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Contract research organizations: a survey of industry views and outsourcing practices

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Contract research organizations: a survey of industry views and outsourcing practices

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CONTRACT RESEARCH ORGANIZATIONS- A SURVEY OF INDUSTRY VIEWS AND
OUTSOURCING PRACTICES

by

Laura Beth Kupsch

A Dissertation Presented to the
FACULTY OF THE USC SCHOOL OF PHARMACY
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF REGULATORY SCIENCE

DECEMBER 2022

Copyright 2022 Laura Beth Kupsch

ii
DEDICATION
In dedication to my parents, Joe and Roni Rasky, who guided me to learning. I also dedicate this work to
my husband, Glenn Kupsch, for providing continuous support and encouragement.
To my children, Evan and Brendon, who continue to teach me- thank you for your love and support in
this journey together.

iii
ACKNOWLEDGEMENTS
The past few years have been an adventure in education, not only academically but personally. The
appreciation I have for my parents, my husband, and my two sons, goes beyond words. Their patience
and encouragement were a constant reminder that you can finish what you started.
I want to thank my Advisor, Dr. Nancy Smerkanich. Her ability to guide and mentor was instrumental in
my educational journey. Her support through all aspects- educationally, professionally, and personally-
was invaluable. Thank you to the staff and personnel in the USC Regulatory Sciences program, who
guided me through my progression on completing this program and survey.
Many were instrumental in my learning journey, including those who were able to shape this dissertation
through a focus group and many content reviews. Thank you to Dr. Frances J. Richmond, Dr. Eunjoo
Pacifici, Dr. Arthur Mayorga, and Paulette Triglia. As advisors, teachers, and colleagues, your comments
and assistance were extremely appreciated.
Finally- one of the most fulfilling aspects of this USC program was meeting the other members of my
Cohort. The support we gave each other in and out of the classroom, as well as the friendships formed,
reminded me how much fun education can be. Thank you.

iv
TABLE OF CONTENTS
DEDICATION .........................................................................................................
................................................................................................................... II
ACKNOWLEDGEMENTS ................................................................................. III
LIST OF TABLES ...................................................................................................
.................................................................................................................. VI
LIST OF FIGURES .................................................................................................
................................................................................................................ VII
ABSTRACT .............................................................................................................
.................................................................................................................. IX
CHAPTER 1. OVERVIEW ................................................................................... 1
1.1 Overview 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 Limitation, Delimitations, Assumptions .............................................................. 5
1.6 Organization of Thesis ......................................................................................... 7
1.7 Definitions ............................................................................................................ 7
CHAPTER 2. LITERATURE REVIEW ............................................................... 8
2.1 Background to the Literature Review .................................................................. 8
2.2 Introduction .......................................................................................................... 9
2.3 Overview of the CRO Industry .......................................................................... 12
2.4 Strategic Resourcing and CRO Engagement ..................................................... 14
2.4.1 CRO Selection ................................................................................ 17
Prior CRO Utilization Experience ....................................................................... 18
Timelines.............................................................................................................. 18
Cost ...................................................................................................................... 19
2.4.2 CRO Outsourcing Models .............................................................. 19
2.4.3 Past Evaluations of Outsourcing Models ........................................ 22
2.5 Regulatory Impact on CROs and Sponsors ........................................................ 27
2.6 Setting Expectations in an Outsourcing Relationship ........................................ 31
2.6.1 Challenges and Continuous Assessment ........................................ 33
2.7 Model Exploration - Vested Outsourcing .......................................................... 36
2.7.1 Vested Outsourcing Model ............................................................. 37
2.7.2 Vested Outsourcing in Practice ...................................................... 43

v
CHAPTER 3.METHODOLOGY ........................................................................ 45
3.1 Purpose ............................................................................................................... 45
3.2 Data Collection and Analysis Methodology ...................................................... 45
3.3 Study Participants and Survey Deployment ....................................................... 46
CHAPTER 4. RESULTS ..................................................................................... 47
4.1. Survey Participation ........................................................................................... 47
4.2. Demographic Profiles of Respondents ............................................................... 48
4.3. Outsourcing to CROs for Clinical Trials- Selection and Evaluation ................. 50
4.4. Outsourcing to CROs for Clinical Trials- Responsibilities ................................ 55
4.5. Outsourcing Models and CRO Management ..................................................... 57
4.6. Sponsor Management of CRO Performance ...................................................... 67
4.7. CRO Outsourcing Approaches ........................................................................... 73
CHAPTER 5. DISCUSSION ............................................................................... 88
5.1 Introduction ........................................................................................................ 88
5.2 Methodological Considerations.......................................................................... 89
5.2.1 Delimitations .................................................................................. 89
5.2.2 Limitations ...................................................................................... 90
5.3 Considerations and Insights from the Survey .................................................... 93
5.3.1 Outcomes, not transactions ............................................................. 95
5.3.2 The What, not the How ................................................................... 97
5.3.3 Defined and Measurable Outcomes .............................................. 100
5.3.4 Pricing Model with Incentives ...................................................... 101
5.3.5 Governance - Insight versus Oversight......................................... 104
5.4 Conclusions and Future Direction .................................................................... 105
REFERENCES .................................................................................................. 108
APPENDICES ................................................................................................... 115
APPENDIX A. 21 CFR PART 312- SPONSOR REQUIREMENTS ... 115
APPENDIX B. SURVEY ...................................................................... 119
APPENDIX C. CROSS TABULATIONS............................................. 149
APPENDIX D. MANAGEMENT STYLES ......................................... 151
APPENDIX E. COMPLETE RESPONDENT COMMENTS ON
OUTSOURCING ................................................................................... 152

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LIST OF TABLES
Table 1: Largest CRO Market Share ................................................................................. 14
Table 2: Transfer of Obligations- Key Requirements ....................................................... 29
Table 3: All Responses ...................................................................................................... 47
Table 4: Respondent Functions- "Other" .......................................................................... 49
Table 5: Company Size and Outsourcing .......................................................................... 51
Table 6: Important CRO Selection Criteria ....................................................................... 54
Table 7: Activity Management- CROs .............................................................................. 56
Table 8: Activity Management - Sponsor ......................................................................... 57
Table 9: Company Size and Outsourcing Models ............................................................. 59
Table 10: Value-added Outsourcing Concepts .................................................................. 64
Table 11: Implementation Leadership ............................................................................... 65
Table 12: Traits for a Successful Outsourcing Relationship ............................................. 72
Table 13: Primary Reasons for Switching CRO Activities ............................................... 73
Table 14: Contracting Approaches .................................................................................... 74
Table 15: Potential Useful Aspects of Contracts for Outsourcing .................................... 75
Table 16: Areas for CRO Performance Improvement ....................................................... 77
Table 17: Respondent Comments for Other Areas for Improvement ............................... 77
Table 18: Respondent Description of Opportunities for Improvement ............................. 79
Table 19: Less Traditional Outsourcing Opportunities per Respondents ......................... 82
Table 20: Considerations for Future CRO Re-engagement .............................................. 84
Table 21: CRO Performance Rankings ............................................................................. 85
Table 22: Additional Respondent Comments on Outsourcing .......................................... 87

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LIST OF FIGURES
Figure 1: Increasing Costs of Clinical Trials .................................................................................11
Figure 2: Commitment to Development ........................................................................................12
Figure 3: Reasons for Outsourcing in Pharma ...............................................................................15
Figure 4: Outsourcing Paradigms ..................................................................................................20
Figure 5: Utilization of Outsourcing Models and Clinical Activities ............................................23
Figure 6: Areas for Improvement and Effectiveness .....................................................................27
Figure 7: Expectations During Outsourcing ..................................................................................31
Figure 8: Sponsor Retained Competencies ....................................................................................33
Figure 9: Vested Outsourcing Framework- Key Relationship “Rules” .........................................38
Figure 10: #1- Outcome-Based Business Model ...........................................................................39
Figure 11: #2- Focus on “The What” .............................................................................................40
Figure 12: #3- Outcomes and Metrics ...........................................................................................41
Figure 13: Effective Collaboration ................................................................................................42
Figure 14: Demographic Profile of Respondents...........................................................................48
Figure 15: Respondent Functions ..................................................................................................49
Figure 16: Years of Experience in Clinical Research ....................................................................50
Figure 17: CRO Utilization ............................................................................................................50
Figure 18: CRO Selection Responsibility ......................................................................................52
Figure 19: Outsourcing Re-evaluation Frequency .........................................................................53
Figure 20: Aspects of Outsourcing Models ...................................................................................58
Figure 21: Sponsor/CRO Management Tools................................................................................60
Figure 22: Outsourcing Development ............................................................................................62
Figure 23: Full Allocation of Management Style to One Category ...............................................66
Figure 24: CRO Management Styles of Sponsors .........................................................................67
Figure 25: Sponsor/CRO Contract Payments- ...............................................................................68
Figure 26: Payments to CROs based on Quality ...........................................................................69
Figure 27: Sponsor Views Regarding Performance of the CRO ...................................................69
Figure 28: Timing of SOW Creation with CROs ..........................................................................70
Figure 29: Switching CROs in Clinical Trials ...............................................................................73

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Figure 30: Company Support of Outcome-based Incentives .........................................................75
Figure 31: Opportunities for CRO Performance Improvement .....................................................78
Figure 32: Opportunities for CROs to Add Value .........................................................................80
Figure 33: Company Support of Less Traditional Outsourcing.....................................................81
Figure 34: Acceptance of CRO input for Clinical Trial Management ...........................................83
Figure 35: Does CRO Innovation Create Value? ..........................................................................86

ix
ABSTRACT
Pharmaceutical companies studying the efficacy and safety of new drugs often rely on outsourcing to
Contract Research Organizations to support clinical trial activities. Sponsors often develop outsourcing
agreements to structure the outsourcing relationship. However, the existing models for outsourcing do
not reflect the advancements made as clinical trials have evolved into complex multinational programs
studying a wide variety of diseases and patient populations. This discrepancy continues to create a lack of
satisfaction with CROs and their capabilities and performance.
This study examined the industry’s perspective on outsourcing collaboration, including the current
practices of clinical research outsourcing and an evaluation of the adequacy of these relationships with
regard to effectiveness and efficiency. A total of 100 respondents, many with current responsibility for
collaborating with a CRO on a clinical trial, participated in the survey. A Vested Outsourcing Framework
developed at the University of Tennessee provided the basis for structuring the survey and examining the
data provided about the current utilization of Contract Research Organizations. This framework was
originally developed with a grant from the United States Air Force, who asked Kate Vitasek and her
colleagues at the University of Tennessee to review Air Force outsourcing and procurement practices
(Vitasek and Manrodt, 2012).
The findings from current research revealed that clinical trial outsourcing remains the norm for managing
clinical trials. Further, the outsourcing models being currently used have remained stagnant. While these
models have been used for many decades, they have been associated with elements of dissatisfaction as
outsourcing relationships have progressed. Exploring new models could advance innovation in clinical
trial conduct and create sponsor-CRO relationships that are based on trust and reward.

1
CHAPTER 1. OVERVIEW
1.1 Overview Introduction
The process of bringing a new medicine to the market is complex and costly. Sponsor companies must
conduct clinical trial programs with significant numbers of patients who can provide data to show that the
experimental drug is efficacious and has a positive benefit to risk profile. Because over 100,000 clinical
trials have been registered in the United States in August 2022 alone, the success of enrolling the right
patient population and acquiring the appropriate data becomes increasingly difficult (ClinicalTrials.gov,
2022; ClinicalTrials.gov, 2019).
Further, demands for more extensive testing by regulatory agencies have also contributed to an increase in
drug development expenditure (FDA, 2019). The reported cost to develop a single new drug varies from
one analyst to another but all show that clinical trials are an expensive investment with a high uncertainty
of return (Dimasi, 2018) (Wouters, McKee and Luyten, 2020). Recent data has also shown that
pharmaceutical companies are attempting to downsize their numbers of in-house personnel even as the
number of clinical trials continue to increase (Getz, 2018a). At the same time, however, companies must
minimize the time to market and hasten return on investment. Thus, they look for outsourcing options as
an alternative to supplement in-house clinical trial activities, to manage the costs and fluctuating labor
requirements posed by these complex research programs.
Outsourcing the complicated requirements of clinical trial programs is not a trivial undertaking for the
pharmaceutical companies sponsoring drug development. Study plan development, physician site
engagement and interactions, supply of materials to the site, and assessment of data collection are only a
few of the many operational areas that are managed during the conduct of a clinical trial. Sponsor
companies require the correct balance of personnel, resources, and patient access to conduct a clinical
trial, often by employing outside personnel. Historically, outsourcing to external parties has been

2
challenging because the outsourced entity requires extensive oversight. Often the work of the outsourcing
vendor is not satisfactory because it proves to be expensive, inefficient and sometimes inadequate
(Anderson, 2008). Thus, the evolving clinical trial industry continues to seek an outsourcing model that
can meet the rigorous requirements of the pharmaceutical industry.
Adding to the complexity, marketing approvals are typically not confined exclusively to one country;
different countries often require that a portion of the patient data be collected within the country in which
approval is sought. Globalization of clinical trials further promotes the use of outsourced vendors that
have expertise in a variety of areas including country-specific regulations, clinical-site capabilities, and
harmonized data-management systems. These new requirements put pressure on companies engaged in
drug development to find efficient ways to conduct their clinical trials (Alsumidaie, 2012). The global
reach of Contract Research Organizations (CROs), as well as the ability to retain personnel with specific
expertise, provides both early-stage and larger pharmaceutical companies an opportunity to seek partners
who can offer the appropriate value and collaboration to design and implement a clinical trial that
accurately reflects modern science and the needs of the patient.
The Contract Research Organization industry has grown exponentially over the past 30 years in response
to the needs of pharmaceutical companies conducting clinical trials. As a service provider to the
pharmaceutical industry, CROs have played an important role in ensuring that new drugs are studied in a
robust and quality manner. The solutions and services that a CRO can provide are varied and continue to
evolve, in line with technologies, scientific advancements, and health authority requirements (Blake,
Fagan and Rask, 2018). However, the outsourcing models used for selection, interaction, and oversight of
CROs have not advanced as rapidly.
For many companies, the working relationships with its CROs continue to be transactional in nature. In
such a model, the sponsor company pays for a service that is completed according to a statement of work,

3
rather than engaging the CRO as a collaborating partner (Getz, 2016). Examples of these services, often
defined in a transfer of obligations, include monitoring visits, safety case processing, and management
and analysis of clinical trial data. Sponsors have tried to redefine their outsourcing models by integrating
concepts such as strategic partner alliances and preferred provider contracts into the existing transactional
based models, but research indicates that the collaboration between sponsor companies and CROs has not
evolved into a consistent approach where both entities share engagement and where the sponsor
empowers the CRO to make many decisions independently. Escalating and unexpected costs,
inefficiencies, and mistrust appear to remain when outsourcing a clinical trial.
1.2 Statement of the Problem
As CROs are used increasingly to extend the clinical capabilities of drug developers, those developers
have had to become heavily involved in the evaluation of the operations, management, and best practices
of those contracted entities. The existing models for outsourcing to CROs do not reflect the
advancements in executing clinical trials, which have evolved into complex multinational programs
studying a wide variety of diseases and patient populations, implementing innovative and adaptive study
designs, risk-based monitoring, and decentralization. Much of the discussion on outsourcing models for
clinical trials comes from the perspective of pharmaceutical companies using preferred providers and
large CROs. In contrast, the outsourcing of clinical trials by small or emerging companies, and how these
companies model outsourcing engagements, have only recently been a subject for review (Brennan, 2014)
(NICE, 2017) (Review, 2016). Smaller companies often lack both the resources and expertise to conduct
clinical trials and may have to rely more extensively on the CRO for support. This thesis examined the
ways in which CROs are utilized by sponsors and the nature of those relationships.

4
1.3 Purpose of the Study
This research aimed to review how large and small pharmaceutical companies are using outsourcing
models when working with CROs to bring potential new drugs through the clinical trial process. A
review of the literature was conducted to analyze how the role of a CRO has evolved as clinical drug
studies have progressed from small simple designs to more complex multinational studies, and how
pharmaceutical companies of different sizes work with outsourcing vendors. The current trends in
outsourcing models, as well as an overview of a novel outsourcing paradigm, are described.
The literature review was extended to explore the views of companies of different sizes regarding their
use of different outsourcing modes and their experiences with those models. This research focused on
sponsor companies headquartered in the United States conducting human clinical trials with
investigational drug products; however, these U.S.-based sponsors may conduct clinical trials world-wide.
A fit-for-purpose survey tool was developed and then critiqued by a focus group of experts in clinical trial
management and/or survey applications. It was disseminated electronically to individuals with
responsibility for CRO selection and oversight. The objective of the survey was to explore industry’s
perspective on outsourcing collaboration, by understanding current practices of clinical research
outsourcing and to evaluate the adequacy of these relationships regarding effectiveness and efficiency. A
Vested Outsourcing Framework, which has been developed as a novel and streamlined approach to
structure the relationships between organizations and contracted outsourcing entities, provided the basis
for examining the data provided about the current utilization of Contract Research Organizations. The
survey analyzed aspects of the Framework that may be currently utilized and provided insight into
parameters that might prove useful for clinical trial programs involving sponsors and CROs.

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1.4 Importance of the Study
The results from this study are important since this provided additional data on how pharmaceutical
companies use outsourcing models when they work with CROs. The data can be used to help industry to
understand what companies recognize to be the efficiencies and deficiencies of the outsourcing
approaches that they are using. Further, the results can provide insight into current and best practices
when choosing an outsourcing paradigm that might best be used when working with a CRO. If the results
offer advantages that may be gained by using specific approaches when collaborating with a CRO, the
information could be used by companies struggling to develop their own programs so that they can
compare alternative models that might provide value.
The results of this research may reveal new challenges in the management and oversight of CROs and
highlight areas for improvement, to streamline the operational aspects of clinical trial programs. Small
and emerging companies, larger pharmaceutical companies, and the CROs that provide outsourcing
services benefit from a current perspective on the challenges and successes of the outsourcing process to
advance a new drug through the clinical development stage.
1.5 Limitation, Delimitations, Assumptions
This paper studied pharmaceutical companies that employ CROs when they conduct clinical trials.
Results may be generalizable to the greater clinical research community but some sectors, like those
producing medical devices or operating internationally, are subject to different regulations and trial design
structures. Thus, care must be taken to limit generalizations to other sectors without further research.
Participants were also delimited to professionals in clinical research, who work with or have worked with
CROs that are contracted to assist with clinical trial operations. Different views might be found if the
views and experience of other professionals, such as regulatory, quality or finance experts, were sought.
Further, it captures only the experience of the sponsoring companies and not the CROs, who may have

6
interesting and different views. Respondents were not selected from persons working in companies based
outside of the United States; however, persons working with CROs with locations outside of the United
States were included. Additionally, respondents were not selected from persons working in other
disciplines such as laboratory, manufacturing, or devices, considering the differences in U.S. and
international contract law and employment law.
The information available may have been limited by the ability of respondents to assess fully the selection
and performance of a CRO. Thus, the respondents may have been focused on a narrow aspect of the
CRO’s capabilities or performance, depending upon the level of experience of the respondent. Their
feedback may also have been limited by factors related to the growth stage of the companies and their
relationship with the most recent CRO with which they have interacted. Respondents may also be
personnel that have been previously employed by a CRO, and this may have limited their ability to give a
sponsor-only perspective.
Another limitation inherent in this study was the potential restrictions of the numbers and structures of the
questions posed to respondents. The survey was designed to be relatively short, in order to encourage the
participation of busy professionals who do not have the time or inclination to complete a time-consuming
survey. Further, respondents may not have taken the time to consider their answers at length if they
perceived the questions to be irrelevant or lengthy; they may even have terminated the survey prematurely
if they found that the questions were confusing or seemingly irrelevant to them. A focus group of experts
was used to improve the validity and content of the survey. However, the results may still be limited in
the depth and scope that can be covered. Further respondents remain anonymous. Thus, the results were
limited to grouped responses. It is assumed that respondents who were guaranteed confidentiality had the
expertise and inclination to provide honest and accurate answers.

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1.6 Organization of Thesis
This thesis is organized into five chapters. Chapter 1 is an overview of the topic of the research. Chapter
2 reviews the available published literature and provides an overview of the history of CROs and how the
different outsourcing models have been utilized for engagement with CROs in the conduct of clinical
trials. This chapter describes the specific areas of the research and provide a novel outsourcing
framework based on the information reviewed. Chapter 3 is the explanation of the methods used.
Chapter 4 includes the results of the research. Chapter 5 analyzes these results and discusses the
limitations, delimitations, and correlations with previously known information. Any additional
recommendations are also noted in Chapter 5.
Appendices to this thesis include the requirements for clinical research conducted in the United States
(Appendix A) and the draft survey (Appendix B).
1.7 Definitions
Contract Research Organization (CRO)- A person that assumes, as an independent contractor with the
sponsor, one or more of the obligations of the sponsor.
Clinical Research- Studies in which people participate as patients or healthy volunteers.
Sponsor- Entity responsible for the initiating and overall responsibility for the clinical research.
Outsourcing- Practice of hiring the services or expertise of an external party.

