Avoca Update: Managing Risk in Outsourced Clinical Trials

1. Avoca Update:
Managing Risk in
Outsourced
Clinical Trials
Partnerships in Clinical Trials Meeting

2. 2
Patricia Leuchten (Moderator)
CEO, The Avoca Group
Coleen Glessner
VP & Head of Clinical Trial Process & Quality
Pfizer
Jamie Macdonald
CEO, INC Research
Patrick Nealon
Senior Director Clinical Operations
Millennium the Takeda Oncology Company
Panel Members

3. 3
2013 Avoca Research: Overview
Objective of 2013 Research
Comprehensive assessment of the
way risk is managed in the
conduct of clinical studies.

4. 4
2013 Avoca Research: Overview
Questions Explored
● Risk-sharing models: What kinds of models are most often used? Under
what circumstances? What are the magnitudes of the incentives/
penalties? Have the incentives been successful? Is the success realized
mostly in time, cost, or quality? What have been the downsides?
● Risk assessment: How is it conducted? Are assessments just qualitative or
also quantitative? Has it been successful or not? In what ways?
● Risk-based management approaches: To what tasks have such
approaches been applied? Have the approaches used quantitative
modeling or have they been qualitative? Have they been successful? If so,
how is success realized? What have been the downsides? How is this work
viewed by regulators?

5. 5
2013 Avoca Research: Overview
234 Respondents
● Sponsors: 113 Respondents
╸ Approximately half in top 20 in terms of revenue
o 66% Pharma
o 26% Biotech
o 5% Device
o 3% Combination/Other
● Clinical Service Providers: 124 Respondents
╸ 60% in top 20 in terms of revenue
o 86% CROs
o 11% Niche
o 3% Laboratories

6. Risk Sharing
Sponsor and
Service Provider
Results

7. 7
Risk-sharing between Sponsors and
Providers
Types of Risk-sharing
● Provider bonuses for achieving milestones and targets
● Provider penalties for missing milestones and targets
● Guarantees of continued work/revenue stream in
exchange for provider commitments
● Provider stake in outcome of study
(e.g., company stock)

8. 8
Sponsors’ Experience with Risk-sharing
When providers
receive rewards
for performance,
most sponsors
report a mix of
positive and
negative
experiences
However, when
providers are
penalized,
experiences
have been
more negative.

9. 9
CROs’ Experience with Risk-sharing
And CROs
report similar
experiences:
Penalties
generally
lead to more
negative
experiences.
54% of sponsors and 58% of providers were most likely to have had
“primarily positive” experiences with guarantees of continued work/
revenue stream in exchange for provider commitments.

10. 10
Comments on Experiences
“These relationships require absolute clarity in roles and responsibilities and up-
front planning assumptions that we have not always had, which has caused
difficulties along the way.”
“The inclusion of provider bonuses and penalties has had a detrimental affect
on study team morale. OK when the target has been reached outright, but lots
of 'extra' negotiating when a negative outcome.”
Sponsors:

11. 11
Comments on Experiences
“Increased work/revenue stream in return for quality deliverables is a good
motivator. With bonuses and penalties a great deal of time can be wasted
attributing blame rather than focusing on timely high quality delivery.”
Providers:

12. Risk Assessment,
Risk Management,
and Risk-based
Monitoring

13. 13
Prevalence of Systematic, Formal Risk
Assessments
38%
18%
16%
14%
14%
For >75% of
outsourced
clinical trials
For 51% - 75% of
outsourced
clinical trials
For 25% - 50% of
outsourced
clinical trials
For 1% - 24% of
outsourced
clinical trials
Never
N=50
39%
19%
26%
13%
3%
N=31
Sponsors CROs
Most sponsors and clinical service providers reported that a
systematic risk assessment process was used for the majority
of their clinical trials, whether in-house or outsourced.

