug Development.................................... 36
2.5.1 Comments Expressed During PFDD Workshops........................................ 36
2.5.2 Responding to PDUFA VII: Continued Focus on PFDD............................ 38
2.6 Barriers Faced by the Pharmaceutical Industry ........................................................ 40
2.6.1 Lack of a Regulatory Framework................................................................ 40
2.6.2 Organizational Culture ................................................................................ 41
2.7 Managing Changes in an Organization..................................................................... 42
2.8 Research Framework................................................................................................. 46
Chapter 3. Methodology ................................................................................................................49
3.1 Introduction............................................................................................................... 49
3.2 Survey Development................................................................................................. 49
3.3 Survey Deployment................................................................................................... 50
3.4 Survey Analysis........................................................................................................ 51
Chapter 4. Results..........................................................................................................................52
4.1 Survey Logistics........................................................................................................ 52
4.2 Demographics........................................................................................................... 53
4.2.1 Company Size.............................................................................................. 53
4.2.2 Focus on Rare Diseases............................................................................... 54
4.3 Organizational Culture.............................................................................................. 61
4.4 Unfreezing................................................................................................................. 67
4.5 Changing................................................................................................................... 69
4.5.1 Organizational Commitment ....................................................................... 73
4.5.2 Adequacy of Resources............................................................................... 78
4.5.3 Knowledge of FDA Guidance Documents.................................................. 83
4.5.4 Adopting PFDD Framework........................................................................ 84
4.5.5 Tools For Collecting Patient Views............................................................. 91
4.6 Freezing..................................................................................................................... 97
4.6.1 Functional Area Roles................................................................................. 98
4.6.2 Financial Commitments............................................................................. 100

vi
4.6.3 Impact of PFDD Implementation .............................................................. 101
Chapter 5. Discussion ..................................................................................................................115
5.1 Introduction............................................................................................................. 115
5.2 Methodological Considerations .............................................................................. 115
5.2.1 Delimitations ............................................................................................. 115
5.2.2 Limitations................................................................................................. 117
5.2.3 Discussions of Results............................................................................... 119
5.2.3.1 Undergoing a Cultural Change ..................................................... 121
5.2.4 Unfreezing ................................................................................................. 123
5.2.4.1 Current Approach to Drug Development...................................... 123
5.2.4.2 Collaboration with Patient Advocacy Organizations.................... 126
5.2.5 Changing.................................................................................................... 127
5.2.5.1 FDA Guidance.............................................................................. 128
5.2.5.2 Lack of Global Standards Around Utility of Patient
Experience Data During Regulatory Decision Making ................ 129
5.2.5.3 Role of Leadership in Promoting PFDD Activities...................... 131
5.2.6 Freezing ..................................................................................................... 132
5.2.6.1 When to Seek Patients’ Input ....................................................... 132
5.2.6.2 Current State of PFDD Adoption in the US ................................. 133
5.2.6.3 Ensuring Sustainable PFDD ......................................................... 134
5.3 Future Directions and Concluding Thoughts.......................................................... 135
References....................................................................................................................................138
Appendix A. Survey.....................................................................................................................154

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List of Tables
Table 1: FDA-led PFDD Public Meetings During Fiscal Years 2013-2017 .......................27
Table 2: Externally led PFDD Meetings 2015-2019............................................................28
Table 3: Patient Perspective Can Uniformly Inform FDA’s Benefit-Risk Framework.......30
Table 4: FDA PFDD Guidance Documents Overview........................................................35
Table 5: Breakdown of “Other (Please Specify)” Affiliated Comments on
Distribution by Job Title ........................................................................................59
Table 6: Breakdown of “Other (Please Add to the Text Box Below)” Affiliated
Comments on Company’s Engagements in PFDD Activities...............................60
Table 7: Count of Companies That Selected Every Phase of Drug Development
When Patients and Their Representatives Are Invited to Provide Their Input......72
Table 8: Breakdown of “Other” Affiliated Comments on “In Which Phase of
Development are Patients and Their Representatives Invited to Provide
Their Input”............................................................................................................73
Table 9: Breakdown of “Other” Affiliated Comments on How Important are the
Patient Perspectives in Drug Development............................................................90
Table 10: Breakdown of “Other” Affiliated Comments on Functional Areas Currently
Engaged in PFDD Activities................................................................................100
Table 11: Breakdown of “Other” Affiliated Comments on PFDD Training Supported
Financially............................................................................................................101
Table 12: Additional Insights into PFDD Insights Related to: Commitment to PFDD.......112

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List of Figures
Figure 1: Top 10 Barriers to Transformation Success...........................................................42
Figure 2: Industry Framework for Stakeholder Assessment of Navigating Change
Process During PFDD Implementation .................................................................47
Figure 3: Distribution of Respondents Whose Company Develops New Drugs and/or
Biologics................................................................................................................53
Figure 4: Distribution of Respondents by Size of the Company...........................................54
Figure 5: Percentage of Company Portfolio Dedicated to Rare Diseases.............................55
Figure 6: Involvement in PFDD Initiatives...........................................................................56
Figure 7: Number of Years Involved in PFDD Discussions and/or Activities .....................57
Figure 8: Distribution of Respondents by Functional Role...................................................58
Figure 9: Distribution of Respondents by Job Title ..............................................................59
Figure 10: Company’s Engagements in PFDD Activities.......................................................60
Figure 11: Company’s Interest in PFDD.................................................................................61
Figure 12: Company’s Level of Commitment to Pursue PFDD as a Long-Term
Aspiration...............................................................................................................63
Figure 13: Inclusion of PFDD Initiatives in Annual Goals and Objectives within Your
Functional Area......................................................................................................64
Figure 14: Extent that Senior Executives Have Discussed Patient Perspectives in Drug
Development..........................................................................................................65
Figure 15: Level of Agreement that Organization Needs to Undergo a Cultural Change
for PFDD to be Fully Integrated into the Drug Development Process..................66
Figure 16: Need to Change the Current Approach to Drug Development to Implement
PFDD .....................................................................................................................67
Figure 17: Level of Urgency for the Organization to Integrate PFDD into its Drug
Development Process.............................................................................................69
Figure 18: Inclusion of Relevant Employees in PFDD Activities ..........................................70
Figure 19: The Need to Include Patient Perspectives During Drug Development
Process ...................................................................................................................71
Figure 20: Phase of Drug Development When Patients and Their Representatives Are
Invited to Provide Their Input................................................................................72
Figure 21: Views on Patients / Representatives’ Regular Participation in Product
Development Discussions......................................................................................74
Figure 22: Views on Whether Sufficient Headcount is Dedicated to PFDD Activities..........75
Figure 23: Views on Whether Sufficient Budget is Dedicated to PFDD Activities ...............76
Figure 24: Views on Whether Training is Provided to Integrate PFDD Activities into
Existing Processes..................................................................................................77
Figure 25: Views on Whether Consultants are Available to Help PFDD Activities...............78
Figure 26: Rating the Utility of FDA Guidance Documents...................................................79

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Figure 27: Rating the Utility of Articles in Trade Publications ..............................................80
Figure 28: Rating the Utility of Information on the FDA Website .........................................81
Figure 29: Rating the Utility of Consultants ...........................................................................82
Figure 30: Rating the Utility of Conferences and Workshops................................................83
Figure 31: Rating the Knowledge of FDA PFDD Guidance Documents ...............................84
Figure 32: Rating the Process of Adoption of PFDD Frameworks Based on the First
Two FDA Guidance Documents on PFDD ...........................................................85
Figure 33: Rating Impact of Disease and its Treatment on the Patient...................................86
Figure 34: Rating Patient’s Perspectives About Potential and Current Treatments................87
Figure 35: Rating Views on Unmet Medical Needs and Available Treatment Options .........88
Figure 36: Rating Enhanced Understanding of the Natural History of the Disease or
Condition................................................................................................................89
Figure 37: Rating the Importance of “Other” Patient Perspectives in Drug
Development..........................................................................................................90
Figure 38: Interviews, Focus Groups and Facilitates Discussions with Patient and
Patient Caregivers..................................................................................................92
Figure 39: Observational Methods (e.g., medical documents, document reviews) ................93
Figure 40: Documents (e.g., scientific publications, medical records, personal
documents, graphics) .............................................................................................94
Figure 41: Audiovisual Materials (e.g., recordings, photographs, sounds, email)..................95
Figure 42: Social Media and Verified Patient Communities...................................................96
Figure 43: Patient Support and/or Advocacy Groups..............................................................97
Figure 44: Understanding Company’s Engagement in PFDD by Function............................99
Figure 45: Understanding Financial Support for Various Types of PFDD Training ............101
Figure 46: Understanding Level of Agreement Regarding Implementation of PFDD –
Timeline for Drug Development Lengthened......................................................102
Figure 47: Understanding Level of Agreement Regarding Implementation of PFDD –
Cost Increase of Drug Development....................................................................103
Figure 48: Understanding Level of Agreement Regarding Implementation of PFDD –
Lacking Regulatory Clarity..................................................................................104
Figure 49: Understanding How Pharmaceutical Companies Train Patients to Prepare
Them to Become Partners in Drug Development ...............................................105
Figure 50: Understanding How Pharmaceutical Companies Train Patients to Prepare
Them to Become Partners in Drug Development ...............................................105
Figure 51: Understanding How Pharmaceutical Companies Train Patients to Prepare
Them to Become Partners in Drug Development ...............................................106
Figure 52: Understanding How Pharmaceutical Companies Train Patients to Prepare
Them to Become Partners in Drug Development ...............................................106
Figure 53: Understanding How Pharmaceutical Companies Train Patients to Prepare
Them to Become Partners in Drug Development ...............................................107

x
Figure 54: Understanding How Pharmaceutical Companies Train Patients to Prepare
Them to Become Partners in Drug Development................................................108
Figure 55: Understanding Company’s Approach to Patient Focused Drug Development ...109
Figure 56: Understanding Level of Difficulty in Implementing Patient Focused Drug
Development........................................................................................................111

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Abstract
Traditionally, engagement of patients in the drug development process came at the late stages,
long after the concept of the study and study protocols had been written. However, this paradigm
has been shifting. Described by the FDA as “a systematic approach of capturing patient-derived
data, inclusive of their needs, experience, perspectives and priorities”, Patient Focused Drug
Development (PFDD) sets the stage for the FDA and the industry to hear directly from patients
about their conditions and therapeutic needs so that patient perspectives can be incorporated
early in the drug development and review processes. The PFDD initiative presents a valuable
collaborative opportunity with the FDA, patients, patient caregivers, and patient advocacy
organizations for a more comprehensive approach to drug development. However, the agency
has yet to determine how to incorporate patient experience data into its review process with
consistency and transparency, particularly when it comes to the determination of benefit-risk
profile of a product. Most importantly, the success of PFDD will rely on the ability of the
pharmaceutical industry to change how it plans and executes drug development by soliciting and
incorporating patient perspectives from the very beginning.
This research, conducted through a survey, explored the perspectives of professionals in
the pharmaceutical industry regarding the adoption and implementation of PFDD. The survey
was structured using Kurt Lewin’s change management framework. Participants included 66 mid
and senior-level professionals from pharmaceutical companies. The findings of this research
indicate that while the pharmaceutical industry acknowledges the significance of PFDD, the
actual implementation is in a state of flux. Larger companies appear to be entering the
“changing” phase, while smaller companies have not yet reached that stage. Additionally, both
large and small companies demonstrate limited efforts in patient education, hindering the

xii
establishment of effective partnerships throughout the drug development cycle. Furthermore, the
research identified several persistent barriers, including an incomplete regulatory framework,
inadequate regulatory guidance, limited human and financial resources, and the necessity for a
cultural shift within organizations to better align with patient-focused approaches to drug
development.

1
Chapter 1. Overview
1.1 Introduction
Drugs are developed to treat patients, yet historically, those end-users had little input into
drug development programs conducted by pharmaceutical industry. Even within patient
engagement programs hosted by the US Food and Drug Administration (FDA), patients typically
had limited roles, involving activities occurring primarily at later stages of drug development and
in the post-marketing period. This paradigm, however, has been shifting. With its genesis as a
conceptual discussion during the fourth authorization of Prescription Drug User Fee Act
(PDUFA IV) (FDA, 2011), “Patient Focused Drug Development (PFDD)” was officially
included in the PDUFA V, also known as Food and Drug Administration Safety and Innovation
Act (FDASIA), which was enacted in 2012. Described by the FDA as “a systematic approach of
capturing patient derived data, inclusive of their needs, experience, perspectives and priorities”
(FDA, 2020a), PFDD has been embraced by the agency as it looks to reshape the regulatory
decision-making process and incorporate patient-centered perspectives (Chalasani, Vaidya and
Mullin, 2018). The adoption of PFDD represents a victory for the multidecade struggle to
advocate for patients by groups like the March of Dimes whose efforts eradicated polio in the
US, families of patients with rare diseases whose efforts led to passage of the Orphan Drug Act
(ODA), and the Acquired Immunodeficiency Syndrome (AIDS) activists whose efforts resulted
in the expansion of access to investigational treatments. But while previous efforts by patient
advocates focused on the legislative and regulatory processes, the full implementation of PFDD
will rely, to a considerable extent, on the actions of the pharmaceutical industry.
The elements of PFDD included in FDASIA required the FDA to improve patient
engagement and incorporate the experiences, needs, and priorities of patients into the drug

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development and review process. This approach was further expanded with the passage of the
21st Cures Act (The Cures Act) in 2016 and PDUFA VI in 2017 (FDA, 2019a). The Cures Act
mandated the FDA to incorporate patient data directly into the regulatory decision-making
process during review of applications by sponsors. Further, the law required the FDA to release a
series of PFDD guidance documents. PDUFA VI, also known as the Food and Drug
Administration Reauthorization Act (FDARA), includes additional provisions to implement
PFDD. For example, FDARA requires the FDA to expand the number of staff working on
PFDD, draft additional guidance documents, organize public workshops, and provide public
web-access to available PFDD tools. Together, PDUFA V, 21st Century Cures Act and PDUFA
VI changed how future therapies are developed by promoting the use of patient experience data
throughout the drug development, regulatory review, and regulatory decision-making process
(FDA, 2019a).
To address its legal mandate, FDA rapidly deployed a number of new initiatives,
including a series of FDA-led PFDD public meetings and the first set of draft guidance
documents that focused on collection of patient input, and methods to identify what is important
to patients (FDA, 2020b). The outcomes from the public meetings and the recommendations
included in the guidance documents will drive the pharmaceutical companies to shift their
engagement practices to earlier in drug development so that patient perspectives, including
outcomes that matter to them, can be incorporated into the design of clinical trials. Traditionally,
patient perspectives had been captured “by proxy” from clinicians, researchers, and regulators
(BIO, 2016). The PFDD initiative sets the stage for the FDA and industry to hear directly from
patients about their experiences, including the burdens imposed by their medical conditions and
their priorities for treatments. Patients are undeniably and uniquely positioned to inform

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pharmaceutical manufacturers about their needs and opinions on specific drugs and their
attributes. Thus, through PFDD, they could influence drug development and regulatory strategies
(Chalasani, Vaidya and Mullin, 2018).
Despite FDA’s support for patient engagement, however, patients and advocacy
organizations still appear to be on the periphery of the decision-making process. In fact, the
PFDD initiative, now over a decade old, is seemingly at a critical juncture. FDA has held many
listening sessions and public workshops to deepen its understanding of patient perspectives, yet
the agency has not developed regulatory standards that guide the pharmaceutical industry on
how to include patient perspectives as a part of its regulatory filings (Crossnohere et al., 2020).
Further, FDA has yet to determine how to incorporate PFDD into its own review process,
including its benefit-risk assessment required for regulatory decision making. An integral part of
the success of PFDD will be the ability of the pharmaceutical industry to change its drug
development paradigm to include patients from the very beginning. This will require fostering an
organizational culture that would be receptive to change, creating a new internal and external
framework for patient engagement, and sustaining the new paradigm through communication
and training (Boutin et al., 2017). In the absence of industry-wide best practice or an established
regulatory framework, individual companies may be forced to adopt their own, perhaps even
unique, approach to operationalizing PFDD. Moreover, assessing the effectiveness of the PFDD
initiative may prove to be challenging for the foreseeable future, at least until more drugs are
approved based on patient experience data.
1.2 Statement of the Problem
Undoubtedly, the PFDD initiative offers pharmaceutical companies a more robust
incentive for incorporating patient perspectives into their development processes. It presents a

4
valuable collaborative opportunity with the FDA, patients, patient care givers, patient advocacy
organizations, and key opinion leaders (KOLs) for a more comprehensive approach to drug
development. At the same time, as the PFDD initiative unfolds, we must acknowledge
uncertainties facing the pharmaceutical industry. For example, calls for standardization of
patient data collection and effective inclusion of perspectives of patients throughout the product
development cycle remain unanswered. While the activities of the FDA and the patient advocacy
groups are typically shared through their websites, it is not clear how the companies are
modifying their infrastructure and day-to-day operations or the challenges they are facing to
meet the regulatory requirements of PFDD.
1.3 Purpose of the Study
The purpose of this study was to gain insight into the ways that pharmaceutical
companies are addressing PFDD. A literature analysis was conducted first to understand the
emergence of patients and patient advocacy organizations in drug development and legislative
actions aimed at advancing the role of patients. Regulatory information, including guidance
documents and transcripts from public meetings, were examined to understand the FDA’s
approach to PFDD as well as the views of key stakeholders. In addition, the study examined the
very real challenges and opportunities facing the pharmaceutical industry as it attempts to
implement PFDD and the models of corporate organizational changes that have occurred to
prioritize this new focus. A survey was developed and distributed to the pharmaceutical
personnel who currently work on drug development programs in clinical development,
regulatory affairs, patient engagement, or patient advocacy, in order to understand how industry
is navigating the organizational and cultural changes required to implement the PFDD initiative.
Further, this survey was validated through a focus group composed of subject matter experts

5
(SMEs) from the pharmaceutical industry and patient advocacy organizations currently
occupying roles in or closely associated with patient engagement, as well as from academic
experts knowledgeable in regulatory science research. The survey was disseminated using an
electronic analysis tool, Qualtrics.
1.4 Importance of the Study
Despite the calls for the pharmaceutical companies to include patient voices early and
often in the drug development cycle, it is unclear how to do this effectively to streamline product
development. Some of the uncertainties stem from the absence of a regulatory framework and
accepted industry standards or established precedence. The results from this survey could inform
how the industry is responding to the new paradigm of PFDD.
The insights gained from this study may help pharmaceutical companies advance their
understanding of operational and strategic gaps faced by companies and benchmark their own
practices against others in the industry. Additionally, the findings from this study could inform
companies about organizational structures that are established in other companies to implement
PFDD. For the regulators and policymakers, the results from this study may inform future laws
and regulatory policies. Finally, the information in this thesis could be important for regulatory
science educators interested in incorporating the evolving patient-focused drug development
model into their curricula.
1.5 Limitations, Delimitations, Assumptions
This research faced several limitations. To date, only the first two of the four planned
FDA PFDD guidance documents have been finalized. The drafts of the third and the fourth
guidance were not released until June 2022 and April 2023, respectively. Because these guidance
documents are so new, the industry may not have had sufficient time for proper implementation

6
into its strategic approach to patient engagement, and for needed cultural and operational
changes to adopt the proposed methods for patient data collection. The results of the survey were
limited by its length. As industry professionals are busy with their daily work responsibilities,
securing their agreement to participate in a survey longer than 15-20 minutes would be difficult.
This might have limited the depth of information obtained. Additionally, the survey results might
have been limited because many professionals who are directly implementing PFDD may be too
busy to complete the survey. Another limitation was the potential for participants to believe that
participating in the survey might attract adverse attention from the FDA. To mitigate this
limitation, all participants were informed of their anonymity and the survey results were
anonymized.
This research was delimited to professionals in pharmaceutical companies and did not
include evaluations of medical devices and related industries. Therefore, the results of this
research may be instructive but not directly applicable to other industries. This research was
delimited to companies operating in the United States and, consequently, would be impacted by
the US FDA initiative. Lastly, this research was delimited in time and scope. The first and
second PFDD guidance documents were published in 2018 and 2019, respectively. Hence, this
research captures only a snapshot of the envisioned practices in scope and time.
I am assuming that my approach to examining the literature provides a comprehensive
understanding of the topic and the survey respondents had been open and honest in sharing their
perspectives.
1.6 Organization of Qualifying Materials
This document contains five (5) chapters. Chapter 1 provides an introduction leading to
the research question. Chapter 2 includes a review of the literature, which covers the following:

7
the early history of drug development, the rise of the modern pharmaceutical industry, the
growing influence of patients in the drug development process, legislative actions to advance the
role of patients, industry’s response to Patient-Focused Drug Development (PFDD), managing
changes in an organization and research framework. Chapter 3 outlines the research methods,
which will include the development of a survey. Chapter 4 provides a detailed summary of the
data collected from the survey responses. Chapter 5 is a discussion of the research results,
including conclusions and implications.