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CHAPTER 2. LITERATURE REVIEW
2.1 Background to the Literature Review
The objective of the literature review was to determine the extent of information available regarding the
trends and approaches related to the outsourcing of clinical trials to CROs. Relevant topics included
outsourcing by companies in the United States over the past half century, including outsourcing by
pharmaceutical manufacturers. Key search terms included Contract Research Organization or CRO,
outsourcing, transfer of obligations, sponsor, vendor, new drug development, and clinical trial.
The electronic library offered by The University of Southern California (USC) provided numerous
articles and books as resources regarding outsourcing as a standalone topic. Over 20,000 peer reviewed
articles were published between 1995 and 2020. This grouping was narrowed to focus on outsourcing
related to clinical trials in the United States. Information on larger companies was primarily found during
this part of the research, so a further search was conducted for information on companies headquartered in
the U.S. that might be considered small (emerging, under 500 employees) to medium sized (under 2000
employees). This yielded over 1,500 search results, and a review of this information was further
conducted to select relevant material and to filter duplicate or repetitive information. This left 86 articles
that addressed outsourcing to CROs specifically, and 68 of these were used as the foundation for the
literature review.
The USC electronic library also allowed access to current market research information
(Marketresearch.com), as well as reputable on-line libraries (ProQuest, PubMed, AcademicOneFile). The
internet search was extended by using general search tools outside of the USC library, including Google,
as well as specific websites known to contain much information about clinical trial management.
Notably, the United States Food and Drug Administration (FDA) and the European Medicines Agency

9
(EMA) websites offered specific information on regulations, guidance, operating procedures, historical
data, and conference presentations.
Additional reading outside of electronic sources included industry-specific periodicals provided from
professional organizations (Drug Information Association, Regulatory Affairs Professionals Society,
Society of Quality Assurance, and the Association of Clinical Research Professionals). These periodicals
offered recent insights from personnel working in the clinical trial field from both sponsor and CRO
organizations. Articles generated by personnel from one entity (sponsor or CRO) that were promotional
in nature were reviewed but not utilized to minimize content bias.
Access to daily electronic mailings and blogs from trade groups were consistently reviewed for any
mention of CROs, outsourcing, or the other relevant terms. These include information from groups such
as CenterWatch, FierceBiotech, TransCelerate BioPharma, and Contract Pharma.
Last, conference materials and presentations were evaluated for any additional information. This helped
to identify any proposed or upcoming guidance documents or regulations in the United States that would
affect relationships with CROs.
Information excluded from extensive review included materials relevant only to outsourcing by
companies outside of the United States. Even though outsourcing is a common practice worldwide, the
focus of this dissertation was how pharmaceutical companies headquartered in the United States handle
outsourcing (on a local and global basis) and focused on respondents involved in clinical trial operations.
2.2 Introduction
Implementation of an outsourcing strategy has been a systematic way for pharmaceutical companies to
leverage capabilities and assets in times of change (Lonsdale, 2000) (Moorcroft, 2017). In the clinical
trial industry, companies, referred to as sponsors, must plan the design of the clinical trial program. The

10
goal is to commercialize their new products to market, even when they may have limited knowledge of
the final path that would be successful to achieve this outcome. Start-up activities attempt to optimize the
trial design, scientific expertise, and knowledge of clinical trial regulations and patient ethics. As the
clinical trial program then proceeds, teams will work to determine the efficacy and safety of the tested
compounds through a series of independent studies with different durations and start and stop dates that
will gradually contribute to a substantial database of information. Because trials are staged and therefore
intermittent in their timing, companies are challenged to concentrate appropriate resources at specific
times to avoid paying for those resources when they are not needed. CROs play an important role in
solving this problem by assisting pharmaceutical companies with time-bound resources, facilities, and
expertise needed to manage a clinical trial. They allow companies to be more flexible with respect to
both the numbers and expertise of needed staff for their clinical trial program (Carroll, 2005).
The ability to launch a clinical study as soon as possible by using outsourced providers can be beneficial
to all stakeholders, including patients and physicians (Dimasi, Smith and Getz, 2018). Therefore, it is not
surprising that the 2017 market for clinical trial outsourcing was estimated near $27 billion, with a
predicted annual growth over the next few years of 7% (Blake, Fagan and Rask, 2018). Phase 3
pharmaceutical studies of efficacy, the largest and longest of these studies, are responsible for the largest
portion of those expenditures. Even greater growth for post-marketing studies is expected and by 2022
the global market for CROs will be near $45.2 billion (Blake, Fagan and Rask, 2018). Even though these
are large numbers, some believe that these figures underestimate the size of outsourced expenditures, with
estimates from one analyst as high as nearly $80 billion dollars a year (Getz, 2018a).
The data available to assess the financial dealings with pharmaceutical and CRO industries are extensive
and relatively current (CSDD, 2014). However, the estimates for expenditures related to the development
of a new drug can vary from one analyst to another, depending on the types of drugs that are studied and
the assumptions that are made. A conservative estimate places the cost at approximately $179 million in

11
the 1970s, and near $800 million in 2003 (Miera, 2014; Suisse, 2016). More recent estimated give much
higher numbers, $2.6 billion if the estimates take into account the costs of discovery, development, and
capital investment (CSDD, 2014) (Hassanzadeh et al., 2014). No matter the figures that are used, clinical
trial costs are estimated to account for over half of the total development expenditures (Figure 1).
Figure 1: Increasing Costs of Clinical Trials

Source: Original Graphic based on (Hassanzadeh et al., 2014) (Carroll, 2005)
A survey of ten large pharmaceutical firms, conducted by the Tufts Center for the Study of Drug
Development (CSDD), made it clear that clinical trials are a lengthy and risky undertaking. According to
this 2016 report, an analysis of 106 investigational drug products from different first-in-therapeutic class
compounds showed that the period from discovery to marketing authorization averages around 11 years,
and from first-in-human trials to marketing authorization can take over 8 years (Dimasi, Grabowski and
Hansen, 2016) (Dimasi, 2018). Progress through this path is not guaranteed to assure market approval;
CSDD has also reported that investigational drugs had a U.S. marketing approval rate of only 16% (Getz,
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1970s 1980s 1990s 2000s
Clinical Trial Costs per Decade (in US billions$)
Clinical Trial Costs per Decade (in US billions$)

12
Lamberti and Kaitin, 2014) (Figure 2). Therefore, it is important for clinical development to maximize
efficiencies and ensure that adequate and useful data are derived from a clinical trial program.
Figure 2: Commitment to Development
Source: Original Graphic
2.3 Overview of the CRO Industry
For much of the twentieth century, pharmaceutical companies typically relied on in-house resources to
manage activities, including clinical trial operations, which included the cleaning and querying of patient
data in medical records and the collection and analysis of this data to determine the results of the clinical
trial program. However, by the early 1970s, the challenges of testing many blockbuster drugs- including
first-generation ulcer medications, anti-depressants, contraceptives and oncology medicines targeting
leukemia and melanoma - led their parent companies to recognize a need for outside experts who could
support activities in specialized or hazardous processes (ASCO, 2017). Further, the more permissive
environment created by the Hatch-Waxman Act of 1984 that allowed generic versions of innovative
medicines to be commercialized more easily put pressure on pharmaceutical companies to become more
efficient and competitive (Rumore, 2009) (Waxman, 2009).
With more competition, the internal resources needed to operationalize clinical programs could not keep
up with the discovery pipelines created to supplement company growth. Consulting services saw an
Time
~11
years
Cost
~2.6
billion
Success
~16%

13
opportunity to mitigate the shortfalls in trained personnel and other in-house resources with outsourcing
options for a variety of activities. First, new contract manufacturers (CMOs) emerged as demand for
space and resources increased in all aspects of pharmaceutical manufacturing (Moorcroft, 2017). Entities
then began to offer services as contractors in other areas of pharmaceutical development, following the
CMO model and offering niche or full-service service options to supplement the increase in workload that
pharmaceutical companies were experiencing in other precommercial activities, including clinical
research. Many of the earliest CROs, including Quintiles (now IQVIA), GH Besselaar (now Covance),
PPD and Parexel, provided support not only for clinical trials, but also for related service needs such
statistical analysis or preclinical testing (Vinluan, 2012).
Typically, CROs were based on the east coast of the United States, where the larger pharmaceutical
companies were also located. However, internal hiring by CROs grew rapidly first in the U.S. and then
overseas so that they could fulfill the growing sponsor requests and demands. For example, one such
outsourcing company, ICON, went from five to nearly 15,000 global personnel in approximately 25 years
(ICON, 2018). A 2013 evaluation of the CRO industry estimated that over 2 million people were
employed by CROs in over 115 countries (Hassanzadeh et al., 2014). In 2011, it was estimated that over
3,100 outsourcing providers were based in the United States, including approximately 650 focused on
clinical research; such large expenditures suggest that determining the appropriate provider and
outsourcing strategy are important activities for companies that are operationalizing a clinical trial (Getz,
2012).

14

Table 1: Largest CRO Market Share
CRO Market Share
IQVIA (Merger of Quintiles and IMS Health) 11%
Covance (Acquired by LabCorp) 8%
Parexel (Acquired by Pamplona Capital) 6%
ICON 4%
PRA Health Sciences (Acquired by Genstar Capital) 4%
Adapted from (Miller, 2011)
2.4 Strategic Resourcing and CRO Engagement
Sponsors have several reasons to outsource strategically- to support global expansion, assure specific
experience and expertise in a particular therapeutic area, or expand its clinical workforce when peak
clinical trial activity requires more staffing (Glass and Beaudry, 2010). A 2018 survey from Contract
Pharma examined outsourcing practices of more than 200 pharmaceutical companies pursuing drug
development (Pharma, 2018). The survey explored the reasons for outsourcing not only clinical trial
activities but also such activities as marketing, packaging, and manufacturing. The majority of
respondents (62%) indicated that their companies were virtual or needed their in-house staff to focus on
core competencies. Figure 3 represents the results of the survey responses, which are consistent with
more general information in the literature regarding the outsourcing of clinical trials.

15
Figure 3: Reasons for Outsourcing in Pharma

Source: Contract Pharma 2018 Annual Outsourcing Survey (Pharma, 2018)
In response to the demand for outsourcing that could address specific needs, niche CROs formed to offer
the specific services- tasks, operations, or expertise in therapeutic area- needed by a sponsor company,
while limiting the integrated layers often associated with a full-service CRO (Vogel and Getz, 2005)
(Hutt, 2012). Some CROs became a primary resource for a sponsor that might need expertise in
international regulatory matters, whereas others specialized in managing novel technologies such as
wearable devices and electronic medical records, or particular techniques such as statistical modeling
(Panetta and Raynor, 2008) (Calaprice and Katz, 2016) (Landhuis, 2018). Some CROs began to serve as
a “rescue” for a previous underperforming CRO, providing a transition of at-risk services but also
potentially increasing timelines and costs (Miseta, 2016). The evolution of CRO business models often
started with specialized services, then became full-service entities. However, more recently, some are
19%
28%
6%
34%
6%
7%
Reasons for Outsourcing
Temporary Lack of Capacity Company is Virtual Lifecycle Management
To Focus on Core Competencies To Reduce Company Size Other

16
circling back to become specialized entities that offer solutions for the emerging therapeutic areas and
technologies (NICE, 2017).
At the same time, much consolidation was taking place amongst CROs (Chung, 2017). Research shows
that approximately 50% of all CRO revenue comes from the six largest CROs (Miller, 2011) (Suisse,
2016) (Blake, Fagan and Rask, 2018). According to a July 2018 analysis of the CRO marketplace, the
five largest CROs make up 35% of the market, valued at $25 billion for the clinical trials segment in the
United States (Blake, Fagan and Rask, 2018). This data also indicates that the remaining market share is
distributed amongst the still remaining smaller or niche CROs (Getz, 2018b) (Table 1).
Part of the reason why CROs have been getting larger may relate to the need for a global reach to satisfy
the requirements of multinational clinical trials. Globalization over the past twenty years has been a
driving force for CROs, as companies recognize the need for advisors and legal entities familiar with the
management of trials in other markets, and particularly in emerging markets (Shapiro, 2008). Sponsors
rely on these entities to give them access and a legal presence in a foreign country, while providing the
expertise needed to navigate local and national regulatory and medical requirements. In addition, local
CROs allow sponsors to have access to various patient populations, and study the appropriate regional,
ethnic and genetic differences required for many marketing applications (Review, 2016). Localized
CROs across the globe have become the target of mergers, acquisitions, and strategic partnerships since
they allow the larger U.S. based CROs to get a footprint in emerging markets (Margherita and Valeria,
2017).
The development of methods to increase speed of communication and to allow companies to store
documents and data, including cloud-based electronic data collection systems and electronic
pharmacovigilance systems, has been instrumental in modernizing clinical trial management. Such
systems are costly to develop and maintain. Thus, when finances and resources are limited, both the

17
sponsor and CRO must join forces to implement innovative ways to managing the studies. The virtual
environment for both sponsors and CROs creates a system that provides an alternate way of distributing
and reviewing information globally and assures that all parties are receiving consistent information and
managing expectations for timely review of the data. By investing in systems such as electronic Trial
Master Files and electronic data transfer programs, companies can potentially improve data quality and
reduce overall timelines (Getz, 2013).
2.4.1 CRO Selection
The selection criteria for a CRO will vary depending on sponsor requirements. The sponsor must
therefore understand their own specific expectations and requirements before contracting with a CRO to
compliment or supplement the activities to be managed internally (Wilkinson et al., 2019). The CRO
then must bring the right competencies, which compliment or supplement the activities that the sponsor
can manage internally. The first step in contracting with a CRO requires the sponsor to determine the
range of offerings that they require and whether those requirements can be satisfied by a single CRO, or a
mix of CROs. The sponsor should complete a thorough review of its own capabilities and may benefit
from completing a gap assessment to determine where they need to bring in third-party services. This
needs assessment includes an appropriate review of the study or program plan, to decide which countries/
patient population will be targeted, the regulatory environment of each of those countries, and what
possible technological capabilities can accelerate the development timeline. Vendors can then be
differentiated according to their reputations for good performance, their specific services offered and their
specific technical and operational competencies (Glass and Beaudry, 2010). Selection and oversight of a
CRO are important factors in maintaining data integrity and safety oversight in a clinical trial. Good
Clinical Practice dictates that sponsors are ultimately responsible for the activities of their vendors, so
CRO/ vendor qualification processes are integral activities to successful study execution (ICH, 2016).
The decision to outsource, and the relevant factors for selection, can be aligned into agreements a priori.

18
Previous analysis on outsourcing indicates that the structure of the contract to assure appropriate oversight
and common goals can assist in minimizing risks to the operations of the clinical trial (Wilkinson et al.,
2019).
Prior CRO Utilization Experience
Having previous experience with a CRO can allow a sponsor to predict if that CRO can manage the
activities to be outsourced. Surveys have shown that new and smaller sponsoring companies tend to rely
on referrals and previous experience with a CRO and look for an outsourcing strategy that can be flexible
and adaptable (Leader, 2014). Often reputation and historical experience will help to determine which
CROs to select, especially in niche therapeutic areas such as pediatrics or ophthalmology. The decision to
select a certain vendor might be beyond the control of the operational staff who will be working with the
CRO, in situations where finances or ongoing contracts dictate constraints on the selections for
outsourcing. Therefore, defining the plan for communication, responsibilities, cost and quality at the
outset can align expectations of the specific study or program (Lipp, 2010).
Timelines
If timelines to complete a clinical trial program are critical to satisfy business priorities, the sponsor will
need to find a CRO that provides their services at a pace consistent with prespecified milestones. Delays
in the execution of a clinical trial can therefore be problematic. The results of the 2018 Tufts CSDD
Outsourcing Survey identified “execution” as a top priority for CRO selection (Getz, 2018a). The CRO
must be able and willing to commit the appropriate resources, often at the risk of decreasing focus on
other projects and increasing the cost that must be charged to the sponsor (Anderson, 2008). The criteria
that will be used to monitor a CRO’s performance with respect to timelines must be predetermined to
manage expectations at the onset of the agreement and should reflect the sponsor’s initial reasons for
selecting the CRO.

19
Cost
The ability to select the best CRO(s) to run a program or clinical trial might be compromised if the
outsourcing decision is driven by costs. Transactional outsourcing models exist to incorporate fixed costs
for certain types of deliverables, such as the completion of monitoring visits or medical review of safety
data. However, the quality of that deliverable may not be factored into the pricing (Getz, 2018b).
Approaching outsourcing from this perspective treats the operations of a clinical trial as a simple set of
tasks, disregarding the many complexities inherent in the regulatory and medical systems. The
sponsoring staff must be sufficiently knowledgeable about clinical trial logistics to detect when pricing is
fair and fees are not exaggerated, and to recognize that unplanned changes will potentially impact the
overall trial costs (Getz, 2018b) (Calaprice and Katz, 2016) (Alsumidaie, 2012). Basing the decision to
outsource on cost estimates alone is only practical in a setting where standard goods or services are
purchased, an unusual situation for clinical trials (Haas, Agrella and Maisto, 2014).
“Scope creep” is a common problem in clinical trials. It occurs when the agreed-upon contracted
deliverables are defined narrowly and the contracted budget does not cover costs that were unanticipated
as the complexities in clinical trial management increase. Sponsors typically compare bids from different
CROs when they are performing due diligence to assess the services and capabilities of various vendors.
Such comparisons help the sponsor to determine if the estimates are reasonable and comparable, and the
degree to which they should become a pivotal factor when making the outsourcing decision, knowing that
the scope of the original contract can evolve as the clinical trial or program advances.
2.4.2 CRO Outsourcing Models
Outsourcing as a strategy to supplement staffing and expertise can be managed by a pharmaceutical
company in various ways that can be reflected in a variety of outsourcing models (Figure 4). Individual
CROs can be utilized as a single entity for a program or as a preferred provider across one or more

20
programs or services. Additionally, outsourcing can be carried out using a combination of CROs. In
these cases, the sponsor can manage the multiple CROs either across a program with multiple trials, or
even on an individual clinical trial, depending on the needs of the sponsor and the specializations of the
CROs.
Figure 4: Outsourcing Paradigms
Source: Adapted from Tufts CSDD 2018 Outsourcing Survey (Wilkinson et al., 2019)
Traditionally, CROs were utilized for selected “transactional” services; multiple CROs could be used to
supply different types of therapeutic or operational expertise (Carroll, 2005) (Haas, Agrella and Maisto,
2014). In some cases, however, the company might develop a relationship with a single CRO that could
handle multiple needs without requiring the company to qualify and interact with several vendors.
Alternatively, the sponsor might handle the trial mostly in-house, and may “in-source” staff from a CRO
to assist when additional help is needed, so that it avoids hiring additional staff into the company itself.
When a clinical trial program is unexpectedly altered or stopped, the use of a CRO allows a
•Single CRO
•Involved in all outsourced operations
Single-Source
•Temporary personnel in specfic disciplines
•Ability to work on multiple projects
Insourcing
•Per-project
•Specific tasks
Transactional
•Per-project
•Full operational outsourcing
Full Service
•One or more preferred CROs
•Full operational outsourcing for a single project(s)
Preferred Provider
•One or more preferred CROs
•Full operational outsourcing across multiple projects/disciplines
Functional Service Provider
•Single CRO
•Operationalizes all outsourced areas for a program
Program-Based Provider

21
pharmaceutical company the flexibility to downsize by amending the contractual relationship with the
CRO to a different outsourcing model.
More recently, trials with intricate designs and complex logistical considerations can require data from a
diverse range of assessments and procedures. The pharmaceutical company may outsource to multiple
vendors as a preferred provider, where there exists a prior relationship based on that need, or as a
functional service provider, where only limited services are provided on a one-time basis.
As full-service CROs became more common, sponsors were able to establish partnerships with preferred
providers, who could perform the array of activities necessary for that clinical trial program (Getz, 2009).
Examples of preferred-provider alliances began to emerge 15 years ago, when larger companies came to
recognize the benefits of such preferred alliances, including cost reductions, decreased start-up times, and
greater alignment amongst the offered services (Alsumidaie, 2012). For example, Wyeth
Pharmaceuticals, prior to its acquisition by Pfizer, had selected Accenture as a preferred provider to
oversee all data management functions and Research Pharmaceutical Services (RPS) to provide all
monitoring activities in the Americas, with corresponding project management support. Eli Lilly utilized
Quintiles as their preferred outsourcing vendor to manage all clinical trial monitoring capabilities.
For larger programs, various combinations of CROs can be used to assure the performance of all of the
functions required during the trial. For example, in 2014, Janssen Pharmaceuticals partnered with both
Parexel and IQVIA to manage their clinical trial monitoring activities cooperatively across the company.
To this end, a joint operating manual was developed that dealt specifically with the policies, procedures,
and responsibilities for each party (Wolfs et al., 2018). This allowed Janssen to select the appropriate
contracted staff from the provider that best fit their needs, while managing these parties in a standardized
manner. Wolfs and colleagues identified that communication and harmonization were key to this alliance
strategy, to recognize more clearly the capabilities and expectations of each partner. The company also

22
gained efficiencies by using integrated personnel and systems to assure smooth study management (Wolfs
et al., 2018).
2.4.3 Past Evaluations of Outsourcing Models
In 2012, Getz and his colleagues surveyed 43 Phase 2 and 3 clinical trials, conducted by 9 pharmaceutical
companies, to identify the outsourcing relationships used to manage these studies (Getz, Lamberti and
Kaitin, 2014). Most were outsourced to a CRO. They then examined 11 functional areas to determine
which operational areas were commonly outsourced. These areas included protocol design, site selection,
patient recruitment, site monitoring, site payments, medical monitoring, data management, statistical
analysis, medical writing, regulatory, and submission preparation. The data were stratified to determine
whether a transactional or a strategic outsourcing strategy was used (e.g., task-based per project versus
longer-term contracted support), or if competencies in the functional areas were retained in-house (Figure
5). Clinical site monitoring was almost always outsourced (95% of the studies). However, areas
requiring specific therapeutic expertise, such as protocol development and regulatory affairs, were
outsourced for less than 25% of the studies. Results suggested that no one outsourcing strategy was
implemented for the execution and management of clinical trials. The types of outsourcing models often
differed between companies and between different studies conducted by the same company. This lack of
consistency in outsourcing strategies shows that sponsor companies may have not realized any value
potential of strategic sourcing opportunities, as the authors of the study noted that the real-life utilization
of CROs leads to several questions regarding efficiency, contract relationships, and the value of
outsourcing.