14. 14
N=40
Review by Regulatory Authorities
Have your approaches to risk assessment and
management been reviewed by any regulatory
authority?
73%
27% Positively
Neutrally
If "Yes", how were they viewed by the
regulatory authority?
N=11
Sponsors
N=34
80%
20%
Positively
Neutrally
N=10
CROs
25%
75%
Yes
No
29%
71%
Yes No
Majority report that approaches to risk assessment and
management are viewed favorably by Regulatory Authorities.

15. 15
N=50
Use of Risk-related information to
determine levels of CRO oversight
24%
22%
20%
14%
20%
For >75% of
clinical trials
For 51% - 75% of
clinical trials
For 25% - 50% of
clinical trials
For 1% - 24% of
clinical trials
Never
How often do your teams use risk-related information to determine the level
and/or type of sponsor oversight that you will employ for your CRO partners?
For over 50% of clinical trials, almost half (46%) of sponsor
respondents use risk-related information to determine level of
oversight

16. 16
8%
9%
75%
73%
40%
57%
70%
8%
9%
50%
43%
30%
8%
9%
10%
0% 20% 40% 60% 80% 100%
For >75%
For 51% - 75%
For 25% - 50%
For 1% - 24%
Never
Very satisfied Generally satisfied
Neither satisfied nor dissatisfied Generally dissatisfied
Very dissatisfied
How often do your teams use risk-related information to determine the level
and/or type of sponsor oversight that you will employ for your CRO partners? N
12
11
10
7
10
Sponsors who use risk information to determine oversight
levels tend to be more satisfied with CRO performance.
Overall Sponsor Satisfaction (by use of risk-related
information to determine levels of CRO oversight)

17. 17
What risks are assessed?
When a systematic
assessment is conducted,
the following risks are
typically formally assessed
(by more than half the
sample):
• Patient enrollment risks
• Vendor performance
risks
• Data quality risks
• Other timeline risks
• Site compliance risks
• Cost risks
• Clinical trial subject
safety risks
• Drug/device supply
related risks

18. 18
Are risk-based approaches leading to
greater efficiency and higher quality?
While not all are
seeing the more
efficient use of
resources
through risk
assessment and
management
approaches…
…most sponsors
ARE seeing
increased
quality, at least
sometimes.

19. 19
Are risk-based approaches leading to
greater efficiency and higher quality?
While not all
are seeing the
more efficient
use of resources
through risk
assessment and
management
approaches…
…most sponsors
ARE seeing
increased quality,
at least
sometimes.

20. 20
Satisfaction Rates of Specific Variables Related to Risk
Management
Sponsor respondents surveyed are,
on average, more satisfied with in-
house teams compared to CROs
and other service providers on a
number of points including:
• Proactive identification of
risks
• Communications regarding
risk-related trial information
• Frequency of review of risk-
related trial information.
Sponsor respondents rate CRO
performance, on average, lower
than CROs rate themselves.

21. 21
N=45
Prevalence of use of Risk-based Monitoring
18%
16%
4%
29%
33%
For >75% of
clinical trials
For 51% - 75%
of clinical
trials
For 25% - 50%
of clinical
trials
For 1% - 24% of
clinical trials
Never
How often do your project/program teams use a risk-based approach to the
monitoring of Investigative Sites for outsourced clinical trials?
18%
20%
15%
29%
18%
N=34
Sponsors CROs
Sponsors and CROs were divided in their reported use of
risk-based monitoring.

22. 22
Opportunities to Enhance Understanding
How would you rate your understanding of best practices in risk
assessment and management in clinical trials? (Sponsor Data)
38%
13%
9%
23%
54%
36%
31%
23%
45%
8%
10%
9%
0% 20% 40% 60% 80% 100%
Executive
Management
Middle
Management
Project
Management
Very strong understanding Good understanding
Fair understanding Poor understanding
N
13
39
11
While executives generally reported a strong understanding,
operational teams may benefit from more training.

24. Thank you!