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Chapter 2. Literature Review
2.1 Early History of Drug Development
As the process of drug development shifts from focusing primarily on scientists and
physicians to focusing on patients, it is helpful to examine how drugs have been developed
historically. It is not known how our ancestors selected medicines from their natural
surroundings. Written records only go back a few thousand years, but it is likely that early
remedies were developed through trial and error for minor ailments like cuts and upset stomachs.
For serious illnesses, our earliest ancestors relied on mysticism, supernatural beliefs, magic, and
religion. Involving patients in the drug development process did not occur until the modern era
with the introduction of clinical trials to demonstrate the safety and efficacy of drugs.
Early medicines focused on “expelling” the disease through vomiting, purgation,
urination, or sneezing, based on the belief that demons were the cause of diseases (Sneader,
2005). It was also common for shamans, ancestors to physicians and religious leaders, to
administer hallucinogenic and psychotropic drugs, including different varieties of mushrooms
and cannabis (La Barre, 2012). In ancient China, India, and Egypt, natural remedies like ginseng,
cardamom, cinnamon, henbane, myrrh, castor oil, fennel, sienna, thyme, and aloe, sourced from
plants, were commonly used (Porter, 1998). Similarly, cypress oil and myrrh, as well as
minerals, vegetables, and fats were used as medicines in Mesopotamia around 2600 BC (Dias,
Urban and Roessner, 2012). The Greeks moved away from supernatural beliefs to more rational
theories regarding the origins of diseases. According to literature, Hippocrates (460-377 BCE),
considered the father of medicine, theorized that nature consisted of four elements: earth, air,
fire, and water. In contrast, he theorized that the human body consisted of four fluids: black bile,
yellow bile, phlegm, and blood. He further conjectured that the fluids are perturbed during an
illness, and the act of purging and bleeding is necessary to bring them back into balance

9
(Yapijakis, 2009). Subsequently, the Greek physician Galen (129 A.D. – 217 A.D.) aligned his
approach with that of Hippocrates and created an extensive apothecary reserves of medicinal
products whose legacy spanned over 15 centuries (Ravina and Kubinyi, 2011; Pasipoularides,
2014). Galen’s belief that nature had the ultimate control over the course of the disease with the
body simply being a vehicle of the soul, was endorsed by the church all throughout the Middle
Ages and his teachings were followed throughout the Renaissance period (Sneader, 2005). As
time progressed, the specialization of those treating diseases increasingly distanced the patient
from the therapy.
A similar type of developmental history characterized therapy in the Arab states. The
Arabian culture brought distinction to the apothecary profession in the 8th century. New drugs
developed in the Arab world included benzoin, camphor, myrrh, musk senna, and alcohol,
among others (Porter, 1998). Abu Bakr Al-Razi (854 AD–925 AD), an Arabian physician, was
one of the first to recommend the testing of drugs on animals before administering them to
humans to reduce safety concerns. He also gave opium as a sedative for patients prior to surgery
to ease their discomfort. As Europe emerged from the Middle Ages, it experienced a new period
of revitalization, including trade, starting around the 13th century. With trade blossoming,
imported herbs from Arab and other countries were used to treat ill patients, and medicine and
pharmacy became established as professions. While some physicians and pharmacists studied
natural remedies and shared their findings with other professionals, patients were excluded from
these discussions.
The Age of Enlightenment of the 17th and 18th centuries was also a period of scientific
revolution (Hall, 1983). During this time, science became its own discipline that focused on
experimental approaches to addressing specific questions and validating preconceived

10
frameworks and theories. New scientific tools, like the telescope and the microscope, were
developed to study the physical and biological worlds. This was also when a selected group of
physicians applied scientific principles to better understand human anatomy, disease processes,
and treatment approaches. They published details of unusual cases, effective treatments, or
results of experiments on humans and animals. Physicians had access to a large selection of
herbal remedies and other natural products to treat their patients. New inorganic remedies, such
as mercury, iron, and lead, also gained favor among physicians.
With a greater understanding of human physiology and the ability of physician-scientists
to disseminate their findings through publication, developing medicines became an evidencebased scientific endeavor. In fact, the first written record of a prospective controlled clinical trial
took place in May 1747 aboard a naval ship, HMS Salisbury, when the Scottish naval surgeon,
James Lind, assigned 12 sailors suffering from scurvy to six treatment groups to test different
potential remedies. His study demonstrated that eating lemons and oranges was more effective in
treating scurvy than other potential remedies, including vinegar and sea water (Baron, 2009).
Although this case highlighted the usefulness of conducting a prospective controlled clinical trial
to demonstrate the safety and effectiveness of therapeutic agents, the practice did not become
legally required until the 1960s when the modern pharmaceutical industry became established
(Bhatt, 2010).
2.2 Rise of the Modern Pharmaceutical Industry
Following Lind’s scurvy trial, human studies were conducted throughout 1800s
(Abraham, 1982), examining the effect of therapies for diseases like smallpox, diphtheria and
cholera that were prevalent during the era. For example, an English doctor named Edward Jenner
(1749 – 1823) conducted a study to confirm anecdotal observations that dairymaids who had

11
been infected with cowpox were subsequently protected from smallpox. Jenner inoculated an 8-
year-old boy with substance from a cowpox lesion, which caused the boy to experience fever and
loss of appetite but no other signs of illness. Two months later, he exposed the same boy to
smallpox several times, but the boy did not develop the disease. Jenner published his findings
and provided the first scientific proof of using vaccination to control an infectious disease
(Riedel, 2017).
While early clinical studies were conducted by individual physicians like Jenner, the
emergence of the pharmaceutical industry in the nineteenth century changed how drugs were
developed and sold. Apothecaries and chemical companies became a new sector focused on
developing and commercializing pharmaceuticals (Daemmrich and Bowden, 2005). Moreover,
advances in biological sciences and organic chemistry prompted the companies to form
partnerships with universities that ushered in a new era of drug discovery and development
(Rang, 2013). These partnerships laid the scientific foundation for a pharmaceutical industry that
would differentiate its products from the quackery of patent medicine companies that, by the late
1800s, represented over 70% of all drug sales (Junod, 2008).
Without a regulatory framework for drugs, however, patent medicines were sold
alongside drugs produced by pharmaceutical companies. The first law to establish regulatory
oversight of drugs was enacted in 1906 and followed by many more laws and amendments as
weaknesses in the regulatory framework were identified, often through tragic incidents (Junod,
2008; Carpenter, 2010). The higher hurdles placed on the drug companies through more stringent
regulatory requirements resulted in the rise of the modern big pharmaceutical industry and the
disappearance, for the most part, of patent medicines. In the following sections, key landmark

12
legislative pieces will be examined to understand how the role of patients has evolved in the drug
development process.
2.2.1 Labeling Mandate Under 1906 Pure Food and Drug Act
As described in the previous section, little was done to regulate drugs before the
twentieth century (Peppercorn, Roberts and Hammond, 2009). The United States was, in fact,
much slower to act in this regard than Great Britain, which banned adulteration of food and
drinks in 1860 and passed a comprehensive Sale of Food and Drug Act in 1875 (Jillian, 2014).
In the United States, activism through publicity and the press helped raise public awareness of
harmful products on the market and prompted legislative action. For example, articles published
by Samuel Adams Hopkins in 1905 exposed the fraudulent claims and advertisements practiced
by patent medicine manufacturers (Fee, 2010). These articles fueled the anger of the public, who
demanded governmental protection against adulterated products. Just a few years prior, nearly
one hundred people became infected with tetanus, including nine children who died after
receiving contaminated smallpox vaccine. This tragedy prompted the passage of the Biologics
Control Act in 1902 and emboldened the public to demand greater federal oversight to include
food and drugs.
Hopkins was accompanied by other activists like Harvey Wiley and Upton Sinclair, who
publicized corrupt and fraudulent practices through newspapers, magazines, and other writings.
In response, the American public engaged in the political and legislative process to bring about
change. Women’s clubs nationwide were especially active in lobbying through demonstrations,
propaganda, and petitions. The public’s call for action and Harvey Wiley’s development of the
bill ultimately resulted in the passage of the Food and Drug Act of 1906 (FDA Consumer
Magazine, 2006). This law was the first federal statutory standard aimed at the protection of

13
patients and ensuring food and drug purity and truthful labeling. It introduced and defined the
two terms – misbranding and adulteration – and prohibited interstate transport of unlawful food
and drugs. It created a new environment in which the government is tasked with protecting the
public from fraudulent and harmful activities of food and drug manufacturers. The 1906 law also
ushered in a new era of public engagement and activism that would have a greater impact over
time. However, it became clear that the new law was too limited in scope because it only
regulated the labeling of the products, not their safety or effectiveness. Hence, harmful products,
including radioactive water advertised for treating various illnesses and eyelash dyes containing
toxic chemicals, continued to be marketed to the unsuspecting public. Although the public and
the newly established Food and Drug Administration pushed for a new law, it would take thirty
more years and a national tragedy for Congress to act.
2.2.2 Safety Mandate Under 1938 Food, Drug, and Cosmetic Act
In 1937, a new formulation of sulfanilamide caused 107 deaths, many of them children,
because there was no requirement for a drug to demonstrate its safety. Indeed, the new
formulation of the elixir consisted of dissolved sulfanilamide in 70% diethylene glycol. The new
formulation was tested for flavor (raspberry), appearance, and fragrance to make it more
appealing and palatable, but not for safety. What was unknown at the time was that diethylene
glycol is a toxic chemical that can cause kidney failure and death. Lacking regulatory
requirements to conduct toxicity studies, the pharmaceutical manufacturer, S. E. Massengill
Company, proceeded with distributing the drug across the United States, and doctors prescribed
the medicine for treating common infections (Ballentine, 1981; Rajendran et al., 2019). Within a
month, there were reports of deaths across 15 states. Recognized as one of the most

14
consequential poisonings of the 20th century, the event caused public outrage and created
overwhelming support for strengthening the national regulatory structure.
Even before the tragedy occurred, the FDA Commissioner at the time, Walter Campbell,
had been advocating for a new law to require that drug manufacturers demonstrate the safety of
their products prior to commercialization. His efforts were met by opposition from the
manufacturers of drugs and patent medicines, and the bill died in Congress year after year
(Cavers, 1939; Aronson, 2016).
The sulfanilamide scandal swayed public sentiment and pushed the bill to advance. On
June 25, 1938, President Franklin Delano Roosevelt signed the Food, Drug, and Cosmetic Act
(FDCA) into law (West, 2018). For the first time, manufacturers of drugs were required to
demonstrate the safety of all new drugs entering the market through the submission of a new
drug application (NDA) containing all completed studies, including any clinical data to
demonstrate that the drug is safe for use (Peppercorn, Roberts and Hammond, 2009; Ballentine,
1981). Further, the law mandated that manufacturers develop drug labeling to provide adequate
directions for use (Junod, 2008). Although the new law gave the FDA the authority over the use
of investigational drugs, the agency did not use this authority to regulate clinical trials until much
later.
The FDCA, as amended, remains a foundation and basis of FDA regulation of drugs
(FDA, 2020c). Even though it was an improvement over the 1906 Act, the 1938 FD&C Act also
suffered from essential shortcomings. For instance, if the FDA did not act within 60 days to
block drug marketing, the drug companies were allowed to continue selling the drug. More
importantly, the FDA had no legal authority to enforce good manufacturing practices (GMPs).
The law was criticized for not going far enough in protecting the interest of consumers and,

15
ultimately, for not adequately protecting public health. Nonetheless, the 1938 FDCA prevented
the thalidomide catastrophe in the US, which has unfortunately had a devastating impact across
Europe in the 1960s (Daemmrich, 2003).
It was also during the mid-nineties that clinical trial conduct underwent scientific
scrutiny. The first placebo-controlled randomized trial was conducted in 1948 by the British
Medical Research Council (MRC) to examine the effects of streptomycin on tuberculosis by
assigning patients randomly to receive either the experimental drug or the placebo (Marshall et
al., 1948). Randomized clinical trials (RCTs) continued to be utilized more broadly by other
investigators and have emerged as a key requirement in drug development. When the results
were published, the scientific community praised and embraced the randomized trial design and
approach to run them. Randomization of patients was seen as a mechanism to help assure that
clinical trials were conducted as scientific experiments to minimize bias and subjective
interpretation of treatment data (Jenkins and Hubbard, 1991). They remain a gold standard for
drug evaluation (Fee and Fox, 1992). Nonetheless, the FDA did not require companies to
conduct RCTs to place new drugs on the market.
2.2.3 Efficacy Mandate Under 1962 Kefauver-Harris Amendments and Emergence of
Benefit-Risk Considerations
In the 1950s and 1960s, thalidomide was widely used across Europe as a sedative and a
tranquilizer to mitigate morning sickness during pregnancy. By the time the drug was linked to
birth defects, over ten thousand babies with limb deformities were born around the world (Kim
and Scialli, 2011). In the US, however, thalidomide was undergoing FDA review by a concerned
reviewer, Dr. Frances Oldham Kelsey, who was reluctant to approve the drug application based
on the sparse evidence presented to her (Rehman, Arfons and Lazareus, 2011). Dr. Kelsey’s
reluctance prevented the commercialization of thalidomide, but, unknown to the FDA, the drug

16
had nevertheless been distributed as experimental samples to 1,200 physicians around the US.
These samples made their way to pregnant women, resulting in the birth of more than a dozen
“thalidomide babies” in the US (Junod, 2008).
The thalidomide tragedy made it clear that the existing US regulatory framework needed
significant enhancements to protect consumers from unsafe drugs entering the market. It
prompted Senator Estes Kefauver’s (D-Tennessee) Antitrust and Monopoly Senate
Subcommittee in 1959 to hold hearings about US drug companies that engaged in aggressive
advertising campaigns without adequate concern for safety or effectiveness. These hearings
focused on finding solutions to strengthen the drug provisions of the 1938 FD&C Act. Congress
unanimously passed the Kefauver-Harris Drug Amendment nearly 25 years after the passage of
the 1938 FDCA and has since been considered one of the most transformative legislative pieces
to change industry practices and the public’s perception of the FDA and its role in protecting
public health.
The legislation, which for the first time required manufacturers to prove efficacy during
clinical trials prior to commercialization, introduced a more patient-centered approach to
determining benefit-risk assessments. The 1962 Amendment gave FDA the authority to oversee
every phase of drug development, from discovery to clinical trials in humans (Daemmrich, 2003;
FDA, 2018c), and introduced several provisions critical to the conduct of clinical trials as we
know them today. It included the requirement to submit an investigational new drug (IND)
application before a drug candidate was allowed to proceed to testing in human subjects.
Additionally, the drug candidate had to go through a more stringent approval process before it
could be placed on the market, effectively changing the 1938 law from requiring a pre-market
notification to a pre-market approval. Further, the new provisions mandated pharmaceutical

17
companies to keep and make records available for inspections, share reports of adverse drug
reactions, and improve the FDA’s ability to better detect and investigate safety signals. The
Amendment also officially transferred regulation of prescription drug advertising from the
Federal Trade Commission (FTC) to the FDA. Further, it required informed patient consent
before initiating human trials and for the drug to demonstrate safety and “substantial evidence”
of effectiveness to obtain FDA approval (Janssen, 1981). Importantly, the proof of effectiveness
required adequate and well-controlled clinical trials. For the first time in the history of US drug
regulation, the review and evaluation of drugs was based on the analysis of both benefits and
risks, a prelude to the introduction of an official benefit-risk framework, a golden standard of the
drug approval process which remains in practice today (Hutt and Temple, 2013).
2.3 Growing Influence of Patients in the Drug Development Process
The earliest evidence of the involvement by patients and their advocates in drug
development process dates to the very early 20th century when Polio devastated communities
across the US. The disease even affected then vice president of the United States, Franklin D.
Roosevelt (The New York Times, 1921). Afterwards, during his second term as the president,
President Roosevelt prompted the formation of a historical grass-roots movement, the National
Foundation of Infantile Paralysis, that would combat the spread of polio (Larsen, 2012). The
intent behind the foundation was to ensure the best possible treatments for polio patients while
the search for a vaccine continued. A brilliant fundraising campaign called “The March of
Dimes” was launched, which asked every American to send a dime to the Office of the President
to help combat Polio. The fundraising campaign continued until 1955, when an effective polio
vaccine became widely available. This was one of the greatest public health achievements of the
20th century and set the stage for future patient advocacy efforts. The campaign’s name, the

18
March of Dimes, was later adopted by the advocacy group that continues its efforts for other
diseases to this day.
2.3.1 The Orphan Drug Act of 1983 and Grass-Roots Rare Disease Advocacy
With the passage of Kefauver-Harris Amendment, pharmaceutical manufacturers
embarked on developing and manufacturing novel drugs throughout the 1960s and 1970s. This
period saw the introduction of contraceptives, benzodiazepines, monoamine oxidase inhibitors,
and numerous oncology treatments to treat conditions for large populations. However, for
patients suffering from rare diseases, treatment options remained few to non-existent. Help for
these patients came from a new law - the Orphan Drug Act (ODA) in 1983 (U.S. Congress,
1983). Fueled by the advocacy of a coalition of dedicated patients, caregivers, and patient
advocates, Congress passed the ODA that would incentivize research and the development of
therapies for the neglected community of patients suffering from rare diseases (Mikami, 2019).
Historically, the limited prevalence of a rare disease was perceived as a hurdle to
commercial profitability. Hence, incentives in the ODA were meant to serve as a financial
stimulant that would incentivize drug manufacturers to develop drugs for these diseases (Kwon,
2018). Key incentives of the ODA include 7 years of marketing exclusivity granted to
pharmaceutical manufacturers, tax credits for expenses incurred during orphan drug
development, and federal grants (Seoane-Vazquez et al., 2008). Over the last few decades, the
success of the ODA has been measured in terms of the number of orphan drug approvals prior to
and post-enactment. For example, over five hundred orphan drugs have been approved during
the 25 years following the enactment of the ODA compared to only ten that were approved prior
to the enactment (IQVIA, 2018). The successful passage of ODA also motivated the engagement
of the broader rare disease community.

19
Abby Myers was a mom looking for answers for her son, who suffered from a rare
disease, and saw advocacy as instrumental in promoting research to find treatments for patients
like her son. Her vision and commitment launched one of the world’s most recognized patient
advocacy organizations, the National Organization for Rare Disorders (NORD), in 1983
(Putkowski, 2010). The coalition of leaders and advocacy organizations that formed NORD has
played a significant role in developing legislation to incentivize innovation to find treatments for
patients who traditionally had no options (Novas, 2009). Currently, NORD is home to more than
three hundred patient advocacy organizations and is a well-recognizable name to those engaged
in developing medicines for rare diseases (NORD, 2020).
What started as a patient-driven movement to raise awareness of the need for therapies to
treat rare diseases culminated in the development of policies that incentivized drug
manufacturers to invest in orphan drug development. In 2020 alone, thirty-one of the Center for
Drug Evaluation and Research’s (CDER) 53 novel drug approvals (58%) were approvals for
treatments of rare diseases (FDA, 2021c). The enactment of historic ODA is a testament to the
importance and influence of patients, patient advocates and grassroots advocacy (FDA, 2018e).
2.3.2 Patients Confront the FDA: HIV and AIDS Crisis
On the heels of the passage of the ODA came another health crisis that prompted another
wave of patient advocacy, stimulated by a sentinel, Centers for Disease Control (CDC)
observation. On June 5, 1981, the CDC’s Morbidity and Mortality Weekly Report (MMWR)
reported five deaths in previously healthy gay men in the Los Angeles area (CDC, 2001). These
five cases were later identified as the first reported cases of Acquired Immunodeficiency
Syndrome (AIDS), at the time, a disease with no existing therapy on the market. What followed
was a deadly AIDS epidemic that ravaged families, communities, and countries around the

20
globe. By the end of 1992, 250,000 Americans had developed AIDS, and 200,000 of them had
died (Heitz, 2020). Desperation by those impacted by HIV/AIDS and their allies gave birth to the
modern-day patient advocacy movement that went beyond just raising awareness of the disease.
The activists focused specifically on challenging the FDA, perceiving the agency as a major
bottleneck for effective, speedy access to experimental HIV/AIDS therapies. The activists
applied consistent pressure by publicly displaying their distrust in the FDA, while at the same
time demonstrating sophisticated knowledge of the HIV/AIDS condition. Their sophistication
and depth of knowledge with regard to the existing regulatory framework gradually secured them
a seat at the negotiating table with the regulators.
The ACT UP advocacy organization was formed in New York City in 1987 when the
activists, many of them HIV/AIDS patients, demanded attention for faster approval and access to
drugs from the US government, FDA, and pharmaceutical companies. The group’s engagement
with FDA is what has been commonly recognized as the first official patient engagement activity
(FDA, 2017a). Among the group’s most prominent accomplishments was the protest at the FDA
on October 11, 1988, when members of the organization stormed the FDA compound demanding
a faster drug approval process. This action effectively pivoted the AIDS advocacy movement
from defensive to offensive. It stimulated reconsideration of how drugs should be developed in
the US and helped to expand access to investigational drugs for patients suffering from serious
conditions (Epstein, 1996). Two years following ACT UP’s seizure of FDA, a Parallel Track
procedure was introduced with the main goal of allowing patients ineligible for entry into a
clinical trial to access drugs still in development directly from the pharmaceutical companies.
Unlike prior advocacy efforts, ACT UP activists mastered the technical language of modern
medicine, interacted directly with the government officials, pharmaceutical industry and science

21
community, and were able to partake credibly and equally in the discussions with expert
stakeholders (Epstein, 1996).
The historic accomplishments by AIDS patients and the ACT UP organization were
likely responsible for other increased opportunities for patient engagement in drug development.
Three years after ACT UP activists stormed the FDA headquarters, the first FDA patient
representative attended an FDA Advisory Committee (Miller, 2018). Eventually, as the focus on
patient engagement grew, the role of FDA Patient Representatives expanded beyond access to
the Advisory Committee (AC), to voting rights as part of decision-making activities that would
recommend how FDA should regulate products. It was a clear victory for patient advocates
when Debra Madden, a two-time cancer survivor, was allowed to cast her vote (Grossman,
2015). The FDA Patient Representative Program has expanded further to include patients as
consultants to the reviewers during drug evaluation process (FDA, 2018a).
2.3.3 Building a New Regulatory Framework: The Role of Patients in Policy Making
Drugs are developed to treat patients, yet patients have traditionally not been part of the
discussions beyond their traditional role as study participants (Wilson et al., 2018). Further,
patients played a role of passive recipients, typically engaged in the discussions after most
critical strategic plans had been made (Anderson and McCleary, 2015). Instead, drug
development was conducted by a large team of experts consisting of researchers, physicians,
statisticians, regulatory, clinical, and safety professionals, and many others. Patients were only
engaged long after the drug development plans had been finalized and the study protocols
written. This means that critically important factors such as burden of disease or currently
available treatments were considered without patient input. But on the heels of legislative
successes discussed above, it became evident that patients and patient advocacy organizations

22
could organize a focused agenda, raise funds, and be heard by the policymakers. In this regard,
patients suffering from rare diseases and their advocates found their voices through an expanding
number of patient advocacy organizations.
Challenges associated with the development of drugs to treat rare diseases are well
known (Augustine, Adams and Mink, 2013). These diseases, by definition, afflict small numbers
of patients and are not amenable to the traditional drug development paradigm of two large trials.
Many are severe conditions symptomatic in infants or children, and if left untreated, are fatal. To
find treatments for thousands of rare diseases that do not have an available existing therapy, an
increasing number of parent-led advocacy organizations are becoming strategic partners in the
planning of drug development studies (Dresser, 2001). Most of these organizations have a
common mission: to help identify, treat, and cure rare diseases utilizing a multitude of platforms,
from education and advocacy to research and patient services (NORD, 2020). For example, two
such organizations, Patient-Parent Muscular Dystrophy (PPMD) and Noah’s Hope, have played
instrumental roles in bringing therapies for Duchenne Muscular Dystrophy (DMD) and Batten’s
Disease to patients in desperate need for life-saving treatment, respectively. The two
organizations will be examined in further detail below.
2.3.3.1 Parent-Patient Muscular Dystrophy
The story of Parent-Patient Muscular Dystrophy (PPMD) began in 1994 when Pat
Furlong, whose two sons lost the battle with Duchenne, co-founded what was to become one of
the most recognized patient advocacy organizations globally. Over the years, PPMD invested “in
every single therapeutic possibility for Duchenne” through strategic engagements across the
entire drug development cycle, from discovery to commercialization (PPMD, 2021a). For
example, its multi-million-dollar Gene Therapy Initiative utilizes the field of gene therapy as a

23
potential for finding a therapy for DMD. To date, PPMD invested over fifty million dollars into
DMD research and development and has helped to add over ten years to the average lifespan of
those with DMD due to PPMD-led advances in care. Additionally, over 600 million dollars in
federal funding has been leveraged by the PPMD community for DMD research (PPMD, 2021a).
PPMD has also had a profound impact on drug approvals for DMD including Sarepta’s
eteplirsen (PPMD, 2016). In addition, PPMD has contributed to the development of regulatory
policy by submitting to FDA, in June 2014, the first-ever draft Guidance for Industry on
Duchenne Muscular Dystrophy. This publication represented a milestone in patient-focused
advocacy because for the first time a patient advocacy organization wrote a regulatory guidance
document related to a condition for which it advocates (PPMD, 2021b).
2.3.3.2 Noah’s Hope
Noah’s Hope was founded by Tracy and Julie VanHoutan, parents who lost two children
in less than two years to CLN2 Batten disease, a rare genetic condition that is debilitating and
terminal by the age of 12. Tracy and Julie devoted their lives to learning about the CLN2 Batten
disease and attended and presented at numerous research conferences and congressional hearings
(FDA, 2010). Along the way, they became recognized as experts on the disease. Their
foundation raises funds for promising research and has played a critical role in bringing the first
drug to treat CLN2 Batten’s disease, Brineura® (cerliponase alfa), to market in 2017 (BioMarin,
2020).
Numerous other examples of parent-patient advocacy exist (Rare Diseases, n.d.; Danny’s Dose,
n. d.; Parent to Parent, 2024) Collectively, they have made significant contributions to the
emergence of patient centricity, inclusion of patient-parent-care giver voice in the development