23
Figure 5: Utilization of Outsourcing Models and Clinical Activities

Source: Adapted from (Getz, Lamberti and Kaitin, 2014).
To understand the efficiency of the outsourcing operations, Getz and his colleagues reviewed
performance metrics for the outsourced activities including but not limited to timeline adherence, change
orders, violations and deviations, and data queries. The study showed no difference in the capabilities of
CROs whether they were part of preferred provider or transactional relationships. However, studies with
preferred providers had a lower rate of changes to the clinical trial program and a smaller number of
patients who were eventually excluded from the study dataset, suggesting that studies involving preferred
providers might have some advantages. In contrast, other studies have concluded that preferred provider
outsourcing may not always be the best strategy (Avoca, 2016) (Getz, 2013). The Avoca Group, a
consulting firm, has looked at the use of preferred providers using annual surveys. In their 2016 report
the authors noted that quality issues with contracted personnel have been a primary reason for
dissatisfaction with the preferred provider model.
0%
20%
40%
60%
80%
100%
120%
Site Identification
and Selection
Patient Recruitment
and Retention
Site Monitoring Medical Monitoring Central site Payment
Administration
Outsourcing Models for Operational Aspects of Phase
2/Phase 3 Clinical Trials (n=43)
Strategic Relationships Transactional In-House

24
Outsourcing models have been characterized in other ways as well. Insight into the advantages and
disadvantages of two types of models, described as “lean” and “standard” models, were explored by
studying fourteen pharmaceutical companies and three CROs (Calaprice and Katz, 2016). “Standard”
models of outsourcing included the transactional or insourcing models, in which the sponsor still took
control of most aspects of the study. The “lean” model included service structures in which the CRO was
given authority to execute most of the operational aspects and the sponsor focused on oversight.
Advantages and disadvantages of these models were ascertained from respondents. The lean model
increased commitment for both sponsor and CRO. This was seen to increase the efficiency of resource
allocation. Further, the closer relationship that developed between the sponsor and CRO led to quicker
problem-solving and implementation of lessons learned. However, other respondents favored the
standard model which they felt was easier to implement and made the best use of existing resources.
The Tufts CSDD CRO Survey in 2018 provided more systematic data, confirming the results of the
earlier study showing that companies of different sizes use a mix of outsourcing models, by soliciting
additional data from 88 respondents regarding the effectiveness of the different oversight models (Getz,
2018a). The deliverables and performance of outsourcing activities and models were also analyzed to
examine in more detail the levels of satisfaction with outsourcing practices, including oversight and
productivity (Wilkinson et al., 2019).
Respondents were provided with types of outsourcing models, reflecting those noted in Figure 4. The
data continued to consolidate the categories of outsourcing models to represent related strategies, such as
preferred provider outsourcing and full-service provider outsourcing, both of which reflect a model where
the CRO has extensive operational responsibilities. The data indicated that the most frequently used
outsourcing models were transactional but could include full-service outsourcing or preferred provider
outsourcing. The prevalence of utilization of these models, where the sponsor allocates more operational
tasks, allows the CRO to have additional autonomy. Structure is built within the CRO to manage a study

25
or program and allows the CRO to operate under their processes and manage the individual personnel
assigned to a particular company or project over time. While this may be an acceptable practice from the
onset, a main area of dissatisfaction noted in the survey data was related to the ability of the CRO, under
these transactional models, to alter practices and personnel. Respondents related this to degradation in
quality, which cannot be easily remediated by the sponsor. Additional areas of dissatisfaction noted from
survey respondents included a lack of innovation and the flexibility to improve operations, which is
consistent with the other survey information available in the literature. The Avoca Group have conducted
surveys regarding outsourcing relationships over the past five years. In the results of the survey published
May 2019, data from respondents with both the sponsor perspective (N=89) and the provider perspective
(N=128) looked at factors related to relationship quality and value. There was a notable gap in
“Relationship Health”- how providers viewed the capabilities of their vendors, and how the vendors
viewed their capabilities as related to providing outsourcing services. The results of these “Relationship
Health” factors, as measured on a 5-point scale (with 5 being the highest rating of satisfaction), showed
that the closest assessment was related to “relationships” satisfaction, with a mean score of 3.9 from the
sponsor side and 4.8 from the CRO side. Measurements of satisfaction with “Overall Work” “Quality”
and “Value” showed a greater disparity between the values from the sponsors and the CROs, and all
categories were higher rated by the CRO respondents. The values of these 2018 ratings mimicked the
results of past surveys and showed a widening gap in perception since 2015. There was no difference in
the four variables reviewed regarding the sponsor impressions for a full-service provider or a functional
service provider (Avoca, 2019c).
The latest survey from Avoca, conducted at the end of 2019 and published in May 2020, was consistent
with data from the previous years, although the gaps on the perception of relationship health in the
variables for relationship and overall work quality slightly narrowed. This survey elaborated on the
reasons for the ratings in the Value, Quality, Overall Work, and Relationships variables. The 2019 survey

26
did note that the functional service provider model was associated with better quality - 14% thought
“much better quality” from a functional service provider versus 4% who thought “much better quality”
from a full-service provider (Avoca, 2020). Other areas where sponsors were “somewhat” or “very”
satisfied, regardless of outsourcing model, included operational expertise (63%) and adherence to
timelines (60%). Consistent with the 2018 CSDD survey, sponsor concerns were related to the impact of
CRO staff turnover (33% somewhat or very satisfied) and the level of proactivity (29% somewhat or very
satisfied). While the data showed improvements in the sponsor perspective of utilizing an outsourcing
model, the inability to meet deliverables, the quality of the outsourced activities, and the amount of
oversight required indicate that current approaches to outsourcing do not correlate with a high level of
satisfaction. Highlights of areas considered by respondents to be improving the collaboration, as well as
those areas that need improvement, are noted in Figure 6.
The data reported from both the Avoca Group and CSDD show that traditional outsourcing models do not
tend to bring greater success in collaborative efforts to complete clinical trials. The fact that many
sponsors are using a mix of outsourcing models, e.g. transactional model while also contracting for in-
house staff, also suggests that pharmaceutical companies may not be maximizing efficiencies (Getz,
2018b). The lack of consistency was noted to be difficult to manage when running concurrent programs.

27
Source: Original Figure
2.5 Regulatory Impact on CROs and Sponsors
As CROs take on larger roles in clinical trial management, health authorities worldwide have had to adapt
their thinking and oversight, to assure that such activities are conducted appropriately with regard to their
different regulations and guidance. Initially, regulations were quite general; they served to guide clinical
trial activities regardless of the entities that were managing different aspects of the trial. In 1980, the U.S.
Code of Federal Regulations (CFR) Title 21 introduced 21 CFR Part 50, Protection of Human Subjects,
which laid out rules for obtaining the consent of a patient enrolling in a clinical trial. In 1987, 21 CFR
Part 312, Investigational Drug Application, expanded on these regulations to recognize the
responsibilities of sponsors, including its responsibilities related to the engagement and oversight of
CROs (FDA, 2018).
Opportunities for Success:
Executive oversight involvement
Timely issue identification
Actionable resolution
Success Measures:
Alignment of timelines, process
and personnel
Well defined responsibilities
Oversight practices
Figure 6: Areas for Improvement and Effectiveness

28
Of particular importance in the U.S. for the operations of CROs was Section 2 of 21 CFR Part 312,
Transfer of Obligations to a Contract Research Organization. This section of the regulation gave the
sponsor permission to transfer the legal obligations of running a clinical research study to a CRO if the
specific responsibilities given to the CRO were documented (Table 2; Appendix A). That documented
transfer of obligations had to be described as part of the associated Investigational New Drug Application,
and later was to be included in the follow-on New Drug Application. These arrangements are subject to
review during regulatory inspections that may be carried out at both the clinical site and sponsor level
when the FDA conducts its reviews before it approves a marketing application. Thus, the FDA has
explicitly recognized the potential involvement of CROs in those studies and regards the CRO as a
“vendor” or “contractor” whose activities are an integral part of the sponsor’s quality system (FDA,
2017).

29
Table 2: Transfer of Obligations- Key Requirements
Requirement Citation
Ensuring that the investigation is conducted in accordance with the general
investigational plan and protocols
21 CFR 312.50
Informing investigators of new observations discovered by or reported to the
sponsor, with respect to adverse effects and safe use
21 CFR 312.55(b)
Reviewing ongoing investigations to include: Monitoring all clinical
investigations; Securing investigator compliance with the agreement contained in
the signed Form FDA 1572, the general investigational plan or other investigator
responsibilities or, alternatively, discontinuing investigational test article
shipment; Requiring the disposal or return by non-compliant investigators of
investigational test article; Notifying the FDA of the termination of the study
site of the non-compliant investigator
21 CFR 312.56
Reviewing and evaluating the evidence relating to the safety and
effectiveness of the investigational test article as such evidence is obtained from
the investigator
21 CFR 312.56(c)
Retaining adequate records under 21 CFR 312, Subpart D, for two years after a
marketing application is approved for the test article; or, if an application is not
approved for the test article, until two years after shipment and delivery of the
test article for investigational use is discontinued and FDA has been notified
21 CFR 312.57(c)
Act as the sponsor’s authorized representative in the United States because the
Sponsor does not have a place of business within the U.S.
21 CFR
312.23(a)(1)(ix)

Additional guidance documents were subsequently introduced to supplement the 1987 update with respect
to the outsourcing of clinical trials that they recognized to be increasingly prevalent. FDA expanded its
guidance on delegating responsibilities to a CRO in the August 2013 Guidance for Industry, Oversight of
Clinical Investigations — A Risk-Based Approach to Monitoring and the September 2013 Guidance for

30
Industry, Electronic Source Data in Clinical Investigations (FDA, 2013b) (FDA, 2013a). Specifically, the
August 2013 Oversight Guidance makes it clear that sponsors are legally obligated to provide the
appropriate oversight to “ensure adequate protection of the rights, welfare, and safety of human subjects
and the quality of the clinical trial data submitted to the FDA”, but that CROs will also be subject to the
guidance when they are delegated responsibilities by the sponsor. The September 2013 Guidance on
Electronic Source Data explicitly specifies that both sponsors and CROs are subject to the rules governing
electronic case report forms, designed to capture clinical data from investigational sites. The
acknowledged importance of CROs is well captured by the former FDA Commissioner, Dr. Scott
Gottlieb, who noted that the FDA:
“…has seen a continued reluctance to adopt innovative approaches among sponsors
and clinical research organizations. We’re committed to advancing more of these
approaches through additional guidance and workshops… that are focused on
overcoming bottlenecks to modernizing trial infrastructure” (FDA, 2019).
The U.S. FDA is not alone in recognizing the increasing use of CROs and the need to consider that use in
their regulatory rules. The International Council for Harmonization (ICH) was implemented in 1990 to
provide harmonized guidance that could be referenced by regulations regarding clinical trial management
worldwide, so that similar expectations would govern work across national boundaries (ICH, 2016). The
EU’s European Medicines Agency (EMA) published a November 2013 Reflection paper, “Risk based
quality management in clinical trials”, which states that the quality management of a clinical trial must
extend to the CROs utilized to conduct a study. In 2017, the addendum of ICH-GCP [ICH E6(R2)] was
updated to add a statement that “The sponsor should ensure oversight of any trial-related duties and
functions carried out on its behalf, including trial-related duties and functions that are subcontracted to
another party by the sponsor’s contracted CRO(s)” (ICH, 2016).

31
2.6 Setting Expectations in an Outsourcing Relationship
An outsourcing relationship in the clinical trial environment is defined initially by a complex set of
contracts, study mandates and regulatory requirements (Figure 7). As the clinical program develops, the
sponsor and CRO must then continue to evaluate its strategy and expectations regarding the management
the clinical trial study or program (Jones and Minor, 2010).
Figure 7: Expectations During Outsourcing
Source:
Adapted from (Getz, 2016)
Alignment with the CRO is needed as the sponsor decides which responsibilities it will retain and which
will be outsourced, so that the two entities can develop a clear plan with milestones and performance
metrics. Contracts and study agreements should also address the ways in which communication and
governance will be managed. The Tufts CSDD Outsourcing Survey put special emphasis on having a
Expectations
Transparency in
costs and fees
CRO
engagement
Experienced
personnel
Comprehensive
processes
Recognition of
deliverables
Therpeutically
aligned

32
clear communication channel to align expectations with deliverables and define ongoing collaboration
between the sponsor and CRO (Wilkinson et al., 2019).
Implementation of oversight meetings via a governance committee creates accountability and provides a
defined methodology for reviewing progress and issues. A recurring theme in the literature is the
importance of managing expectations not only at the outset of the sponsor/CRO relationship but also as it
progresses through the clinical trial program (Lou, 2018). Before a trial begins, it is important to
delineate clearly the responsibilities of each party and to understand how decisions and issues will be
escalated and managed (Fassbender, 2016). The way that responsibilities are shared will vary with the
project because some activities and information may not be appropriate to share (Calaprice and Katz,
2016). Based on reviews of the existing literature, these areas that cannot be outsourced fully may
include those with proprietary scientific expertise, company knowledge, or relationships with certain Key
Opinion Leaders (Figure 8) (Margherita and Valeria, 2017). The sharing of pertinent knowledge in an
outsourcing model strengthens the relationship with CRO and builds upon the capabilities of the CRO.

33
Figure 8: Sponsor Retained Competencies

2.6.1 Challenges and Continuous Assessment
As might be apparent from the above discussion, much of the real work of managing a clinical trial that
involves one or more CROs is not in the initial contracting process but rather in the ongoing
administration and oversight. The sponsor must review the ongoing performance of its CRO by assessing
its personnel, procedures, and capabilities. While cost, expertise, and availability of personnel are large
drivers in the CRO selection process, the sponsor must rely as well on the “soft skills” of the CRO as the
clinical trial program progresses. Sponsors and CROs will be involved together in a complex governance
process to assure ongoing corrective actions and program adjustment (NICE, 2017). Previous evaluations
suggest however, that a “disconnect” often exists between sponsor expectations and CRO performance.
An absence of policies or guidance from management can result in misunderstandings that increase the
numbers of spending and management issues (Getz, Lamberti and Kaitin, 2014). Attention also can be
focused on the day-to-day operational activities rather than routine assessments of performance or
Internal
Expertise
Scientific
Knowledge
Project
Management
Quality
Oversight
Regulatory
Leadership
Technical
Knowledge
Therapeutic
Relationships

34
compliance. Further, outsourcing relationships, like most other business relationships, have inherent
issues that are not easy to manage or measure, and often cannot be predicted. Thus, a robust
communication and governance system with these challenges in mind must be put into place early and
used effectively. It is often not easy for a company to accept a CRO as a collaborative partner (Anderson,
2008). The sponsor may interpret the need for effective oversight as the need to be involved in all the
trial details. However, there is a balance between effective management and “micro-managing”, which
can get in the way of the CRO to perform their obligations effectively (Margherita and Valeria, 2017).
Yet companies are reluctant to cede control because they fear the repercussions of regulatory inspections
that will be part of regulatory reviews. The FDA has routinely inspected CROs working on behalf of a
sponsor and have found issues leading to corrective actions and warning letters. For example, the CRO,
ICON, and its sponsor both received warning letters from the FDA in 2009, for an antibiotic trial in which
ICON was monitoring clinical trial sites on behalf of a sponsor (Getz, 2010). In that trial, the FDA
identified data integrity issues that were not addressed by ICON and caused delays in the approval of the
marketing application (FDA, 2009). While it cannot be determined if outsourcing was the cause for the
data integrity issue, having a collaborative risk management plan in place may have allowed the sponsor
to continuously evaluate critical areas that were being completed by the CRO and assess gaps in
performance (Brennan, 2014).
For CROs, administrative oversight is complicated further by the fact that they seldom work for one
sponsor. Each of the companies with which the CRO will contract has its own procedures, staffing
structure and operating model that integrates with the procedures and processes of the CRO (Getz, 2013).
Managing the expectations of many sponsors with specific requests, while simultaneously having internal
systems in place to meet the requirements of regulators, can create challenges in how a CRO guides
employees in both process and time management. The implementation of a robust transfer of obligations
and the precise wording in any documents delineating responsibilities have the potential to assist with

35
oversight, and mitigate any confusion caused by internal or external processes. Nevertheless, the
relationship between a sponsor and CRO can also be affected by factors beyond the contracted
arrangement and may affect the way that the CRO responds to changes in scope or unexpected requests.
For example, requests to perform a trial within condensed timeline can be problematic for a CRO because
it may be necessary for the CRO to sacrifice its own internal processes, perhaps even at the risk of
skirting regulatory requirements. This can damage the collaboration between the sponsor and CRO and
put data integrity and patient safety at risk. However, a larger sponsor company that can potentially
contract for additional studies or tasks might be more persuasive to have its request managed by the CRO
if the CRO is interested in assuring an ongoing relationship from which it might gain substantial later
revenue. A smaller company with a smaller, time-limited contract might not be given the same
consideration. Thus, some feel that small companies are placed at a disadvantage if the CRO anticipates a
greater financial return by engaging with a larger pharmaceutical company offering a program based or
preferred provider contract (Hassanzadeh et al., 2014) (LaMotta, 2018). This lack of commitment to
align expectations, staff involvement, and communication can result in ineffective oversight practices, as
outsourced resources can be directed to other projects and sponsor demands (Getz, 2018a) (Avoca, 2020).
Regardless of the outsourcing model or models a sponsor employs, regulations and ethics require that
there must be sponsor oversight; however, the sponsor determines the necessary level of oversight and
how this is adapted into their outsourcing model (ICH, 2016). Tools such as risk-based assessments and
key performance metrics can be part of an outsourcing model that allows the sponsor and CRO to
periodically review the status of specific activities that drive compliance and data integrity, such as study
deviations and issue resolution (Littlefield, Harrison and Goodwin, 2015). Determining the metrics to be
collected, and a consistent review of these metrics collaboratively by the CRO and sponsor, allows for
ongoing reviews of areas that are performing well or need additional attention (Fassbender, 2016). The
information collected by these metrics could be protocol or program specific, and could also address the

36
adequacy of processes and communication of issues and corrective actions. The risk assessment process
determines areas of potential concern, and how to manage those concerns, before they happen. The risk
assessment aligns with the metrics being collected to correlate areas of possible concern. All relevant
parties should complete the review of this information in a timely manner, so decisions and actions can be
taken to contain or mitigate concerns. Failure to collect or review metrics and risk information
appropriately may cause additional issues that decrease the reliability of the CRO’s performance, and
which cause additional activities to be added into the original scope of work (Howley and Malamis,
2014).
2.7 Model Exploration - Vested Outsourcing
Various outsourcing models for clinical trials have been evaluated with respect to frequency of use as
well as the impact on timelines and cost savings. The literature identifies several areas for improvement
in the collaborations between sponsors and CROs. The fundamentals of successful collaboration,
including well-defined roles and oversight practices, have also been noted. However, the data have
consistently shown that the current outsourcing models do not seem to improve efficiencies, costs or
collaboration (Haas, Agrella and Maisto, 2014) (Wilkinson et al., 2019).
The push for shorter development times requires innovative thinking and an increase in operational
efficiency. An outsourcing framework that focuses on collaboration and sharing the responsibility for
outcomes and deliverables, while still recognizing appropriate oversight and guidance, provides an
evolving paradigm for sponsors outsourcing to a CRO (Getz, 2016). However, additional factors may
need to be considered when structuring relationships for the resource-limited early-stage sponsor. These
smaller companies are vital for the development of new drugs for challenging or untreated diseases,
because they can often work more efficiently and with less business risk than large sponsor companies
(Calaprice and Katz, 2016) (Ioannou, 2018). These companies typically rely on collaborative outsourcing

37
models with their CROs, that as partners can bring needed expertise to the conduct of clinical trials
(Leader, 2014).
The Vested Outsourcing Framework has been developed as a novel and streamlined approach in the
relationships between organizations and contracted outsourcing entities (Vitasek and Manrodt, 2012).
This Framework defines five guiding principles that emerged from research into successful outsourcing
relationships, and further explored the core elements needed to implement the five rules. The
applicability of this Framework in the collaboration between pharmaceutical companies and CROs was
discussed in a White Paper entitled “Unpacking CRO Outsourcing- Harnessing Innovation and Added
Value in Pharma CRO Outsourcing”. The concepts in this white paper were initially conceived by the
University of Tennessee as part of a research project funded by the United States Air Force (Vitasek and
Manrodt, 2012). The researchers looked at outsourcing relationships over a variety of industries as well
as government contracts with a variety of suppliers. This research resulted in defining a framework for an
outsourcing model that focused on ways that both the buyer and seller both have a vested interest in a
successful outcome (Figure 9). Further development was sponsored by a large pharmaceutical company,
to determine if the five principles that are the foundation of Vested Outsourcing are feasible in the current
CRO outsourcing practices.
2.7.1 Vested Outsourcing Model
Vested Outsourcing is a model that conceptualizes the important elements in collaborative relationships
between organizations and their suppliers; in the management of clinical trials, this addresses the
relationships between sponsors and CROs. It is framed by what is called “key relationship rules”, that are
illustrated in Figure 9.

38
Figure 9: Vested Outsourcing Framework- Key Relationship “Rules”

The Vested Outsourcing Model defines Five Principles, each supported by action items or “core
elements”, as described in more detail below.
1. Focus on outcomes, not transactions
The research on previous agreements for clinical trial outsourcing emphasize the need to be flexible and
have distinct milestones with little ambiguity related to responsibilities and expectations (Haas, Agrella
and Maisto, 2014). The current practice for contracts between sponsors and CROs typically specifies
transactional line items, such as personnel and tasks, and thus may not offer incentives for the
performance of a CRO. This practice does not recognize the impact that might come from changing
regulations and science advancements, common during the conduct of clinical trials. In the Vested Model,
the contract is structured with outcome-based incentives. There two elements that define this Principle-
Business Model Map and Shared Vision/ Statement of Intent (Figure 10).
The
"What"
Clear
Outcomes
Offer
Incentives
Insight
Outcomes

39
Figure 10: #1- Outcome-Based Business Model

The Business Model Map is an open-source tool designed to capture key elements of an outsourcing
relationship and assists to align goals and expectations. The mapping exercise breaks down categories of
operations, which can then be reviewed for risks, advantages, dependencies, and strategic impact. The
creation of the Business Model Map allows the parties to structure a collaborative pathway which
establishes the guiding principles and expectations for the collaboration, including communication,
perspective, trust/ confidence, flexibility, focus, and feedback.
2. Focus on the what, not the how
The details of how tasks will be accomplished are replaced with a focus on what needs to be done. In the
Vested Outsourcing Model, the shift to deliverables without confined direction allows the CRO to
accomplish the task in a way that works best in each situation. This shifts accountability to be a shared
concept, and relies on one key element, Statement of Objectives/ Workload Allocation (Figure 11).
Shared Vision
and
Statement of
Intent
•Define
joint
vision
•Map
potential
outcomes
•Align
Goals
Business
Model
Map
Vested
Outsourcing
Model

40
Figure 11: #2- Focus on “The What”

3. Clearly defined and measurable desired outcomes
The utilization of metrics provides a method for sponsor oversight and for the CRO to determine their
effectiveness, but the metrics need to be useful and keep the end in focus. These metrics need to measure
the information in the elements of Rule #2, focusing on what work needs to be done and not detailed
descriptions of how that is accomplished. In doing so both the sponsor and CRO will have a clear
understanding of what defines a successful goal. Two elements support this aspect of the model, which
focus on collaboration and a clear definition of the desired outcomes (Figure 12). This allows the CRO to
provide input into what defines success and to have valuable metrics that guide from transaction focused
to outcome focused.
Transfer of
Obligations
•Sponsor defines
scope of
outsourcing
Statement of
Objective
•Jointly
developed
•Describes
intended results
Performance
Work
Statement
•Defines details of
work to be done
•Defines details of
expected results

41
Figure 12: #3- Outcomes and Metrics

4. Pricing model with incentives that optimize for cost/service tradeoffs
Current models for CRO outsourcing focus on transactions and deliverables, rather than incentives. In the
Vested Outsourcing Model, the concept of a Request for Solution replaces the commonly used Request
for Proposal process (Vitasek, Kling and Keith, 2016). This flexible approach to the pricing models
requires that both the sponsor and CRO innovate as they price a project. The sponsor should recognize
the lowest price does not correlate with the best performance and find ways to contractually reward the
CRO for novel approaches to conducting the clinical trial. While this may not affect the overall cost, this
may add value to the bidding process and clinical trial execution through process improvement and
partnership. The element supporting Rule 4 focuses on an agreed pricing model that rewards innovation.
Bottom line cost is not the focus, and the delivery of the outcomes noted in Principle #1 are done through
innovative operations. This involves an investment of trust by the sponsor, and a commitment by the
Element 4
Define Desired Outcomes
Collaborative
Limited, High-Level Metrics
Define Success
Measurements
CRO Proposes Solutions
Element 5
Measure Performance
Align perfomance to
strategy
Regular governance review
of metrics
Rule #3
Measurable Outcomes

42
CRO to perform to meet those outcomes. The CRO now shares a responsibility in decision and
outcomes.
5. A governance structure with insight rather than oversight
The fifth and final principle of Vested Outsourcing concentrates on managing the relationship with
insight, rather than sponsor oversight. Because the management of an outsourcing relationship typically
is “owned” by the sponsor, with the CRO acting as the supplier of services, discussions tend to revolve
around CRO operations, rather than then integration of the work by the sponsor and CRO (Vitasek, Kling
and Keith, 2016). The governance structure is configured to take advantage of the capabilities and
innovative opportunities available to the CRO, and to assure consistent communication paths that respond
to risks in a timely manner. The supplier is focused on meeting predefined goals and can use its best
judgement on how to achieve those goals with less sponsor oversight, guiding the governance team to
works collaboratively and consistently. There are four elements associated with the management of the
collaboration (Figure 13).
Figure 13: Effective Collaboration

Element 7: Relationship
Management
•Joint Policies
•Flexible governance
structure
•Management of
partnership
Element 8:
Transformation
Management
•Recognizes changing
business needs
•Change management
in place
•Mutual accountability
•Reward innovation
and continuous
improvement
Element 9: Exit
Management
•Recognize business
needs change
•Develop an upfront,
agreed exit plan
Element 10: Special
Concerns and External
Requirements
•Specific to the
relationship
•Governance insight
recognizes market/
business challenges

43
2.7.2 Vested Outsourcing in Practice
The Vested Outsourcing Framework offers a practical approach to relationships between buyers and
sellers of goods. However, challenges might arise when translating these principles to relationships with
service providers such as CROs rather than vendors supplying tangible goods. A White Paper from the
University of Tennessee Haslam College of Business studied the Vested Outsourcing Framework in the
pharmaceutical industry and examines specifically the relationship between a large sponsor company and
a larger CRO (Vitasek, Kling and Keith, 2016). The research included a review of outsourcing trends and
challenges to develop a general understanding of the interactions between sponsors and CROs.
Additionally, conversations were held with stakeholders from both perspectives. An assessment of
defined business models was also conducted (as previously published by the Haslam College of
Business), and these were related to the data derived from the researchers’ review of CRO outsourcing.
These business models included the categories of “Preferred Provider Model”, “Basic Provider Model”,
and “Approved Provider Model”, which aligned with the Tufts CSDD models shown in Figure 4. The
observations from the research were consistent with the information in the literature: outsourcing to CROs
trends toward a “pay-for-service” system, and there was a lack of sponsor internal alignment on CRO
selection, contracting, utilization, or management.
A Business Model Map was utilized by the Tennessee researchers to look at existing business models and
the areas of dependency in the outsourcing relationship (Keith et al., 2017). Areas of risk tolerance, as
rated by interviewees, were mapped out and scored by the researchers. It concluded that a relational
outsourcing model, such as the Vested Outsourcing Model, added value to assure a successful
collaboration between entities. Interviewees noted that the five elements of Vested Outsourcing are not
routinely integrated into any one CRO outsourcing paradigm. Nevertheless, some of the concepts
presented by the model, including shared risk and reward, innovation, and engagement, were highly
related or critical to the success of the outsourcing relationship.

