Challenges and opportunities in clinical trial recruitment in an age of personalized medicine.

1. Patient Recruitment
Brief overview by InnoAction Advisory Services
(www.innoaction.co)

2. • The clinical trial recruitment market is estimated to be between $1.2-$1.8B
• Since 2000, the number of studies being conducted has gone up from ~5K to nearly
~150K, globally, increasing complexity, as well as site & patient recruitment demand
• At the same time regulatory requirements have increased the size of trials, requiring
on average 3.5-4K patients per trial (and increasing shift towards PMx)
• Patient recruitment remains the biggest factor in enrollment and trial delays – now
taking an average of ~8 years from the start of a trial to approval
• Patient recruitment costs average at ~6% of trial costs, going up to 10%, while
doubling the timelines for Phase II-IV trials to meet desired enrollment levels
• Further, 11% of sites end up enrolling no patients, while an additional 37% of sites
chronically under enroll patients for trials
• Little has changed by way of operating model or technology impact to create step-
wise change in the patient recruitment model over the decades
Confidential – Do not copy or distribute | 1
Executive Summary

3. • On average, less than 5% of patients in a therapeutic category are aware about
clinical trials, and even fewer raise their hand to participate in a trial
• Of patients that are identified, 2-3% actually make it past screening, into randomized
selection, and trial completion
• However, of those that do participate in trials, most have a positive experience, and
~90% would participate in trials again
• There is a significant opportunity take a patient-centric approach, combined with
technology, data, and analytics to grow the size of the patient recruitment pie
• However, this will require a rethink to traditional processes and operating models
– Leveraging data and analytics for practical protocol design
– Early input from key investigators on protocol design
– Use of technology and data to identify patient concentrations by geography
– Selecting appropriate sites based on patient availability
– Working closely with sites to attract and maintain patients throughout the trials
– Patient-centric design e.g. using local infrastructure & mobile/ remote tools
Confidential – Do not copy or distribute | 2
Executive Summary

4. There is significant opportunity to redefine patient recruitment
Patient Recruitment Challenges Market Opportunity
Very low awareness of trials by patients Digital awareness & education
High fear & trust issues by patients Medical education
Low patient convenience & access Patient-centric design
Low awareness of trials by physicians Targeted physician education
Complex (exclusionary) trial protocols Protocol feasibility assessment & investigator feedback
Poor use of data & automation Digital, mobile, & big data investments
Inefficient trial/ recruitment processes Redesigning some processes
Privacy rules and concerns Allowing for dynamic patient consent

5. Industry will need to enhance its connectivity & engagement assets
to drive more efficient & patient-centered trials
Portal a. Develop patient consent-based portal
b. Allow patients ability to upload personal data
c. Create linkage between providers-patients
d. Provide effective education & communication
e. Allow for patient & provider referrals
f. Provide visualization & planning tools for
protocol feasibility & patient recruitment
g. Enable researchers to conduct privacy/
consent-based searches
h. Enable near-patient collection & virtualization
of trials (smart phones, devices, data mgmt.)
i. Link Lab, AP, Gx & external data sources over
time for precision medicine services
j. Create deeper engagement (incentives,
gamification, social networks …)

6. Industry will carefully have to navigate privacy rules & regulations
as well as physician and patient concerns to establish trust
Key Privacy Use Cases Regulatory Feasibility Considerations
Link to general clinical trials site on
portal  Follow communication SOP
Link to specific clinical trial based on
patient lab values on portal  Allowed under HIPAA research provision
Outreach to health volunteers  Follow communication SOP
Outreach to patients who fit trial criteria  Allowed under HIPAA research provision
Sharing identifiable patient & trial info
with patient’s physician  Only data for physician’s patients
Sharing identifiable patient info with
third party  Requires patient consent
Outreach to patient’s physician within
network  No restrictions
Sharing physician information with
investigators (for trial recruitment)  Follow communication SOP
Sharing de-identified patient info with
third party  Compliance with de-identification SOP

7. The monetization model will evolve as the solution matures,
leveraging various potential revenue streams
Base License
Fee
Patient ID +
Recruitment Fee
Value-added
Services Fee
• Traditional software/ data
licensing fees
• Annual license based on
users/ seats
• Per patient fee for identified
patients that meet criteria
• Per patient fee for patients
recruited into trial
• Project fees for using “near
patient” infrastructure
• Potential “freemium” model
for patients and providers
• Potential advertising
revenues on portal(s)

8. • While clinical trial protocol design and recruitment services are highly inefficient and
cost sponsors billions of dollars, change to traditional models has been very slow
• Historically, few data and technology driven players have been successful in shifting
the clinical trials paradigm
– Lack of appropriate and statistically representative data
– Inability to create patient and provider scale on their platforms
– Long cycle times selling to Pharma & CRO’s
– Lack of pharma R&D and healthcare knowledge
• One size does not fit all – the solution(s) have to be carefully designed and curated
by disease area, and should align with Pharma R&D spend
• No one organization can “build” the entire solution – partnerships are a critical
success factor e.g. data, technology, advocacy groups, media partners, etc.
• Traditional top-down models for solutions development have generally failed
– Iterative approaches that use human-centered design & agile development can de-risk
– Patient & provider-centricity should sit at the heart of the approach
Confidential – Do not copy or distribute | 7
Risks & Challenges