24
of medicines, and the introduction of FDA’s Patient-Focused Drug Development initiative
leading to the landmark legislation examined in the sections that follow.
2.4 Legislative Actions to Advance the Role of Patients: Prescription Drug User Fee Act
(PDUFA) V, 2
1st Century Cures Act, PDUFA VI and PDUFA VII
From the 1960s to the 1990s, the series of laws and regulations that were established
placed a heavy burden on FDA resources and regulatory processes. As a result, the drug approval
process in the US showed minimal progress for the next two decades. Further, over the same
period, the speed of FDA drug reviews dramatically declined. By 1979 it would take FDA
nearly three years (35 months) to review a new drug application, in stark contrast to only 14
months in 1963 (GAO, 1995).
To address the widening gap in drug review times, patient advocacy organizations and
pharmaceutical sponsors demanded change. Their work ultimately culminated in the enactment
of the first Prescription Drug User Fee Act (PDUFA) in 1992 (Zelenay, 2005), which demanded
a faster review process- twelve months for a standard review and six months for a priority
review- in return for user fees to underwrite this effort. But the new law had a sunset clause
(H.R. 6181, 1992). that required it to be re-authorized every 5 years. The reauthorization
mechanism was designed to assure that the FDA and the industry would be held to the terms of
the Act, and that each new iteration would be a vehicle to renegotiate its terms. Hence, over the
next several cycles of PDUFA renewals, an increasing number of new legislative initiatives were
added that built on top of the existing ones introduced in the previous PDUFA term.
The first PDUFA reauthorization in 1997 (PDUFA II) as part of Food and Drug
Administration Modernization Act (FDAMA) focused on establishing standards for scheduling
meetings, providing additional review guidance, and shortening review times for standard review
from twelve months to ten months (S. 830, 1997). Similarly, PDUFA III supported initiatives for

25
post-approval safety activities, in addition to Good Review Manufacturing Practices,
improvements to performance management, and rolling applications (H.R. 3448, 2002). On
October 1, 2007, PDUFA IV added mandatory advisory committees, enhancement of safety
surveillance, procedures to analyze drug safety data, and Risk Evaluation and Mitigation
Strategies (REMS) (H.R. 2900, 2007). This reauthorization was perhaps the first opportunity that
the FDA and regulators took to broaden the FDA’s stakeholder engagement process for future
reauthorizations by requiring the FDA to consult with representatives of patient and consumer
advocacy groups as well as congressional committees, scientific and academic experts, and
healthcare professionals. The law specifically requires the FDA to publish a Federal Register
notice requesting public input on the reauthorization before beginning its negotiations with the
industry. In addition, FDA must hold discussions with representatives of patient and consumer
advocacy groups at least monthly while the agency is negotiating with industry (Thaul, 2013). It
was during one of these discussions that the genesis of patient engagement emerged. According
to the public meeting transcripts from April 2010, Marc Boutin from the National Health Council
asked for “patient involvement at all levels throughout the FDA and within the discussions of
what is going to be in PDUFA V.” More importantly, Boutin argued that “it is critically
important that the patient perspective be there” (FDA, 2011). These statements acknowledged
that patients, rather than healthy people, are the experts on their diseases who best understand the
benefit-risk of the medication. Marc Boutin called for a development of an objective, qualitative
benefit-risk framework that includes robust patient input and participation (NHC, 2011; FDA,
2011).
Over the last twenty years PDUFA reauthorizations have greatly contributed to faster
drug review and advancement of drug development through introduction of various initiatives.

26
What started as a mechanism to provide the FDA with needed resources also provided a means
to change the regulatory framework based on stakeholder needs. Thus, over time, the scope of
PDUFA broadened to become an important legislative instrument that would allow the FDA to
apply the user fees to cover a range of drug development processes from preclinical development
to post-approval surveillance (Dabrowska and Thaul, 2018). The genesis of patient engagement
measures in PDUFA IV continued in PDUFA V and might be considered a new era of engaging
the public in the reauthorization process. PDUFA V was followed by the 21st Century Cures Act
that further advanced inclusion of patients into the drug development process.
2.4.1 Prescription Drug User Fee Act V – Food and Drug Administration Safety and
Innovation Act (FDASIA): Listening to Patient Perspectives
From a historical perspective, PDUFA V, often called FDASIA, prompted new
approaches to involve patients early in the drug development process. FDASIA required FDA to
develop structured benefit/risk assessment in the new drug approval process that would include a
process to obtain patient perspectives on benefits and risks (S. 3187, 2012). FDASIA also added
the new FFDCA Section 569C, “Patient Participation in Medical Product Discussion,” directing
the HHS Secretary to solicit the views of patients during the medical product development
process and consider the perspectives of patients during regulatory discussions. Specifically, the
FDA was to engage the public to nominate disease areas that could benefit from patient
perspectives on disease severity or unmet medical need. Thus, Patient Focused Drug
Development (PFDD) was established by FDA as a mechanism for obtaining patient
perspectives that could be helpful in the development and regulatory review of drugs.
Under FDASIA, FDA was committed to obtaining patient perspectives on twenty disease
areas (FDA, 2013) But when the agency announced notice for public comment and offered 39
potential disease areas, 4500 comments across 90 disease areas were submitted, a majority by

27
individual patients. Nonetheless, during the fiscal years 2013 to 2017, FDA led 24 diseasespecific PFDD meetings (Table 1), to obtain patient perspectives on their “specific experiences
that matter most to patients, patient perspectives on meaningful treatment benefits, and how
patients want to be engaged in the drug development process” (FDA, 2021a). These meetings
were attended by large numbers of patients, caregivers, and patient advocates. Following each
PFDD meeting, FDA released a “The Voice of the Patient” report that captured testimonies of
patients in addition to the comments provided to the FDA docket.
Table 1: FDA-led PFDD Public Meetings During Fiscal Years 2013-2017
(Source: Food and Drug Administration)
After successfully coordinating and hosting twenty-four PFDD meetings, FDA
recognized that many more disease areas needed to be addressed. Instead of leading additional
PFDD meetings, however, the agency encouraged external parties, mostly patient organizations,
to continue the effort (Valentine, 2016). In December 2015, FDA officially invited patient
organizations to plan and host their own meetings after submitting a Letter of Intent (LOI) to
FDA (FDA, 2015). FDA provided directions on how to conduct an externally led PFDD
meeting, including submission of LOI at least 1 year ahead of the anticipated meeting describing
the importance of the meeting in the context of the diseases, and specifying details of the

28
meeting plan (FDA, 2019b). The first official externally led PFDD meeting, hosted by the
Myotonic Dystrophy Foundation (MFD) on September 15, 2016, was attended by over 200
community members, industry professionals, academic researchers, and FDA staff. The
discussion focused on two key areas: 1) experience of living with the symptoms of Myotonic
Dystrophy that are most burdensome to patients, and 2) perspectives on the effectiveness and
burden of current strategies to manage these symptoms and preferences about what would
constitute a clinically meaningful treatment. The meeting was followed by the release of a
“Voice of the Patient” report. From 2015 to 2019, more than twenty “Externally-led” PFDD
meetings were held (Table 2).
Table 2: Externally led PFDD Meetings 2015-2019
(Source: Food and Drug Administration)
Examination of a 2015 PFDD meeting with Huntington’s Disease (HD) patients and their
advocates reveals the types of discussions that took place in these forums. The meeting, attended
by approximately 50 patients and their representatives in-person and many others via webcast,
focused on two key topics: 1) disease symptoms and daily impact that matter most to patients
and 2) perspectives of patients on current approaches to treating HD (FDA, 2016). Over twothirds of those patients listed cognitive impairment, including difficulties with concentrating and

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completing complex tasks, as their top symptom. For example, one participant stated that “the
most significant symptoms of Huntington’s Disease are the ones you cannot see.” This is
different from the historical perspective of Huntington’s Disease, which was thought to be
primarily a movement disorder. In fact, the disease used to be called Huntington’s Chorea,
reflecting the dance-like gestures of the patients. As a result, the therapies were directed at
alleviating the symptoms of uncontrolled movement rather than cognitive decline. According to
the HD patients, however, an ideal treatment would decrease the progression of the disease rather
than just provide symptomatic relief. FDA plans to incorporate these perspectives into a benefitrisk assessment framework, a cornerstone of drug evaluation and approval. For the first time in
the history of the US drug approval process, the regulatory review will include not only scientific
evidence, but also the patient’s personal experience (Johnson and Zhou, 2016).
If the patient input is to be credible, it is important that the process to obtain that input be
systematic and methodologically sound. The FDA’s Benefit Risk Framework (Table 3) already
has areas where patients can contribute. Their perspectives on how their condition impacts their
daily living can inform the therapeutic context for weighing benefits against risks. Patients are
also best positioned to provide insights into the current treatment options to assess whether
current therapies are adequate to meet their needs, if there are subpopulations with a particular
unmet need, and what gaps still remain in understanding the needs of the patients.

30
Table 3: Patient Perspective Can Uniformly Inform FDA’s Benefit-Risk Framework
Adopted from: Theresa M. Mullin, PhD, FDA, CDER, “How to Promote Patient Centricity? An
FDA Perspective”, DIA Europe, June 2020
2.4.2 The 21st Century Cures Act: Mandating the Implementation of PFDD
Another step forward for patients is evident in the passage of the 21st Century Cures Act
in December 2016 and specifically, the Patient Focused Drug Development section (Title III,
Subtitle A, Sections 3001-3004 of “Cures Act”) (H.R. 34, 2016). This section added provisions
to strengthen patient involvement in the drug development process. It added a new section
requiring that patient experience data and related information submitted and reviewed as part of a
new drug application be publicly available upon approval of that NDA. In addition, the law
required that draft and final guidance be developed regarding the collection of patient experience
data and the use of such data in drug development within the next 5-year period. Further, it
required that the use of patient experience data in regulatory decision-making be assessed and
published on FDA’s website on or before June 1 of 2021, 2026, and 2031. Hence, the Cures Act
mandates the FDA to act on implementing PFDD.

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2.4.3 Prescription Drug User Fee Act (PDUFA) VI – Food and Drug Administration
Reauthorization Act (FDARA): Providing Guidance to Implement PFDD
PDUFA VI, which came on the heels of the Cures Act, was even more prescriptive for
the FDA to implement PFDD. Under the topic of “Enhancing Regulatory Decision Tools to
Support Drug Development and Review”, PDUFA VI required the FDA to incorporate the
patient’s voice in drug development and decision making. It also called for the FDA to expand
its staff, organize public workshops, make accessible publicly available tools on its website, and
draft a series of four guidance documents, each to be issued annually from 2018 to 2021. The
language in PDUFA VI is quite clear as to the goal of each guidance document. The first
document should describe approaches to collect patient experience data on burden of disease and
current therapy; the second how to identify disease-related issues that are most important to
patients; the third how to develop meaningful outcome measures that could be useful in clinical
trials; the fourth how the identified outcome measures could be incorporated into endpoints for
regulatory decision making. Development of each guidance document required that input from
stakeholders be obtained through public workshops (FDA, 2018d). To date, the FDA has issued
the first two guidance documents and is developing the last two. These guidance documents will
be examined more closely below to understand how the FDA is approaching the implementation
of PFDD.
2.4.3.1 Guidance 1. Patient-Focused Drug Development: Collecting Comprehensive and
Representative Input
As described above, the Cures Act commits the FDA to issue methodological guidance to
support PFDD. The language in Cures Act section 3002(c)(1) specifies that the guidance should
address:

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“Methodological approaches that a person seeking to collect patient experience
data for submission to, and proposed use by, the Secretary in regulatory decision
making may use, that are relevant and objective and ensure that such data are
accurate and representative of the intended population, including methods to
collect meaningful patient input throughout the drug development process and
methodological considerations for data collection, reporting, management, and
analysis.” (FDA, 2020d).
Hence, this first guidance document provides a general overview of how to obtain data on
patient experience, including what would be considered patient experience data, how to collect
and ensure data quality. According to the guidance document, patient experience data could
include a wide spectrum of information that point to the “experiences, perspectives, needs, and
priorities of patients” related to their diseases (FDA, 2020d). For example, patient experience
data could be related to the impact of the disease, the burden of treatment, views on potential
future treatments, and what would be considered by the patients as acceptable tradeoffs of
benefits relative to risks. The FDA makes it clear that collection of patient experience data can
take place at any time during drug development, from a variety of settings, including clinical
trials, advisory and public meetings, and social media. The guidance document next describes
methodological approaches to collecting patient experience data based on scientific principles.
Hence, the first step is to identify the research goal or questions to be addressed. These should
then drive the selection of target population, study design, and research setting. The methods and
standards for data collection and analysis must also meet FDA’s expectations for quality. For
example, the sampling approach must demonstrate that the obtained information is representative
of the target population; the collection of patient experience data must comply with all national,
local, and institutional requirements for human subject protection; and the data collection is
appropriate and standardized.

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2.4.3.2 Guidance 2. Patient-Focused Drug Development: Methods to Identify What is
Important to Patients
This document, issued as a draft guidance on October 1, 2019, and finalized in February
2022, describes methods that can be used to identify what matters most to patients living with a
disease. These findings can inform clinical outcome measures that can be incorporated into drug
development programs and provide insights into patient preferences. Specifically, the document
explores qualitative and quantitative methods that may be considered in obtaining patient input.
Under qualitative research, the proper use of one-on-one interviews and focus groups, including
the types of interviews (semi-structured, structured, and unstructured) and the modes of focus
groups (in-person and telephone or online), are examined in detail. Ultimately, the selection of
the methods should be based on the research objective and target population. Under quantitative
research, survey methods are thought to be most appropriate for obtaining patient input. The
survey instrument could be self-administered or interviewer-administered, as appropriate. For
example, a self-administered instrument would allow participants to respond at their own pace,
while an interviewer-administered instrument would input from hearing-impaired individuals.
This guidance document also provides information on how to develop survey instrument
instructions and questions, including types of questions and examples (FDA, 2019c).
2.4.3.3 Guidance 3. Patient-Focused Drug Development: Selecting, Developing or Modifying
Fit-for-Purpose Clinical Outcomes Assessments
This guidance document discusses approaches to selecting, modifying, developing, and
validating Clinical Outcome Assessments (COAs) to measure outcomes of importance to
patients in clinical trials (FDA, 2018f). This guidance, when finalized, will, as appropriate, revise
or supplement the 2009 guidance Patient Reported Outcome Measures: Use in Medical Product
Development to Support Labelling Claims. Notably, the guidance emphasizes the importance of

34
avoiding misleading claims while allowing for flexibility in selecting the concept of interest in
the context of use and in the amount and type of evidence needed to establish fit-for-purpose
COAs, especially for indications with high unmet medical need.
2.4.3.4 Guidance 4: Patient-Focused Drug Development: Incorporating Clinical Outcome
Assessments into Endpoints for Regulatory Decision Making
The fourth and last of the series, a draft guidance document required under 21st Cures Act
and PDUFA VI, has been released for public comment in April 2023 (FDA, 2023d).
This particular guidance provides recommendations on the regulatory use of clinical
outcome assessments (COAs), both as endpoints and within endpoints. It includes considerations
for aligning COAs with FDA’s expectations for endpoints and how to format COA data in
regulatory submissions. These recommendations apply to drugs, biologics, and devices.
Each of the four guidance documents were presented as discussion documents during
public meetings (FDA, 2020b). Although these discussion documents have been publicly
available on the FDA website to view and download, the official draft guidance documents were
issued much later than mandated under 21st Century Cures Act. In the FDA commitment letter
for PDUFA VI implementation, the agency specified that third draft guidance document would
be issued by the end of Fiscal Year (FY) 2020 and fourth by the end of FY2021 (FDA, 2017b).
The first two guidance documents focused on how to collect patient perspectives, while
the third and the fourth guidance documents focus on clinical outcome assessments considered
sufficiently robust for utilization in regulatory decision making. To this end, the discussion
document related to the third guidance provides a roadmap for selecting and developing clinical
outcome assessments (COAs) that are meaningful for patients and can be used as potential study
instruments for the purpose of measuring clinical benefit of a treatment intervention (“fit-forpurpose”) (FDA, 2020d). This discussion document provides diagrams and examples to help

35
guide the sponsors. The discussion document related to the fourth guidance considers approaches
for using fit-for-purpose COAs to establish clinical trial endpoints. The COAs on their own are
not the same as the endpoints. An endpoint, for example, could incorporate several different
COAs to indicate if the study intervention provides a meaningful clinical benefit (FDA, 2020d).
This discussion document also includes real and hypothetical examples to highlight how COAs
could be incorporated into robust and reliable endpoints. Table 4 below provides an overview of
the four guidance documents.
Table 4: FDA PFDD Guidance Documents Overview
(Adopted from Food and Drug Administration)
2.4.4 Prescription Drug User Fee Act (PDUFA) VII: FDA Advances Patient Focused Drug
Development
PDUFA VII went into effect on October 1, 2022, and continues to embrace the inclusion
of patient voice throughout the drug development cycle by including several performance goals.
More specifically, the Reauthorization Performance Goals document Part 1: “Ensuring the
Effectiveness of the Human Drug Review Program”, Section L “Enhancing Regulatory Decision

36
Tools to Support Drug Development and Review” lists initiatives which will build on the
successes of PFDD from previous years. More specifically, FDA will conduct several activities
to ensure the advancement of PFDD initiative throughout PDUFA VII term and beyond. Among
them are developing a virtual catalog of Clinical Outcome Assessments (COAs) and related
endpoints and issuing guidance by September 2026 on the use and submission of patient
preference information.
The inclusion of PFDD activities in the PDUFA VII commitment letter indicates
continued support and interest in the utilization of patient perspectives throughout the drug
development process. Lastly, while most of FDA’s patient engagement activities have
historically been within the Center for Drug Evaluation (CDER), and the Center for Devices and
Radiological Health (CDRH), PDUFA VII acknowledges the rapidly evolving field of cell and
gene therapies and the growing interest in expanding PFDD into this field.
2.5 Industry’s Response to Patient-Focused Drug Development
As FDA prepared to publish its guidance documents on PFDD, the FDA held a series of
four workshops between December 2017 and December 2019. These public workshops aimed to
provide a forum for stakeholders including patients, patient advocates, academic researchers,
healthcare practitioners, drug developers, and others to voice their ideas and perspectives (FDA,
2018d).
2.5.1 Comments Expressed During PFDD Workshops
It is clear from the transcripts of these workshops that stakeholders responded positively
to the PFDD initiative and the need to include patient experience data early and throughout the
drug development cycle. The first workshop focused on one of the industry’s main concerns
about the initiative, the setting of clear expectations by the FDA for “collection, analysis,

37
submission, and utilization of patient experience data” (FDA, 2018d). The pharmaceutical
industry was represented by professionals from various functional areas, including quantitative
safety and epidemiology, global health economics, and patient-centered outcomes, almost
entirely from large companies, including AbbVie, Allergan, Amgen, AstraZeneca, Eli Lilly,
Genentech, Glaxo-Smith Kline, Novartis and Pfizer (FDA, 2018d) (FDA, 2018b).
Industry participants raised concerns about the challenges of engaging patients and
getting their feedback on clinical trial design, including information on the final target patient
population, early in the drug development process when there may be little information (FDA,
2018d). They also asked the FDA to describe how it intends to use patient input to inform riskbenefit assessment, labeling, and regulatory decision-making. Testimony by Dr. Danielle Friend,
previously the Director of Science and Regulatory Affairs with Biotechnology Innovation
Organization (BIO), the largest biotechnology industry association in the US, explained that the
industry was looking for clear opportunities to engage the FDA as they plan to collect patient
experience data. The discussion identified that such practices will likely evolve as the industry
develops approaches to gathering patient input. Hence, the agency was urged to be flexible
during this early stage of PFDD while the industry is learning how to integrate patients early in
the drug development process and determining what methods to utilize when providing patient
experience data that is representative of a particular patient population (FDA, 2018)(FDA,
2018d).
What also emerged from the workshop discussions was that the industry needs to
fundamentally change how it conducts product development. According to Marc Boutin from
National Health Council, during a public workshop held on December 6, 2019, this
transformation requires changing the culture of organizations into an environment where “many

38
parties that have vested interest in the status quo” (FDA, 2019d). He further stated that for
PFDD to be fully integrated into the product development process, there must be tangible linkage
to “retention, recruitment, salaries, and bonus” to sustain the change and avoid reverting back to
the “old culture where this becomes just a tick the box and not truly meaningful” (FDA, 2019d).
Large pharmaceutical companies, well-represented during FDA workshops and other
public meetings, will likely be well-resourced to implement PFDD successfully. However, small
to mid-size pharmaceutical companies may not have the resources or the capacity to address
PFDD. Their lack of representation in the public meetings particularly brings into question their
level of engagement and awareness. Making the issue more challenging is that these small and
midsize pharmaceutical companies conduct the early phases of drug development, where the
inclusion of patient perspectives in the drug development process needs to occur.
2.5.2 Responding to PDUFA VII: Continued Focus on PFDD
PDUFA VII was enacted allowing for the user fee process to continue. After successful
negotiations between the FDA and the pharmaceutical industry, an agreement was reached,
finalizing the commitment language and performance goals. But before the start of these
negotiations, the FDA convened a public meeting to obtain the public’s input as required by law
(Section 736B(f)(2) of the FD&C Act). During the meeting, held in July 2020, Pharmaceutical
Manufacturers of America (PhRMA) and BIO, representing the industry, called for continuing
patient-centric drug reviews as one of the major focus areas for PDUFA VII. During session 4,
both organizations acknowledged the wide support for PFDD by key stakeholders and conveyed
the industry’s support for the approach. Additionally, they identified cell and gene therapies as
focus areas for PDUFA VII and the need for the agency to “think differently about how to
conduct those product reviews” (FDA, 2020g). A subsequent breakout subgroup meeting