44
This research will further explore the aspects of the Vested Outsourcing Framework as they relate to
contracting of clinical trials with CROs by surveying whether the “rules” outlined in model are included
in current CRO/Sponsor relationships and focusing on which elements are being utilized. This
framework can help identify gaps in how CROs and companies function and inform both large and small
pharmaceutical companies on how to employ the best outsourcing models when working with CROs to
bring potential new drugs through the clinical trial process.

45
CHAPTER 3. METHODOLOGY
3.1 Purpose
The purpose of this study was to survey clinical research professionals within the pharmaceutical and
biotechnology industries based in the United States regarding their utilization and collaboration with
Clinical Research Organizations for clinical trial outsourcing. Using the Vested Outsourcing Framework,
as defined by Kate Vitasek at the University of Tennessee, electronic survey questions were designed to
collect information regarding current practices of outsourcing and to evaluate how these might relate to a
model that promotes collaborative relationships and measures outcome based results, rather than fee-for-
service models (Vitasek and Manrodt, 2012). Information derived from this survey was further evaluated
to see trends in outsourcing models or collaborative methodologies between sponsor companies of
various sizes or stages of development.
3.2 Data Collection and Analysis Methodology
Survey development was initiated through review of the literature regarding historical and current
outsourcing practices and models between the pharmaceutical industry and CROs. A draft survey was
created and presented to a designated focus group consisting of members in academia and invited industry
members with expertise and responsibilities for CRO selection and oversight. This focus group was set
up to review the proposed questions and fine-tune the information being requested from study
participants. The focus group was held over a 90-minute virtual call with attendees. The information
discussed during the focus group was recorded and utilized to refine the survey questions, to collect the
necessary information to formulate an adequate survey.
The final initial survey was prepared using the web-based survey tool, Qualtrics
(http://www.qualtrics.com). Potential survey participants were selected through industry experts and

46
through clinical trial professional associations. The final survey included 33 questions, with multiple
choice questions, as well as scale-based responses and rank ordered responses. Questions were designed
with “skip-logic” to allow respondents to by-pass questions that were not applicable to their area of
experience (Appendix B). Questions in the survey primarily consisted of close-ended questions, which
will included “yes/no”, multiple choice, and scaled items.
Results were summarized using descriptive statistics including graphical presentations and any cross-
tabulations. All open text and/or comment fields were reviewed to determine any commonalities or
trends. Questions with rank orders were calculated by applying a weight to the responses. The ranked
score was calculated for each of the category responses, and, for example, the option ranked highest was
multiplied by “X”, and the next category was multiplied by “X-1”, and so on. The total weighted score
was summed to get the final rank order for the category responses, and then sorted highest ranking to
lowest ranking.
3.3 Study Participants and Survey Deployment
The final survey was created using and Qualtrics software, which was also used deployment of the survey
and for the statistical/descriptive analysis of the data. The Qualtrics survey was emailed to prospective
participants directly or be available as an anonymous web link. Survey participants were solicited from a
range of available networks, including personal contacts of through websites such as LinkedIn, to ensure
respondents come from a broader experience pool. Networking referrals were also requested, and
participants were be solicited via email (primarily) or through personal messaging.
The survey was made available for approximately 11 weeks in order to obtain an adequate sample size for
analysis. Survey data will be maintained in an electronic data base and will be made available to
respondents as requested after the study data is analyzed.

47
CHAPTER 4. RESULTS
4.1. Survey Participation
The survey was launched on 30 March 2021 and closed to participation on 17 June 2021. Links to the
survey were provided to 154 participants with whom I had direct contact as a colleague or as a referral
from colleagues; 38 of these individuals started the survey and 37 provided responses. Additionally, the
survey was provided using an anonymous link to several groups whose members or users included
personnel working for sponsor companies in a clinical research discipline, including USC colleagues,
Society of Quality Assurance (SQA) and LinkedIn. An additional 63 anonymous persons completed the
survey; 59 entered through the anonymous link and 4 through a social media post. Overall, 100
respondents completed at least one question (Table 3).
Table 3: All Responses
Distribution Channel Audience Size Surveys Started Responses Completion Rate
Social Media N/A N/A 4 N/A
Invite Over Email 154 38 37 97%
Anonymous Link N/A N/A 59 N/A
Total -- -- 100 --

Personal or identifying information was removed to confirm the anonymity of the respondents.
Respondents were selected from persons working at pharmaceutical or biotechnology companies and who
have roles in which they interact with clinical Contract Research Organizations.

48
4.2. Demographic Profiles of Respondents
Similar numbers of respondents worked in small/ emerging companies (defined as having 1-500
employees) and large companies (with greater than 2001 employees). Of 100 respondents, 44% indicated
that they worked for a large company, and 43% for a small/ emerging company. The remaining 13%
were employed at a medium sized company (with 501-2000 employees) (Figure 14).
Figure 14: Demographic Profile of Respondents
Which category best describes the size of your company?

Respondents worked in a variety of disciplines related to clinical research and in several operational areas
that might interact with CROs (Figure 15). Nearly half of the 100 respondents (46%) worked in clinical
operations and another 10% in the clinical development field, a department often aligned with clinical
operations. Eighteen percent worked in regulatory affairs/ strategy (18%, 18/100). Other disciplines
included Program/Project Management (10%, 10/100), Clinical Quality Assurance (4%, 4/100), Data
Management (4%, 4/100), and Pharmacovigilance (1%, 1/100). Almost 10% of the respondents defined
themselves in the Other category (8%, 8/100). These respondents indicated they work in areas such as
Medical Affairs and Nonclinical Development (Table 4). One individual defined their role as Principle
Investigator [sic].
43
13
44
0
10
20
30
40
50
Small / Emerging (1-500
employees)
Medium (501-2000 employees) Greater than 2,001 employees
N of Respondents
N=100

49
Figure 15: Respondent Functions
Which area best describes your primary role at your current company (Select one)?

Table 4: Respondent Functions- "Other"
“Other” Comments
Nonclinical
Medical Affairs
Oversee a clinical department that include all of the above
Project/Program Management, RA/Strategy
Principle Investigator
Business and quality management support

Most of the 100 respondents had extensive experience with clinical research (Figure 16). Three-quarters
(75%) had worked in clinical research for more than ten years. In the other quarter, 16 had worked in
clinical research for 5-9 years and 9 had worked in clinical research for less than five years.
1
3
4
8
10 10
18
46
0
5
10
15
20
25
30
35
40
45
50
N of Respondents
N = 100

50
Figure 16: Years of Experience in Clinical Research
How many years have you worked in the clinical research industry?

4.3. Outsourcing to CROs for Clinical Trials- Selection and Evaluation
Of 100 respondents, 81% confirmed that their current company outsources their clinical trial programs to
a CRO (Figure 17); 16% did not outsource to a CRO and 3% were unsure.
Figure 17: CRO Utilization
Does your current company outsource to a CRO for clinical trial programs?

9
16
75
N=100
Less than 5
≥5 to ≤10
Greater than 10
81
16
3
0 20 40 60 80 100
Yes
No
Unsure
N=100

51
Most companies of all sizes outsourced operations for a clinical trial program to a CRO. Proportions
were highest in medium- and small-sized companies (Medium, 92%, 12/13; Small, 86%, 37/43), and
somewhat lower in large companies (73%, 32/44) (Table 5).
Table 5: Company Size and Outsourcing

Which category best describes the size of your company?

Total
Respondents
Small / Emerging
(1-500 employees)
Medium
(501-2000
employees)
Greater than
2,001 employees
Does your
current
company
outsource to a
CRO for clinical
trial programs?
Total Count 100 43 13 44
Yes 81 (81%) 37 (86%) 12 (92%) 32 (73%)
No 16 (16%) 5 (12%) 1 (8%) 10 (23%)
Unsure 3 (3%) 1 (2%) 0 (0.0%) 2 (5%)

The 81 respondents whose company outsourced to a CRO were asked to explain their level of
engagement in CRO selection or oversight. Most indicated that they had responsibility for CRO selection
and oversight, either as an individual or as part of a team (70%, 57/81) (Figure 18). Almost twenty
percent had no responsibility (20%, 16/81) and ten percent had no current responsibility for CRO
selection or oversight (10%, 8/81).

52
Figure 18: CRO Selection Responsibility
Do you have responsibility for CRO selection and oversight during the clinical trial study or program, as
an individual or as part of a team?

Forty-three respondents who were not currently involved in outsourcing included some who were in a
company that was not currently outsourcing (16/43), some who were unsure of their company’s
outsourcing status (3/43), and some at a company that does currently outsource but without a former or
current role for CRO selection and oversight (no role formerly, 16/43 and no role currently, 8/43,
respectively). These individuals were asked how often their companies evaluated their outsourcing
strategy (Figure 19). Of the 23 respondents, more than half (61%, 14/23) reported that this evaluation is
done when outsourcing each clinical trial, but a minority reported that it was evaluated once a year (22%,
5/37), or without a set strategy (17%, 4/23). An additional 20 respondents did not provide a follow-up
selection regarding outsourcing re-evaluation frequency (47%, 20/43).

57
16
8
0 10 20 30 40 50 60
Yes
No
Not currently
N of Respondents
CRO Selection
Responsibility
N = 81

53
Figure 19: Outsourcing Re-evaluation Frequency
How often does your company evaluate its strategy for clinical trial outsourcing?

The 57 individuals who were responsible for CRO selection and oversight were asked to evaluate their
most recent experience working with a CRO, by considering the importance of 6 criteria; 47-48
respondents answered. A ranked score was calculated for each of the 6 category responses, where the
option ranked as very important (V) was multiplied by 3, somewhat important (S) was multiplied by 2,
and least important (L) was multiplied by 1. The total weighted score was summed to get the final rank
order for the category responses, with 1 representing the most important element for CRO selection
(Table 6).
Experience and capability in the therapeutic area was ranked as the most important consideration; it was
ranked by most as very important (V: 83%, 39/47) and as somewhat important by a minority (S: 14%,
30/47). Reputation and previous experience ranked second and was also second when the number
choosing it as “very important” was used as a metric (V: 70%, 33/47); eight considered it somewhat
important (S: 17%, 8/47) and none as least important. Cost and global reach had similar but somewhat
lower rankings; about half identified these as very important (Cost: 54%, 26/48; Global: 51%, 24/47) and
somewhat less than half as somewhat important (Cost: 44%, 21/48; Global: 45%, 21/47). Only one and
two respondents, respectively, felt that cost and global reach were least important. Being a preferred
5
14
4
0 2 4 6 8 10 12 14 16
Once a year
When outsourcing each clinical trial
They don't; we just hire a CRO when we need without…
N of Respondents
N=23

54
provider was ranked lowest of the provided choices (V: 19%, 9/47; S: 45%, 21/47) and more than a third
identified that it was least important (L: 36%, 17/47). Seven respondents identified other areas of
importance. Three individuals suggested additional “very important” areas as: recommendation from
someone who used them recently; communication; and experience of assigned staff. Somewhat
important, identified by another three, were: communication; turnover; and the proximity of PM to
sponsor (time zones). One additional response without a ranking of importance was “speed to first site
open and first patient treated”.
Table 6: Important CRO Selection Criteria
Considering your most recent experience with using a CRO for a clinical trial, how important are the
following for selection of the CRO?
Category
Very
Important (V)
N (%)
Somewhat
Important (S)
N (%)
Least
Important (L)
N (%)
Weighted
Ranking
Total
Therapeutic area/
Capabilities
(technology/ niche
services)
39 (83) 8 (17) 0 (0)

1 (133)
47
Reputation/ Previous
Experience
33 (70) 14 (30) 0 (0)
2 (127)
47
Cost 26 (54) 21 (44) 1 (2)
3 (121)
48
Global reach 24 (51) 21 (45) 2 (4) 4 (116) 47
Preferred Provider 9 (19) 21 (45) 17 (36) 5 (86) 47
Other, please specify 3 (43) 3 (43) 1 (14) 6 (16) 7

55
4.4. Outsourcing to CROs for Clinical Trials- Responsibilities
Specific responsibilities for clinical trial activities must be divided between trial sponsors and CROs.
Respondents were presented with 12 activities and asked if primary responsibility was held by the
sponsor (SP) or the CRO (CRO), or if the responsibility was shared between the two entities (B).
Responses are provided in Table 7 for activities that were identified most commonly as the responsibility
of the CRO (or a combination of both parties), and in Table 8 for activities that were most commonly
identified as the responsibility of the sponsor (or a combination of both parties).
The three activities for which CROs were responsible most commonly were site payments (CRO: 79%,
37/47; SP: 19%, 9/47; B: 2%, 1/47), site monitoring (CRO: 77%, 37/48; SP: 8%, 4/48; B: 15%, 7/48) and
trial master file (CRO: 63%, 30/48; SP: 17%, 8/48; B: 21%, 10/48). Data management was identified by
about half as the responsibility of the CRO (CRO: 46%, 22/48); the others either assigning the
responsibility to the sponsor (SP: 29%, 14/48) or to both (B: 25%, 12/48). Patient recruitment was more
commonly viewed as a shared effort or as a CRO responsibility than as one assumed by the sponsor
(CRO: 38%, 18/48; SP: 19%, 9/48; B: 44%, 21/48).

56
Table 7: Activity Management- CROs
Considering the current clinical trial you are outsourcing, who has primary responsibility for the
management of the following functions?
Category Responsibility N (%)
CRO Sponsor
(SP)
Combination
(B)
Total
Site Payments 37 (79) 9 (19) 1 (2) 47
Site Monitoring 37 (77) 4 (8) 7 (15) 48
Trial Master File 30 (63) 8 (17) 10 (21) 48
Data Management 22 (46) 14 (29) 12 (25) 48
Patient
Recruitment
18 (38) 9 (19) 21 (44) 48

The two activities conducted most commonly by the sponsor were medical writing and clinical supply
management (SP: 69%, 33/48 and 67%, 32/48, respectively); CROs were seen to have sole responsibility
for these activities in only 19% (9/48) and 6% (3/48) of responses and the activity was shared by 13%
(6/48) and 27% (13/48), respectively.
The remaining activities were distributed more evenly across the different players and were often
conducted as joint activities. About half of the respondents identified that site selection/ identification
and regulatory presence/expertise were shared responsibilities (54%; 26/48, each); they were less
commonly considered to be the sole responsibility of the sponsor or CRO (site selection/ identification:
SP: 35%, 17/48; CRO: 10%, 5/48 vs regulatory presence/expertise (SP: 29%, 14/48; CRO: 15%, 8/48).
Medical monitoring was also viewed most commonly as a shared activity but about half of the responses
assigned the activity to the sponsor or CRO (SP: 31%, 15/48; CRO: 25%, 12/48; B: 44%, 21/48).
Statistics and third-party vendor management were also assigned more evenly across the CRO, sponsor,

57
or both (Statistics: SP: 44%, 21/48; CRO: 33%, 16/48; B: 23%, 11/48 and third-party vendors: SP: 38%,
18/48; CRO: 23%, 11/48; B: 40%, 19/48, respectively).
Table 8: Activity Management - Sponsor
Category Responsibility N (%)
Sponsor (SP) CRO Combination
(B)
Total
Medical Writing 33 (69) 9 (19) 6 (13) 48
Clinical Supply Management 32 (67) 3 (6) 13 (27) 48
Statistics 21 (44) 16 (33) 11 (23) 48
Site Identification/ Site Selection 17 (35) 5 (10) 26 (54) 48
Regulatory presence or expertise 14 (29) 8 (17) 26 (54) 48
Medical Monitoring/ Pharmacovigilance 15 (31) 12 (25) 21 (44) 48
Third- party vendor management 18 (38) 11 (23) 19 (40) 48

4.5. Outsourcing Models and CRO Management
Respondents were asked to identify their outsourcing models from 6 offered choices; multiple answers
were permitted (Figure 20). Only a few companies used a model in which one CRO performed all the
work involved in a single clinical trial (Y: 11%, 5/47; N: 89%, 42/47; Unsure (U): 0%, 0/47) or managed
all the clinical trials in the portfolio (Y: 13%, 6/46; N: 87%, 40/46; U: 0%, 0/46). Most instead had used
a model in which the CRO provides a specific function (Yes: 94%, 44/47; No: 6%, 3/47; U: 0%, 0/47)
and/or a model in which the CRO provided a range of integrated services (Yes: 89%, 42/47; No: 2%,
1/47; U: 9%, 4/47). Only 13% of the respondents used an outsourcing model where the CRO was
awarded all activities for the individual clinical trial (Yes: 13%, 14/46; No: 65%, 30/46; U: 4%, 2/46).
Responses were split more evenly when asked if they pay the CRO per task or if they do not (Yes: 40%,
19/48; No: 42%, 20/48; U: 19%, 9/48).

58
Figure 20: Aspects of Outsourcing Models
Which types of outsourcing model(s) do/did you use in the most recent clinical trial that you outsourced?

When these choices were stratified by company size (Table 9), patterns of use were broadly similar, but
numbers in each category were too small for a more specific evaluation.

19
42
14
6
44
5
20
1
30
40
3
42
9
4
2
0 0 0
0
5
10
15
20
25
30
35
40
45
50
Pay per task
(N=48)
CRO provides a
range of
integrated
services (N=47)
CRO is awarded
all activities for
the clinical trial
(N=46)
One CRO
manages all your
clinical trials
(N=46)
CRO provides a
specific function
or functions
(N=47)
CRO does all the
work for your
trial or program
(N=47)
N of Respondents
Yes, we use this No, we do not use this

59
Table 9: Company Size and Outsourcing Models

Which category best describes the size of
your company?
Small /
Emerging
(1-500
employees)
Medium
(501-2000
employees)
Greater
than 2,001
employees
Which types of
outsourcing model(s)
do/did you use in the
most recent clinical
trial that you
outsourced?
Total Respondents
26
N (%)
12
N (%)
10
N (%)
Pay per task
Yes, we use this 8 (31) 6 (50) 5 (50)
No, we do not use this 15 (58) 3 (25) 2 (20)
Unsure 3 (12) 3 (25) 3 (30)

CRO provides
a range of
integrated
services
Yes, we use this 23 (92) 11 (92) 8 (80)
No, we do not use this 1 (4) 0.0 (0) 0.0 (0)
Unsure 1 (4) 1 (8) 2 (20)

CRO is
awarded all
activities for
the clinical trial
Yes, we use this 8 (32) 3 (27) 3 (30)
No, we do not use this 16 (64) 8 (73) 6 (60)
Unsure 1 (4) 0.0 (0) 1 (10)

One CRO
manages all
your clinical
trials
Yes, we use this 5 (20) 0.0 (0) 1 (10)
No, we do not use this 20 (80) 11 (100) 9 (90)
Unsure 0.0 (0) 0.0 (0) 0.0 (0)

CRO provides
a specific
function or
functions
Yes, we use this 24 (96) 11 (92) 9 (90)
No, we do not use this 1 (4) 1 (8) 1 (10)
Unsure 0.0 (0) 0.0 (0) 0.0 (0)

CRO does all
the work for
your trial or
program
Yes, we use this 2 (8) 1 (8) 2 (20)
No, we do not use this 23 (92) 11 (92) 8 (80)
Unsure 0.0 (0) 0.0 (0) 0.0 (0)

Respondents were asked to identify whether they use one or more of 7 listed tools or processes when
working with CROs (Figure 21). Respondents were permitted to give multiple answers. Most used
recurring meetings (88%, 43/49) and/or had an oversight plan (82%, 40/49). A smaller majority had
communication plans (75%, 37/49), metrics (71%, 35/49) and/or risk management assessment procedures
(67%, 33/49). Only about half used co-monitoring methods (51%, 25/49) or employed a governance

60
committee (45%, 22/49). Rarely (6%, 3/49) the respondents offered two additional management tools
were used, and one suggested a tool for the future. These were audits (N=1) and clinical operations
oversight and management (N=1), with the one respondent indicating they were planning on
implementing governance meeting with the CRO in the future (N=1).
Figure 21: Sponsor/CRO Management Tools
How do you manage CROs? Please select all that apply. (49 respondents, N=238 selections)

Respondents were also asked about 11 implementation activities that they might have used when
developing an outsourcing relationship with the CRO; multiple choices were permitted, so choices were
ordered by frequency of use (Figure 22). Most respondents (76%, 34/45) indicated that they implemented
a clear statement of workload allocation, objectives, and outsourcing needs into their outsourcing
relationship. More than half included a review of performance to see if objectives are met (62%, 28/45),
a mutually defined list of outcomes and how these are measured (52%, 24/45), and recognition of
unforeseeable circumstances and how these are managed (51%, 34/45). About half had methods to
recognize continuous improvement and continuity (49%, 22/45). Less frequently, respondents
incorporated a fee per task or activity completed (40%, 18/45), methods for the management of changes
43
40
37
35
33
25
22
3
0 5 10 15 20 25 30 35 40 45 50
Recurring meetings
Oversight plan
Communication plan
Metrics
Risk assessment
Co-monitoring
Governance committee
Other, please specify
N of Respondents
Management Tools

61
to the business (33%, 15/45), fair pricing for quality output (31%, 14/45), policies that define working
relationships, including attitudes and behavior (29%, 13/45), a shared vision or statement of intent with a
focus on capabilities and gaps (22%, 10/45), and/or a shared business map, defining the business of both
parties and the potential outcomes (18%, 8/45). A cross-tabulation of respondent company size with the
different categories for implementation was performed to provide an accurate breakdown of the number
of respondents in each category, and to determine if there were any differences in how outsourcing
aspects might be applied (Appendix C). The distributions of choices appeared similar cross all size of
companies, although the utilization of a clear statement of workload allocation was chosen by the
majority of those in the larger companies (89%, 8/9). Only 8/45 respondents (18%, 8/45) specified they
utilize a shared business map which defines the business of both parties and the potential outcomes. Of
note, companies defined as small/ emerging (N=25) provided the most input (56% of the overall
responses).