9. Industry overview & challenges
Confidential – Do not copy or distribute | 8

10. A 2012 Tuft’s estimate put the US patient recruitment market at $1B

11. 37% of sites under-enroll, while 11% don’t enroll at all

12. Recruitment is the biggest contributor to enrollment & trial delays

13. Lack of awareness is a significant issue in patient recruitment
Source: Harris Interactive, Centerwatch
16%
84%
Unaware or
unsure that trials
was an option
Aware but
unwilling
Top 5 Reasons Physicians Don’t Refer Patients
to Trials
n = 6,000
Reasons patients did not participate in trials
Of these, 75%
would have enrolled
had they known it
was possible

14. Patient recruitment can account for up to 10% of a trial’s budget,
while comprising a significant amount of economic risk

15. Reasons why patients don’t participate in clinical trial (based on
physician survey)
(8*, 0%)
(6, 2%) (7, 1%)
(1, 44%)
(4, 18%)
(3, 10%)
(2, 17%)
(5, 8%)
1. Lack of knowledge on where to look for information on
clinical trials
2. Lack of knowledge about what clinical trials actually
are (e.g., objectives and processes)
3. Lack of trust in the purpose of clinical trials
4. Fear of clinical trial processes, potential adverse
effects, or receiving a placebo
5. Lack of patient referrals from physicians
6. Extensive inclusion / exclusion criteria that prohibit
many patients from qualifying
7. Barriers to accessing clinical trials
8. Other*
 A total of 169 respondents chose one of the above as
the most important reason that so few patients choose
clinical trials as a treatment option
 The following three accounted for 79% of the total
responses
 Lack of knowledge on where to look for information on
clinical trials (74)
 Fear of clinical trial processes, potential adverse effects,
or receiving a placebo (31)
 Lack of knowledge of what clinical trials actually are (e.g.,
objectives and processes) (28)
* “Other” includes lack of motivation, patient demographics, and insurance issues
Total Number of Respondents 169

16. Appendix (additional industry/ market insights)
Confidential – Do not copy or distribute | 15

17. Over the last 13 years, the number of registered studies has grown
by 25x, with increasing complexity of patient recruitment

18. While US & EU still account for ~70% of global trials, other regions
continue to make headway, especially East Asia

19. High level study management process
PI reviews
protocol
synopsis
If PI wishes to
proceed,
confidentiality
agreement
signed
Full protocol with
site
questionnaires
sent to site
Questionnaires
returned &
reviewed, site
visit conducted
Final docs
submitted – IRB
approval,
consent forms
Contract
negotiation and
signing
Patient
enrollment
preparations
Enrollment
initiated
Enrollment
completed
Data analysis &
reporting
Study lock-up

20. Site challenges in patient recruitment
Develop IIP
and CSA
Site Selection
Recruitment
Outreach/
Advertising
Patient
Follow-Up
Recruitment
Monitoring
• Site selection strategy
and patient recruitment
strategies not coupled
• Site evaluation and
selection process not
driven by a
standardized set of
performance metrics
• Site assessment
evaluation only
focused on recruitment
#’s and does not
include assessment of
other factors such as
geographic location or
local demographics
• No clear accountability
or decision rights for
patient recruitment
strategy & effectiveness
• Lack of standardized
processes for
development of patient
recruitment strategy
• Minimal enforcement
and encouragement of
study teams to leverage
in-house patient
recruitment expertise
• Lack of metrics and
data used to drive
outreach/ advertising
strategy
Key Factors Affecting Recruitment
Key Issues in Patient Recruitment Process
• Lack of metrics defined
to capture effectiveness
of recruitment practices
• Lack of standardized
metrics and process to
track patient follow-up
for all sites

21. Site challenges in patient recruitment
Unfavorable perception of industry
Competition for limited # patients
Lack of awareness by patients
Lack of awareness & support by
physicians
Competition for limited # sites
Practical barriers facing patients
Complex protocols
ExplanationIndustry Challenges
• 7% of public believes Rx companies care about public good
• 14% of Americans believe drug companies “honest” (similar
ratings for tobacco, oil and used car sales)
Source: Decision Resources, ResearchAmerica!, Harris Interactive; Tufts CSDD
• Even in TA’s with more “involved” patient base (e.g., breast
cancer in US), inadequate number of patients to fully assess
all drugs in pipeline (over 750 breast cancer trials currently
recruiting, over 160 in NY alone)
• Nearly 85% of patients in a survey stated they were
unaware that trials were an option
• 31% of physicians surveyed did not refer patients to trials
due to lack of information
• Also report unwillingness to “lose control” of patient care,
concerns of admin burdens, concerns of patient reactions to
referrals
• From 2001-2005, only 8,600 new investigators compared to
over 35,000 new studies
• Language barriers, transportation issues, family obligations,
financial barriers all cited as reasons why qualified patients do
not enroll
• From 2002-2006, mean number of inclusion criteria rose
from 10 to 26; for exclusion criteria from 21 to 23

22. Key insights & feedback from sponsors

23. Top mentions of clinical trial recruitment services companies

24. Quintiles patient networks rank high with sponsors

25. Social and mobile trends are highly favorable in the healthcare
industry and can drive innovation in clinical research

26. Myths about social and mobile solutions in healthcare …

27. Top reasons consumers chose to participate in clinical research

28. Most people who participate in studies would do so again …

29. Research volunteers by phase of research

30. Study participant experiences

31. Illustrative trial process & timelines
1. Limited marketing expertise
and planning insight put sites
at risk of failure
2. Challenges in patient recruiting
require greater investment in more
personalized emerging channels

32. Illustrative benefits of improving trial process & timelines