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between CBER and the industry held in October 2020, discussed the need to incorporate the
elements of PFDD in the development of gene therapy products (FDA, 2020e). Specifically, one
of the three industry proposals called for holding PFDD meetings to understand the perspectives
of patients and their caregivers on gene therapy product development (FDA, 2020e). The
remaining two proposals included clarifying standards required for the utilization of expedited
pathways for gene therapy products and more effectively leveraging the prior knowledge of
sponsors in the development and review of gene therapy products. Indeed, many pharmaceutical
companies have information from their prior experiences, like data on different viral vectors,
which could be valuable for those working in this area. Since October 2020, six additional CBER
breakout meetings have been held to discuss these proposals in more depth. The final language
resulting from these negotiations was issued before the commencement of PDUFA VII on
October 1, 2022 (FDA, 2021c; FDA, 2020f). Although PFDD remains a key element, as
evidenced in the PDUFA VII discussions, it is still uncertain how the approach will be
implemented across the various stakeholders.
In their 2020 article, Leah Howard from the National Psoriasis Foundation, Annie
Kennedy from EveryLife Foundation, and others argue that PFDD was at a critical juncture, at
the precipice of a “full-scale adoption” (Howard, 2020). While specific approaches taken by
individual organizations to implement PFDD were likely to be different, the authors suggest four
priority areas -- Transparency: a call for information sharing; Authenticity: ensuring the role of
patient organizations in delivering authentic patient and caregiver perspectives; Consistency:
ensuring that the science of patient input is used consistently across FDA’s centers; and
Comprehensiveness: making the product available to the patients in a timely manner by
eliminating barriers between approval and market access (Howard, 2020). In the absence of

40
industry-wide best practices, tools, and shared experiences, however, we have only a limited
understanding of the industry's challenges in implementing PFDD.
2.6 Barriers Faced by the Pharmaceutical Industry
Most literature discusses a particular aspect of patient-centered drug development but
fails to elaborate on how the different components could be integrated into a broader framework
(Burke et al., 2019). This need was underlined at the 2015 multi-stakeholder event held at the
FDA and co-hosted by the National Health Council (NHC) and Genetic Alliance to examine the
gaps in patient engagement. This meeting, attended by government officials, the pharmaceutical
industry, patient organizations, and academia identified that a lack of regulatory framework and
organizational culture were two critical barriers to implementing PFDD (Avalere, 2015). These
barriers are further examined in the sections below.
2.6.1 Lack of a Regulatory Framework
Many have identified that PFDD lacks an industry-accepted, agency-endorsed regulatory
framework. This deficiency creates a conflict for the pharmaceutical sponsors regarding
perceived risks and “must-do” priorities (Bloom et al., 2018). It prompts each company to create
its own approach, including organizational structure, standard procedures, and assessment
measures. For example, Pfizer has launched a Patient Centricity Team Tool (PCTT), a computerbased survey platform designed to probe patient-focused activities performed by its product
development teams (Ashkenazy and Schneider, 2016). The tool examines 20 areas of patientcentric activities categorized across 4 dimensions of PFDD -- people, purpose, process, and
actions. This tool aims to provide product development teams with a way to assess if and how
they are incorporating patient-centric activities into the drug development process. Development
of such tools, and more importantly, broadly sharing the knowledge gained throughout the

41
process, would allow for an expedient paradigm shift toward PFDD within the pharmaceutical
industry, enabling earlier and more effective integration of patient perspectives into the drug
development process.
2.6.2 Organizational Culture
Each organization's unique culture determines the expected behaviors and beliefs
reflected in an organizational strategy and structure. That culture affects its drug development
strategies within a traditional context that has previously developed drugs for the patients, not
with the patients. Instead, FDA’s PFDD initiative places patients in the center of drug
development by considering patients as “partners”. According to the transcripts from the
December 6, 2019, FDA workshop on PFDD, Marc Boutin, previously from the National Health
Council, now Vice President of Patient Engagement at Novartis, argues that changing
organizational culture includes inspiration, information, and intimidation. To date, work by
patient communities, regulators, the pharmaceutical industry, and scientists have generated
considerable inspiration. For its part, the FDA is providing the “information” component through
its release of PFDD guidance documents. However, Boutin argues that cultural change will
require a certain level of coercion, or “intimidation” factor, within the pharmaceutical industry.
The complexity of initiatives such as PFDD requires “all in”, multi-functional engagement, longterm commitment, and senior-level support. For example, hundreds if not thousands of people
within each organization must be vested in embracing the idea of PFDD (FDA, 2019d). Many
may also see patient involvement as driven by regulatory concerns. When patient involvement is
carried out as a checklist activity, a deeper commitment to PFDD may be lacking throughout the
drug development process, and the collected information may not be acted upon. Furthermore,
patient engagement is considered by many as a soft science that may pose unknown risks for the

42
pharmaceutical company (Wicklund, 2015; Hoos et al., 2015). For patient perspectives to
become integrated into drug development at the earliest stages, a cultural change must occur
within an organization through a mandate from senior leadership and a clear regulatory
framework (Avalere, 2015).
2.7 Managing Changes in an Organization
“Change is the law of life and those who look only to the past or present are certain to
miss the future.” – John F. Kennedy
Change is essential for organizations to moving forward successfully (Kanter, 2008).
However, organizational change for an initiative such as PFDD will trigger resistance, the most
common barrier to change management (Jooste, 2015). This resistance may be reinforced by the
current absence of industry standards, laws and regulations (Figure 1). Widely considered the
founding father of change management, Kurt Lewin, describes it in a 3-step approach:
unfreezing, changing, and refreezing (Cummings, Bridgman and Brown, 2015).
Figure 1: Top 10 Barriers to Transformation Success
Source: (Cisco, 2013).

43
Unfreezing: Lewin argued that the system must be destabilized to eliminate the learnings
of previous approaches and to change the “quasi-stationary” equilibrium of the status quo
(Burnes, 2004). The initial “unfreezing” stage will meet significant resistance to change,
particularly where communication about the need for change is unclear and where the
management fails to include employees in the process of change initiative (Levasseur, 2001).
The day-to-day activities of employees can be affected significantly by certain types of changes.
For example, their ability to complete their activities may now depend on many different
methods and a broader collection. Changes in the work environment can affect the mental health
of employees and increase the risk of depression, anxiety, and stress (Bamberger et al., 2012).
Alleviating the psychological impact on employees will allow for the more effective progression
of the organizational change process. This would be best accomplished by having a clear
understanding of the most common reasons why people object to change. Indeed, this
consideration would give the organization an opportunity to “plan change strategy to address
these factors” (Torben, 2011). Specifically, to implement change management associated with
PFDD, employees should understand the reasons why change must take place. These
explanations should include the relevance of laws and FDA guidance documents that have
created an expectation to incorporate patient experience data in the product development process.
It will be important to persuade people who will be most impacted by the change to support the
change. To aid in that effort, managers leading the change must focus on educating the personnel
about the nature and urgency of implementing PFDD. activity often deemed to be important in
the unfreezing step is engaging employees and making them part of that change (Levasseur,
2001). An unfreezing step's ideal outcome is recognizing and accepting that change must occur.

44
Acknowledging the need for change or unfreezing the status quo represents a critical goal as only
then can a company move forward with change effectively (Levasseur, 2001).
Changing: The second step, changing, recognizes that controlling or predicting change is
difficult, and that it will take continuous learning and research to migrate successfully from one
set of learned behaviors to a new, desired one. The “changing” stage of implementing PFDD will
depend upon, but is not limited to, a few key parameters: the extent of understanding of the
current PFDD regulatory and legal frameworks, the alignment with the company’s culture, and
the openness to a more robust input by patients on clinical trial design. How early during the
drug development cycle an organization plans to consider patient experience data (PED) will
determine how successful change management will be. Suppose patients are engaged early,
during the discovery and pre-clinical phases. In that case, their perspectives will permeate the
entire development process and be more effective than they would be if the patients were
engaged only during Phase 2 or 3 of the development cycle. It will be important to examine
when and how patients and patient advocacy organizations should be included in the drug
development discussions and what the proposed PFDD approach will look like for the
organization. Once an agreement on the new PFDD practice has been reached, new internal
processes, best practices, and standard operating procedures (SOPs) must be developed, and all
stakeholders of the new system must be identified and engaged. Teamwork and collaboration
among stakeholders and management’s ability to lead by example are essential for successfully
executing the second step.
Freezing: As PFDD becomes integrated into the strategic direction of an organization,
the new paradigm will need to be reinforced because, otherwise, the change could be short-lived
(Lewin, 1947a). In this final step of organizational change, the goal is to solidify the desired new

45
set of behaviors to ensure permanent and lasting change. In Schein’s writing, personal refreezing
is distinguished from relational refreezing. For personal refreezing to take place, employees are
encouraged to pick solutions that fit them best, empowering them to participate actively in the
change process (Schein, 1999). When this approach is practiced, leaders are viewed as neutral
facilitators, not managerial authoritarianists (Desmond and Wilson, 2019), and employees are
placed in the position to demonstrate competencies around the newly introduced PFDD
initiative. Relational freezing, however, is best achieved by training the group that previously
supported the activities associated with old behaviors or activities. Lewin argued that individual
acceptance of change will not last until the group's “norms and routines are also transformed”
(Burnes, 2004). Hence, successful PFDD implementation, according to Lewin’s 3-step model,
will require “changes to organizational culture, norms, policies and practices” (Cummings and
Huse, 1989). Because PFDD is still an evolving field, the industry will have to embrace a
learning culture to sustain the change. Further, Boutin et al. argue that to achieve sustainable
patient engagement, pharmaceutical companies must establish a culture and processes and secure
adequate human and financial resources to overcome existing barriers (Boutin et al., 2021;
Cavaller-Bellaubi, 2021). Freezing, Lewin’s last step in implementing organizational change
should be of particular importance to organizations as 70% of change initiatives ultimately fail to
be adopted and sustained (Burnes and Jackson, 2011).
Each of Lewin’s three steps in change management, unfreezing, changing, and
refreezing, are likely to present different sets of challenges for PFDD within the pharmaceutical
industry, due to its highly regulated and cross-functional nature. The changes that are
implemented will need to closely adhere to FDA’s approach and guidance. Also, the PFDD
initiative should be viewed as a company-wide endeavor, across all the major functional areas.

46
While clinical, regulatory, patient engagement, and patient advocacy functions might spearhead
the process, partners in other functions such as research and quality are essential for the effective
integration of the initiative. Further, a clear and consistent messaging from top leadership is
essential for the organizational change to be successful, as inadequate engagement of key
stakeholders at the beginning could lead to an unfavorable environment in the later stages of
implementation.
2.8 Research Framework
What is evident from the literature review above is that much is left to accomplish if
engagement of patients in the drug development process within the pharmaceutical industry is to
become successfully implemented. Indeed, the lack of agreed-upon, industry-wide best practices
remain a significant challenge for realizing the full potential of PFDD in drug development and
regulatory decision making. Additionally, companies need to implement this new patientfocused approach to drug development within a specified timeframe while navigating a complex
ecosystem that sees an interplay between the two critical stakeholders, Food and Drug
Administration (FDA) and Patient Advocacy Organizations (Figure 2).

47
Figure 2: Industry Framework for Stakeholder Assessment of Navigating Change
Process During PFDD Implementation
The goal of this research was to understand how pharmaceutical companies (“Industry”)
are navigating the changes required to implement a complex initiative like the patient-focused
drug development that could impact multiple functions within research and development
organizations and beyond, including regulatory strategy, regulatory policy, clinical development,
patient engagement, and patient advocacy. I am interested in understanding the fundamentals
and challenges associated with implementing the Patient-Focused Drug Development initiative
within the industry. Of particular interest is to address inquiries related to the following two
areas:
1. “Which step of change management are companies finding most difficult and why?
2. “What are the differences across small, medium, and large companies in how
Patient-Focused Drug Development initiative is implemented?
This research utilized a survey to gain insight into the implementation of PFDD from the
perspectives of pharmaceutical professionals working in clinical development, regulatory

48
strategy, regulatory policy, patient engagement, and patient advocacy roles. Building upon the
information provided earlier, the survey was organized using Lewin's change management
model, encompassing three phases of change. Further, Fixsen’s Implementation Model, which
can last between 2-4 years, suggests that every implementation undergoes four distinct stages,
with specific tasks and deliverables: 1) exploration and adoption, 2) preparation and installation,
3) initial implementation, and 4) full implementation (Fixsen et al., 2009). The model uses
similar constructs as Lewin’s change management model. For example, Fixsen’s “Exploration”
phase corresponds with Lewin’s “Unfreezing” stage, while his two distinct “Implementation”
phases (“Initial Implementation” and “Full Implementation”) correspond to Lewin’s “Change”
phase. Fixsen’s last phase, “Full Implementation” corresponds to Lewin’s “Freezing” stage
(Fixsen et al., 2015).

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Chapter 3. Methodology
3.1 Introduction
The survey was developed with one stakeholder group in mind: pharmaceutical
companies developing new drugs and/or biologics. Specifically, an online platform, Qualtrics,
was used as tool to host the study survey. The views of the pharmaceutical industry professionals
were sought from those in mid-to-senior positions involved in drug development, including those
in clinical development, regulatory strategy, regulatory policy, patient advocacy, and patient
engagement. The survey questions were developed based on the information obtained from the
literature review in Chapter 2, which forms the basis of this study. Additionally, questions were
refined with the guidance of a focus group to validate the survey questions and ensure quality
data collection. The survey was administered to the professionals who were preselected based on
their current role and experience with PFDD initiative.
3.2 Survey Development
The survey instrument was developed based on information obtained from the literature
review in Chapter 2 and consisted of 35 questions that were developed with a targeted
completion time of approximately 20 minutes. The survey began with a set of demographic
questions with the goal of identifying the characteristics of the respondents and organizations in
which they work. The set of questions that followed aimed to uncover the challenges
experienced throughout the PFDD implementation. Lewin’s Change Management Model served
as a framework to compose the questions. In particular, the questions were structured to examine
three key areas: 1) culture – a key driver of organizational behavior, 2) process – how to achieve
implementation while acknowledging that the regulatory framework for PFDD is still under
development; and 3) resources – human and financial resources needed for sustainable

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implementation of PFDD. Questions were designed to also identify where challenges are present
at different stages of the change: unfreezing (exploration), changing (initial and full
implementation), and refreezing (full implementation). Questions were designed to exclude
respondents from medical device and related industries and those who do not participate in
PFDD discussions or activities in their companies. The Qualtrics survey platform was selected
because of its known versatility to develop questions in a wide variety of formats, from yes/no
answers to multiple-choice, matrix, and ranked preference, and finally, open-text boxes which
will be included to capture additional comments from study participants. The focus group
comprised subject matter experts (SMEs) with diverse experience from the pharmaceutical
industry, academia, and patient advocacy organizations who currently hold roles in patient
engagement.
3.3 Survey Deployment
After the input of the focus group was incorporated to refine the survey questions, the
survey was first pilot tested in three individuals. After pilot testing was completed the survey was
administered to a group of pharmaceutical industry professionals. These individuals worked in
one of the following departments: regulatory strategy, regulatory policy, clinical development,
patient engagement, or patient advocacy. The survey was made available through an openaccess anonymous link distributed by email. Employees were selected based on either previous
or current acquaintance with the author of this research. Further, these employees were asked for
the contact information of professionals in their expanded networks who satisfy this study’s
inclusion/exclusion criteria. Additional SMEs were recruited through LinkedIn. At least 150
professionals were contacted to participate in the survey, and snowball method was used to
encourage these preselected professionals to forward the survey to other appropriate individuals.

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The Qualtrics software could send an introductory invitation and periodic reminders to those
who had not completed the survey. The expected response rate was 70 participants to complete
the entire survey. The email generated by the Qualtrics tool included a brief message describing
the purpose and general approach to the study. The email also explained that the survey is
anonymous, ensuring confidentiality. Each participant was given the option to decline to
participate in the survey. Respondents who did not complete the survey after a week received
reminders by email from the Qualtrics system to encourage them to complete the survey. The
survey remained open to participants for approximately 5 weeks. Survey results were stored
electronically in the Qualtrics system and were to be shared with respondents.
3.4 Survey Analysis
Data collected by online survey was analyzed utilizing various statistical methods to
identify patterns, trends and correlations between the research questions and the demographic
information describing the participant’s professional skill set. Open text and comments fields
were analyzed to identify common themes, evaluated for content, and analyzed for patterns.
Additionally, companies with more than 20,000 employees are referred to as “large”, 5,001-
20,000 employees as “mid-size”, 250-5,000 as small, and with less than 250 employees as “very
small”. Lastly, in many instances, data were cross tabulated against the size of the company to
present the views of each of the four sizes of surveyed companies.

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Chapter 4. Results
4.1 Survey Logistics
The survey was distributed from mid-August through mid-September 2022 and was
closed on September 22, 2022. During this time survey links were emailed to 80 recipients who
were also encouraged to invite additional colleagues to complete the survey. Accordingly, 69
surveys were opened. Of the sixty-five of respondents who started the survey, fifty-nine
completed the survey whereas six partially completed it. Of the partially completed surveys, two
respondents who answered forty-nine and sixty-six percent of the questions respectively were
included in the total count, while the other four respondents who answered less than 40% of the
questions were excluded from the total count. Respondents were further filtered out from
analysis if their companies do not develop drugs and or biologics (question 2) or if they were
involved in neither PFDD discussions nor activities (question 5), resulting in additional five
respondents (8%, 5/65) to be excluded from the. The overall completion rate for the direct email
group was 86% (59/69).
The survey was also posted on social media LinkedIn which allowed me to share the
survey publicly with individuals that meet the qualifying criteria for survey completion. Posting
on LinkedIn secured an additional thirteen (13) surveys, which were opened—seven of those
completed the survey. Out of six respondents that did not complete the survey, three
discontinued after answering “no” to the question number two, “does your company develop new
drugs/biologics?” Survey question number two used skip logic methodology, designed to
eliminate respondents who did not meet the qualifying criteria to participate in the survey. The
other three LinkedIn respondents completed less than 45% of the survey questions and were not
counted in the total count. The overall completion rate for respondents who opened the survey
via LinkedIn was 54% (7/13).

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In summary, the total number of completed and partially completed surveys (>45% of
questions answered) was 66. Since not all questions were answered by all participants, the
number of respondents for each question is noted.
4.2 Demographics
The respondents were asked to identify if their company developed new drugs and/or
biologics. Nearly all respondents answered “Yes” (96%, 77/80). Only three respondents (4%)
answered “No” (Figure 3). Using the “skip logic” capability of Qualtrics survey software, the
survey ended for the respondents who answered “No”.
Q2. Does your company develop new drugs and/or new biologics? (N=80)
Figure 3: Distribution of Respondents Whose Company Develops New Drugs and/or
Biologics
4.2.1 Company Size
To gauge the size of the companies represented in this research, the respondents were
asked how many employees worked in their companies. As shown in Figure 4, respondents from
large (37%, 28/76) and very small companies (32%, 24/76) were represented in similar
proportions. In comparison, (20%, 15/76) of the respondents were from small companies, and
(12%, 9/76) were from mid-size companies.

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Q3. What is the size of your company? (N=76)
Figure 4: Distribution of Respondents by Size of the Company
More than 20,000 employees
5,001-20,000 employees
251-5,000 employees
Less than 250 employees
4.2.2 Focus on Rare Diseases
The survey asked respondents about the portion of their portfolio dedicated to rare
diseases (Figure 5). Among respondents from very small companies, most (70%, 16/23) reported
that more than 50% of their company’s portfolio is dedicated to rare diseases, followed by 17%
(4/23) who indicated a 10-50% range, and 13% (3/23) who indicated less than 10%. In small
companies, two-thirds of the respondents (67%, 10/15) stated that more than 50% of their
company’s portfolio is dedicated to rare diseases, followed by 27% (4/15) who indicated 10-
50%, and one respondent who indicated more than 50%.

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Among large companies, approximately half of the respondents (52%, 14/27) indicated
that 10-50% of their company’s portfolio was dedicated to rare diseases, followed by one-third
(33%, 9/27) who indicated less than 10%, and 15% (4/27) who indicated greater than 50%. On
the other hand, most of the respondents from mid-size companies indicated that less than 10% of
their company’s portfolio is dedicated to rare diseases (44%, 4/9), followed by one-third (33%,
3/9) who indicated 10-50%, and two (22%, 2/9) who indicated more than 50%. Interestingly,
more than two-thirds of respondents from small and very small companies indicated that more
than 50% of their company’s portfolio is dedicated to rare diseases.
Q4. What percentage of your company’s portfolio is dedicated to rare diseases? (N=74)
Figure 5: Percentage of Company Portfolio Dedicated to Rare Diseases
Less than 10%
10-50%
Greater than 50%
When asked about their involvement in PFDD initiatives in their company (Figure 6), the
majority of the respondents (67%, 51/67) indicated that they participated in both PFDD
discussions and activities. Only (18%, (14/76) were involved in PFDD discussions exclusively,
while fewer (4%, 3/67) indicated they were involved in PFDD activities only. Eight respondents

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(11%, 8/67) indicated they were involved in neither PFDD discussions nor activities. The survey
for these 8 respondents ended using the skip-logic capability of the Qualtrics survey tool, as they
lacked the necessary expertise and were not sufficiently informed about the PFDD initiative to
continue.
Q5. Which of the following statements best describe your involvement in PFDD initiative in your
company? (N=76)
Figure 6: Involvement in PFDD Initiatives
Respondents were asked about their level of engagement in PFDD discussions and
activities (Figure 7). Nearly half (43%, 29/68) of the respondents reported a duration of
involvement in PFDD activities and/or discussions ranging from three to ten years. Additionally,
one-third (31%, 21/68) indicated that their participation spanned less than three years, and about
one-fourth (26%, 18/68 indicated over 10 years.

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Q6. How long have you been involved in PFDD discussions and/or activities? (N=68)
Figure 7: Number of Years Involved in PFDD Discussions and/or Activities
To characterize the functional role of the respondents within their companies, they were
asked to select the functional area that best described their current role (Figure 8). Most
selections (57%, 39/68) were for Regulatory Affairs, Strategy, or Policy, followed by over onefourth (26%,18/68) for Patient Engagement or Patient Advocacy, 12% (8/68) for Clinical
Development, 3% (2/68) for Medical Affairs, and 1% (1/68) for Other (unspecified).

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Q7. Which of the following best describes your functional role in the company? (N=68)
Figure 8: Distribution of Respondents by Functional Role
Regulatory Affairs, Strategy, or Policy
Patient Engagement or Patient Advocacy
Clinical Development
Medical Affairs
Other
To characterize the role within their organization, respondents were asked to select the
level that most accurately described their current position (Figure 9). Most frequently,
respondents were Vice President or Higher (40%, 27/68). Others were Senior
Director/Executive Director (28%, 19/68), Associate Director/Director (28%, 19/68), and
Manager/Senior Manager (3%, 2/68). One respondent (1%, 1/68) who works for a “small
company/startup” selected “Other (please specify)” and has indicated his/her level as “Head”,
“Director” (Table 5).