62
Figure 22: Outsourcing Development
Considering the most recent clinical trial you worked on, which of the following were implemented into
your outsourcing relationship? Please select all that apply.

If respondents indicated that they had used a particular approach from the above list, they were asked to
rate that activity as having high value (H), some value (S), or no value (N). They could also decline to
answer for any of the individual approaches (Table 10). Of the twenty-six individuals who implemented
a clear statement of workload allocation, objectives, and outsourcing needs, most rated it as having high
value (H: 69%, 18/26; S: 30%, 8/26; N: 0%, 0/26). Respondents also assigned a high value to a mutually
defined list of outcomes and how these are measured (H: 68%, 13/19; S: 26%, 5/19; N: 5%, 1/19). Fewer
respondents had implemented a shared vision or statement of intent, with a focus on capabilities and gaps,
but all ranked this as having high value (H: 100%, 5/5; S and N 0%, 0/5, respectively). A review of
performance to see if objectives are met was ranked as having high value and some value in similar
numbers (H: 55%, 12/22; S: 46%, 10/22; N: 0%, 0/22). A similar type of split was noted for three other
approaches, including recognition of continuous improvement and continuity (H: 50%, 7/14; S: 50%,
8
10
13
14
15
18
22
23
24
28
34
0 5 10 15 20 25 30 35 40
Shared business map defines roles of both…
Shared vision or Statement of Intent- capabilities and…
Define policies for working relationships, attitudes,…
Fair pricing for quality output
Management of changes to the business
Fee per task or activity completed
Recognition of continuous improvement/continuity
Recognition and management of unforeseeable…
Mutually defined list of measured outcomes
Review of performance to see if objectives are met
Clear statement workload allocation, objectives,…
N of Respondents
Areas Implemented
N = 45

63
7/14; N: 0%, 0/14), fee per task or activity completion (H: 43%, 6/14; S: 50%, 7/14; N: 7%, 1/14), and
policies that define working relationships, including attitudes and behavior (H: 44%, 4/9; S: 56%, 5/9; N:
0%, 0/9). Categories ranked as predominantly high value by respondents included shared business map,
defining the business of both parties and the potential outcomes (H: 60%, 3/5; S: 20%, 1/5; N: 20%, 1/5),
and recognition of unforeseeable circumstances and how these are managed (H: 56%, 10/18; S: 39%,
7/18; N: 6%, 1/18). Management of changes to the business (H: 25%, 3/12; S: 75%, 9/12; N: 0%, 0/12)
and fair pricing for quality output (H: 33%, 3/9; S: 67%, 6/9; N: 0%, 0/9) were more highly ranked as
having some value versus high value or no value.

64
Table 10: Value-added Outsourcing Concepts
Of the concepts that were implemented, what has had the most value to your recent clinical trial? (37
respondents, N=153 selections)
Category
High value,
implementation
worked (H)
N (%)
Some
value (S)
N (%)
No value
(N)
N (%)
Total
Responses
Shared business map, defining the business of both parties and
the potential outcomes
3 (60) 1 (20) 1 (20) 5
Shared vision or Statement of Intent, with a focus on
capabilities and gaps
5 (100) 0 (0) 0 (0) 5
A clear statement of workload allocation, objectives, and
outsourcing needs
18 (69) 8 (30) 0 (0) 26
Mutually defined list of outcomes and how these are measured 13 (68) 5 (26) 1 (5) 19
A review of performance to see if objectives are met 12 (55) 10 (46) 0 (0) 22
Fair pricing for quality output 3 (33) 6 (67) 0 (0) 9
Policies that define working relationships, including attitudes
and behavior
4 (44) 5 (56) 0 (0) 9
Recognition of continuous improvement and continuity 7 (50) 7 (50) 0 (0) 14
Recognition of unforeseeable circumstances and how these are
managed
10 (56) 7 (39) 1 (6) 18
Management of changes to the business 3 (25) 9 (75) 0 (0) 12
Fee per task or activity completion 6 (43) 7 (50) 1 (7) 14

Respondents were asked about the division of responsibility related to different aspects of contract
development- whether held by the sponsor (SP), CRO (CRO), or a combination of both (B)- when
implementing the outsourcing strategies into their contract (Table 11). Responses could also be identified
as not applicable (N), or they were unsure (U).
About two thirds of respondents identified that the two organizations shared three aspects, mutual
agreement of deliverables (SP:11%, 4/37; CRO: 0%, 0/37; B: 78%, 29/37; N: 5%, 2/37; U: 5%, 2/37),
defined metrics (SP: 5%, 14/37; CRO: 8%, 3/37; : 68%, 25/37; N: 3%, 1/37; U: 8%, 3/37), and alliance

65
building (SP: 11%, 4/37; CRO: 5%, 2/37; B: 65%, 24/37; N: 14%, 5/37; U: 5%, 2/37). Three other
elements most commonly shared but in a lower proportion were shared vision or statement of intent (SP:
14%, 5/37; CRO: 3%, 1/37; B: 43%, 16/37; N: 32%, 12/37; U: 8%, 3/37), business model map (SP: 11%,
4/37; CRO: 5%, 2/37; B: 38%, 14/37; N: 32%, 12/37; U: 14%, 5/37), and payments based on end results
versus tasks completed (SP: 24%, 9/37; CRO: 8%, 3/37; B: 38%, 14/37; N: 22%, 8/37; U: 8%, 3/37).
These latter three elements were identified as not applicable by many respondents. The final aspect,
reward for innovation, was identified as not applicable by more than half of the respondents, and several
others were unsure; however, of those who did have a view, most (9/11) identified that it was a shared
activity (SP: 3%, 1/37; CRO: 3%, 1/37; B: 16%, 9/37; N: 57%, 21/37; U: 22%, 8/37).
Table 11: Implementation Leadership
When developing the contract with your CRO, who leads these efforts?
Category
N =37
Sponsor
(SP)
N (%)
CRO
(CRO)
N (%)
Both (B)
N (%)
Not
Applicable
(N)
N (%)
Unsure
(U)
N (%)
Total
Business Model Map 4 (11) 2 (5) 14 (38) 12 (32) 5 (14) 37
Shared Vision or Statement of Intent 5 (14) 1 (3) 16 (43) 12 (32) 3 (8) 37
Defined metrics 5 (14) 3 (8) 25 (68) 1 (3) 3 (8) 37
Payments based on end results versus
tasks completed
9 (24) 3 (8) 14 (38) 8 (22) 3 (8) 37
Alliance building 4 (11) 2 (5) 24 (65) 5 (14) 2 (5) 37
Mutual agreement of deliverables 4 (11) 0 (0) 29 (78) 2 (5) 2 (5) 37
Reward for innovation 1 (3) 1 (3) 9 (16) 21 (57) 8 (22) 37

66
The same 37 respondents were asked to specify how they view their company’s management style,
defined according to Vested Outsourcing as either as insight (a collaborative alliance), oversight (we
closely manage the CRO) or a combination of both (Figure 23). Respondents were also allowed to
provide a different answer by choosing other, please specify.
Fifteen of the 37 respondents assigned their management style to one of two offered categories (41%,
15/37), 9 as a combination of both insight and oversight (60%, 9/15) and 5 as oversight alone (34%,
5/15). One respondent chose other, without providing supplemental text (7%, 1/15). None selected
insight as their company’s style (0%, 0/15).
Figure 23: Full Allocation of Management Style to One Category

Twenty-two of the 37 respondents indicated they use a combination of management styles for CRO
outsourcing (Figure 24). On average, 61% of the management style was oversight, 27% was insight, 11%
was both insight and oversight, and 1% was noted as “other”. The individual data for the 22 respondents
who identified that the management style was a combination between insight, oversight, both or other is
presented in (Appendix D).
0
5
9
1
Insight
Oversight
A Combination of
Both
Other
0 2 4 6 8 10
N=15
Insight Oversight
A Combination of Both Other

67
Figure 24: CRO Management Styles of Sponsors
Considering your most recent clinical trial, what percentage would you give to your company's
management style of your CRO?

4.6. Sponsor Management of CRO Performance
Respondents were also asked to specify the basis for payments to the CRO(s) from three options, and
multiple selections were permitted; 36 respondents provided 46 answers (Figure 25). Two options, pay
per line item achieved, regardless of quality of the outcome and payments milestones were used in similar
proportions (Per line item: 61%, 22/36; per milestone: 50%,18/36). Fewer identified that performance-
based tasks were used (17%, 6/36 responses).
27%
61%
11%
1%
N=22
Insight
Oversight
Both
Other
Management
Styles

68
Figure 25: Sponsor/CRO Contract Payments-
For the current clinical trial you are working on, how are payments made to your CRO? Select all that
apply. (36 respondents, N=46 selections*)
*Respondents could provide more than one selection.
Respondents were also asked whether the payments varied according to the quality of the completed task
(Figure 26). Most respondents (78%, 29/37) indicated that quality had no impact on payments. Only 2
respondents (5%, 2/37) indicated the payment would vary based on quality, and the remaining 6
respondents (16%, 6/37) were unsure. The 2 respondents who noted that the payment does vary were
asked to provide additional insight and noted: “some money back for poor quality work but only
negotiated after issues arise”; “# of site monitoring, # of sites activated etc. are tasks”.
6
18
22
0 5 10 15 20 25
Current contract performance-based task
Milestones
Current contract pays per line item not quality
N of Respondents
Payment Strategy
N=36

69
Figure 26: Payments to CROs based on Quality
Does your payment vary based on the quality of the tasks completed?

When respondents were asked whether performance expectations were being met by the CRO(s) with
which they were currently working, the majority felt that the CRO mostly (68%, 25/37) or occasionally
(27%, 10/37) met expectations (Figure 27). Very few respondents noted the CRO always met
expectations (5%, 2/37). No respondents identified that the CRO never met expectations (0%, 0/37).
Figure 27: Sponsor Views Regarding Performance of the CRO
For the clinical trial you are currently working on, do you feel your CRO meets your expectations for
performance?

2
6
29
1 5 25
Yes, please specify
Unsure
No
N of Respondents
Quality impact on Payment
N=37
0
2
10
25
Never
Always
Occasionally
Mostly
0 5 10 15 20 25 30
Frequency of CRO
Meeting Expectations
N of Respondents
N = 37

70
Respondents who answered always or mostly (N=27) were requested to describe at what point they
created a Statement of Work (SOW) (Figure 28). All but one answered this question (96%, 26/27). Most
commonly, they created the SOW after the Master Service Agreement (MSA) or at the same time (46%,
12/26 and 19%, 5/26, respectively), or in parallel with its development (15%, 4/26). Two of the
respondents identified that the SOW was created prior to signing the MSA (8%, 2/26). Respondents who
answered occasionally or never (N=10) were asked to specify the areas in which the CRO could improve
performance (Table 16).
Figure 28: Timing of SOW Creation with CROs
At what point does your company create a Statement of Work (or similar) with your CRO(s)?

The 26 respondents who mostly or always felt that their CROs met performance expectations were also
asked to rank, from a list of 8 options, the most important traits for ensuring a successful relationship with
their CRO (Table 12). A ranked score was calculated for each option; the option ranked as most
important (M) was multiplied by 8, the second most important option was multiplied by 7, and so on until
the least important (L) was multiplied by 1. The total weighted score was summed to get the final rank
order for the category responses, with the highest number ranked as 1, the most important element for a
0
2
3
4
5
12
0 2 4 6 8 10 12 14
Other
Prior to signing the MSA
I Don't Know
In parallel with the MSA
At the same time as the Master Service Agreement…
After the MSA is signed
N of Respondents Timing of SOW Completion
N = 26

71
successful CRO relationship. Using this method quality was ranked as the most important trait. Near
one-third of the respondents (31%, 8/26) selected quality as the most important trait; 19% (19%, 5/26)
and 31% (31%, 8/26) selected it as the second and third most important trait, respectively. No respondent
placed quality in 6th, 7th, or 8th place. The next highest-ranking trait was trust (M: 15%, 4/26 vs. L: 4%,
1/26).
Other traits for successful outsourcing relationships that respondents considered most important included
partnership (M: 15%, 4/26 vs. L: 4%, 1/26), alignment of priorities, (M: 8%, 2/26 vs. L: 8%, 2/26), and
data integrity (M: 4%, 1/26 vs. L: 12%, 3/26). Core competencies was ranked 6
th
(M: 19%, 5/26; L: 19%,
5/26). Two choices, timing and value were ranked lowest (timing: M: 0%, 0/26 and value: M: 8%, 2/26).
Nearly one-third of respondents (individually) ranked these as last (L:27%, 7/26 for both).

72
Table 12: Traits for a Successful Outsourcing Relationship
Which of the following do you think is the most important trait for ensuring a successful relationship with
your CRO? Please rank, in order, with 1 for the most important and 8 for the least important?

Ranking N (%)
1
(Most
Important)
(M)
2 3 4 5 6 7
8
(Least
Important)
(L)
Weighted
Ranking
Total
Category
Quality 8 (31) 5 (19)
8
(31)
1 (4)
4
(15)
0 (0) 0 (0) 0 (0)
1 (168)
26
Trust 4 (15) 6 (23) 2 (8) 1 (4)
4
(15)
5
(19)
3 (12) 1 (4)
2 (129)
26
Partnership 4 (15) 3 (12)
3
(12)
4
(15)
5
(19)
4
(15)
2 (8) 1 (4)
3 (128)
26
Data integrity 1 (4) 6 (23)
4
(15)
7
(27)
1 (4)
3
(12)
1 (4) 3 (12)
4 (127)
26
Alignment of
priorities
2 (8) 2 (8)
5
(19)
4
(15)
8
(31)
1 (4) 2 (8) 2 (8)
5 (121)
26
Core
competencies
5 (19) 0 (0)
3
(12)
2 (8) 1 (4) 2 (8) 8 (31) 5 (19)
6 (99)
26
Timing 0 (0) 2 (8) 1 (4)
5
(19)
3
(12)
6
(23)
2 (8) 7 (27)
7 (86)
26
Value 2 (8) 2 (8) 0 (0) 2 (8) 0 (0)
5
(19)
8 (31) 7 (27)
8 (78)
26

Respondents were asked whether they had switched to different CRO for their most recent clinical trial
(Figure 29). Of 38 respondents, nearly half (42%, 16/38) did not switch and were satisfied with their
current CRO. Four individuals indicated they had not switched and have asked their CRO to take on
more work (11%, 4/38). However, 5 respondents (13%, 5/38) had switched CROs, either because the
CRO lacked expertise in some areas (40%, 2/5) or had issues related to quality (75%, 3/5) (Table 13).
Four respondents had switched CROs by moving to an insourcing model (11%, 4/38). Nine respondents
noted that they are considering a CRO switch in the future (16%, 6/38), or would like to switch CROs,
but it was not practical (8%, 3/38).

73
Figure 29: Switching CROs in Clinical Trials
Have you had to switch CROs for any aspects in your most recent clinical trial? Please provide the
answer that best fits the situation in the current clinical trial on which the CRO is working.

Table 13: Primary Reasons for Switching CRO Activities
Comments for Primary Reason
incompetent
for specific expertise
CRO quality of work
Global footprint and experience with Regulatory submissions.
poor performance by the CRAs

4.7. CRO Outsourcing Approaches
The way that companies support their CRO activities was explored through a series of questions. First,
they were asked to describe their companies’ approaches when contracting with a CRO from 4 options
5
4
6
3
16
4
0 2 4 6 8 10 12 14 16 18
Yes (please provide the primary reason)
Yes, we moved to an insourcing model
We are considering a switch in the future
No, we would like to but it is not practical
No, we are satisfied with our CROs work
No, we have asked our CRO to take on more
work
N of Respondents
Changing CROs (Y or N)
N= 38

74
(Table 14). Fifty-one selections were made by 39 individuals. The option selected most commonly was
review and documentation of risks, dependencies, and strategy (45%, 23/51). Second was documentation
of a collaborative pathway, where there is a vested interest in the success of the CRO to manage the trial
and third was outcome-based incentives (26%, 13/51 and 14%, 7/51, respectively). Eight respondents
selected none of the above (16%, 8/51); only one respondent added a comment of “CRO capabilities,
target investigators, budget”.
Table 14: Contracting Approaches
Prior to study start-up, what approach does your company currently support when contracting with a
CRO to manage a clinical trial? Select all that apply. (39 respondents, N=51 selections)
Category N of Responses (%)
Outcome-based incentives 7 (14)
Review and documentation of risks, dependencies, and strategy 23 (45)
Documentation of a collaborative pathway, where there is a vested interest in the success of the
CRO to manage the trial
13 (26)
None of the above 8 (16)

Respondents who answered none of the above were asked whether any of the approaches might be
considered useful in the future. Four respondents (50%, 4/8) indicated yes and none indicated no (0%,
0/8). Three of the four yes respondents (75%, 3/4) provided the comments in Table 15.

75
Table 15: Potential Useful Aspects of Contracts for Outsourcing
If you answered "None of the above", do you feel any of the approaches might be useful in the future?
Responses (N=3)
All of these would be helpful but this is difficult because we often use a different CRO for each study.
Outcomes based incentives would be helpful in achieving recruitment goals as well as database closure
Planning upfront with pre-selection criteria, weighing scores across CROs evaluated, and considering payments tiered by
quality/timeliness would be improvements.

The survey also explored outcome-based incentives (Figure 30), by giving two specified options and a
third to choose other. Most of the 27 respondents chose time to database lock from last subject visit
(41%, 11/27). Eight chose time from contract to first subject in and 8 gave other responses (30%, 8/27,
each). Comments gave additional views; half noted that they do not use incentives (50%, 4/8), and a
quarter that they used both time to database-lock and time to first-subject-in (25%, 2/8). Two responses
identified different incentive paths, recruitment milestones and time from protocol finalization to site
initiated (13%, 1/8, each).
Figure 30: Company Support of Outcome-based Incentives
What outcome-based incentives does your company support?

11
8
8
0 2 4 6 8 10 12
Time to database lock from last subject
visit
Time from contract to first subject in
Other (please specify)
N of Respondents
Outcomes-based
Incentives
N=27

76
Respondents were asked about ways in which the CRO could improve its performance from five specified
choices as well as an option to select Other (Table 16). A ranked score was calculated for each of the 6
category responses; the option ranked as greatest need (G) was multiplied by 6, the second most
important option was multiplied by 5, and so on until the least need (L) was multiplied by 1. The scores
for each option were then summed to get the final rank order for the category responses, with the highest
number ranked as 1, being the greatest need for CRO performance improvement.
Communication to sponsor was the area ranked most as the first or second area where improvement is
needed (37%, 15/41, each); few respondents ranked it as lowest (as 3rd: 15%, 6/41; as 4th: 7%, 3/41; as
5th: 5%, 2/41; as 6th: 0%, 0/41). Meeting deadlines was ranked 2
nd
, and 12% of respondents note this as
the greatest need for improvement, while 2% note this as an area with the least need for improvement (G:
12%, 5/41 versus L: 2%, 1/41). Oversight of internal staff was ranked as the 3
rd
greatest area where
improvement was needed; 44% of respondents note this as an area with either the greatest need for
improvement or the second greatest area with a need for improvement (15%, 6/41 and 29%, 12/41,
respectively). This category was also noted by 13/41 respondents as the area that least needed
improvement (ranked 5: 24%, 10/41, and L:7%, 3/41, respectively). Relationships with clinical sites was
as area where need for improvement had a variety of rankings between a greatest need and a least need;
however most individuals responded neutrally with a “3” or “4” ranking (ranked 3: 24%, 10/41, and
ranked 4: 32%, 13/41).
Of note, therapeutic expertise was less of a concern for the majority of respondents who ranked this as
either the 4
th
(34%, 14/41), 5
th
(37%, 15/41), or 6
th
(5%, 2/41) area for improvement, versus the 19% of
individuals who considered this the greatest area for improvement, or second greatest area for
improvement, (12%, 5/41 and 7%, 3/41, respectively).

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Eight respondents indicated they had other areas for improvement (20%, 8/41; ranked 1: 15%, 6/41;
ranked 2: 2%, 1/41; and ranked 4: 2%, 1/41). Of the six text responses provided, one respondent noted
that the CRO was too new, and one indicated “N/A” (16%, 1/6, each). The remaining four responses are
related to operational areas, staff turnover, and quality/knowledge (Table 17).
Table 16: Areas for CRO Performance Improvement
In which areas do you feel your CRO could improve performance? Please rank, in order, with 1 as the
greatest area where improvement is needed.

Ranking of Areas for Improvement
N (%) (N=41)
1
(Greatest
Need) (G)
2 3 4 5
6
(Least
Need) (L)
Weighted
Ranking
Category
Communication to Sponsor 15 (37) 15 (37) 6 (15) 3 (7) 2 (5) 0 (0)
1 (202)
Meeting deadlines 5 (12) 6 (15) 15 (37) 8 (20) 6 (15) 1 (2)
2 (157)
Oversight of internal staff 6 (15) 12 (29) 8 (20) 2 (5) 10 (24) 3 (7)
3 (157)
Relationship with clinical
sites
4 (10) 4 (10) 10 (24) 13 (32) 8 (20) 2 (5)
4 (141)
Therapeutic expertise 5 (12) 3 (7) 2 (5) 14 (34) 15 (37) 2 (5)
5 (127)
Other (please provide an area
for improvement)
6 (15) 1 (2) 0 (0) 1 (2) 0 (0) 33 (81)
6 (77)

Table 17: Respondent Comments for Other Areas for Improvement
“Other” Responses for Areas for Improvement (N=6)
Reduce staff turnover rate
Quality and knowledge
Proactive Project Management
Statistics
Wanted to skip this; CRO too new
N/A

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Respondents were asked whether the CRO could improve performance in other ways (Figure 31). Over-
two thirds (68%, 19/28) pointed to other performance-improvement opportunities (Table 18), including
suggestions related to transparency, risk management, and staffing interventions.
Figure 31: Opportunities for CRO Performance Improvement
Are there any other ways you feel your CRO could improve performance?