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Q8. Please indicate the level of your current position (N=68)
Figure 9: Distribution of Respondents by Job Title
Table 5: Breakdown of “Other (Please Specify)” Affiliated Comments on Distribution
by Job Title
Other (please specify)
Director, but in this small company / startup I spearheaded the rare disease efforts (Head? Director?)
To understand the extent of company’s engagement in PFDD activities, respondents were
asked to select “all that apply” statements which best describe their company’s current or to-date
engagements in PFDD (Figure 10). As can be seen in Figure 10, responses were distributed quite
evenly across four listed PFDD activities. Most respondents (85%, 58/68) identified that their
companies had formed meaningful collaboration with patient advocacy organization(s). Threefourths (74%, 50/68) identified that their companies utilize methods for identifying what is
important to patients (PFDD Guidance 2), while (69%, 47/68) identified that their companies
utilize best practices for collecting patient experience information as described in PFDD
Guidance 1. Over two-thirds (68%, 46/68) identified that their companies attend or had attended

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“FDA-led PFDD meetings” and/or “Externally led PFDD meetings”. Lastly, three respondents
(4%, 3/68) identified that their companies also engage in “Other” activities (Table 6). “Other”
listed activities included: 1. being active in advancing PFDD policies globally, 2. having
achieved approved labeling claims consistent with PFDD guidance, and 3. having been engaged
in cross-industry initiatives and consortia to further develop PFDD methods relevant to FDA
PFDD guidances three and four.
Q9. In your opinion, which statements best describe your company’s current or to-date
engagements in PFDD activities? Please select all that apply. (N responders= 68; N responses = 204)
Figure 10: Company’s Engagements in PFDD Activities
Table 6: Breakdown of “Other (Please Add to the Text Box Below)” Affiliated
Comments on Company’s Engagements in PFDD Activities
Other
My company has been active in advancing PFDD policies globally.
My company has achieved approved labeling claims consistent with PFDD guidance.
My company has engaged in cross-industry initiatives and consortia to further develop PFDD methods
relevant to guidances 3 & 4.

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4.3 Organizational Culture
The next section of the survey included a series of questions regarding the company’s
culture. To understand the company’s interest in PFDD, the respondents were asked to indicate
the following: 1. whether their company is interested in PFDD but does not have the experience
to implement it, 2. is aware of PFDD, but is not interested in it, or 3. is actively pursuing
adoption of PFDD (Figure 11). As seen in Figure 11, most respondents across all companies are
actively pursuing adoption of PFDD with the highest rate observed from the small companies
(93%, 13/14), followed by large (84%, 21/25 ), midsize (78%, 7/9) and very small companies
(58%, 11/19).
Q10. In your opinion, which statements below best describe your company’s interest in PFDD?
(N=67)
Figure 11: Company’s Interest in PFDD
Interested in PFDD, but does not have the experience to implement
Aware of PFDD, but not interested
Actively pursuing adoption of PFDD

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Respondents were asked to indicate the company’s level of commitment to pursue PFDD
as a long-term aspiration. According to the survey results (Figure 12), most respondents from
large (88%, 22/25), small (79%, 11/14) and mid-size (78%, 7/9) companies indicated their
companies have committed financial and/or human resources to pursue PFDD. The remaining
respondents from large (12%, 3/25) and mid-size companies (22%, 2/9) selected “expressed
interest in pursuing PFDD but has not yet secured financial and/or human resources” while
remaining respondents from small companies (21%, 3/14) selected “don’t know”. In contrast,
most respondents from very small companies were equally divided between “committed
financial and/or human resources to pursue PFDD” (42%, 8/19) and “expressed interest in
pursuing PFDD but has not yet secured financial and/or human resources” (42%, 8/19)
followed by two respondents (11%, 2/19) who selected “has not yet shown interest to adopt
PFDD” and one (5%, 1/19) who selected “don’t know”.

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Q11. In your opinion, what is your company’s level of commitment to pursue PFDD as a longterm aspiration? (N=67)
Figure 12: Company’s Level of Commitment to Pursue PFDD as a Long-Term
Aspiration
Has not yet shown interest to adopt PFDD
Has expressed interest in pursuing PFDD; but not secured financial and/or human
resources
Has committed financial and human resources to pursue PFDD
Don’t know
Respondents were asked to indicate if PFDD initiatives are included in annual goals and
objectives within their functional area (Figure 13). Most respondents from large companies
selected “yes” (80%, 20/25), followed by “no” (16%, 4/25), and “don’t know” (4%, 1/25). In
comparison, about half of the respondents from mid-size companies selected “yes” (56%, 5/9),
while the remaining respondents were equally divided between “no” (22%, 2/9) and “don’t
know” (22%, 2/9). The respondents from small companies were almost equally divided between
“yes” (57%, 8/14) and “no” (43%, 6/14). In contrast, most respondents from very small
companies selected “no” (53%, 10/19), followed by “yes” (37%, 7/19) and “don’t know” (11%,
2/19).

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Q12. Are PFDD initiatives included in the annual goals and objectives within your functional
area? (N=67)
Figure 13: Inclusion of PFDD Initiatives in Annual Goals and Objectives within Your
Functional Area
Yes
No
Don’t know
Respondents were asked how often senior management of their company discusses
patient perspectives in drug development (Figure 14). Across all company sizes, nearly all
respondents indicated either “very frequently” or “somewhat frequently”. Specifically, most
respondents from large companies indicated “somewhat frequently” (56%, 14/25), followed by
“very frequently” (44%, 11/25). Similarly, most respondents from mid-size companies selected
“somewhat frequently” (67%, 6/9) followed by “very frequently” (23%, 2/9) and “rarely” (11%,
1/9). In comparison, most respondents from small companies selected “very frequently” (64%,
9/14), followed by “somewhat frequently” (29%, 4/14) and “rarely (7%, 1/14). Lastly, most
respondents from very small companies selected “very frequently” (47%, 9/19), followed by
“somewhat frequently” (37%, 7/19), and “rarely” (16%, 3/19).

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Q13. To what extent have you heard senior executives of your company speaking of including
patient perspectives in drug development? (N=67)
Figure 14: Extent that Senior Executives Have Discussed Patient Perspectives in Drug
Development
Very frequently (at least once a month)
Somewhat frequently (quarterly)
Rarely (yearly)
Respondents were asked to indicate if they agree, and if so, to what extent, did their
company need to undergo cultural change for PFDD to be fully integrated into the drug
development process (Figure 15). According to the survey results, nearly three fourths of the
respondents from large companies indicated they either “strongly agree” (40%, 10/25), or
“somewhat agree” (32%, 8/25), followed by “somewhat disagree” (16%, 4/25) and “neither
agree nor disagree” (12%, 3/25).
In comparison, two-thirds of the respondents from mid-size companies indicated
“somewhat agree” (56%, 5/9) or “strongly agree” (11%, 1/9), while (22%, 2/9) indicated “neither
agree nor disagree”, and (11%, 1/9), followed by “somewhat disagree”.
Half of the respondents from small companies indicated either “somewhat agree” (29%,
4/14) or “strongly agree” (21%, 3/14). The rest of the respondents from small companies were

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equally distributed between “somewhat disagree” (14%, 2/14), “strongly disagree” (14%, 2/14)
and “don’t know” (14%, 2/14), while one respondent (7%, 1/14) selected “neither agree, nor
disagree”.
None of the respondents from very small companies selected “strongly agree”, while
nearly half selected “somewhat agree” (47%, 9/19), followed by (26%; 5/19) “neither agree nor
disagree”. Two respondents selected (11%, 2/19) “somewhat disagree” and two selected (11%,
2/19). One respondent (5%, 1/19) selected that they “don’t know” if their company needs to
undergo a cultural change for PFDD to be fully integrated into drug development process.
Q14. Do you agree that your organization needs to undergo a cultural change for PFDD to be
fully integrated into the drug development process? (N=67)
Figure 15: Level of Agreement that Organization Needs to Undergo a Cultural Change
for PFDD to be Fully Integrated into the Drug Development Process
Strongly agree
Somewhat agree
Neither agree nor disagree
Somewhat disagree
Strongly disagree
Don’t know

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4.4 Unfreezing
The respondents were asked to indicate if there is a need to change the current approach
to drug development in order to implement PFDD (Figure 16). Most of the respondents from
mid-size (89%, 8/9), large (70%, 16/23), and small companies (57%, 8/14) indicated there is a
need for change. In contrast, most respondents (56%, 10/18) from very small companies
indicated no need for change.
Twenty two percent of respondents (22%, 4/18) from very small companies indicated
they “don’t know”, with lower frequencies of this answer by respondents from mid-size (11%,
1/9), and small (7%, 1/14) companies.
Q15. Do you think there is a need to change the current approach to drug development in your
company to implement PFDD? (N = 64)
Figure 16: Need to Change the Current Approach to Drug Development to Implement
PFDD
Yes
No
Don’t know

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To further understand their views regarding PFDD integration into the company’s drug
development process, the respondents were asked to indicate the level of urgency: short-term
(less than 1 year), medium-term (1-3 years), long- term (greater than 3 years), already
integrated, or don’t know (Figure 17). Among respondents from large companies, around onethird (35%, 8/23) indicated already integrated, while others thought the integration would be
medium-term (39%, 9/23), followed by short-term (22%, 5/23) and long-term (4%, 1/23). On the
other hand, two-thirds of respondents from mid-size companies thought the integration would be
medium-term (67%, 6/9), followed by one respondent each who indicated already integrated,
short-term, and long-term, Respondents from small and very small companies had similar
responses. Specifically, 43% of respondents from small companies (43%, 6/14) indicated already
integrated, while 36% (5/14) thought medium-term and 14% (2/14) short-term. One respondent
selected don’t know. Similarly, 39% of respondents from very small companies (7/18) indicated
already integrated, while 44% (8/18) selected medium-term and 17% (3/18) short-term.

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Q16. What do you think is the level of urgency for your organization to integrate PFDD into its
drug development process? (N = 64)
Figure 17: Level of Urgency for the Organization to Integrate PFDD into its Drug
Development Process
Short term (less than 1 year)
Medium term (1-3 years)
Long term (greater than 3 years)
My company has integrated PFDD into its drug development process
Don’t know
4.5 Changing
Respondents were asked to indicate if they agree, and if so, to what extent their
company’s senior management actively promotes the inclusion of relevant employees in PFDD
activities (Figure 18). According to the survey results, almost all respondents across companies
of varying sizes agreed. Specifically, about half of the respondents (54%, 13/24) from large
companies selected “agree” followed by “strongly agree” (17%, 4/24) and “somewhat agree”
(17%, 4/24) while two respondents selected “neither agree nor disagree” (8%, 2/24) and one
selected “somewhat disagree” (4%, 1/24). Most respondents in mid-size companies were equally
divided between “agree” (38%, 3/8) and “somewhat agree” (38%, 3/8) with the remaining
respondents equally divided between “strongly agree” (13%, 1/8) and “neither agree nor

70
disagree” (13%, 1/8). Most respondents in small companies selected “agree” (50%, 7/14)
followed by “strongly agree” (29%, 4/14) and “somewhat agree” (21%, 3/14). Respondents from
very small companies were similarly distributed across “strongly agree” (33%, 6/18), “agree”
(28%, 5/18), and “somewhat agree” (22%, 4/18), while one respondent selected “neither agree
nor disagree” (6%, 1/18) and two selected “cannot comment” (12%, 2/18). Across all company
sizes only one respondent selected “somewhat disagree”.
Q18. In my opinion, Senior Management (e.g., CEO, Head of Research & Development, Chief
Medical Officer, etc.) of my company actively promotes the inclusion of relevant employees in
PFDD activities. (N = 64)
Figure 18: Inclusion of Relevant Employees in PFDD Activities
Strongly agree
Agree
Somewhat agree
Neither agree nor disagree
Somewhat disagree
Cannot comment
The respondents were asked to indicate if their company communicated the need to
include patient perspectives during the drug development process. According to the survey
results (Figure 19), most respondents across companies of varying sizes answered “yes” [mid-

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size companies (88%, 7/8), large (87%, 20/23), small (86%, 12/14), and very small (72%,
13/18)]. Three respondents from very small companies answered “no” (17%, 3/18), followed by
one each from mid-size (13%,1/8), small (7%,1/14), and large companies (4%, 1/23). Two
respondents each from large (9%, 2/23) and very small companies (11%, 2/18), and one from a
small company (7%, 1/14) indicated they “do not know”.
Q19. Does your company communicate the need to include patient perspectives during drug
development process? (N = 63)
Figure 19: The Need to Include Patient Perspectives During Drug Development Process
Yes
No
Don’t know
To understand at what point during the drug development process were patients and their
representatives invited to provide input, respondents were asked to select appropriate phase(s) of
drug development (Figure 20). Most of the respondents selected late clinical phase (75%, 47/63)
followed by early clinical (67%, 42/63), post approval (49%, 31/63), preclinical (38%, 24/63),
and discovery (17%, 11/63). Seven respondents selected “other” (11%, 7/63). Further analysis
was performed to gain insight into respondents who selected all phases of development. Three

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respondents from large (11%, 3/28), one from mid-size (11%, 1/9), two from very small (8%,
2/24), and one respondent (7%, 1/15) from small company selected all five phases of drug
development (Table 7).
Q20. In which phase of drug development are patients and their representatives invited to
provide their input? (select all that apply) (Nrespondents = 63, N
responses =162)
Figure 20: Phase of Drug Development When Patients and Their Representatives Are
Invited to Provide Their Input
Table 7: Count of Companies That Selected Every Phase of Drug Development When
Patients and Their Representatives Are Invited to Provide Their Input
Total Number of
Respondents
(Figure 4)
Number of
Respondents Who
Selected All Phases
% of Respondents
Who Selected All
Phases
Large 28 3 11%
Mid-size 9 1 11%
Small 15 1 7%
Very
small 24 2 8%

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Table 8: Breakdown of “Other” Affiliated Comments on “In Which Phase of
Development are Patients and Their Representatives Invited to Provide
Their Input”
Other
Not seeing an outreach with the current trials
Throughout the process, but asset dependent
Assessment of new indications and protocol design
Don’t know
I only work in these phases and can’t speak to the others
Patient input sometimes is obtained before, after, or independent of a development program, and used
for reasons other than for regulatory decision-making. So it might be conveyed to market access
people, or packaging developers, etc., even if not conveyed to clinical or regulatory.
4.5.1 Organizational Commitment
Respondents were asked to provide their views on select activities related to PFDD: 1.
Patients / representatives participate regularly in product development discussions (Figure 21), 2.
Sufficient headcount is dedicated to PFDD activities (Figure 22), 3. Sufficient budget is
dedicated to PFDD activities (Figure 23), 4. Training is provided to integrate PFDD activities
into existing processes (Figure 24), and 5. Consultants are available to help with PFDD activities
(Figure 25).
Respondents were asked if patients / representatives regularly participate in the product
development process. Most indicated they either “somewhat agree” (44%, 28/63) or “strongly
agree” (16%, 10/63) followed by “somewhat disagree” (13%, 8/63) and “strongly disagree”
(11%, 7/63). Five respondents selected “neither agree nor disagree” (8%, 5/63) and another five
selected “don’t know’ (8%, 5/63).

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Q21. Please provide your views on the following statements related to PFDD activities at your
company.
Q21 1. Patients / representatives participate regularly in product development discussions
(N=63)
Figure 21: Views on Patients / Representatives’ Regular Participation in Product
Development Discussions

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Q21 2. Sufficient headcount is dedicated to PFDD activities (N=64)
Respondents were asked if sufficient headcount is dedicated to PFDD activities. The
results were mixed. While most respondents were in agreement [“somewhat agree” (33%, 21/64)
and “strongly agree” (16%, 10/64)], similar numbers were in disagreement [“somewhat
disagree” (27%, 17/64) and “strongly disagree” (8%, 5/64)] followed by “neither agree nor
disagree” (14%, 9/64) and “don’t know” (3%, 2/64).
Figure 22: Views on Whether Sufficient Headcount is Dedicated to PFDD Activities

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Q21 3. Sufficient budget is dedicated to PFDD activities (N=64)
Respondents were asked if a sufficient budget is dedicated to PFDD activities. The results
here were mixed. While most respondents were in agreement [“somewhat agree” (34%, 22/64)
and “strongly agree” (17%, 11/64)], similar results were observed in disagreement and neutral
[“somewhat disagree” (23%, 15/64), “strongly disagree” (9%, 6/64), and “neither agree nor
disagree” (13%, 8/64)] followed by “don’t know” (3%, 2/64).
Figure 23: Views on Whether Sufficient Budget is Dedicated to PFDD Activities

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Q21 4. Training is provided to integrate PFDD activities into existing processes (N=64)
Respondents were asked if training has been provided to integrate PFDD activities into existing
processes. The results were mixed. Nearly half of the respondents were in agreement
[“somewhat agree” (28%, 18/64) and “strongly agree” (17%, 11/64)] followed by about a third
who were in disagreement [“somewhat disagree” (9%, 6/64) and “strongly disagree’ (23%,
15/64)]. The rest of the respondents neither agreed nor disagreed (16%, 10/63) or did not know
(6%, 4/63).
Figure 24: Views on Whether Training is Provided to Integrate PFDD Activities into
Existing Processes
Respondents were asked if consultants are available to help with PFDD activities. Most
respondents selected “somewhat agree” (31%, 20/64) followed by “strongly agree” (23%,
15/64), “neither agree nor disagree” (16%, 10/64), “somewhat disagree” (11%, 7/64), “don’t
know” (13%, 8/64), and “strongly disagree” (6%, 4/64).

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Q21 5. Consultants are available to help with PFDD activities (N=64)
Figure 25: Views on Whether Consultants are Available to Help PFDD Activities
4.5.2 Adequacy of Resources
Respondents were asked to rate the utility of the following resources for the adoption of
PFDD: 1. FDA guidance documents (Figure 26), 2. Articles in trade publications, blogs, etc.
(Figure 27), 3. Information of FDA website (Figure 28), 4. Consultants (Figure 29), and 5.
Conferences and workshops (Figure 30).

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Q22. Please rate the utility of the following resources for adoption PFDD
Q22 1. FDA guidance documents (N=64)
Respondents were asked to rate the utility of FDA guidance documents for adoption of
PFDD within pharmaceutical industry (Figure 26). Responses were overall positive. Over half
selected “very useful” (55%, 35/64), followed by “moderately useful” (31%, 20/64) and “slightly
useful” (13%, 8/64). One respondent indicated “not at all useful” (2%, 1/64).
Figure 26: Rating the Utility of FDA Guidance Documents

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Q22 2. Articles in trade publications, blogs, etc. (N=63)
Respondents were asked to rate the utility of trade publication articles for PFDD
adoption. Nearly all respondents found the resource to be useful, with most selecting
“moderately useful” (48%, 30/64), followed by “very useful” (24%, 15/64) and “slightly useful”
(19%, 12/64). In comparison, three respondents selected “not at all useful” (5%, 3/64), and
another three selected “don’t know” (5%, 3/64).
Figure 27: Rating the Utility of Articles in Trade Publications

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Q22 3. Information on the FDA website (N=62)
Respondents were asked to rate the utility of the information on the FDA website for the
adoption of PFDD. Nearly all respondents found the resource to be useful with most selecting
“moderately useful” (48%, 30/62) followed by “very useful” (29%, 18/62), and “slightly useful”
(19%, 12/62). In comparison, two respondents indicated that the resource was “not at all useful”
(3%, 2/62).
Figure 28: Rating the Utility of Information on the FDA Website

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Q22 4. Consultants (N=64)
Respondents were asked to rate the utility of consultants for adoption of PFDD. The
responses were mostly positive with most selecting “moderately useful” (39%, 25/64) followed
by “very useful” (31%, 20/64) and “slightly useful” (14%, 9/64). In comparison, four
respondents selected “not at all useful” (6%, 4/64) and six respondents indicated they “don’t
know” (9%, 6/64).
Figure 29: Rating the Utility of Consultants

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Q22 5. Conferences and workshops (N=64)
Respondents were asked to rate the utility of conferences and workshops for adopting
PFDD. Nearly all responses were positive, with most selecting “moderately useful” (44%,
28/64), followed by “very useful” (34%, 22/64) and “slightly useful” (17%, 11/64). One
respondent selected “not at all useful” (2%, 1/64), while two selected “don’t know” (3%, 2/64).
Figure 30: Rating the Utility of Conferences and Workshops
4.5.3 Knowledge of FDA Guidance Documents
Respondents were asked to rate their knowledge of FDA PFDD guidance documents 1
and 2 (Figure 31). According to the survey results, most respondents across companies of
varying sizes selected “moderately knowledgeable” [mid-size (75%, 6/8), large (71%, 17/24),
small (71%, 10/14), and very small (61%, 11/18)]. While none from the large companies
indicated they were highly knowledgeable, one respondent from a mid-size company (13%, 1/8)
and almost one-fourth of respondents from small and very small companies selected “highly
knowledgeable” (Small: 22%, 4/18; Very Small: 21%, 3/14). In comparison, nearly one-third of
respondents from large companies rated their knowledge as “not knowledgeable/ novice” (29%,

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7/24), followed by slightly less than one-fifth from very small companies (17%, 3/18), one
respondent from a mid-size (13%, 1/8), and one from a small company (7%, 1/14).
Q23. How would you rate your knowledge of the FDA PFDD guidance documents 1 and 2
(N=64)
Figure 31: Rating the Knowledge of FDA PFDD Guidance Documents
Highly knowledgeable (expert)
Moderately knowledgeable
Not knowledgeable / Novice
4.5.4 Adopting PFDD Framework
Respondents were asked where their company was in adopting the PFDD framework based on
the first two FDA guidance documents (Figure 32). According to the results, most respondents
from the mid-size, small and large companies selected “partially adopted PFDD framework”
[mid-size (71%, 5/7), small (56%, 5/9), and large (50%, 11/22)] compared to two respondents
from very small companies (14%, 2/14). While none of the respondents from small companies
selected “fully adopted PFDD framework”, this answer was selected by a minority of large
companies (18%, 4/22), mid-size companies (14%, 1/7) and very small companies (29%, 4/14).
One-third of respondents from small companies indicated that their companies “started having

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internal discussions” (33%, 3/9); somewhat lower percentages were observed for large (27%,
6/22), very small (21%, 3/14), and mid-size (14%, 1/7) companies. Of the different groups, only
respondents from very small companies indicated that their companies “have not started any
PFDD related activities” (36%, 5/14). One respondent from a small company (11%, 1/9) and
another from a large company (5%, 1/22) selected “don’t know”.
Q24. Looking at FDA’s PFDD guidance documents 1 and 2, where is your company in terms of
process of adopting this framework? (N = 52)
Figure 32: Rating the Process of Adoption of PFDD Frameworks Based on the First
Two FDA Guidance Documents on PFDD
Fully adopted PFDD framework based on FDA guidance 1 and 2
Partially adopted PFDD framework based on FDA guidance 1 and 2
Started having internal discussions
Not started any activities
Don’t know

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Respondents were asked to rate the importance of patient perspectives in drug
development: 1. Impact of disease and its treatment on the patient (Figure 33), 2. Patients’
perspectives about potential and current treatments (Figure 34), 3. Views on unmet medical
needs and available treatment options (Figure 35), 4. Enhanced understanding of the naral
history of the disease or condition (Figure 36), and 5. Other (Figure 37).
Q25. In your opinion, how important are the following patient perspectives in drug
Development?
Q25 1. Impact of disease and its treatment on the patient (N=62)
All respondents indicated that patient perspectives on the impact of disease and its
treatment on the patient are “very important” (92%, 57/62) or “somewhat important” (8%, 5/62).
Figure 33: Rating Impact of Disease and its Treatment on the Patient

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Q25 2. Patients’ perspectives about potential and current treatments (N=61)
Nearly all of the respondents indicated that patient perspectives about potential and
current treatments are “very important” (80%, 49/61) or “somewhat important” (16%, 10/61).
One respondent (2%, 1/61) indicated it is “not important’, while one respondent (2%, 1/61)
selected “cannot comment”.
Figure 34: Rating Patient’s Perspectives About Potential and Current Treatments

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Q25 3. Views on unmet medical needs and available treatment options (N=62)
All the respondents indicated patient views on unmet medical needs and available
treatment options are “very important” (87%, 54/62), or “somewhat important” (13%, 8/62).
Figure 35: Rating Views on Unmet Medical Needs and Available Treatment Options

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Q25 4. Enhanced understanding of the natural history of the disease or condition (N=62)
Nearly all the respondents indicated an enhanced understanding of the natural history of
the disease or condition is “very important” (77%, 48/62) or “somewhat important” (21%,
13/62). One respondent (2%, 1/62) indicated it is “not important”.
Figure 36: Rating Enhanced Understanding of the Natural History of the Disease or
Condition

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Q25 5. Other (N=17)
Seventeen respondents selected “other” patient perspectives in drug development are
important (Table 9); (53%, 9/17) indicated these “other” activities are very important; (41%,
7/17) indicated that they cannot comment, and one respondent (6%, 1/17) indicated somewhat
important.
Figure 37: Rating the Importance of “Other” Patient Perspectives in Drug Development
Table 9: Breakdown of “Other” Affiliated Comments on How Important are the
Patient Perspectives in Drug Development
Other
Barriers to trials, appropriate use of new technologies as part of trials and other aspects of trial design
They Inform benefit-risk assessment
Rare disease communities know better than anyone about their disease. Physicians see too few patients
and don’t ask the right questions to be true experts.
Understanding of the acceptance and patient perspective on common endpoints and outcome measures
Patient preferences on desired benefits and acceptable risks
Patient preference
Understanding travel logistics for a CT and LTFU for patients/families. What are their needs and/or
continued participation in a trial
Understanding of the patient journey and impact to caregivers and families
Benefit/risk: what is acceptable to patients
PFDD Meetings with patients, caregivers, FDA
Again, this depends on the disease and the particular therapy

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4.5.5 Tools For Collecting Patient Views
Respondents were asked to identify tools and methods to collect patient views as part of
their company’s approach to PFDD (Figure 37 - Figure 42).
Q26. My company uses the following tools and methods to collect patient views as part of its
approach to PFDD.
Q26 1. Interviews, focus groups and facilitated discussions with patient and patient caregivers
(N-62)
According to the survey results, most respondents across companies of varying sizes
answered “yes” to using interviews, focus groups, and facilitated discussions with patient and
patient caregivers [mid-size (100%,8/8), small (92%, 12/13), large (87%, 20/23), and very small
(78%, 14/18)]. Three respondents from very small companies indicated they don’t know (17%,
3/18), followed by two from large (9%, 2/23), and one (8%, 1/13) from small companies. Lastly,
only one respondent (6%, 1/18) from a very small company selected “no” as did another one
respondent from a large company (4%, 1/23).

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Figure 38: Interviews, Focus Groups and Facilitates Discussions with Patient and
Patient Caregivers
Yes
No
Don’t know

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Q26 2. Observational methods (e.g., medical documents, document reviews) (N=62)
Around three-fourths of respondents from large, small, and mid-size companies selected
“yes” to using observational methods like medical documents and document reviews [large
(78%, 18/23), small (77%, 10/13), and mid-size (75%, 6/8)]. The remaining respondents in these
groups were distributed between “no” [small (15%, 2/13), mid-size (8%, 1/13), and large (9%,
2/23)] and “don’t know” [large (13%, 3/23), mid-size (13%, 1/8), and small (8%, 1/13)]. The
respondents from very small companies, on the other hand, were almost evenly distributed across
“yes” (39%, 7/18), “no” (28%, 5/18), and “don’t know” (33%, 6/18).
Figure 39: Observational Methods (e.g., medical documents, document reviews)
Yes
No
Don’t know

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Q26 3. Documents (e.g., scientific publications, medical records, personal documents, graphics)
(N=62)
According to the survey results, most respondents across companies of varying sizes
answered “yes” to using documents like scientific publications and medical records to collect
patient views [mid-size (100%, 8/8), small (92%, 12/13), large (87%, 20/23), and very small
(67%, 12/18). Two respondents from very small companies selected “no” (11%, 2/18) as did one
respondent from a small company (8%, 1/13). Lastly, four respondents from very small
companies selected “don’t know” (22%, 4/18) as did three from large companies (13%, 3/23).
Figure 40: Documents (e.g., scientific publications, medical records, personal
documents, graphics)
Yes
No
Don’t know

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Q26 4. Audiovisual materials (e.g., recordings, photographs, sounds, email) (N=61)
According to the results, most respondents across all companies indicated that they did
not know that they used audiovisual materials like recordings and photographs. Respondents
from large companies were almost evenly distributed between “yes” (43%, 10/23) and “don’t
know” (39%, 9/23), while the rest selected “no” (17%, 4/23). About four out of five respondents
from very small companies selected “yes” (41%, 7/17), while the rest were equally split between
“no” (29%, 5/17) and “don’t know” (29%, 5/17). Most respondents from mid-size companies
selected “don’t know” (50%, 4/8), with the rest equally split between “yes” (25%, 2/8) and “no”
(25%, 2/8). Similarly, most respondents from small companies also selected “don’t know” (46%,
6/13), followed by “yes” (31%, 4/13) and “no” (23%, 3/13).
Figure 41: Audiovisual Materials (e.g., recordings, photographs, sounds, email)
Yes
No
Don’t know

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Q26 5. Social media and verified patient communities (N=62)
According to the survey results, most respondents across companies of varying sizes
answered “yes” to using social media and verified patient communities [mid-size (75%, 6/8),
large (61%, 14/23), very small (50%, 9/18), and small (46%, 6/13)]. The remaining respondents
in the mid-size companies selected “no” (25%, 2/8). The respondents in the other groups were
split between “no” [small (23%, 3/13), very small (22%, 4/18), and large (9%, 2/23) and “don’t
know” [small (31%, 4/13), very small (28%, 5 /18), and large (30%, 7/23)].
Figure 42: Social Media and Verified Patient Communities
Yes
No
Don’t know

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Q26 6. Patient support and/or advocacy groups (N=62)
According to the survey results, nearly all respondents across companies of varying sizes
answered “yes” to using patient support and/or advocacy groups to collect patient views [large
(96%, 22/23), small (92%, 12/13), very small (89%, 16/18), and mid-size (88%, 7/8). The
remaining respondent from a large company selected “don’t know” (4%, 1/23) as did the one
from a small company (8%, 1/13). The remaining respondent from a mid-size company selected
“no” (13%, 1/8) whereas the two remaining respondents from very small companies were split
between “no” (6%, 1/18) and “don’t know” (6%, 1/18).
Figure 43: Patient Support and/or Advocacy Groups
Yes
No
Don’t know
4.6 Freezing
To understand which functional areas were taking the lead for PFDD activities,
respondents were asked to identify the roles of various functional areas as leading, contributing,
or not involved.

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4.6.1 Functional Area Roles
Q27. Which of the functional areas in your company are currently engaged in Patient Focused
Drug Development activities? Select all that apply (N= 61)
Most respondents identified that patient engagement and/or advocacy functional areas
(see Q27-2) contributed by “leading” (67%, 41/61) followed by “contributing” (21%, 13/61),
“don’t know” (8%, 5/61), and “not involved” (3%, 2/61). On the other hand, most identified that
regulatory affairs played roles by “contributing” (67%, 41/61) (see Q27-1), followed by
“leading” (18%, 11/61), “not involved” (11%, 7/61), and “don’t know” (3%, 2/61). A similar set
of selections was observed for pre-clinical and/or clinical development (see Q27-3) [contributing
(60%, 36/61), leading (23%, 14/61), not involved (10%, 6/61), and don’t know (7%, 4/61)].
A slightly different profile was observed for medical affairs (see Q27-4)in that most
respondents selected “contributing” (62%, 38/60), followed by “don’t know” (18%, 11/61),
“leading” (11%, 7/61), and “not involved” (8%, 5/61). Several respondents (18%, 11/61)
selected “other” functional areas (Table 10).

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Figure 44: Understanding Company’s Engagement in PFDD by Function
Q27-2. Patient Engagement and/or Patient
Advocacy
Q27-1. Regulatory Affairs (N=61)
Q27-3. Pre-clinical and/or Clinical
Development (N=60)
Q27-4. Medical Affairs

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Table 10: Breakdown of “Other” Affiliated Comments on Functional Areas Currently
Engaged in PFDD Activities
Other
Market Access (two respondents)
Portfolio Management
VEO
Integrated Evidence Generation
Medical Affairs doesn’t exist yet
Clinical operations
Safety (two respondents)
Health Outcomes including PRO Center of Excellence
Our Patient-Centered research methodologies lead much of this work. They are part of our larger data
science group
4.6.2 Financial Commitments
Respondents were asked to select one or more of 5 choices to identify which PFDD activities are
financially supported by their companies (Figure 45). Nearly all respondents indicated their
companies support external conferences, workshops, or seminars (86%, 48/56). Similarly, threefourths indicated their company provides financial support for internal presentations by subject
matter experts (75%, 42/56). Less chosen were financial support for certification programs (11%,
6/56) and undergraduate or graduate PFDD courses (4%, 2/56). Several respondents (7%, 4/56)
selected “other” training (Table 11).

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Q28 What type of patient focused drug development training is supported financially by your
company? (Select all that apply) (N
respondents=56, N
responses=102)
Figure 45: Understanding Financial Support for Various Types of PFDD Training
Table 11: Breakdown of “Other” Affiliated Comments on PFDD Training Supported
Financially
Other
I don’t know the specifics
None I am aware of
We have our own training complementing PFMD trainings
Consultants
4.6.3 Impact of PFDD Implementation
Respondents were asked to indicate their level of agreement with the following
statements regarding implementation of PFDD in their company: 1. Implementing PFDD would
lengthen the timeline for drug development, 2. Implementing PFDD would increase the cost of
drug development, and 3. Regulatory clarity on what is required to implement PFDD is currently
lacking.

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Q29. What is your level of agreement with the following statements regarding implementation of
PFDD?
Q29 1. Implementing PFDD would lengthen the timeline for drug development (N=62)
Over one-third of respondents selected “disagree” (37%, 23/62) that implementing PFDD
would lengthen drug development timeline, followed by “neither agree nor disagree” (31%,
19/62), “agree” (15%, 9/62), “strongly disagree” (11%, 7/62), “strongly agree” (5%, 3/62), and
“cannot answer” (2%, 1/61).
Figure 46: Understanding Level of Agreement Regarding Implementation of PFDD –
Timeline for Drug Development Lengthened

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Q29 2. Implementing PFDD would increase the cost of drug development (N=62)
Respondents were asked to select their level of agreement with whether implementing
PFDD would increase the development cost. According to the survey results, respondents across
all companies were similarly distributed across “agree” (29%, 18/62), “neither agree nor
disagree” (27%, 17/62), and “disagree” (24%, 15/62). Much less frequently chosen were the
choices, “strongly disagree” (15%, 9/62), “cannot answer” (3%, 2/62), and “strongly agree”
(2%, 1/62).
Figure 47: Understanding Level of Agreement Regarding Implementation of PFDD –
Cost Increase of Drug Development

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Q29 3. Regulatory clarity on what is required to implement PFDD is currently lacking (N=62)
Respondents were asked if they agreed that regulatory clarity is currently lacking on what
is required to implement PFDD. Over half of the respondents selected “agree” (39%, 24/62) or
“strongly agree” (16%, 10/62) followed by “neither agree nor disagree” (23%, 14/62), “disagree”
(19%, 12/62), strongly agree (2%, 1/62), and “cannot answer” (2%, 1/62).
Figure 48: Understanding Level of Agreement Regarding Implementation of PFDD –
Lacking Regulatory Clarity

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Q30. To prepare patients to become partners in drug development, my company provides
trainings for the participants in the following areas
Q30 1. Drug development process (N=61)
Respondents were asked if their company provides patients with training about the drug
development process. Nearly half of the respondents selected “no” (43%, 26/61), one-third
selected “don’t know” (33%, 20/61), and one-fourth selected “yes” (25%, 15/61).
Figure 49: Understanding How Pharmaceutical Companies Train Patients to Prepare
Them to Become Partners in Drug Development
Q30 2. Clinical trial design (N=61)
Respondents were asked if their company provides patients with training about clinical
trial design. Most respondents selected “no” (38%, 23/61) followed closely by “don’t know”
(36%, 22/61), and “yes” (26%, 16/61).
Figure 50: Understanding How Pharmaceutical Companies Train Patients to Prepare
Them to Become Partners in Drug Development

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Q30 3. Understanding clinical trial data (N=59)
Respondents were asked if their company provides patients with training to understand
clinical trial data. Most respondents selected “no” (39%, 23/59), followed closely by “don’t
know” (36%, 21/59), and “yes” (25%, 15/59).
Figure 51: Understanding How Pharmaceutical Companies Train Patients to Prepare
Them to Become Partners in Drug Development
Q30 4. Understanding benefits, risks, and uncertainties associated with medical product use
Respondents were asked if their company provides patients with training to understand
the benefits, risks, and uncertainties associated with medical product use. Most respondents
selected “yes” (36%, 22/61), followed closely by “no” (34%, 15/61), and “don’t know” (30%,
18/61).
Figure 52: Understanding How Pharmaceutical Companies Train Patients to Prepare
Them to Become Partners in Drug Development

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Q30 5. Engaging effectively with health care professionals. medical-product sponsors, and
regulators
Respondents were asked if their company provides patients with training to effectively
engage with health care professionals, medical product sponsors, and regulators. Most
respondents selected “yes” (43%, 26/61), followed by “don’t know” (33%, 20/61), and “no”
(25%, 15/61).
Figure 53: Understanding How Pharmaceutical Companies Train Patients to Prepare
Them to Become Partners in Drug Development

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Q31. My company provides trainings on drug development concepts to informal caregivers (e.g.,
parents or other family members, and/or close friends of patients) (N= 62)
Respondents were asked if their company provides informal caregivers with training on
drug development concepts. Most respondents selected “don’t know” (40%, 25/62), followed
closely by “no” (39%, 24/62). Twenty-one percent answered “yes” (21%, 13/62).
Figure 54: Understanding How Pharmaceutical Companies Train Patients to Prepare
Them to Become Partners in Drug Development

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Q32. In my opinion my company’s approach to Patient Focused Drug Development is: (please
feel free to add comments in the space provided) (N= 60)
When asked to describe the sufficiency of their company’s approach to PFDD, most
respondents from mid-size (88%, 7/8), large (55%, 12/22), and small companies (46%, 6/13)
selected “somewhat insufficient”. The remaining respondent from a mid-size company selected
“sufficient” (13%, 1/8). In contrast, the remaining respondents from large companies were split
between “sufficient” (36%, 8/22) and “insufficient” (9%, 22/60), and in small companies were
split between “sufficient” (38%, 5/13) and “don’t know” (15%, 2/13). Unlike the other groups,
most respondents from very small companies selected “sufficient” (53%, 9/17), followed by
“insufficient” (29%, 5/17), and “somewhat sufficient” (18%, 3/17).
Figure 55: Understanding Company’s Approach to Patient Focused Drug Development
Sufficient
Somewhat insufficient
Insufficient
Don’t know

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Q33. Overall, what do you think is the level of difficulty for your current company to implement
patient-focused approach to drug development? (N= 60)
When asked to describe the level of difficulty involved in implementing PFDD in their
company, most of the respondents from large companies selected difficult [“somewhat difficult”
(55%, 12/22) and “very difficult” (9%, 2/22)] compared to easy [“somewhat easy” (18%, 4/22)
and “very easy” (5%, 1/22)] or “neither easy nor difficult” (14%, 3/22). In contrast, most
respondents from mid-size companies selected “neither easy nor difficult” (63%, 5/8), followed
by “somewhat difficult” (38%, 3/8). On the other hand, most respondents from small companies
were equally split between “somewhat difficult” (38%, 5/13) and “neither easy nor difficult”
(38%, 5/13), followed by “cannot answer” (15%, 2/13) and “very easy” (8%, 1/13). Most
respondents from very small companies were similarly split between “neither easy nor difficult”
(35%, 6/17) and “somewhat difficult” (29%, 5/17). The remaining respondents in this group were
equally split between “somewhat easy” (18%, 3/17) and “very easy” (18%, 3/17).

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Figure 56: Understanding Level of Difficulty in Implementing Patient Focused Drug
Development
Very easy
Somewhat easy
Neither easy nor difficult
Somewhat difficult
Very difficult
Cannot answer

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Q34. Please use this space below to provide any additional insights into PFDD that you would
like to share. Your insights will be very important for understanding this new and emerging area.
Table 12: Additional Insights into PFDD Insights Related to: Commitment to PFDD
Our company has made a commitment to PFDD throughout the lifecycle of drug development, but that
also requires a culture change, meaningful relationship building with patient communities, and
reengineering of underlying R&D processes and expectations. Greater clarity on how regulators
evaluate and put weight on patient experience data in actual benefit/risk decision-making is critical.
FDA's guidance series has been helpful, but more case studies are needed.
PFDD is applied 100% across the development portfolio and also supports discovery/ pre-clinical
teams before a product transition to development.
The company and our Patient Affairs team was built with PFDD in mind from the beginning, therefore,
it didn’t necessarily add costs or time to the drug development process. We are in pre-clinical have not
fully integrated the PFDD process for a program, to date, but the intention is to do so as the programs
move forward. Our corporate culture has a patient-facing foundation and the conversations I have with
colleagues on the core teams show the genuine interest in the patient perspective.
As stated, PFDD is an evolving space. It's an exciting time to work in drug/therapeutics development
and it is nice to see that the industry is actively working to better serve its most important constituents.
My organization is actively working to do a better job of incorporating PFDD principles into its
activities, and I am proud of the approaches we are taking. That said, there is always more that can be
done, and I ’don’t know that any organization will ever manage to be "perfect". But, as the saying
goes, ‘don’t let perfect, be the enemy of good.
While we are doing a number of activities to advance PFDD, it still is somewhat fragmented overall.
There is an understanding of the importance of PFDD, and the value added, but the trade off with speed
and cost is always a consideration. Systematic incorporation of patient experience along the
development cycle is a culture shift that will take time. I am optimistic that we are moving in the right
direction every day.
Lack of resources and money.
PFDD is a journey regardless how committed a company is and requires resources and a culture shift.
Insights Related to: PFDD in Rare Diseases
Explaining the potential value of PFDD in rare disease drug development has found sufficient support
to further explore this topic in our potential rare disease clinical development, in the (clinical stage)
startup companies that I've worked with, in my experience. The inclusion of PFDD and additional
RWD etc is also explored for it's potential 'contextual picture of efficacy value for the FDA/ EMA at
the time of potential approvals, and thus, in my humble opinion, a drug developer in the rare space
cannot do without. I am also sensing the increased support for e.g. Goal Attainment Scales as
endpoints, and these personalized goals are an interesting and personalized extension of PFDD.
* ‘the contextual picture of efficacy is a partial quote from Billy Dunn at the Amylyx AdCom in March
2022 in regard to the potential value of neurofilament light chain and biomarkers in general in rare
neurodegenerative disease drug considerations for approval. Although PFDD is not the same as
biomarkers, I inferred his interest and support in having additional data available“ a "contextual picture

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of efficacy", besides the primary endpoint, as the pre-specified endpoints may not be fully relevant to
the disease or patients.
Very important especially for rare diseases. Critical for the patient experience data to be included in
labeling.
Insights Related to: Regulatory Precedent and FDA Guidance
We are torn between the two poles: the regulatory precedent for a given disease, vs. new insights from
patients about what’s important to them. I have seen patient ad boards become nonproductive when
they turned into round-robins of every symptom the patients experienced or strayed into nondevelopment topics (lack of support from their primary physician, diagnostic odyssey, cost of SOC,
burden of treatment). It can be very hard to turn a mass of patient input into measurable parameters that
will be acceptable to the FDA.
Another challenge is that small companies can’t afford to develop new disease-specific PROs, for
instance, until they know their drug has a high probability of success which is typically too late in the
development timeline to allow for full agreement with the FDA by the time the pivotal studies need to
be designed. The best success I've had with PFDD is for trial design: spacing of visits, ordering of
assessments, minimizing useless but time-consuming assessments. That is especially true in pediatric
trials where every needle stick, every test needs to be considered very carefully.
The FDA does not always follow their own guidance which creates a conflict in implementing PFDD.
A further complication for a global company is a lack of alignment/different approaches by global
regulatory bodies (i.e. FDA & EMA).
In some situations, I think increased regulatory flexibility, with regards to PFDD and achieving
labeling related to it, would greatly enhance integration of PFDD. I answered that PFDD would
increase time and cost of drug development. I see this as partly the result of overly
prescriptive/stringent PFDD guidance.
Getting the guidances into requirements will help move PFDD initiatives along in many companies.
This would go a long way with legal, compliance and regulatory.
While regulators clearly more and more appreciate the ‘patient voice’ and is critical to benefit/risk, it is
still difficult to translate, in timely manner, input into valid endpoints/clinical assessment tools (to
regulators satisfaction)
People are always talking about the voice of the patient but tools for implementing into drug
development are missing.
Obtaining patient views is important to develop the right treatments for THEM. Nevertheless, patients
usually talk about their treatments with physicians, not with companies. Sometimes this tends to be
forgotten. Physicians should, whenever possible and useful, be included in discussions to hear what
patients think and want. Also, discussions about what can be provided in labeling is fair - most patients
would nevertheless not see this, even physicians often ‘don’t read labeling as they should. Other means
of educating both groups have to be explored, at least for the 'average' medication.
General Insights
I believe PFDD is an integral part of the entire drug development and commercialization continuum!!!

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There is a spectrum spanning from the reasonably educated and highly to the committed investigatorresearcher, to the controversial 'right-to-try.' All voices are valid which should be weighted differently
depending on the domain under evaluation.
From patient advocates: You should do nothing about us without us.
The implementation and integration of PFDD may depend on the lifecycle of the product. The other are
we need to consider is "representativeness" - not only engaging "professional patients".
Looking forward to seeing the data that is coming out of this and learning from other industry experts.