9
19
No
Yes, please describe
0 2 4 6 8 10 12 14 16 18 20
N of Respondents
N=28

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Table 18: Respondent Description of Opportunities for Improvement
Respondent Comments (N= 19)
Communication
Resources
• improve CRO staff motivation, accountability,
ownership
• Knowledge, pro-activity, communication
• Avoid over promise and under deliver, if a timeline
provided by sponsor is unreasonable, don’t promise
and fail.
• routine reporting along with risks identified and
mitigations planned
• Be more proactive vs. a reactive approach
• Transparency about issues/challenges met with the
study or sites
• Transparency, ownership of deliverables, proactivity
• More proactive thinking and planning of about next
steps to move the project forward.
• Update all systems, provide more visibility to their
processes and more transparency when there are
issues
• Acting in more of a collaborative partnership
• Forward thinking is an area in need of improvement
• Bringing solution options with problems and
recommending a pathway rather than asking sponsor
for a solution
• Ensuring/securing internal resourcing
available to support shift in timeline, strategy
or needs of a trial.
• Proactive Project Management
• Internal project oversight
• offer their staff incentives to remain long-term
• Invest in the company with the accountability
of each task.
• They need to do a better job at allocating
quality team members to our projects
• Toooooo many

Respondents were also asked whether they agree that their current CRO adds value to the clinical trial
from 6 options; they also had the opportunity to add a comment if they chose “other” (Figure 32). Most
respondents ranked management of clinical trial sites and documentation management as the two areas
with highest value added (A). However, 8% and 20% of respondents respectively were unsure (U), and
15% disagreed (D) for each of these selections (clinical site management: A: 77%, 30/39; D: 15%, 6/39;
U: 8%, 3/39 and document management: A: 65%, 26/40; D: 15%, 6/40; U: 20%, 8/40). Close behind was
data management and database closure (A: 62%, 24/39; D: 15%, 6/39; U: 15%, 6/39). Interacting with
Regulatory Agencies had a somewhat lower rating, in part because more respondents were unsure (A:
49%, 19/39; D: 28%, 11/39; U: 23%, 9/39). Least value was assigned to management of third-party
vendors such as clinical labs, but responses were still split quite evenly between agree and disagree (A:

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41%, 16/39; D: 41%, 16/39; U: 18%, 7/39). One respondent commented that “feasibility expertise” was
also an area in which the CRO added value.
Figure 32: Opportunities for CROs to Add Value
Please indicate the areas you believe your current CRO adds value to your clinical trial.

Respondents were asked whether their company would support a less traditional approach to outsourcing
a clinical trial, in which the CRO had more ownership and/or less structured payments per task (Figure
33). Of the 60 respondents, one-third indicated that their company would support a less traditional
approach, either by choosing yes, possibly or on a limited basis (2%, 1/60; 13%, 8/60; 18%, 11/60,
respectively). However, most had negative responses of probably not (62%, 37/60), and 3 of definitely
not (5%, 3/60).
0 5 10 15 20 25 30 35
Management of clinical trial sites
Data management and database closure
Interacting with Regulatory Agencies
Documentation Management
Management of third party vendors, such as clinical
labs
Other (please specify)
Areas Value is Added by the CRO
N= 39-40
Unsure Disagree Agree

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Figure 33: Company Support of Less Traditional Outsourcing
Do you feel your company would support a less traditional approach to outsourcing a clinical trial,
where the relationship between your company and the CRO allows for more ownership by the CRO
and/or less structured payments per task?

When asked about these less traditional approaches to outsourcing, all 20 respondents with positive
answers gave comments (Table 19). Sixteen comments (75%, 16/20) could be grouped into one or more
of 4 themes; 4 had nonspecific answers, such as “N/A” or “None” (25%, 4/20).

1
8
11
37
3
0 5 10 15 20 25 30 35 40
Yes, please describe in the following…
Possibly, please describe in the following…
On a limited basis, please describe in the…
Probably not
Definitely not
N of Respondents
Company Support
N = 60

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Table 19: Less Traditional Outsourcing Opportunities per Respondents
Please describe the less traditional approaches to outsourcing you feel your company would support.
Categories Comment (N= 20)
CRO Capabilities • Smaller niche providers
• Technological solutions to make it easier for the sites to implement the
study
• specific vendor mgr role
• Decentralized trials support (COVID-19 resulted in many trial
disruption and having support from Decentralized trial platform will
benefit patient experience)
Selection Process • Utilize CRO based on geographical region and not one CRO fits all
• Perhaps outsourcing specific functions centrally.
• Selecting a single vendor for a task such as data management for all
studies and that outsourcing site management to different CROs using
a bidding process
• My company is currently considering a CRO Preferred Provide which
isn't unusual for large companies but is unusual for startup biotech
companies.
• Current company is a mix between CRO and internal clinical
operations staff which the company supports for better oversight and
trial management
Contractual Arrangements • Outcome based payment structure; KPI or milestone driven bonus/loss
approach
• Not paying fee for service but rather shared success
• Give ownership of the project. The full-Service module is not common
but may improve the accountability and delivery of the project.
Staffing • Hiring individual contract CRAs that team members have worked with
before and we know perform well.
• Contracting in freelance monitors but there is a shortage of good
monitors
• Hiring our own CRAs (contactors) so we know the issues in real time;
Partnering with a company who promotes and supports more paperless
processes.

A five-point Likert Scale was used to ask respondents about the extent to which they believed that the
company would adopt suggestions from the CRO regarding the management of their clinical trial (Figure
34). Over half somewhat agreed that their company would adopt CRO suggestions (58%, 23/40), one-
quarter neither agreed nor disagreed (23%, 9/40), and only 13% somewhat disagreed (13%, 5/40). Only a
few responses were at the extremes of agree or disagree (5%, 2/40 and 3%, 1/40, respectively).

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Figure 34: Acceptance of CRO input for Clinical Trial Management
Do you believe your company adopts the CRO's suggestions for managing your clinical trial?

Respondents were asked to rank six criteria that might be used when re-engaging their CRO for a future
clinical trial (Table 20) and had the option to specify “other” criteria. A ranked score was calculated for
each of the 6 category responses, where the option ranked as most important (M) was multiplied by 6, the
second most important option was multiplied by 5, and so on until the least important (L) was multiplied
by 1. The total weighted score was summed to get the final rank order for the category responses, with
the highest score ranked as 1, being the most important consideration for reengaging with a CRO on a
future clinical trial.
Meeting deadlines was overall ranked as the most important consideration for re-engaging with the CRO
for a future clinical trial; this was individually ranked as the most important consideration by 6 of the
respondents (16%, 6/38) and as second highest by 17 of the respondents (45%, 17/38).
Personnel/relationships were ranked 2
nd
, however as an individual category was the most important
consideration overall (34%, 13/38). Cost was ranked 3
rd
but had the highest number of people noting it as
the least important consideration (8%, 3/38). Therapeutic expertise (ranked 4
th
) and regional expertise
(ranked 5
th
) were scored as more neutral, with 13% (5/38) and 5% (2/38) respondents categorizing these
as most important, respectively.
2
23
9
5
1
0 5 10 15 20 25
Agree
Somewhat agree
Neither agree nor disagree
Somewhat disagree
Disagree
N of Respondents
Respondent Perspective-
Acceptance of CRO Input
N = 40

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Three respondents out of the 38 provided their own choice as the most important criteria, specifically
“site management”, “quality assigned project teams”, and “proactive approach” (3%, 1/38, each), while
the remaining 35 respondents noted other as the lowest areas for consideration for re-engagement with
their CRO, without providing a specific answer (ranked 6
th
).
Table 20: Considerations for Future CRO Re-engagement
What are the most important considerations for re-engaging with your CRO for a future trial? Please
rank, with 1 being the most important.
Category
N = 38
1
(Most
Important)
(M)
2 3 4 5
6
(Least
Important)
(L)
Weighted
Ranking
Total
Meeting deadlines 6 (16)
17
(45)
4 (11) 6 (16) 5 (13) 0 (0)
1 (165)
38
Personnel/
relationships
13 (34) 6 (16) 6 (16) 5 (13) 7 (18) 1 (3)
2 (162)
38
Cost 9 (24) 2 (5) 11 (29) 8 (21) 5 (13) 3 (8)
3 (145)
38
Therapeutic expertise 5 (13) 7 (18) 7 (18)
11
(29)
8 (21) 0 (0)
4 (142)
38
Regional expertise 2 (5) 6 (16) 10 (26) 8 (21)
12
(32)
0 (0)
5 (130)
38
Other (please specify) 3 (8) 0 (0) 0 (0) 0 (0) 1 (3) 34 (90)
6 (54)
38

Respondents were asked to rank six categories of CRO performance on a scale between 1 and 10, where
“1” reflected lowest performance and “10” reflected highest performance (Table 21). A ranked score was
calculated for each option; the option ranked lowest area of performance (LP) was multiplied by 1, the
second lowest by 2, and so on until the area of highest performance (HP) was multiplied by 6. The total
weighted score was summed to get the final rank order for the category responses, with the lowest number
ranked as 1, being considered as the area the CRO performs the lowest.

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Of the 31 respondents, providing qualified personnel was ranked as the lowest area of performance.
Recognizing internal weaknesses was next identified as a low performing area, followed by assigning
accountability and offering constructive solutions. Attention to your study and staff retention were the
areas ranked as higher performing (5
th
and 6
th
, respectively.
Table 21: CRO Performance Rankings
Considering your current trial, on a scale of 1-10, with 1 being the lowest and 10 being the highest, how
do you feel your CRO performs in the following areas?
Category
Ranking (Lowest to Highest) N=31
N (%)
1
(Lowest)
(LP)
2
3
4
5
6
7
8
9
10
(Highest)
(HP)
Weighted
Ranking
Providing
qualified
personnel
1 (3) 0 (0)
2 (6)
2 (6)
4
(13)
8 (26)
7 (23)
1 (3)
5
(16) 1 (3)
1 (118)
Recognizing
internal
weaknesses
3 (10) 1 (3)
3
(10)
5
(16)
7
(23)
5 (16)
4 (13)
3 (8)
0 (0)
0 (0)
2 (125)
Assigning
accountability
1 (3) 0 (0)
2 (6)
2 (6)
5
(16)
7 (23)
6 (19)
4
(13)
3
(10)
1 (3)
3 (136)
Offering
constructive
solutions
2 (5) 2 (6)
0 (0)
4
(13)
4
(13)
6 (19)
7 (23)
4
(13)
2 (6)
0 (0)
4 (137)
Attention to
your study
0 (0) 0 (0)
2 (6)
2 (6)
1 (3)
3 (10)
8 (26)
11
(35)
3
(10)
1 (3)
5 (152)
Staff retention
1 (3) 1 (3)
2 (6)
2 (6)
4
(13)
3 (10)
9 (29) 4
(13)
5
(16)
0 (0) 6 (195)

Respondents were asked if allowing the CRO to innovate would add value even if the CRO would be
more expensive than others (Figure 35). Approximately 52% (31/60) indicated a positive answer of
definitely yes or probably yes (17%, 10/60 and 35%, 21/60, respectively). Over one third suggested that it
might or might not create more value (37%, 22/60). Seven thought that CRO innovation would probably
not create value (12%, 7/6), and none chose definitely not (0%, 0/60).

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Figure 35: Does CRO Innovation Create Value?
Do you think that allowing the CRO to provide innovation into how the clinical trial is managed could
create more value, even if the cost of the initial contract is above average of other bids?

At the end of the survey, respondents were offered an opportunity to provide additional comments
regarding the outsourcing relationship with their CRO. The information from these 15 comments was
broken into five categories- Accountability, Oversight. Performance, Sponsor Company, and
Relationships (Table 22). All complete comments are provided in Appendix E.

10
21
22
7
0
0 5 10 15 20 25
Definitely yes
Probably yes
Might or might not
Probably not
Definitely not
N of Respondents
Would CRO Innovation
Create Value?
N = 60

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Table 22: Additional Respondent Comments on Outsourcing
Is there anything additional you want to add that may help describe the outsourcing relationship you
have with your CRO?
Accountability
• For a true relationship, the CRO must also have ownership and accountability for delivering a quality
program in a defined timeframe. There needs to be penalties for not delivering in a cooperative manner.
• usually with the majority of CROs there is lack of ownership. The reasons for that might be manifold, i.e.
Sponsors SOPs to be followed, sponsors study team micro manage the CRO, (too) strict contract
conditions, most common: CRO staff overstrained and/ or unwilling to take responsibility
• there needs to be more accountability for oversight of their personnel with clear understand what they
review and document clear components of overview, often is vague. Initial Task orders is a commitment
to time, cost, quality based on what was contracted for. often we see the default is to do change order
instead of being accountable for what was committed when nothing has changed in protocol.
• CRO management has changed over the last few years…
Oversight
oversight methods should be defined internally by sponsor
Performance
• Hire more qualified individuals who are accountable for doing a good job.
• CRO is supposed to be full service, but we struggle with them performing up to our expectations for a
first-in-human trial….
Sponsor company
• … are more comfortable implementing the same SOW/working model every time. We would benefit from
more up front planning and including the CRO in strategy discussions.
• Our company is moving to discontinue use of CROs and utilize an in-house model for all new projects.
The cost savings has been significant.
• As long as Sponsor has full approval power over the clinical protocols, the CRO could provide whatever
innovative suggestions they wish.
• …Our small and relatively young company would not be comfortable giving away these decisions… We
had to hire internal staff to handle those responsibilities as the CRO proved to be ineffectual…
Relationships
• … it is difficult to release ownership to the CRO fully. Sometimes the relationships come down to the
right teams on both sides and whether they are healthy and collaborative. It is important to recognize the
need to make changes to the team in order to improve ownership and relationships.
• Trust but confirm
• Strategic partnership

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CHAPTER 5. DISCUSSION
5.1 Introduction
The last decade has seen a dramatic increase in the use of Contract Research Organizations to manage and
execute clinical trials. However, the relationships between CROs and sponsors remain challenging.
Industry surveys suggest that many sponsors have been dissatisfied with the performance of their CROs,
and more specifically the ability of CROs to oversee quality and to contribute in a proactive way to by
offering innovative new approaches and value-creating ideas (Avoca, 2020). One possible explanation
for this dissatisfaction is the typical use of traditional transactional approaches that structure the
contractual relationship as a service rather than a partnership. Of interest and concern, then, is the extent
to which these challenges are recognized and addressed using different models that create a less
transactional outsourcing relationship (Dubin, 2019).
A novel approach to outsourcing, Vested Outsourcing, has been put into practice in other industries. In
this model, the business owner and the supplier share incentives for successful outcomes (Vitasek and
Mandrodt, 2012). This exploratory study was conducted to examine the current perspectives of industry
regarding the use and challenges of different types of partnerships with CROs. It further explored the
potential usefulness of partnering frameworks with some form of vested outsourcing to shape their CRO
relationships. It therefore sought additional insight not previously explored in the clinical literature into
which facets of a Vested Outsourcing framework could be introduced and how current outsourcing
practices could be advanced.

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5.2 Methodological Considerations
5.2.1 Delimitations
This exploratory study focused on pharmaceutical companies that employ CROs when they conduct
clinical trials; therefore, delimitations were important to define the boundaries of the study and reduce the
confounding that might occur if groups of respondents with different goals and experiences were
represented in the same sample (Theofanidis and Fountouki, 2018a). Results may be generalizable to
clinical trials in other companies, like those producing medical devices or headquartered outside of the
United States. However, these are subject to different regulations and trial design structures (Faris and
Shuren, 2017). Thus, I cannot assume that the results can be generalized to other sectors without further
research. Participants were also delimited to professionals in clinical research who work with or have
worked with CROs that were contracted to assist with clinical trial operations. By drawing the sample
from a specific subgroup of professionals associated most closely with the CRO partnership, the results
are less likely to be confounded or blurred by adding the views of others who may have a more peripheral
and limited understanding of the contractual arrangements (Bresee, 2014). Consequently, the survey was
not disseminated to personnel who engage with CROs for other reasons, such as laboratory contracting
and so would not have experience aligned with the intended survey purpose. Additionally, the results
may have limited application to using a different method of contracting for other areas of pharmaceutical
outsourcing, such as product supply agreements, where a contract is written with the narrow intent to
supply a select item with a defined deliverable.
In any partnering relationships, there are two partners. The results presented here have captured the
experience of the sponsor companies but not of the other partners, the CROs. This delimitation was
deliberate because CROs are likely to have different views from those who hire them (Banerjee and
Chaudhury, 2010). For example, sponsors and CROs can perceive their performance and relationships
differently, as noted in previous surveys (Avoca, 2019c), potentially blurring the results of the survey

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(Johnson and Wislar, 2012). Nonetheless, these views are important to explore in the future, to provide a
balanced picture of the potential alignments and concerns of the other partner in the relationship.
Questions in this survey were designed with the use of a single framework; the core objective was the use
of a vested outsourcing paradigm for collaboration, and this determined the scope of the questions
(Theofanidis and Fountouki, 2018b).
At the time of this survey, a shift in the clinical trial environment was remaking the way that clinical sites
were managed by the sponsor and CRO (Xue et al., 2020). The lockdown caused by the Covid-19
pandemic hampered the performance of site-based activities, including clinical site start-up activities and
routine monitoring. The results of this current survey capture experiences just before that pandemic. The
data may not reflect changing views resulting from those experiences, when acceleration of innovations in
areas such as remote data capture and telemedicine, required a shift in the collaboration between sponsors
and CROs (Berron, 2021). This is an area that might be fertile ground for exploratory retrospective
studies once the Covid pandemic is under better control, and as companies revert to more traditional in-
person activities.
5.2.2 Limitations
This study was conducted using an online survey. Electronic surveys are more efficient than paper-based
surveys. They allow the researcher to reach a wider audience, provide reminders of survey availability,
and allow data to be collected confidentially (Sue, 2012). However, certain challenges are well-known to
be associated with this type of survey, including its ability to reach qualified respondents and to obtain a
response and completion rate high enough to assure acceptable validity (Manfreda et al., 2008).
First, it was important to assure an adequate sample of respondents who could represent the overall
population of interest. Each individual and each company in this population can be expected to have
different experiences that can contribute to the richness of the dataset, so care was taken to assure that

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respondents were sampled from relevant, albeit different, disciplines and from companies of different
sizes to minimize bias (Orcher, 2017). Approaching personal contacts known to work in the field of
clinical research provided a reasonable response rate (25%; 38/154). This response rate is similar to
response rates typically seen for web-based surveys of seasoned professionals (Sauermann and Roach,
2012). I was able to reach a different pool of respondents by adding a second method of outreach in
which potential participants were contacted using web-based networking sites such as Linked-In or social
media. This method increased the number of responses. However, it was not possible to assess the
response rate from individuals contacted by this method because those individuals were all given the
same weblink. As a result, it was unclear how many potential respondents read the invitation but did not
choose to participate in the survey.
Once respondents have opened a survey it is also important that they are willing and able to complete it.
In some cases, failure to progress will occur because respondents recognize early that their backgrounds
are not well matched to the questions that will be asked. To some extent, this problem was addressed
early by asking certain screening questions, designed to assure that those participating in the survey were
appropriate candidates with valid views to share (Gordon and McNew, 2008). Although this screen
reduced the size of the respondent pool, it helped to assure that the results were not confounded by the
answers of participants with little or no experience with CRO management or interaction. It therefore
increased the likelihood that data would be of higher value- a focus on quality over quantity (Moss,
2022). Nonetheless, certain questions were narrower in scope or required a particular type of expertise,
so I anticipated that some respondents might decline to answer sone of the questions. A “skip logic”
method was also used to present some questions only to those with appropriate experience, in order to
provide more depth on a particular area. For example, not all individuals had the type of experience that
might allow them to comment usefully on their company’s strategy around outsourcing or to offer their
personal insight in to CRO innovation. Structuring the questions in this way appeared to assure that

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respondents finished the survey, as reflected in the high completion rate from email respondents (97%,
37/38). The strong completion rate was evidence that the survey topic and questions were of interest to
the respondents.
An additional limitation that must always be considered when using survey methods is its appropriateness
of its questions for the objectives of the research and the capabilities of the respondents to answer. If the
respondent is dealing with a CRO for only a limited facet (e.g., only data management or only
pharmacovigilance activities), some of their answers to questions may not be applicable or even degrade
the validity of the research (Taherdoost, 2016). For example, some respondents may be focused on a
narrow aspect of the CRO’s capabilities or performance, depending upon the level of experience of the
respondent. Previous experience can also introduce bias into the survey, which has been documented in
other research related to cultural or political perceptions (Mayer, 2021). In this case, respondents may
have been previously employed by a CRO, and this may limit their ability to give a sponsor-only
perspective or may cause them to have pre-conceived views that do not allow them to answer from the
sponsor’s perspective, as directed by the questions in the current survey. Thus, care was taken to
encourage participants to focus on their current sponsor-based responsibilities for CRO management.
Surveys are also limited because they have restrictions related to the numbers and structures of the
questions posed to respondents. As noted above, this necessarily put constraints on the scope of the
study, which in this case was exploratory in nature given the paucity of previous literature on this topic.
By limiting the number of questions, I tried to assure that the survey could be completed in about 15
minutes. This was important because busy professionals do not have the time or inclination to complete a
time-consuming survey. It is well documented by social scientists that respondents may not take the time
to answer questions carefully if they perceive the questions to be irrelevant or lengthy; they may even
leave a survey prematurely if they find that the questions are confusing or seemingly irrelevant (Kato and
Miura, 2021). However, the need to minimize the number and structures of the questions may have not

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allowed respondents to provide more extensive input about their views and experiences, thus limiting the
depth of the survey results. However, I am satisfied that the current survey provided additional insight
into CRO/sponsor collaborations well beyond what had been captured in earlier studies. Some of these
areas included more specifically the types of tools that respondents might be willing to use in the future,
and areas in which they could see benefit when designing their relationships with CROs.
In this survey, an effort was made to include companies of different sizes. The way that relationships are
built and the resources that are available for clinical studies can vary greatly according to company size,
and these different views might be hidden in the grouped responses, especially of the respondent pool is
biased toward companies at one end of the size range (Madrigal, 2012). This was one area that was not
clearly distinguished in previous research, where sample sizes were skewed toward larger companies
(Wilkinson et al., 2019). Thus, responses were stratified according to company size to see whether
differences appeared to exist in their views. In this current survey, no true outliers between respondents
from small, medium, or large-sized companies could be determined that would show any real trend on
CRO collaborations based on company size. The relatively small numbers of participants in the resultant
subgroups restricted my ability to identify any but extreme differences in the thinking of small versus
large or medium sized companies.
5.3 Considerations and Insights from the Survey
The literature review presented above has made clear that the role of a CRO has evolved as clinical drug
studies progress from small simple designs to more complex multinational studies. As CROs take a
larger role, however, difficulties related to communication and collaboration are often reported (Getz,
2016). In other sectors, “vested outsourcing” approaches have been used to engage both parties in a more
cooperative relationship in which they are motivated to invest in the success of the projects. The

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principles of the Vested Outsourcing Framework, as described in Chapter 2, appeared to offer a way to
improve the relationships according to five rules:
(1)“focus on outcomes, not transactions; (2) focus on the what not the how; (3)
clearly defined and measurable desired outcomes; (4) pricing model with incentives
that optimize for cost/service tradeoffs; and (5) a governance structure with insight,
rather than oversight.”
These rules suggested domains of interest that helped to direct the development of the survey questions
(Figure 9). An in-depth review of the results of this survey, as they relate to the five rules of the Vested
Outsourcing Framework, gives more insight regarding the usefulness of such approaches to move the
relationship between CRO and sponsor from transactional to innovative. These five tenets will be used to
organize the discussion below.