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Chapter 5. Discussion
5.1 Introduction
Adoption and implementation of PFDD is reshaping the pharmaceutical industry, but it
confronts challenges that require further attention. While recognition of the importance of
involving patients early in the drug development process continues to gain momentum, the
challenges pharmaceutical companies face in doing so have been under-explored. This research
study delves into these critical aspects. The findings in this study provide insights from experts
within the pharmaceutical industry as to how PFDD is being implemented within individual
companies. To ensure the meaningful interpretation of this research and its conclusions, it is
essential to examine the study’s methodological considerations, including its limitations and
constraints.
5.2 Methodological Considerations
5.2.1 Delimitations
As discussed in Chapter 2, patient-focused drug development (PFDD) constitutes a
multifaceted ecosystem that involves the FDA, patients, caregivers, patient advocacy
organizations, and the pharmaceutical industry, among other stakeholders. This research,
however, focuses solely on one stakeholder: the pharmaceutical industry.
This research is also temporally delimited. The survey for the study was conducted
during the period between mid-August through September 22, 2022. Therefore, the findings of
this study will reflect the viewpoints held during that specific timeframe. It is worth noting that
all four of the PFDD guidances were introduced within the past five years, with only the first two
having been finalized by the time the survey was distributed (FDA, 2023b). As of January 2024,
the third and the fourth PFDD guidance documents remain in draft format (FDA, 2024) and were

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released for public comments much later than mandated by PDUFA VI requirements.
Consequently, the full implementation of PFDD requirements and provisions, including the
issuance of additional guidance documents for the pharmaceutical industry, has yet to occur.
Therefore, it is important to note that the findings presented in this study may have limitations in
their ability to forecast the future state of the PFDD environment accurately. Furthermore, the
persistence of these perspectives over time remains uncertain.
The regulatory framework around the utility of patient experience data (PED) varies
greatly among major regulatory bodies. To avoid the potential confusion that might arise if
respondents reported on experiences from different countries, the participant pool was delimited
to individuals employed by companies operating within the U.S. regulatory framework.
Particular emphasis was placed on identifying suitable respondents to ensure that their responses
would offer insights and ensure the validity and generalizability of the survey findings.
Consequently, the surveyed population was restricted to professionals who are familiar with
PFDD initiatives and are actively involved in PFDD discussions and activities within their
respective companies. It is evident that this objective was met, as most of the respondents held
senior positions within their organizations, making them well-positioned to provide in-depth
insights into various challenges associated with the implementation of PFDD.
The study was further delimited by adopting a single framework to define its scope: Kurt
Lewin’s change management framework (Cummings and Huse, 1989). This framework offered a
structured method for examining how the pharmaceutical industry implements PFDD in its drug
development process during a period of transformation. While it was selected because of its
prominent use in organizational change research, there are multiple other frameworks that we
might have applied in lieu of, or addition to it as well.

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5.2.2 Limitations
For the successful execution of this research, it was imperative to secure active
participation from experts employed by companies operating within the U.S. regulatory
framework, particularly those who are engaged in PFDD discussions and activities within their
respective organizations. To fulfill this essential requirement, I leveraged a well-established
network of experts who were active in industry groups such as Pharmaceutical Research and
Manufacturers in America (PhRMA), Biotechnology Innovation Organization (BIO), and
Alliance for Regenerative Medicines (ARM). To involve these experts, I chose to employ a
survey-based approach known for its cost-effectiveness in collecting data from a broad
respondent base. Before officially launching the survey, a focus group was convened to review
and enhance the questionnaire. The aim was to ensure that the questions were suitable and easily
comprehensible while minimizing the potential for respondent fatigue. There are, however, a
number of limitations associated with using surveys for data collection. First, responses are
subjective; there is no way to verify the truth of the responses. Second, the response rate may be
highly influenced by participants’ interests, the structure of the survey, communication methods,
and confidentiality. Another concern was that respondents might provide an unchecked email,
hence not responding to the survey (Saleh & Bista, 2017). Further, it was important to ensure
respondents didn’t drop off from the survey at critical questions to gather meaningful data. To
mitigate that risk, I have limited the number of questions to 35, and introduced a variety of
formats to introduce a question (Moy & Murphy, 2016). The survey link was distributed to the
email addresses of potential respondents who had previously expressed their willingness to
participate. The link was also made available on LinkedIn as an open invitation to potential
respondents who are currently engaged in PFDD discussions and activities. Both approaches

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amount to a form of convenience sampling; hence, our ability to generalize these findings to all
pharmaceutical companies operating in the US market is limited.
As noted above, since respondents were recruited from a small network of experts, the
generalizability of my sample to the broader pharmaceutical industry population may be limited.
Moreover, with only one person from a company typically participating in the survey, it was not
possible to infer that their responses were representative of the company’s position. For example,
if individuals representing different roles and departments within a single company participated
in the study, their views could have been triangulated to obtain a more robust, multi-dimensional
assessment of the company’s position regarding PFDD. In addition, most respondents were at
senior levels and, hence, the results may not reflect views of those in more junior levels of
organizations. Indeed, to gain insights into the implementation of new initiatives like PFDD
within the industry, it would have been preferable to gather perspectives from respondents at
different organizational levels and then triangulate results. Otherwise, there is a risk of atomistic
fallacy in inferring that the views of a single individual are truly representative of the
organization as a whole (Diez, 2002).
Acknowledging that PFDD is in a process of gradual implementation throughout the
pharmaceutical industry drug development lifecycle, robustness of the data would have been
improved if this study had been done after the fourth guidance document on PFDD had been
finalized. Additionally, the term “culture change” was not defined in the survey, and it is
possible that different respondents may have interpreted it differently.
There was also a degree of concern regarding survey distribution during the COVID-19
pandemic, a period when the workload for employees across industries was acknowledged to be
more strenuous compared to pre-pandemic times (dos Santos et al., 2022; Castro, 2020). The

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survey was not piloted with anyone in the pharmaceutical industry, hence missing an opportunity
to modify so as to ensure clarity of questions for respondents.
It was my assumption that all respondents would provide truthful and accurate responses.
I accepted the results of this study as truthful as the anonymity of the survey doesn’t provide an
opportunity to confirm the accuracy of responses. Lastly, this was an exploratory effort and
future research could learn from these limitations.
5.2.3 Discussions of Results
The global interest in patient-centered drug development has been steadily growing. As
highlighted in Section 2.4, the U.S. FDA’s PFDD initiative has been in effect for over a decade.
To gain insights into the pharmaceutical industry’s perspectives on PFDD, I utilized the FDA’s
draft regulatory framework around patient-focused drug development (FDA PFDD Guidance 1
and 2). Specifically, I sought to understand the viewpoints of professionals within the
pharmaceutical industry who are actively involved in PFDD discussions and activities. These
professionals encompassed various roles, including clinical development, regulatory strategy,
regulatory policy, patient engagement, and patient advocacy. The study explored how these
individuals perceive PFDD in the context of their company’s culture and approach to change
management to embrace PFDD adoption within the context of Lewin’s Change Management
Model or organizational change. The results of this study reveal that PFDD is viewed as
necessary and important but not yet fully adopted and implemented. As discussed in Chapter 2,
Lewin’s Change Management Model closely resembles the landscape of Fixsen’s
Implementation Model which undergoes four distinct stages: 1) exploration and adoption, 2)
preparation and installation, 3) initial implementation, and 4) full implementation (Fixsen et al.,
2009). Although Kurt Lewin’s Change Management Model has been widely used in the field of

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psychology (Hussain et al., 2018), it also allows for examining the three distinct phases of
organizational change. As I wanted to examine the impact of organizational culture on PFDD
within the pharmaceutical industry, in addition to a three-pronged approach to the adoption and
implementation of PFDD, it seemed appropriate to utilize it for this research. To my knowledge,
this is the only study to examine the adoption of PFDD within the pharmaceutical industry based
on the first two finalized FDA guidance documents on PFDD, applying the theoretical Change
Management approach. The use of theory to guide this research is notable strength and allows
me to link results to a larger body of research that has used Lewin’s model to date as further
described below. The Impact of Organizational Culture on the Adoption of ‘FDA’s PFDD
Initiative
A company’s organizational culture plays a pivotal role in shaping its ability to adopt
PFDD initiatives in a sustainable manner (Berwick, 2003; Weiner, 2009). Pharmaceutical
companies that embrace innovation, promote reasonable risk-taking, and reward continuous
pursuit of new learnings will more readily implement new innovations (Ingersoll et al., 2000).
The state of organizational readiness is achieved through a multi-dimensional lens, primarily
employee’s desire to implement change and their capability to execute. Success of PFDD
implementation within pharmaceutical industry will greatly depend on the state of organizational
readiness (Sweeney & Whitaker, 1994; Hardison, 1998; Weiner, 2009). More substantial
promotion of organizational readiness will take place in companies with a culture of flexibility
and an openness to revisiting current procedures (Eby et al., 2000).
Indeed, if the long-term sustainability of PFDD is to be accomplished, it will depend on
the company’s culture. Senior leadership that embodies and promotes PFDD culture play an
important role in this regard as leadership can inspire and guide the organization through the

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stages of PFDD adoption and implementation. Moreover, positive company culture can foster
uptake of PFDD by motivating employees in pharmaceutical companies to embrace and actively
participate in PFDD activities. Further, positive company culture can make it easier to rally
employees behind changes that must take place for full adoption and implementation of PFDD.
A resilient culture will help employees cope with uncertainty and help them to adapt to evolving
circumstances more effectively. Companies with an adaptive culture will more readily embark
on transformative journeys such as implementation and adoption of PFDD processes and policies
(Hollister et al., 2021). Pharmaceutical companies that value adaptability and learning will
enable the employees to respond quickly to external initiatives driving PFDD. Additionally, in
terms of securing adequate resources for the adoption of PFDD, culture can significantly affect
the recruitment and retention of key talent (Sheridan, 1992). An organization prioritizing
conformity over creativity inevitably stifles meaningful discussions about the necessary changes
required to embed patient voices throughout the entire drug development cycle.
If a company maintains a rigid hierarchical structure and suppresses open and transparent
communication, its employees are less likely to share their insights about the evolving PFDD
regulatory framework. Therefore, the successful adoption and implementation of PFDD within
the pharmaceutical industry necessitates a transformation in organizational culture, a
reevaluation of existing norms, and an adaptation of current policies and practices. This
transformation aligns with Kurt Lewin’s 3-step Change Management model (Cummings and
Huse, 1989).
5.2.3.1 Undergoing a Cultural Change
In light of the research findings, it is evident that a prevailing sentiment among most
respondents is the necessity for their respective companies to undergo a transformative cultural

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shift in order to fully integrate PFDD into drug development process (Figure 15). As one
respondent stated, “systematic incorporation of patient experience along the development cycle
is a culture shift that will take time.” This cultural transformation is not merely a one-time event
but an ongoing process that demands sustained organizational commitment to ensuring patient
involvement in both the drug development cycle and post-approval settings. To achieve this
desired transformation, companies must cultivate an organizational culture that is inherently
patient-focused (Boutin et al., 2017). This entails embracing patient perspectives
comprehensively, including activities aimed at identifying patient-related treatment outcomes
and actively involving patients in regulatory reviews. It also extends to reporting side effects
caused by their medicines (CIOMS Working Group, 2022).
The influence of a company’s culture on individual employee alignment with the broader
organizational context has been well documented (O’Reilly, Chatman & Caldwell, 1991; Nongo
& Ikyanyon, 2012). Hence, the sustainability of a company’s commitment to PFDD hinges on its
long-term commitment to this transformative endeavor that would foster successful recruitment
and retention of key talent to drive PFDD initiatives. The findings of this study highlight a
noteworthy trend: pharmaceutical companies are increasingly emphasizing the importance of
integrating patient perspectives into the drug development process among their employees
(Grom, 2019; PharmaVoice Team, 2019). This communication represents a positive sign of the
much-needed shift in culture towards greater incorporation of patient viewpoints in
drug development. Such a transformation is crucial for the industry’s ongoing progress and
success. For instance, one respondent exemplified effective communication within their
organization by stating:

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“Our company has made a commitment to PFDD throughout the lifecycle of drug
development, but that also requires a culture change, meaningful relationship
building with patient communities, and reengineering of underlying R&D
processes and expectations.” - survey respondent
5.2.4 Unfreezing
The goal during the unfreezing stage is to disrupt the current “status quo” in the
pharmaceutical company so that it opens opportunities for new learnings to take root. During
this phase, pharmaceutical companies undergoing adoption of PFDD must identify current silos,
available resources, norms, and policies and practices for inclusion of patients in the drug
development process (Cummings and Huse, 1989). Additionally, during this stage,
pharmaceutical companies should take inventory of their relationships with relevant patient
advocacy organizations. These relationships can indeed be unfamiliar as either party might lack
experience in working with the other. However, both advocacy organizations and pharmaceutical
industry share one common goal: improving and extending patients’ lives, hence timely and
meaningful interactions are vital (EveryLife Foundation of Rare Diseases, 2021). Lastly, during
this stage it is critical to define the roles and responsibilities of cross-functional stakeholders
involved in PFDD activities. Data from this research asserts that most companies have moved
beyond this phase.
5.2.4.1 Current Approach to Drug Development
Shifting from the traditional approach of drug development to a patient-focused approach
requires significant commitment to prepare the organization for change. According to Everett
Rogers’ theory of diffusion in innovations, the first wave of pharmaceutical company adopters to
implement PFDD are referred to as “innovators”, driven by their enthusiasm and excitement for
change. These innovator companies are less concerned about societal pressures and what current
climate on PFDD dictates. For example, the intent of PFDD is to engage patients as early as

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discovery and pre-clinical phase of development and throughout the development cycle. Once
the “innovators” set the stage, early adopters in pharmaceutical industry will embark on the
PFDD implementation journey. They believe benefits of implementing PFDD in their respective
organizations might outweigh the disadvantages of not doing so. Remaining are subsequent early
and late majorities whose main reason for adopting PFDD will be due to societal pressures. For
example, pressure comes from patient’s advocacy organizations, specifically those operating in
rare disease and high unmet medical need arenas, whose highly informed and effective advocacy
efforts have been discussed in Chapter 2. Lastly, pharmaceutical companies lagging behind tend
to be less concerned about societal norms, and often take their time to embark on innovation
initiatives like PFDD (Dearing & Cox, 2018).
The findings from this study indicate that the industry is somewhat divided in its
acknowledgement of the need to change the prevailing method of drug development for the full
implementation of PFDD. While larger companies see the need, as reflected by 70% of survey
respondents, more than a half of the respondents from very small companies do not (Figure 16).
However, it is reasonable to consider that respondents from very small companies who indicated
that there is no need for change, might have expressed that view because the change had already
taken place. Additionally, many of the very small companies typically do not plan past the
research and development phase. If a startup’s pipeline shows promise, larger companies swiftly
target them for takeovers or mergers during early stages of product development (Bansal et al.,
2018). This raises concerns about their willingness to embrace long-term initiatives such as
PFDD. Potential laggards in PFDD implementation within very small companies might express
concerns about revealing intellectual property information during early patient engagement
activities.

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Furthermore, this study suggests the need for increased direction from the FDA. Despite
the FDA’s advocacy for the gathering of patient experience data (PED) throughout the
development process, there is an obvious need for clear and transparent guidance regarding the
utilization of this data during drug evaluation and regulatory decision-making. This policy gap
has created a dilemma for pharmaceutical companies contemplating the adoption of PFDD. In a
recent study by Pinto et al. (2023), authors aimed to describe “current practices and challenges
related to collection, submission, and use of patient experience data in regulatory decision
making, review documents, and approved product labeling”. The results of that study, based on
an online survey of experiences (part 1), and best-worst exercise for prioritizing PED
advancement efforts (part 2) (Pinto et al., 2023), indicate that the most critical challenge with
PED collection remains not knowing if or how PED is used during the drug evaluation process.
To add to the uncertainty of PFDD implementation within pharmaceutical industry, the final
FDA guidance on “Benefit-Risk Assessment for New Drug and Biological Products” (FDA,
2023a) was released to the public six months after the intended PDUFA VI commitment date.
While the guidance acknowledges that patient experience data and related information may be
used in benefit-risk assessment, it does not provide further clarity or transparency about the
extent how the FDA considers PED during drug candidate evaluation (FDA, 2018g).
The FDA acknowledges that patients are experts about their condition and the outcomes
of a particular medical treatment and lists the different types of patient experience data that can
inform all stages of benefit-risk assessment. The FDA also notes that it must balance patient
perspectives in the context of the overall benefit-risk determination and that even when some
patients experience the benefit of the treatment, the approval decision will be based on the
benefit for the overall population. In the section, “Collecting Patient Experience Data During

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Development to Inform Benefit-Risk Assessment,” the FDA states that collecting patient
experience data at the beginning of the drug development process can identify unmet patient
needs and define the patient population. Companies are advised to engage with the Agency early
to get timely feedback from the FDA. While the guidance document contains a wealth of
information, it fails to adequately explain how the collected data is considered during the
benefit-risk determination, leaving perhaps the most critical question unanswered.
Drug development is a long and demanding process, fraught with substantial risks for
pharmaceutical companies. Introducing additional uncertainty into the assessment and regulatory
decision-making steps presents a tangible threat to the widespread adoption of PFDD within the
industry.
5.2.4.2 Collaboration with Patient Advocacy Organizations
From the formation of National Foundation of Infantile Paralysis in the early 20th century
(March of Dimes, 2023), NORD (2020) and ACT UP (2023) in the early 1980’s, Patient-Parent
Muscular Dystrophy (PPMD) in 1994, and EveryLife Foundation in 2009, patient advocacy
organizations have emerged as a critical partner in drug discovery. The introduction of PFDD
has only amplified the opportunity for more meaningful collaboration between pharmaceutical
companies and patients and their advocates. This research uncovered that while most
pharmaceutical companies have formed meaningful collaborations with patient advocacy
organizations and use patient and/or advocacy group support to collect patient views, they
continue to demonstrate limited efforts in educating patients about the drug development
process. Drug development is a long process; hence, it is critical to approach the collaboration
with patient advocates through an early and long-term lens. The effectiveness and sustainability
of this collaboration will depend on reliable internal processes for engagement within a

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pharmaceutical company. Identifying internal company silos should be prioritized as they
typically adversely impact progression of collaboration. Further, the education of the company’s
legal and compliance functions should begin and continue throughout the collaborative process
with patient advocates. More specifically, informing legal and compliance functions on
expectations grounded within patient-focused drug development initiatives and collaboratively
developing company-specific processes and agreements to ensure interactions that are mutually
meaningful and effective. Lastly, pharmaceutical companies should engage with PAO’s early in
the process so that their collaboration can inform meaningful planning and decision making
(EveryLife Foundation for Rare Diseases, 2021). As one respondent, also a patient advocate,
stated: “From patient advocates: you should do nothing about us without us.”
5.2.5 Changing
The successful implementation of complex changes often hinges on the critical precursor
of organizational readiness for change (Armenakis et al., 1993). According to Kotter (1996), a
significant portion of unsuccessful large-scale organizational change efforts is attributed to the
failure to establish adequate readiness, Key indicators of company’s capability to implement
PFDD include awareness about how demanding are the tasks, how available are the resources,
and what are the factors surrounding specific situations. Level of organizational readiness will
depend on how well these indicators are embraced. The more robust the organizational readiness,
the more likely it will be that employees implementing PFDD will display eagerness, persistence
and cooperation (Weiner, 2009), During changing phase, pharmaceutical companies should
move from “old” ways of developing drugs to the new “desired” state, which embraces early and
continuous patient engagement. Changing as well as challenging well-established processes and
strategies for developing drugs will bring uncertainty among employees, causing resistance,

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anxiety, and confusion (Jooste, 2015). During the changing stage, companies undergoing the
adoption of PFDD will have to ensure openness to inclusion of patient experience throughout the
drug development cycle. It will start with the alignment on the company’s culture toward the
utilization of patient-focused data to effectively navigate the existing regulatory framework.
Critical to the success of the initial implementation (“changing”) stage and moving onto the full
implementation (“freezing”) stage of PFDD within the pharmaceutical industry is successfully
navigating through uncertainty and adapting to new ways of approaching drug development. The
findings of this research indicate that while the pharmaceutical industry acknowledges the
significance of PFDD, the actual implementation is in a state of flux. Larger companies appear to
be entering the “changing” phase, while smaller companies have not yet reached that stage.
5.2.5.1 FDA Guidance
The evolution of patient engagement at FDA dates to the 1980s, during the early days of
the HIV/AIDS epidemic, when the first HIV/AIDS patient group was founded (FDA, 2019e).
Over the next four decades, the FDA has introduced numerous initiatives to capture the patient’s
voice. However, the first draft guidance on PFDD did not emerge until 2018 (FDA, 2018h),
more than three decades after patient engagement at FDA was introduced. More surprisingly,
more than a decade after the PFDD initiative was launched, only the first and the second of the
planned four methodical fit-for-purpose guidance documents on PFDD have been finalized, with
the third and the fourth remaining in the draft format as of January 2024. None of the currently
available FDA guidance documents address the question about how FDA considers PED during
drug evaluation and benefit-risk assessment. More specifically, current guidance documents fail
to explain “worth” of PED compared to the data obtained in human clinical trials. Better
Empowerment Now to Enhance Framework and Improve Treatments Act of 2023 (BENEFIT

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Act) requires FDA to consider relevant PED during benefit/risk assessments and requires FDA to
issue a public statement about how the data was considered during drug candidate evaluation and
benefit-risk assessment. Indeed, this would be a welcomed policy change which would benefit
the entire PFDD ecosystem, not only the patients, FDA, and pharmaceutical industry.
Currently, the incomplete regulatory framework around utilization of patient experience
data during drug evaluation remains a significant hurdle for the pharmaceutical industry (Pfizer,
2022; Janssen, 2022). Further, this research uncovered that most respondents agreed when asked
if there is lack of regulatory clarity on what is required to implement PFDD. The pharmaceutical
industry depends on sound and consistent guidance and a complete regulatory framework if it is
to achieve permanent change and adoption of PFDD.
“The FDA does not always follow their own guidance which creates a conflict in
implementing PFDD.” - survey respondent
“Getting the guidances into requirements will help move PFDD initiatives along in many
companies. This would go a long way with legal, compliance and regulatory.” – survey
respondent
5.2.5.2 Lack of Global Standards Around Utility of Patient Experience Data During
Regulatory Decision Making
Many pharmaceutical companies embark on the complex journey of global development
for their drug candidates. An area in which standards and regulations around PFDD will need to
evolve relates to how global health authorities measure “worth” of patient experience data during
drug evaluations and determination of benefit-risk. First, in terms of existing regulatory guidance
for PFDD, FDA remains the only health authority that has published them. Although European
Medicines Agency (EMA) has a long history of patient engagement and is focused on ensuring
patient involvement in the regulatory decision-making processes, it is yet to publish a single
guidance document for industry solely focused on patient-focused drug development issues

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(EMA, 2023). It is much the same for the rest of the world. Continuation of adoption and
implementation of PFDD in the US will continue to gain momentum as other regulatory agencies
put forward their own regulatory frameworks around utility of patient experience data during
regulatory reviews and drug evaluation process. Indeed, global convergence about “worth” of
patient experience data might stimulate more robust response to PFDD among companies with
global aspirations.
Current lack of transparency and understanding around what and how data has been
utilized during the determination of benefit risk at FDA remains unclear and presents as a
significant concern to pharmaceutical companies (CIOMS, 2022). The role that patient
experience data plays in FDA’s benefit-risk assessments continues to evolve as evidenced by
October 2023 publication of a guidance on “Benefit-Risk Assessment for New Drugs and
Biological Products”. The guidance, published more that eleven years after the initiation of
PFDD initiative, recognizes the importance of patient experience data in the context of benefitrisk assessments. Indeed, the Agency indicates that patient experience data can inform “nearly
every aspect of FDA’s benefit-risk assessment” (FDA, 2023a) Although the guidance mentions
that “FDA carefully weighs and considers the patient perspective” it fails to describe what that
includes. Lastly, there is significant need for global convergence on regulatory guidance for
PFDD, specifically in the context of PED utility during benefit risk determination. As stated by
two respondents:
“A further complication for a global company is a lack of alignment/different approaches
by global regulatory bodies (i.e., FDA & EMA).”
“While regulators clearly more and more appreciate the ‘patient voice’ and is critical to
benefit/risk, it is still difficult to translate, in timely manner, input into valid endpoints/clinical
assessment tools (to regulators satisfaction).”