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5.3.1 Outcomes, not transactions
The current study, like others before it, suggests that current outsourcing is most often transactional, and
is structured most commonly with traditional models in which the CRO is a single-source, preferred
provider, or full-service provider. In this study, at least half of the respondents used one of these models,
to contract with a CRO to take advantage of its service capabilities or expertise for a specific function or
grouping of tasks. Regardless of the specific microstructures of the contracts, they appear to fit an
approach described by Vitasek and Manrodt (2012), as “grounded, for the most part, in non-flexible task-
oriented contracts that focus primarily on risk avoidance, liability limitation and lowest possible cost”. In
this situation, the contract defines a specific service(s) (Figure 25). While milestone payments were often
built into the contract for those services, no recognition or reward appeared to be incorporated to
incentivize the CRO deliver better services, for example, by implementing an improved process. Instead,
most respondents indicated they managed the activities of the CRO by using recurring meetings,
oversight plans and/or communications plans. Despite these activities, communication was still ranked as
the greatest area in which the CRO(s) could improve performance. These findings suggest that the
current approach to outsourcing, even at the onset of the contracting process, might be improved by more
attention to joint planning.
Further, companies appeared only infrequently to provide the CRO with the opportunity to manage all the
clinical trials or the workload for an entire trial/program. Thus, the CRO would have relatively little
opportunity to participate in the overall business or development strategy that would dictate how the
clinical trial would be executed. The transactional nature may also be suggested by the finding that about
a third of the respondents admitted that the CRO was hired without a specific strategy. This is not to say
that these relationships were developed without attention to performance or outcomes. For example,
more than half of the respondents identified that they evaluated the work of the CRO after the clinical trial
was complete, and this would presumably provide a way to filter out a substandard vendor for

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consideration when a new trial is planned. However, it does not necessarily provide a mechanism to
assure that the next trial is conducted by a now more trusted CRO, but in a way that improves on its
practice. Further, many noted that they had limited ongoing evaluation of sponsor outsourcing strategies
and nearly a third noted that CROs were hired without a set strategy.
A more participatory relationship, with features like those typical of vested outsourcing approaches
elsewhere, appear to have been adopted by only a minority of respondents (Ohms, 2020). In those cases,
the company and CRO identified more explicitly not only the workload allocation but also objectives and
outsourcing needs for both parties when the relationship was developed. This approach is similar to that
laid out by Vitasek and Manrodt who identified the usefulness of a “business model map” as an early step
in the development of a vested outsourcing framework, to define a joint vision and to align the goals and
expectations of both partners. Those who had used a more vested type of approach indicated that it was
“highly valuable” in their most recent clinical trial. For the companies that followed this path, elements
of the relationship were usually defined by certain standardized documents, such as a Transfer of
Regulatory Obligations (TORO) or activity-specific documents such as a data management plan.
Also identified as useful by Vitasek and Manrodt is the explicit development of shared vision statement to
identify the intent of the relationship and to foster better practices in areas such as communication, trust,
flexibility, focus, and feedback (Vitasek and Manrodt, 2012). The statement of intent focuses on this
shared vision concept, in which both partners define a pathway for collaboration in setting deliverables
and agreed desired results. Further studies may be needed to understand the extent to which the vision
statement was embedded in the TOROs or management plans by those who used a more vested approach.
Nonetheless, respondents who had implemented this type of joint planning in their current outsourcing
strategy all indicated that this was of high value to the outsourcing relationship. However, success may
depend to some extent on the capabilities of the CRO to take on broader responsibilities, outside
execution of task deliverables. Certain critical areas for improvement suggest this planning consider soft

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skills in addition to qualifications or expertise. In this survey, respondents felt that the CROs were least
positioned to recognize internal weaknesses or offer constructive solutions. CROs were ranked as higher
performing in areas such as attention to the study and providing qualified personnel; these two areas may
not be ranked as a lower performing area because, even though a recognized issue in the industry, can be
remediated through staffing changes and allocation of resources (Carroll, 2005).
5.3.2 The What, not the How
Clinical trial management differs from some types of outsourcing activities because they are heavily
regulated by federal agencies that require the sponsor to oversee any outsourced clinical trial activities
(FDA, 2017). Thus, it is possible that many companies regard this directive to require the use of
traditional “command-and-control” approaches that can devolve into micro-management. Nevertheless,
CROs are hired specifically because they have extensive experience, and, indeed, often more experience,
than the sponsor with the logistics and potential pitfalls of clinical trials. This expertise was clearly
important for CRO selection to respondents here. They identified that therapeutic area and capabilities
(e.g. technology, niche services) and reputation/previous experience were the two most important criteria
for CRO selection as suggested also by previous surveys (Glass and Beaudry, 2010). This is not
surprising. A highly capable CRO can give the sponsor the confidence to delegate many responsibilities
to the CRO, that at least in theory, should support the objectives laid out in the business model map, and
the deliverables/ results in the shared vision/ statement of intent. Essentially, the sponsor and CRO can
together focus on the “what”- the end-goals- rather than dictating the details of the “how”. Then, the
sponsor should be able to shift responsibility to the CRO, that can then manage how to carry out the work.
If the first stage of goal setting has been shared, it may be easier to continue that collaboration, in which
the CRO can offer options or suggest solutions to problems, rather focus on providing certain routine
tasks (Wilkinson et al., 2019).

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Getz identified that “execution” is a top priority for CRO selection, but current practices focus on the
delivery of tasks, not the design of solutions to execute those tasks in a manner that improves the process
(Getz, 2018a). Findings here suggest that sponsors are typically giving CROs the responsibilities for
certain routine tasks, such as site payments and Trial Master File management. However, they are also
commonly given responsibilities for site monitoring and data management, areas more amenable to
innovative approaches that build on the expertise of the CRO. In contrast, certain science-based
functions, such as medical writing and statistics, were primarily managed by the sponsor. This split is not
surprising and probably would not change much even with the introduction of vested approaches, because
these identified activities usually occur at the end of the study after the data has been analyzed and the
CRO has mostly completed its activities. However, areas in which there may be more room for
cooperation might be in site identification, regulatory work, and medical monitoring, which already
appear to be managed by splitting responsibilities between CROs and sponsors. The results of this survey
were consistent with findings in the literature, that CROs are typically chosen for their special trial
expertise; nonetheless the management of responsibilities in data driven or scientific areas are not part of
the assigned activities. Considering the high cost of clinical trial execution, taking the time to interact
with the CRO to develop collaborative solutions to the clinical trial challenges might ultimately decrease
trial costs and encourage the CRO staff to come up with innovative processes and solutions to achieve the
desired outcomes. This survey noted that the typical Statement of Work, or SOW, is created after the
Master Service Agreement is signed, or at the same time/ in parallel. Refocusing the SOW into a
statement of objectives, to describe necessary outcomes rather than set tasks, can define better the
expected results of the clinical trial collaboration.
One of the reasons why activities are not assigned to the CRO could be related to the ongoing
performance of the trial once the CRO has been engaged. Survey comments suggest that sponsors can
become less comfortable to hand over critical or key clinical trial activities as the relationship between the

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CRO and sponsor progresses (Table 18). CROs who “over promise and under deliver” are often
perceived to lack transparency and accountability. This loss of confidence might seem counterintuitive.
One might expect that the CRO and sponsor would become more comfortable with each other as work
progresses, and trust and performance would improve. However, such degradation of ongoing
relationships is not unusual in many types of outsourcing relationships. For example, Vitasek and
colleagues examined outsourcing practices of the U.S. Air Force and observed that the business model
and the relationship in outsourcing deals often have fundamental flaws, including a focus on cost over
value and the contractual restrictions which cause misaligned processes and outcomes. These flaws result
in direct negative or unconscious behaviors that drive unintended consequences (Vitasek, Ledyard and
Manrodt, 2010). Proponents of vested outsourcing suggest that a more collaborative structure could be
helpful in avoiding mistrust, a lack of collaboration, and poor-quality work.
Another reason why sponsors might not want to outsource more of the “how” to CROs could also relate
to the perceived inability of the CROs to handle certain types of activities to the level by the company and
regulators. In this survey, respondents indicated that CROs were “mostly” or “occasionally” meeting the
sponsor’s expectations for performance expectations. Attention was often drawn to weaknesses related to
staff turnover, project management, and quality and knowledge related to the trial (Table 18). These
results are not a ringing endorsement of CRO capabilities and suggest areas for improvement that might
depend on increasing the competence of CRO personnel in some arenas before companies can trust their
contributions. One area in which respondents appeared to see most need for improvement was in
communication. Other areas that were highlighted, such as meeting deadlines and oversight of internal
staff, might also be improved by attention to communication.
Nevertheless, most respondents did not see a need to replace the CRO that they are using, perhaps
suggesting that they do not have confidence that a switch would give better outcomes. Thus, it might
seem that solutions for improving the communication and interactions with the current CRO may create

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better ways to improve performance. As noted in the literature, a key solution to this problem requires
the partners to identify, mitigate and manage issues that stem from communication difficulties (Miseta,
2016). A focused effort by both parties to strengthen the communication is a key element of “what”
needs to be achieved, rather than dictating how outcomes need to be fulfilled.
5.3.3 Defined and Measurable Outcomes
The value of defining a business map and statement of intent, described above, comes from its ability to
negotiate desired outcomes in ways that are clear to both parties. It further provides a basis for both
parties to determine that a project is on track. In a clinical trial, setting realistic expectations is important
so that the CRO can achieve these project outcomes.
Outcomes for project management should not be confused with efficacy outcomes that the company
hopes to prove by using trial data, to gain regulatory approval. Those types of efficacy outcomes depend
on the performance of the drug, not the clinical team. The trial sponsor hopes that the study will
successfully prove the hypothesis for which the protocol was designed to test, a desired goal that often
cannot be achieved and certainly cannot be “managed” to assure a positive outcome (Getz, Lamberti and
Kaitin, 2014). In contrast, project outcomes in the context of a partnering relationship are the shared
practical goals for logistical performance, such as meeting recruitment timelines or assuring that
documentation complies with regulatory expectations. From these goals come metrics to measure the
effectiveness of the strategy and make corrections based on that data. Aligned outcome goals are
important because they can give the CRO the opportunity to propose creative or flexible solutions that
improve performance in ways that might not have been anticipated by the company by itself.
Inconsistent and meaningless metrics not only cause inefficiencies, but these can also damage the
collaborative outsourcing model to which the sponsor and CRO should be striving (Getz, 2016).
One concern when defining outcomes is that they can sometimes set rigid constraints on a project and
thus remove the ability of the partners to create better approaches to a strategy or problem. The Vested

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Outsourcing Model suggests that metrics be high level and kept to a minimum. This more minimalistic
approach is also advocated by experts in more specific studies of clinical research practices (Miseta,
2016; Getz, 2016). For example, Miseta suggests that metrics such as the number of executed site
monitoring visits or timeliness of these visit reports might be less meaningful to process improvement
than metrics that describe the quality of these deliverables more generally (Miseta, 2021). Ideally, these
key performance indicators are created during contract discussions, so both parties are aware of the
expectations from earliest stages. This kind of approach can open the door to a higher level of CRO
engagement and confidence, and further encourage the CRO to think about innovative ways to
accomplish the project goals. In this survey, such decisions about metrics did appear to be considered at
the time of contract development in discussions led jointly by both the sponsor and CRO. Further,
respondents felt there was high value in their most recent clinical trial to implementing a mutually
defined list of outcomes, with parameters on how these outcomes will be measured.
5.3.4 Pricing Model with Incentives
The Vested Outsourcing Model suggests that outcome-setting is to some extent a foundation for another
“rule”, to implement a pricing model with incentives that reinforce performance of higher quality. It
assumes that better performance will create higher value, for which reward is appropriate. In this study,
metrics to indicate quality of performance were not related to payment or reward. In fact, the majority
(61%) indicated that quality of deliverables had no impact on the payments made to the CRO. This result
may suggest an area for improvement, given that previous studies have reported that quality of CRO
deliverables, along with value, relationship, and overall work, is an important trait to ensure a successful
outsourcing relationship (Avoca, 2019c).
Agreement on a pricing model that awards innovation, and is not simply a pay per task model, is an
alternative to current outsourcing paradigms (Miseta, 2021). When a higher value is placed on better
performance, and this results in a higher reward, the CRO may be incentivized to assume the risks

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associated with changing operational models related to the staffing, processes, quality, and timelines.
Rewarding a CRO financially, in a pricing structure that is equivalent to or better than the currently
utilized outsourcing models, might bring higher productivity. In common current systems, however,
transactions and deliverables defined in narrow terms by the contract give the CRO no motivation to
complete their tasks in the most efficient and effective manner. This system of transactions and
deliverables can even reinforce the perceptions that CROs are taking on clinical trial work that is beyond
the scope of their capabilities, rather than being strategic partners (Friedhoff, 2009).
In this study, responses were mixed when respondents were asked if CRO innovation might create more
value, regardless of additional cost. Further, they were split when asked about whether they supported
paying the CRO to provide innovation for how the clinical trial is managed if it created more value but
was more costly than other contract bids. About half of the respondents felt that reward for innovation
was a reasonable approach. Areas such as time to database lock from first subject entered or last subject
visit and time from contract to first subject in were two examples of outcome-based incentives that
companies would support, as were recruitment milestones and time from protocol finalization to site
initiated.
When considering a change in outsourcing model, it is worthwhile to consider its effect on current pricing
structures and paradigms. Traditionally, CROs have charged a set price per activity. Thus, CROs may
take a risk when offering constructive ideas to improve processes or efficiency. The suggested process
improvements might lower its billable income, if the changes reduce the number of billable activities or
hours for CRO personnel, or the number of change orders which also come with an extra financial
recompense (Avoca, 2019c). Sponsors might also have concerns about the new flexibility. They might
be dissatisfied if the innovative solutions were to increase costs if, for example, the changes required extra
staffing or document revision. Thus, care must be taken during contract-setting to discuss such issues in a
collaborative manner. For the CRO, the risks or unknowns related to revenue predictions might be

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balanced if the sponsor found the new approaches to be valuable and thus favored the same CRO for
ongoing collaborations and contracts. Further, if the innovative changes strengthened the reputation of
the CRO as capable of high-quality work, this in itself might give it a competitive advantage that might
increase the likelihood that its services would be sought by others, thus increasing the longer-term return
on investment. Of particular value might be innovations that could decrease the length of the trial or
increase communication. As shown by the results reported here, companies ranked meeting deadlines as
the most important consideration for re-engaging with a CRO, ahead of considerations related to
personnel and relationships. These in turn were considered more important than the cost or therapeutic
and regional expertise of the CRO. Interestingly, the highest-ranking reason for initial CRO selection
was therapeutic capabilities, indicating the areas that are most valued at the onset are not the criteria that
are considered as important during execution of the clinical trial outsourcing collaboration, and do not
align with sponsor expectations for operational execution. This data suggests that current methods for
engaging with a CRO might be reconsidered, to address the inconsistencies in the way that CROs are
selected and outsourcing strategies are executed identified here and in previous outsourcing surveys
(Getz, 2016; Avoca, 2019a).
Sometimes, risk-taking and innovation is forced upon the sponsor and CRO. During the Covid-19
pandemic, for example, those managing clinical trials had to pivot their approaches and use less traditional
approaches such as decentralized trial management. CROs were able to offer modify their methods for
conducting the trial, while still complying with regulations. Forced changes, such as remote monitoring
and electronic data collection, may have cost the CRO and sponsor more in the short term, as they were
implemented, but have over time proven to be important value-added innovations, that may allow trials in
future to become more time and cost effective (Xue et al., 2020).

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5.3.5 Governance - Insight versus Oversight
The relationship between a sponsor and CRO is necessarily asymmetric, because, as discussed above, the
sponsor has a regulatory obligation to oversee the CRO and bear responsibility for its actions. However,
a fine line exists between governance and micromanagement. It underlies the fifth and final rule of the
vested outsourcing model that “a governance structure should have insight rather than oversight”. The
rule would assume that the relationship between a CRO and sponsor should be managed more equally,
considering that the CRO was selected based on its specialized capabilities and experience. Once goals
are aligned, the CRO should be encouraged to use its judgment on how these goals might be achieved. At
the same time, sponsors should use governance in a way that provides insight into the methods that could
be used to improve trial conduct, rather than simply policing the CRO in a way that questions their
expertise and capabilities. Previous surveys have also advocated for governance that is strategic and
collaborative rather than reactive (Getz, 2009). Examples where these approaches have great value can
be found more widely in health care. For example, an inpatient healthcare system in British Columbia
utilized a vested outsourcing framework to develop distinct governance teams with responsibility to focus
on relationship, finance and efficiencies, and quality. Two years after implementing this structure, the
participants considered the formerly contentious relationship between the parties to be “collaborative” and
“supportive” (Frydlinger, Hart and Vitasek, 2019).
Most respondents in this study used some type of performance review to see if objectives were being met,
and found this task was of high or some value to their clinical trial. Not all used a formal governance
committee, but several facets related to governance were seen as valuable elements to be implemented
into the clinical trials. These included recognition of continuous improvement, management of
unforeseeable circumstances, and policies around the relationship. These elements underline the fact that
governance models are not confined to the early stages when contractual relationships are developed but
extend throughout the whole time of the trial. This survey could further be expanded, to see if the

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utilization of joint policies and plans, which recognize the changing needs of the business and the mutual
accountability of the activities around change, are practical and allow for collaborative response.
Nonetheless, results here suggest that governance of the sponsor/ CRO relationship has not progressed
past the reactive approach. Respondents indicated their company uses oversight as a stand-alone
management style, where the sponsor closely manages the CRO. Use of an insightful collaborative
alliance as a sole management style was only in place with oversight as a method to manage the alliance.
Further, most respondents agreed only modestly or were ambivalent when asked if their companies would
adopt suggestions from the CRO regarding the management of the clinical trial. The results seem to
suggest that personnel working in sponsoring companies have some confidence that CRO input could be
valuable in their collaboration, but still are wary that the CRO would not be allowed to contribute
substantially to the planning and oversight (Margherita and Valeria, 2017).
5.4 Conclusions and Future Direction
This survey was an opportunity to determine how industry is currently structuring and interacting with
Contract Research Organizations and to explore ways in which their collaborations on clinical trial
programs might be improved. It showed that transactional outsourcing models remain the predominant
approach when managing clinical trials, corroborating earlier surveys, as observed in earlier studies by
Tufts CSDD and The Avoca Group (Wilkinson et al., 2019; Avoca, 2019b). These approaches are based
on the definition of contractually dictated tasks and payments. Much less common was the use of
innovative outsourcing models that focus on a shared responsibility for the quality of deliverables.
However, less traditional approaches that focus on collaboration rather than “command and control”
principles may offer the opportunity to improve quality of deliverables and optimize efficiencies in the
clinical trial process. Processes for selecting the CRO, defining the structure of the contract and setting
mutually established goals, including overall project objectives, are all areas in which companies might

106
support a less traditional outsourcing approach. Shifting the focus to relevant and informative metrics
related to high-level outcomes rather than task completion may foster more satisfying relationships
between the sponsor and CRO (Avoca, 2019c).
Respondents in the current survey seemed to support the view that the CRO should have more ownership
and accountability and be encouraged to offer solutions for trial problems. Vested outsourcing
approaches could enhance the relationship between sponsors and CROs in several areas through better
alignment of expectations and sharing of responsibilities and expertise. The clinical trial industry may
continue to miss opportunities for creating a partnership if they approach the engagement of the CRO as if
it were capable only of low-level tasks. In turn, this can create a self-fulfilling prophecy that CROs
become less capable and innovative, by hiring less competent staff and focusing only on simple
transactional tasks, if that is all that is expected.
To my knowledge, no data has been collected on sponsor companies that have fully integrated vested
outsourcing into the relationships with CROs. It would be useful to understand the level of utilization of
the five rules of Vested Outsourcing, as outlined by Vitasek and colleagues, in a comprehensive manner.
Additional insight would need to be gathered into how the facets of a vested outsourcing framework have
been introduced, and if there was any impact on the collaboration between sponsor and CRO, and any
improvement to the perception of the quality of deliverables by the CRO.
If models are to be changed, leaders from both the sponsor and CRO would have to change their thinking
and planning. Change is well known to be difficult. The partners would need to be educated and guided
in the vested outsourcing process; recognition by CROs, sponsors, and regulators in the clinical trial
industry would have to confront the factors that might contribute to their reluctance to adopt a novel
framework for outsourcing. However, results here identified that the few companies that have
implemented more collaborative approaches see those efforts as valuable. Other companies might be

107
encouraged to consider if innovative collaboration models could help them to improve the quality of their
relationships and the efficiency of clinical trial operations and processes.
The Covid-19 pandemic was an indication that tasks normally delivered by a CRO, based on standard
legacy processes, could shift to a different paradigm. As expectations had to become more strategic than
secretarial, new opportunities were presented to test the acceptability and practicality of innovative and
collaborative outsourcing. All concerned parties, including sponsors, CROs, regulators, and investigators,
were forced to develop hybrid approaches and implement new technology to collect data for clinical
trials. A repeat of this current survey would be valuable over the next year to determine if the changes
implemented during the Covid-19 pandemic will in the future see the wider adoption of more
collaborative approaches between the sponsor and the CRO. Further, such changes in approach might
result in changes in the structure and competencies of the CROs, an area not investigated in this research.
The results here are useful, but they represent only one stakeholder. To understand the nature and
challenges of changes, the views of the CROs also should be studied, to see the complete picture of
opportunities and challenges with these relationships. A vested outsourcing relationship requires
collaboration of the sponsor and CRO, and all perspectives are integral to creating an effective
framework.

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APPENDICES
APPENDIX A. 21 CFR PART 312- SPONSOR REQUIREMENTS
Requirement Citation
Ensuring that the investigation is conducted in accordance with the general investigational plan
and protocols
21 CFR
312.50
Maintaining an effective IND with respect to the investigations 21CFR
312.50
Ensuring that Food and Drug Administration (FDA) and all participating investigators are
promptly informed of significant new adverse effects or risks with respect to the drug
21 CFR
312.50
Selecting qualified investigators 21 CFR
312.53(a)
Controlling the shipment of investigational test article 21 CFR
312.53(b)
Upon written request by FDA, submitting records or reports (or copies of them) relating to the
clinical investigation to FDA
21 CFR
312.58(a)
Discontinuing shipments of investigational test article to any investigator who has failed to
maintain or make available records or reports of the clinical investigation to FDA: If the
investigational drug is listed in any schedule of the Controlled Substances Act (21 U.S.C. 801;
21 CFR part 1308), required records regarding shipment, delivery, receipt and disposition of the
drug shall be made available to the properly authorized employee of the Drug Enforcement
Administration (DEA) of the U.S. Department of Justice for inspection and copying; the sponsor
shall assure proper storage of the investigational drug in a securely locked, substantially
constructed cabinet, or other securely locked enclosure, to which access is limited to prevent
theft or diversion of the substance into illegal channels of distribution
21 CFR
312.58(b)
Disposing of unused investigational test article 21 CFR
312.59

116
Requirement Citation
Maintaining written records of test article disposition 21 CFR
312.57/ 21
CFR
312.59
Submission of written IND safety reports to FDA and all participating investigators 21 CFR
312.32
Qualifying the investigators by obtaining required information and commitments 21 CFR
312.53(c)
Selecting monitors 21 CFR
312.53(d)
Providing an investigator brochure 21 CFR
312.55(a)
Informing investigators of new observations discovered by or reported to the sponsor, with
respect to adverse effects and safe use
21 CFR
312.55(b)
Reviewing ongoing investigations to include: Monitoring all clinical investigations; Securing
investigator compliance with the agreement contained in the signed Form FDA 1572, the general
investigational plan or other investigator responsibilities or, alternatively, discontinuing
investigational test article shipment; Requiring the disposal or return by non-compliant
investigators of investigational test article; Notifying the FDA of the termination of the study site
of the non-compliant investigator
21 CFR
312.56
Upon request from any properly authorized officer or employee of FDA, permitting at
reasonable times, access to, copying of, and verification of records and reports relating to the
clinical investigation
21 CFR
312.58(a)
Retaining reserve samples of any test article and reference standard identified in, and used in any
of the bioequivalence or bioavailability studies described in, 21 CFR 320.38 to 320.63 and
releasing the reserve samples to the FDA upon request, in accordance with, and for the period
specified in 21 CFR 320.38
21 CFR
312.57(d)

117
Requirement Citation
Assuring return of unused investigational test article from each investigator whose participation
in the clinical study is discontinued or terminated
21 CFR
312.59
Submission of protocol amendments (includes new protocol, changes in protocol, and the
addition of any new investigator’s information)
21 CFR
312.30
Submission of annual reports within 60 days of the anniversary date that the IND went into
effect
21 CFR
312.33
Reviewing and evaluating the evidence relating to the safety and effectiveness of the
investigational test article as such evidence is obtained from the investigator
21 CFR
312.56(c)
Reporting information relevant to the safety of the test article to the FDA 21 CFR
312.56(c)
Submitting to the FDA annual reports on the progress of the investigation 21 CFR
312.56(c)
Determining whether an investigational test article presents an unreasonable and significant risk
to subjects, and if so, to perform the following: Discontinuing investigations that present the risk
as soon as possible or in no event later than five working days after making the determination;
Notifying the FDA of the discontinuance; Notifying all IRBs/IEC for study sites that participated
in the investigation of the discontinuance; Notifying all investigators who at any time
participated in the investigation of the discontinuance; Assuring the disposition of all outstanding
stocks of the investigational test article; Preparing and submitting to the FDA a full report of the
discontinuance action
21 CFR
312.56-
312.59
Maintaining adequate records showing receipt, shipment, or other disposition of the
investigational test article
21 CFR
312.57(a)
Maintaining complete and accurate records showing any financial interest as described in 21
CFR 54.4, paid to clinical investigators by the sponsor of the covered study, and all other
financial interests of investigators concerning Part 54,
21 CFR
312.57 (b)
Retaining adequate records under 21 CFR 312, Subpart D, for two years after a marketing
application is approved for the test article; or, if an application is not approved for the test article,
21 CFR
312.57(c)

118
Requirement Citation
until two years after shipment and delivery of the test article for investigational use is
discontinued and FDA has been notified
Authorizing alternative disposition of unused supplies of investigational test article, provided
this alternative disposition does not expose humans to risks from the test article
21 CFR
312.59
Submission of information amendments on the IND that is not within the scope of a protocol
amendment, IND safety report or annual report
21 CFR
312.31
Act as the Sponsor’s authorized representative in the United States because the Sponsor does not
have a place of business within the U.S.
21 CFR
312.23(a)(
1)(ix)

119
APPENDIX B. SURVEY
GENERAL INFORMATION

Thank you for participating in this survey to examine how Contract Research Organizations (CROs) are
used when outsourcing a clinical trial. Your responses are very important to this research, and will be
kept confidential. The survey results will be compiled and presented as part of the overall analysis. This
survey should take approximately 15 minutes to complete. If you cannot answer a question, please feel
free to skip or come back to it.

Please answer the survey considering your most recent experience outsourcing a specific clinical trial to a
CRO, where you had responsibility for selection and/or oversight of the CRO activities, individually or as
a member of a team. If this experience involved several CROs, please focus on the CRO that was
transferred the majority of the work.

120
Q1 Which category best describes the size of your company?
o Small / Emerging (1-500 employees) (1)
o Medium (501-2000 employees) (2)
o Greater than 2,001 employees (3)
Q2 Which area best describes your primary role at your current company (Select one)?
o Clinical Development (1)
o Clinical Operations (2)
o Project or Program Management (3)
o Data Management (4)
o Pharmacovigilance (5)
o Regulatory Affairs/ Strategy (6)
o Clinical Quality Assurance (7)
o Other (8) ________________________________________________

121
Q3 How many years have you worked in the clinical research industry?
o Less than 5 years (1)
o 5+ to 10 years (2)
o Greater than 10 years (3)

Q4 Does your current company outsource to a CRO for clinical trial programs?
o Yes (1)
o No (2)
o Unsure (3)

Skip To: Q5 If Does your current company outsource to a CRO for clinical trial programs? = Yes
Skip To: Q22 If Does your current company outsource to a CRO for clinical trial programs? = No
Skip To: Q22 If Does your current company outsource to a CRO for clinical trial programs? = Unsure

122
Q5 Do you have responsibility for CRO selection and oversight during the clinical trial study or program,
as an individual or as part of a team?
o Yes (1)
o No (2)
o Not currently (3)

Skip To: Q9 If Do you have responsibility for CRO selection and oversight during the clinical trial study or pro... = Yes
Skip To: Q22 If Do you have responsibility for CRO selection and oversight during the clinical trial study or pro... = No
Skip To: Q22 If Do you have responsibility for CRO selection and oversight during the clinical trial study or pro... =
Not currently

123
Q6 In the past five years, approximately how many studies have you been part of the team responsible for
decision making regarding CRO selection?
o None (1)
o 1-4 (2)
o 5-9 (3)
o 10 or more (4)

124
Q7 Why did your company choose to use a CRO(s)? Please select all that apply.
▢ We lack internal resources (1)
▢ We lack internal expertise (2)
▢ Our company mandates using a CRO (3)
▢ It is cost effective to outsource (4)
▢ Other, please specify (5) ________________________________________________

Q8 Do you use a separate CRO selection process for each clinical trial?
o Yes (1)
o No (2)

125
Q9 Considering your most recent experience with using a CRO for a clinical trial, how important are the
following for selection of the CRO?
Very Important (1) Somewhat Important (2) Least Important (3)
Reputation/ Previous
Experience (1)
o o o
Therapeutic area/
Capabilities (technology/
niche services) (2)
o o o
Cost (3)
o o o
Global reach (4)
o o o
Preferred Provider (5)
o o o
Other, please specify (6)
o o o

126
Q10 Considering the current clinical trial you are outsourcing, who has primary responsibility for the
management of the following functions?
Responsible Party
CRO (1) Sponsor (2) Combination (3)

127
Site Identification/ Site
Selection (1)
o o o
Patient Recruitment (2)
o o o
Trial Master File (3)
o o o
Site Monitoring (4)
o o o
Data Management (5)
o o o
Medical Monitoring/
Pharmacovigilance (6)
o o o
Statistics (7)
o o o
Medical Writing (8)
o o o

128
Site Payments (9)
o o o
Third- party vendor
management (10)
o o o
Regulatory presence or
expertise (11)
o o o
Clinical Supply
Management (12)
o o o

129
Q11 Which types of outsourcing model(s) do/did you use in the most recent clinical trial that you
outsourced?
Yes, we use this (1) No, we do not use this (2) Unsure (3)
Pay per task (1)
o o o
CRO provides a range of
integrated services (2)
o o o
CRO is awarded all
activities for the clinical
trial (3)
o o o
One CRO manages all
your clinical trials (4)
o o o
CRO provides a specific
function or functions (5)
o o o
CRO does all the work for
your trial or program (6)
o o o

130

Q12 How do you manage CROs? Please select all that apply.
▢ Governance committee (1)
▢ Oversight plan (2)
▢ Risk assessment (3)
▢ Metrics (4)
▢ Co-monitoring (5)
▢ Recurring meetings (6)
▢ Communication plan (7)
▢ Other, please specify (8) ________________________________________________

131
Q13 Considering the most recent clinical trial you worked on, which of the following were implemented
into your outsourcing relationship? Please select all that apply.
▢ Shared business map, defining the business of both parties and the potential outcomes
(1)
▢ Shared vision or Statement of Intent, with a focus on capabilities and gaps (2)
▢ A clear statement of workload allocation, objectives, and outsourcing needs (3)
▢ Mutually defined list of outcomes and how these are measured (4)
▢ A review of performance to see if objectives are met (5)
▢ Fair pricing for quality output (6)
▢ Policies that define working relationships, including attitudes and behavior (7)
▢ Recognition of continuous improvement and continuity (8)
▢ Recognition of unforeseeable circumstances and how these are managed (9)
▢ Management of changes to the business (10)

132
▢ Fee per task or activity completion (11)
Carry Forward Selected Choices from "Considering the most recent clinical trial you worked on, which of the
following were implemented into your outsourcing relationship? Please select all that apply."

133
Q14 Of the concepts that were implemented, what has had the most value to your recent clinical trial?

134

High value,
implementation worked
(1)
Some value (2) No value (3)
Shared business map,
defining the business of
both parties and the
potential outcomes (x1)
o o o
Shared vision or
Statement of Intent, with
a focus on capabilities and
gaps (x2)
o o o
A clear statement of
workload allocation,
objectives, and
outsourcing needs (x3)
o o o
Mutually defined list of
outcomes and how these
are measured (x4)
o o o
A review of performance
to see if objectives are
met (x5)
o o o

135
Fair pricing for quality
output (x6)
o o o
Policies that define
working relationships,
including attitudes and
behavior (x7)
o o o
Recognition of continuous
improvement and
continuity (x8)
o o o
Recognition of
unforeseeable
circumstances and how
these are managed (x9)
o o o
Management of changes
to the business (x10)
o o o
Fee per task or activity
completion (x11)
o o o
Q15 When developing the contract with your CRO, who leads these efforts?

136
Sponsor (1) CRO (2) Both (3)
Not Applicable
(4)
Unsure (5)
Business Model
Map (1)
o o o o o
Shared Vision
or Statement of
Intent (2)
o o o o o
Defined metrics
(3)
o o o o o
Payments based
on end results
versus tasks
completed (4)
o o o o o
Alliance
building (5)
o o o o o
Mutual
agreement of
deliverables (6)
o o o o o

137
Reward for
innovation (7)
o o o o o
Q16 Considering your most recent clinical trial, what percentage would you give to your company's
management style of your CRO?
Insight- our outsourcing model is a collaborative alliance : _______ (1)
Oversight - we closely manage the CRO and their activities : _______ (2)
A combination of both : _______ (3)
Other, please specify : _______ (4)
Total : ________
Q17 For the current clinical trial you are working on, how are payments made to your CRO? Select all
that apply.
▢ The current contract pays per line item achieved, regardless of the quality of the outcome
(1)
▢ The current contract is based on performance-based task (2)
▢ Milestones (3)

138
Q18 Does your payment vary based on the quality of the tasks completed?
o Yes, please specify (1) ________________________________________________
o No (2)
o Unsure (3)

Q20 At what point does your company create a Statement of Work (or similar) with your CRO(s)?
o At the same time as the Master Service Agreement (MSA) (1)
o Prior to signing the MSA (2)
o After the MSA is signed (3)
o In parallel with the MSA (4)
o I Don't Know (5)
o Other (6) ________________________________________________

139
Q21 Which of the following do you think is the most important trait for ensuring a successful relationship
with your CRO? Please rank, in order, with 1 for the most important and 8 for the least important?
Please drag and drop your selection in the order you want it ranked.
______ Partnership (1)
______ Value (2)
______ Quality (3)
______ Data integrity (4)
______ Trust (5)
______ Core competencies (6)
______ Alignment of priorities (7)
______ Timing (8)

Q22 How often does your company evaluate its strategy for clinical trial outsourcing?
o Once a year (1)
o When outsourcing each clinical trial (2)
o They don't; we just hire a CRO when we need without a set strategy (3)
o I don't know (4)

140
Skip To: Q34 If How often does your company evaluate its strategy for clinical trial outsourcing? = I don't know

Q23 Have you had to switch CROs for any aspects in your most recent clinical trial? Please provide the
answer that best fits the situation in the current clinical trial on which the CRO is working.
o Yes (please provide the primary reason) (1)
________________________________________________
o Yes, we moved to an insourcing model (2)
o We are considering a switch in the future (3)
o No, we would like to but it is not practical (4)
o No, we are satisfied with our CROs work (5)
o No, we have asked our CRO to take on more work (6)

141
Q24 Prior to study start-up, what approach does your company currently support when contracting with a
CRO to manage a clinical trial? Select all that apply.
▢ Outcome-based incentives (1)
▢ Review and documentation of risks, dependencies, and strategy (2)
▢ Documentation of a collaborative pathway, where there is a vested interest in the success
of the CRO to manage the trial (3)
▢ Other, please provide (4) ________________________________________________
▢ None of the above (5)

Skip To: Q26 If Prior to study start-up, what approach does your company currently support when contracting
with... = Outcome-based incentives
Skip To: Q25 If Prior to study start-up, what approach does your company currently support when contracting
with... = None of the above

Display This Question:
If Prior to study start-up, what approach does your company currently support when contracting with... =
None of the above

142
Q25 If you answered "None of the above", do you feel any of the approaches might be useful in the
future?
o Yes (please elaborate) (1) ________________________________________________
o No (please elaborate) (2) ________________________________________________
o I don't know (3)
Q26 What outcome-based incentives does your company support?
o Time from contract to first subject in (1)
o Time to database lock from last subject visit (2)
o Other (please specify) (3) ________________________________________________
Q27 In which areas do you feel your CRO could improve performance? Please rank, in order, with 1 as
the greatest area where improvement is needed. Please drag and drop your selection in the order you
want it ranked.
______ Communication to Sponsor (1)
______ Relationship with clinical sites (2)
______ Therapeutic expertise (3)
______ Meeting deadlines (4)
______ Oversight of internal staff (5)
______ Other (please provide an area for improvement) (6)

143
Q28 Are there any other ways you feel your CRO could improve performance?
o No (1)
o Yes, please describe (2) ________________________________________________
o I don't know (3)
Q29 Please indicate the areas you believe your current CRO adds value to your clinical trial.

144
Agree (1) Disagree (2) Unsure (3)
Management of clinical
trial sites (1)
o o o
Data management and
database closure (2)
o o o
Interacting with
Regulatory Agencies (3)
o o o
Documentation
Management (4)
o o o
Management of third
party vendors, such as
clinical labs (5)
o o o
Other (please specify) (6)
o o o
Q30 Please describe the less traditional approaches to outsourcing you feel your company would support.
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________

145
________________________________________________________________

Q31 Do you believe your company adopts the CRO's suggestions for managing your clinical trial?
o Agree (1)
o Somewhat agree (2)
o Neither agree nor disagree (3)
o Somewhat disagree (4)
o Disagree (5)
Q32 What are the most important considerations for re-engaging with your CRO for a future trial? Please
rank, with 1 being the most important. Please drag and drop your selection in the order you want it
ranked.
______ Personnel/ relationships (1)
______ Cost (2)
______ Therapeutic expertise (3)
______ Regional expertise (4)
______ Meeting deadlines (5)
______ Other (please specify) (6)

146
Q33 Considering your current trial, on a scale of 1-10, with 1 being the lowest and 10 being the highest,
how do you feel your CRO performs in the following areas?
0 1 2 3 4 5 6 7 8 9 10

Staff retention ()

Attention to your study ()

Assigning accountability ()

Recognizing internal weaknesses ()

Providing qualified personnel ()

Offering constructive solutions ()

147
Q34 Do you think that allowing the CRO to provide innovation into how the clinical trial is managed
could create more value, even if the cost of the initial contract is above average of other bids?
o Definitely yes (1)
o Probably yes (2)
o Might or might not (3)
o Probably not (4)
o Definitely not (5)
Q35 Do you feel your company would support a less traditional approach to outsourcing a clinical trial,
where the relationship between your company and the CRO allows for more ownership by the CRO
and/or less structured payments per task?
o Yes, please describe in the following section (1)
o Possibly, please describe in the following section (2)
o On a limited basis, please describe in the following section (3)
o Probably not (4)
o Definitely not (5)

148
Skip To: Q36 If Do you feel your company would support a less traditional approach to outsourcing a clinical tria... =
Yes, please describe in the following section
Skip To: Q36 If Do you feel your company would support a less traditional approach to outsourcing a clinical tria... =
Possibly, please describe in the following section
Skip To: Q36 If Do you feel your company would support a less traditional approach to outsourcing a clinical tria... =
On a limited basis, please describe in the following section

Q36 Is there anything additional you want to add that may help describe the outsourcing relationship you
have with your CRO?
________________________________________________________________

End of Block: Default Question Block

Start of Block: Block 1

Q19 For the clinical trial you are currently working on, do you feel your CRO meets your expectations for
performance?
o Always (1)
o Mostly (2)
o Occasionally (3)
o Never (4)
End of Block: Block 1

149
APPENDIX C. CROSS TABULATIONS
A cross-tabulation of respondent company size with the different categories for implementation was
performed to provide an accurate breakdown of the number of respondents in each category, and to
determine if there were any differences in how outsourcing aspects might be applied. The
implementation of these concepts was similar cross all size of companies, although slightly higher in the
larger companies for a clear statement of workload allocation, objectives, and outsourcing needs (89%,
8/9). Only 8/45 respondents (18%, 8/45) specified they utilize a shared business map which defines the
business of both parties and the potential outcomes. Of note, companies defined as small/ emerging
(N=25) provided the most input (56% of the overall responses).

Which category best describes the size of your company?
Total
Small / Emerging
(1-500 employees)
Medium
(501-2000
employees)
Greater than 2,001
employees
Considering
the most
recent
clinical trial
you worked
on, which of
the following
were
implemented
into your
outsourcing
relationship?
Please select
all that
apply.
Total Count (Answering) 100 43 13 44
Responding to this
question
N=45
(%) N=25 (%) N=11 (%) N=9 (%)
Shared business map,
defining the business of
both parties and the
potential outcomes 8 (18) 5 (20) 2 (18) 1 (11)
Shared vision or Statement
of Intent, with a focus on
capabilities and gaps 10 (22) 6 (24) 1 (9) 3 (33)
A clear statement of
workload allocation,
objectives, and outsourcing
needs 34 (76) 19 (76) 7 (64) 8 (89)
Mutually defined list of
outcomes and how these
are measured 24 (53) 14 (56) 7 (64) 3 (33)
A review of performance
to see if objectives are met 28 (62) 16 (64) 6 (55) 6 (67)
Fair pricing for quality
output 14 (31) 4 (16) 4 (36) 6 (67)
Policies that define
working relationships,
including attitudes and
behavior 13 (29) 8 (32) 2 (18) 3 (33)

150
Recognition of continuous
improvement and
continuity 22 (11) 11 (44) 6 (55) 5 (56)
Recognition of
unforeseeable
circumstances and how
these are managed 23 (51) 14 (56) 5 (45) 4 (44)
Management of changes to
the business 15 (33) 8 (32) 2 (18) 5 (56)
Fee per task or activity
completion 18 (40) 7 (28) 4 (36) 7 (78)

151
APPENDIX D. MANAGEMENT STYLES
Management styles by individuals who indicated they use a combination of different styles.

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22
Insight 90 60 50 30 30 30 25 25 25 20 20 10 10 10 0 40 40 20 0 10 25 15
Oversight 10 40 50 70 70 70 75 75 75 80 80 90 80 80 90 40 40 60 80 40 25 30
Both 0 0 0 0 0 0 0 0 0 0 0 0 10 10 10 20 20 20 20 30 50 55
Other 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 20 0 0
0
10
20
30
40
50
60
70
80
90
100
% Allocated to Managemnet Style
Management Styles
N=22
Insight Oversight Both Other

152
APPENDIX E. COMPLETE RESPONDENT COMMENTS ON OUTSOURCING
Is there anything additional you want to add that may help describe the outsourcing relationship you
have with your CRO?
Accountability
• For a true relationship, the CRO must also have ownership and accountability for delivering a quality
program in a defined timeframe. There needs to be penalties for not delivering in a cooperative manner.
• usually with the majority of CROs there is lack of ownership. The reasons for that might be manifold, i.e.
Sponsors SOPs to be followed, sponsors study team micro manage the CRO, (too) strict contract
conditions, most common: CRO staff overstrained and/ or unwilling to take responsibility
• there needs to be more accountability for oversight of their personnel with clear understand what they
review and document clear components of overview, often is vague. Initial Task orders is a commitment
to time, cost, quality based on what was contracted for. often we see the default is to do change order
instead of being accountable for what was committed when nothing has changed in protocol.
• CRO management has changed over the last few years as there have been M&A for a "one stop shop" this
can be proven in the cases such as Thermo Fisher acquiring PPD. This means that the way the CRO are
managed and outsourced may change and also the expectations, expertise, may change as the lines become
more blurred.
Oversight
oversight methods should be defined internally by sponsor
Performance
• Hire more qualified individuals who are accountable for doing a good job.
• CRO is supposed to be full service, but we struggle with them performing up to our expectations for a
first-in-human trial. We wind up taking on their work because they cannot do it fast enough and/or lack
the understanding of the complexities of our trial.
Sponsor company
• I find that larger Pharma companies say they want innovation, but in general are more comfortable
implementing the same SOW/working model every time. We would benefit from more up front planning
and including the CRO in strategy discussions.
• Our company is moving to discontinue use of CROs and utilize an in-house model for all new projects.
The cost savings has been significant.
• As long as Sponsor has full approval power over the clinical protocols, the CRO could provide whatever
innovative suggestions they wish.
• We are in multiple phase 1 studies. Therefore most decisions regarding enrollment, eligibility, data
questions, etc are made by the sponsor. Our small and relatively young company would not be
comfortable giving away these decisions. The CRO mostly manages CRA site monitoring, and PV safety
reporting and management. we had to pull back data management and biostats from the CRO. We had to
hire internal staff to handle those responsibilities as the CRO proved to be ineffectual. This is a very
large, supposedly reputable CRO. An internal decision to choose this CRO is based on speed to site
initiations and first pt treated. I do not agree that this should be such a high facor in deciding on a CRO,
but it is often used.
Relationships

153
• Since I work for a startup biotech, it is difficult to release ownership to the CRO fully. Sometimes the
relationships come down to the right teams on both sides and whether they are healthy and collaborative.
It is important to recognize the need to make changes to the team in order to improve ownership and
relationships.
• Trust but confirm
• Strategic partnership

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Asset Metadata

Creator Kupsch, Laura Beth (author)

Core Title Contract research organizations: a survey of industry views and outsourcing practices

School School of Pharmacy

Degree Doctor of Regulatory Science

Degree Program Regulatory Science

Degree Conferral Date 2022-12

Publication Date 09/27/2022

Defense Date 09/27/2022

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

Tag clinical research,collaboration,CRO,governance,OAI-PMH Harvest,outsourcing,outsourcing framework,outsourcing model,sponsor,trial,vested outsourcing

Format application/pdf (imt)

Language English

Contributor Electronically uploaded by the author (provenance)

Advisor Pire-Smerkanich, Nancy (committee chair), Mayorga, Arthur (committee member), Pacifici, Eunjoo (committee member), Richmond, Frances (committee member)

Creator Email kupsch@usc.edu,lkupsch@me.com

Permanent Link (DOI) https://doi.org/10.25549/usctheses-oUC112059662

Unique identifier UC112059662

Legacy Identifier etd-KupschLaur-11251

Document Type Dissertation

Format application/pdf (imt)

Rights Kupsch, Laura Beth

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Source 20221003-usctheses-batch-985 (batch), University of Southern California (contributing entity), University of Southern California Dissertations and Theses (collection)

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