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Much remains to be done globally if pharmaceutical companies are to embark on global
drug development with long-term commitment to collection and utilization of patient experience
data. Without a doubt, this would be a welcomed development for the entire ecosystem of
stakeholders.
5.2.5.3 Role of Leadership in Promoting PFDD Activities
Senior leaders of pharmaceutical companies will play a critical role in guiding the
company through the changes necessary for the adoption of PFDD. Indeed, their ethical conduct
during organizational change, voice, visibility, accessibility, and openness to feedback from
employees implementing changes are fundamental to the success and long-term sustainability of
PFDD (Hussain et al., 2018). During this change, senior leaders of pharmaceutical companies
should talk about their vision for implementing PFDD in their company and be able to
effectively communicate how the adoption of PFDD will benefit the entire ecosystem in drug
development: the patient, the company, and the industry. How the leadership asserts its style of
management will decide about the success of adoption and implementation of PFDD. Indeed,
transformative leaders, those displaying charismatic approach along with intellect and
individualized nuances will identify talent needed for sustainability of PFDD (Bass, 1985)
Often, transparent communication about the reasons behind the change, which according to
research by Morgan and Zaffane (2010) reveals significant negative effects on trust, can
alleviate concerns around uncertainty while at the same time building a new patient-focused
culture and providing a sense of direction. This research shows that senior management actively
promotes the inclusion of relevant employees in PFDD activities. Certainly, this is a welcomed
sign for the long-term sustainability of PFDD.

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5.2.6 Freezing
To ensure the long-term success for adoption and integration of PFDD, pharmaceutical
companies will have to promote active participation of their employees in PFDD activities (Oreg,
Vakola & Armenakis, 2022). The importance of leadership, establishment of common vision,
and providing employees with an effective framework cannot be underestimated and will be
critical for achieving goals associated with the implementation of PFDD (Keown, et al., 2014).
According to Kurt Lewin’s Action Research (1946), described as an iterative process where fact
finding and evaluation of PFDD activities will lead to action, pharmaceutical companies will
need to undergo several cycles of fact finding and engage in various activities until the objective
of PFDD adoption and implementation has been completed. Throughout this iterative process, in
order for PFDD to sustain its long-term success, senior leadership of pharmaceutical companies
will have to ensure that employees voluntarily engage in democratic process of decision making
in the context of PFDD adoption (Lewin, 1947b). Although the findings from this research
indicate that the industry as a whole has not yet entered the freezing phase, there are indications
that the companies with dedicated infrastructure and resources for PFDD initiatives are emerging
from the changing phase and entering the freezing phase.
5.2.6.1 When to Seek Patients’ Input
“The company and our Patient Affairs team was built with PFDD in mind from
the beginning, therefore, it didn’t necessarily add costs or time to the drug
development process. We are in pre-clinical and have not fully integrated the
PFDD process for a program, to date, but the intention is to do so as the
programs move forward. Our corporate culture has a patient-facing foundation
and the conversations I have with colleagues on the core teams show the genuine
interest in the patient perspective.” (survey respondent)
PFDD calls for early engagement of patients (e.g., as early as the launch of a discovery
program)(CTTI, 2015), and results from this study indicate that most respondents agree on the

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need for companies to communicate about the inclusion of patient perspectives during drug
development process. Indeed, some companies have demonstrated commitment to early patient
engagement during the development of their drug candidates. As one respondent stated: “PFDD
is applied 100% across the development portfolio and also supports discovery/ pre-clinical
teams before a product transition to development.” However, this research confirms that most
companies include patients only when the asset reaches clinical development stage and post
approval (Figure 20), while only seven respondents across all company sizes indicated that their
respective companies engage patients early and throughout the drug development cycle, perhaps
indicating adoption of PFDD framework (Figure 21). Hence, current broader practice in
pharmaceutical industry is not meeting the intent of PFDD. Moreover, findings in this study
point to the missed opportunity by pharmaceutical industry to gain critical, early patient insight
about impact of disease and its treatment on the patient. These include signs, symptoms, chief
complaint, burden of living with the condition, burden of treatment and burden with participating
in clinical trials. Additionally, during early engagement patients can provide experience about
potential and current treatment options. More specifically, expectations of benefits and risk
tolerance associated with the treatment (FDA, 2020h). Lastly, these early engagements can help
identify unmet patients’ needs and define the intended population.
5.2.6.2 Current State of PFDD Adoption in the US
This research indicates that most mid-to-large size companies are still in the process of
adopting PFDD. This is partly due to the still evolving PFDD framework as the third and the
fourth guidance documents remain in the draft format.

134
PFDD is an evolving space. It's an exciting time to work in drug/therapeutics
development and it is nice to see that the industry is actively working to better
serve its most important constituents. My organization is actively working to do a
better job of incorporating PFDD principles into its activities, and I am proud of
the approaches we are taking. That said, there is always more that can be done,
and I ’don’t know that any organization will ever manage to be "perfect". But, as
the saying goes, don't let perfect, be the enemy of good. - survey respondent
Nonetheless, mid-to-large size companies demonstrated awareness of the PFDD initiative
which allows for initiation of internal processes and assessments. Perhaps informative was also a
finding that more than one third of very small companies (36%) did not start any of the PFDD
activities (Figure 32). As previously described, this finding might at least partially be due to the
lack of awareness about PFDD initiative. This trend must be addressed should the engagement
rate in activities around patient experience data collection in very small companies increase.
Very small companies, frequently funded by venture capitalist firms, lack resources for
regulatory policy and intelligence and regulatory advocacy functions which play a critical role in
keeping the organizations informed about external drug development landscape and emerging
initiatives. Lastly, very small companies heavily focus on internal activities directed toward asset
development leaving the developments in an external environment inadequately covered, hence
contributing toward lack of awareness of existing and upcoming regulatory science initiatives
such as patient-focused drug development.
5.2.6.3 Ensuring Sustainable PFDD
After a successful campaign of promoting PFDD internally, senior leaderships’ long-term
commitment to organizational change is critical to its sustainability. According to the survey
results most companies have demonstrated long term commitment to PFDD by securing financial
and/or human resources (Figure 12), and budgeting funds for attendance of external conferences,
workshops and seminars to build on existing expertise (Figure 45). Indeed, the adoption and

135
implementation of PFDD is a long journey that requires adequate resources to ensure long-term
sustainability. Historically, pharmaceutical companies did not include patients in the
development process. Hence, there were no separate roles within pharmaceutical companies
dedicated to leading PFDD activities. Indeed, these activities were embedded into existing roles
of employees across research and development without proper coordination and resource
allocation to measure effectiveness adequately.
“PFDD is a journey regardless how committed a company is and requires resources and
a culture shift.” (survey respondent)
5.3 Future Directions and Concluding Thoughts
Recognizing the indispensable role of patient perspectives throughout the drug
development cycle is vital for the entire healthcare ecosystem. However, achieving meaningful
patient engagement within the pharmaceutical industry remains elusive. The present research has
delved into the underlying reasons for this challenge, revealing that PFDD is acknowledged as
necessary and important but hasn’t been fully adopted and implemented. Of particular interest to
this study was understanding the differences in the adoption and implementation of PFDD across
companies of varying sizes. The findings suggest a variance in the degree of adoption and
implementation of PFDD, with challenges more pronounced among smaller companies
(Figure 32). While larger companies appear to be entering the “changing” phase of Kurt Lewin’s
Change Management Framework or the “initial implementation” phase of Fixsen’s
Implementation Framework, smaller companies face obstacles due to resource constraints. The
gap in adoption and implementation of PFDD between larger and smaller companies is
anticipated to persist until sufficient human and financial resources are secured. One way to
measure a company’s cultural shift toward a long-term commitment to PFDD is by taking
inventory of current and planned human and financial resources for various activities across

136
different stages of drug development. For instance, are there currently dedicated patient
engagement roles in the company? Is there a plan to invest in recruitment, ensure adequate
compensation, and develop a career path for those interested in PFDD positions? These types of
questions should be explored in future research.
Recognizing the importance of pre-competitive information sharing is critical to foster a
cultural shift within the industry. Specifically, there is a need for sharing experiences related to
the internal and operational aspects of adopting PFDD. Pharmaceutical companies play a pivotal
role in engaging with critical stakeholders, ranging from patients and caregivers to regulators and
investors. Hence, they are exceptionally positioned to serve as a central figure within the drug
development ecosystem. This is especially relevant when it comes to sharing insights gained
from early engagement with patients, which can be of significant value to other stakeholders.
“While we are doing a number of activities to advance PFDD, it still is somewhat
fragmented overall. There is an understanding of the importance of PFDD, and
the value added, but the trade off with speed and cost is always a consideration.
Systematic incorporation of patient experience along the development cycle is a
culture shift that will take time. I am optimistic that we are moving in the right
direction every day.” (survey respondent)
Finally, this research reveals a notable shortcoming in the industry’s engagement in the
area of patient education. While the PFDD initiative aims to position patients as partners
throughout the drug development process, the lack of effort in educating and training them limits
their ability to contribute effectively in that role. Pharmaceutical companies can play a more
impactful role in their interaction with patient advocacy organizations and patient communities.
Many patient advocacy organizations lack the capability to elevate the voice of their patients
simply because they lack human and financial resources or adequate knowledge of existing
resources elsewhere. While PFDD is widely accepted as important throughout the drug

137
development ecosystem, the organizational changes required to make this a reality have yet to
transpire.

138
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154
Appendix A. Survey
The Impact of FDA Patient-Focused Drug
Development (PFDD) on US Drug Development
Strategies
Start of Block: Default Question Block
Q1 Dear Survey Respondent,
This survey is designed to capture your views and experience with the implementation of Patient
Focused Drug Development (PFDD) in your company. PFDD is defined as a systematic
approach to help ensure that patients’ experiences, perspectives, needs, and priorities are
captured and meaningfully incorporated into the development and evaluation of medical
products throughout the medical product life cycle. This survey is part of research associated
with the Doctor of Regulatory Science degree at the University of Southern California. Your
answers are important to the success of the study and are completely anonymous. At the end of
the survey, there will be an option to voluntarily participate in a follow-up phone interview. You
can also receive the survey results upon request once the study is completed. Thank you in
advance for your participation.
End of Block: Default Question Block
Start of Block: Demographics
Q2 Does your company develop new drugs and/or new biologics?
o Yes (1)
o No (2)
Skip To: End of Survey If Does your company develop new drugs and/or new biologics? = No

155
Q3 What is the size of your company?
o Less than 250 employees (1)
o251-5,000 employees (2)
o5,001-20,000 employees (3)
o More than 20,000 employees (4)
Q4 What percentage of your company's portfolio is dedicated to rare diseases?
o Less than 10% (3)
o10-50% (4)
o Greater than 50% (5)
Q5 Which of the following statements best describe your involvement in PFDD initiative in your
company?
oI am only involved in PFDD discussions (2)
oI am involved in PFDD activities (1)
oI am involved in both PFDD discussions and activities (3)
oI am involved in neither PFDD discussions nor activities (4)
Skip To: End of Survey If Which of the following statements best describe your involvement in PFDD initiative in your
compa... = I am involved in neither PFDD discussions nor activities

156
Q6 How long have you been involved in PFDD discussions and/or activities?
o Less than 3 years (1)
o3-10 years (2)
o More than 10 years (4)
Q7 Which of the following best describes your functional role in the company?
o Regulatory Affairs, Strategy, or Policy (1)
oPatient Engagement or Patient Advocacy (2)
o Clinical Development (3)
o Medical Affairs (4)
o Other (please specify) (5) __________________________________________________
Q8 Please indicate the level of your current position.
o Vice President or higher (1)
oSenior Director / Executive Director (2)
o Associate Director / Director (3)
o Manager / Senior Manager (5)
o Other (please specify) (4) __________________________________________________

157
Q9 In your opinion, which statements best describe your company's current or to date
engagements in PFDD activities? Please select all that apply.
▢ My company utilizes best practices for collecting patient experience information
(PFDD Guidance 1) (2)
▢ My company utilizes methods for identifying what is important to patients (PFDD
Guidance 2) (1)
▢ My company attends or has attended FDA-led PFDD meetings and/or Externallyled PFDD meetings (3)
▢ My company has formed meaningful collaborations with patient advocacy
organization(s) (10)
▢ Other (please add to the text box bellow) (5)
__________________________________________________
End of Block: Demographics
Start of Block: Culture
Q10 In your opinion, which statement below best describes your company's interest in PFDD?
o My company is aware of PFDD, but has competing interests (6)
o My company is interested in PFDD, but does not have the expertise to implement (7)
o My company is aware of PFDD, but not interested (8)
o My company lacks awareness of PFDD (9)
o My company is actively pursuing adoption of PFDD (11)

158
Q11 In your opinion, what is your company's level of commitment to pursue PFDD as a longterm aspiration?
o My company has not yet shown interest to adopt PFDD (2)
o My company has expressed interest in pursuing PFDD but has not secured financial
and/or human resources (3)
o My company has committed financial and human resources to pursue PFDD (4)
o Don't know (1)
Q12 Are PFDD initiatives included in the annual goals and objectives within your functional
area?
o Yes (1)
o No (2)
o Don't know (3)
Q13 To what extent have you heard senior executives of your company speaking of including
patient perspectives in drug development?
o Very frequently (at least once a month) (1)
oSomewhat frequently (quarterly) (2)
o Rarely (yearly) (3)
o Never (5)

159
Q14 Do you agree that your organization needs to undergo a cultural change for PFDD to be
fully integrated into the drug development process?
oStrongly agree (1)
oSomewhat agree (2)
o Neither agree nor disagree (3)
oSomewhat disagree (4)
oStrongly disagree (5)
o Don't know (6)
End of Block: Culture
Start of Block: Unfreezing
Q15 Do you think there is a need to change the current approach to drug development in your
company to implement PFDD? (Please feel free to provide your comments)
o Yes. In the text box below, please tell us how. (1)
__________________________________________________
o No (2) __________________________________________________
o Don't know (3) __________________________________________________

160
Q16 What do you think is the level of urgency for your organization to integrate PFDD into its
drug development process?
oShort term (less than 1 year) (1)
o Medium term (1-3 years) (2)
o Long term (greater than 3 years) (3)
o My company has integrated PFDD into its drug development process (6)
o Don't know (4)
Display This Question:
If Does your company communicate the need to include patient perspectives during drug development pr... =
Yes
Q17 What mechanism(s) does your company use to communicate the need to include patient
experience data during drug development process? (select all that apply)
▢ Company town hall meetings (1)
▢ Newsletters (2)
▢ Functional area meetings (3)
▢ Corporate website (4)
▢ Other (7) __________________________________________________
End of Block: Unfreezing
Start of Block: Changing
Q18 In my opinion, senior management (e.g., CEO, Head of Research and Development, Chief
Medical Officer, etc.) of my company actively promotes the inclusion of relevant employees in
PFDD activities.

161
oStrongly agree (1)
o Agree (2)
oSomewhat agree (3)
o Neither agree nor disagree (4)
oSomewhat disagree (5)
o Disagree (6)
o Cannot comment (7)
Q19 Does your company communicate the need to include patient perspectives during drug
development process?
o Yes (1)
o No (2)
o Don't know (3)

162
Q20 In which phase of drug development are patients and their representatives invited to provide
their input? (select all that apply)
▢ Discovery phase (1)
▢ Pre-clinical phase (2)
▢ Early Clinical (Phase 1 or 2a) (3)
▢ Late Clinical (Phase 2b or 3) (4)
▢ Post-approval (5)
▢ Other (6) __________________________________________________

163
Q21 Please provide your views on the following statements related to PFDD activities at your
company.
Strongly
agree (1)
Somewhat
agree (2)
Neither
agree nor
disagree
(3)
Somewhat
disagree
(4)
Strongly
disagree
(5)
Don't
know (6)
Patients or
their
representatives
participate
regularly in
product
development
discussions (1)
o o o o o o
Sufficient
headcount is
dedicated to
PFDD activities
(2)
o o o o o o
Sufficient
budget is
dedicated to
PFDD activities
(3)
o o o o o o
Training is
provided to
integrate PFDD
activities into
existing
processes (4)
o o o o o o
Consultants are
available to
help with PFDD
activities (5)
o o o o o o

164
Q22 Please rate the utility of the following resources for adopting PFDD.
Very useful
(1)
Moderately
useful (2)
Slightly
useful (3)
Not at all
useful (4)
Do not know
(5)
FDA guidance
documents
(1) o o o o o
Articles in
trade
publications,
blogs, etc. (2)
o o o o o
Information
on FDA
website (3) o o o o o
Consultants
(5) o o o o o
Conferences/
Workshops
(6) o o o o o
Others (4) o o o o o
Q23 How would you rate your knowledge of the FDA PFDD guidance documents 1 and 2?
Guidance 1.pfdd Collecting Comprehensive and Representative Input
Guidance 2.pfdd Methods to Identify What is Important to Patients
o Highly knowledgeable (expert) (1)
o Moderately knowledgeable (2)
o Not knowledgeable/ Novice (3)
Display This Question:
If How would you rate your knowledge of the FDA PFDD guidance documents 1 and 2? Guidance 1 pfdd Col...
!= Not knowledgeable/ Novice

165
Q24 Looking at FDA's PFDD guidance documents 1 and 2, where is your company in terms of
the process of adopting this framework?
Guidance 1.pfdd Collecting Comprehensive and Representative Input
Guidance 2.pfdd Methods to Identify What is Important to Patients
Please add comments in the space provided.
o My company has not started any activities (1)
__________________________________________________
o My company has started having internal discussions (2)
__________________________________________________
o My company has partially adopted PFDD framework based on guidance documents 1 and
2 (3) __________________________________________________
o My company has fully adopted PFDD framework based on guidance documents 1 and 2
(4) __________________________________________________
o Don't know (5)

166
Q25 In your opinion, how important are the following patient perspectives in drug development?
Very important
(1)
Somewhat
important (2)
Not important
(4)
Cannot
comment (6)
Impact of the
disease and its
treatment on
the patient (1)
o o o o
Patients’
perspectives
about potential
and current
treatments (2)
o o o o
Views on unmet
medical needs
and available
treatment
options (3)
o o o o
Enhanced
understanding
of the natural
history of the
disease or
condition (4)
o o o o
Other (5) o o o o

167
Q26 My company uses the following tools and methods to collect patient views as part of its
approach to PFDD.
Yes (1) No (2) Do not know (3)
Interviews, focus
groups and facilitated
discussions with
patient and patient
care givers (1)
o o o
Observational
methods (e.g.,
medical documents,
document reviews)
(2)
o o o
Documents (e.g.,
scientific
publications, medical
records, personal
documents, graphics)
(3)
o o o
Audiovisual materials
(e.g., recordings,
photographs, sounds,
email) (4)
o o o
Social media and
verified patient
communities (5) o o o
Patient support
and/or advocacy
groups (6) o o o
End of Block: Changing
Start of Block: Freezing

168
Q27 Which of the functional areas in your company are currently engaged in Patient Focused
Drug Development activities? (Select all that apply)
Leading (1) Contributing (2) Not involved (3) Don't know (4)
Regulatory
Affairs (1) o o o o
Patient
Engagement
and/or Patient
Advocacy (2)
o o o o
Pre-clinical
and/or Clinical
Development (3) o o o o
Medical Affairs
(4) o o o o
Other (6) o o o o
Q28 What type of patient focused drug development training is supported financially by your
company? (Select all that apply)
▢ Internal presentations by subject matter experts (1)
▢ Certification programs (2)
▢ Undergraduate or graduate courses (3)
▢ External conferences, workshops or seminars (4)
▢ Other (6) __________________________________________________

169
Q29 What is your level of agreement with the following statements regarding implementation of
PFDD?
Strongly
agree (1) Agree (2)
Neither
agree nor
disagree
(3)
Disagree
(4)
Strongly
disagree
(5)
Cannot
answer (6)
Implementing
PFDD would
lengthen the
timeline for
drug
development
(1)
o o o o o o
Implementing
PFDD would
increase the
cost of drug
development
(2)
o o o o o o
Regulatory
clarity on
what is
required to
implement
PFDD is
currently
lacking (3)
o o o o o o

170
Q30 To prepare patients to become partners in drug development, my company provides
trainings for the participants in the following areas:
Yes (1) No (2) Don't know (3)
Drug development
process (1) o o o
Clinical trial design
(2) o o o
Understanding
clinical trial data (3) o o o
Understanding
benefits, risks, and
uncertainties
associated with
medical product use
(4)
o o o
Engaging effectively
with health care
professionals,
medical-product
sponsors, and
regulators. (5)
o o o
Q31 My company provides trainings on drug development concepts to informal caregivers (eg,
parents or other family members, and/or close friends of patients).
o Yes (1)
o No (2)
o Don't know (3)

171
Q32 In my opinion, my company's approach to Patient Focused Drug Development is:
(please feel free to add comments in the space provided)
oInsufficient (1) __________________________________________________
oSomewhat insufficient (2) __________________________________________________
oSufficient (3) __________________________________________________
o Don't know (4)
Q33 Overall, what do you think is the level of difficulty for your current company to implement
patient-focused approach to drug development?
o Very easy (1)
oSomewhat easy (2)
o Neither easy nor difficult (3)
oSomewhat difficult (4)
o Very difficult (5)
o Cannot answer (6)
Q34 Please use the space below to provide any additional insights into PFDD that you would like
to share. Your insights will be very important for understanding this new and emerging area.
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________

172
Q35 Would you be willing to participate in a follow-up phone interview?
o Yes (1)
o No (2)
End of Block: Freezing

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Asset Metadata

Creator Bozic, Mladen Karlo (author)

Core Title The impact of FDA Patient-Focused Drug Development (PFDD) on US drug development strategies: a survey of views from pharmaceutical product companies

School School of Pharmacy

Degree Doctor of Regulatory Science

Degree Program Regulatory Science

Degree Conferral Date 2024-05

Publication Date 01/31/2024

Defense Date 01/17/2024

Publisher Los Angeles, California (original), University of Southern California (original), University of Southern California. Libraries (digital)

Tag change management,company culture,drug development strategies,OAI-PMH Harvest,organizational readiness,patient engagement,patient-focused,pharmaceutical industry

Format theses (aat)

Language English

Contributor Electronically uploaded by the author (provenance)

Advisor Pacifici, Eunjoo (committee chair), Bain, Susan (committee member), Richmond, Frances (committee member), Yearsley-Smith, Meredith (committee member)

Creator Email bozic@usc.edu,mladen.bozic@gmail.com

Permanent Link (DOI) https://doi.org/10.25549/usctheses-oUC113817101

Unique identifier UC113817101

Identifier etd-BozicMlade-12649.pdf (filename)

Legacy Identifier etd-BozicMlade-12649

Document Type Dissertation

Format theses (aat)

Rights Bozic, Mladen Karlo

Internet Media Type application/pdf

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Source 20240131-usctheses-batch-1124 (batch), University of Southern California (contributing entity), University of Southern California Dissertations and Theses (collection)

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