December 9, 2016 This symposium brought together a variety of experts to discuss key ethical and legal questions regarding offers of payment to research participants. Panels covered: - Why payment is offered to research participants - Regulatory parameters governing payment - Whether payment to research participants should be considered exceptional, compared to payment in other contexts - How offers of payment affect participants - How to define coercion and undue influence with regard to paying research participants - Which factors should be considered when evaluating proposed payments - The problem of low payment This event was free and open to the public. This event was part of the collaboration between the Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics at Harvard Law School and the Regulatory Foundations, Ethics, and Law Program of Harvard Catalyst | The Harvard Clinical and Translational Science Center at Harvard Medical School. Cosponsored by the MRCT Center of Brigham and Women's Hospital and Harvard. Learn more on our website: http://petrieflom.law.harvard.edu/events/details/paying-research-participants

1. What do the data show about the
influence of payment on participant
perceptions and behaviors?
Scott D. Halpern, M.D., Ph.D.
Associate Professor of Medicine, Epidemiology, and Medical Ethics & Health Policy
Director, Fostering Improvement in End-of-Life Decision Science (FIELDS) program
Deputy Director, Center for Health Incentives and Behavioral Economics (CHIBE)

2. 1. Payment may be an undue inducement
2. Payment may be an unjust inducement
3. Payment may dissuade participant disclosure of
contraindications
Conceptually coherent concerns that rest on
empirically testable facts
Halpern SD. Amer J Med Sci 2011

3. Experimental survey studies refute these
concerns (and suggest ethical virtues of payment)
Centers for Disease Control and Prevention. Cigarette Smoking Among Adults and
Trends in Smoking Cessation -- United States, 2008. MMWR 2009;58(44):1227-32.

4. 142 hypertensive patients
recruited from clinics
6 failed quiz126 Patients
10 refused to participate
due to time
Trial description & knowledge
assessment
Vary payment offered ($100, $1000, $2000)
Vary risk (10%, 20%, 30% chance of side effects, e.g. vomitting)
Assess participation across 9 trials administered in random sequence
Halpern SD, et al. Arch Intern Med 2004; 164:801-3.

5. Model of Undue Inducement
Risk
% Willing to
Participate
$0
$$$
$$$
Main Effect of Payment = Rational Tradeoff
Payment x Risk Interaction = “Blunted” risk evaluation
(i.e., an undue inducement)

6. Incentives for RCTs: Undue inducement?
Payment:
p = 0.001
Payment-by-risk interaction:
p = 0.12
Halpern SD, et al. Arch Intern Med 2004; 164:801-3.

7. Undue inducement (kidneys)?
Payment (family):
p = 0.31
Payment (waitlist):
p < 0.001
Payment-by-risk interaction:
p = 0.87
Halpern SD, et al. Ann Intern Med 2010; 152:358-65.

8. Model of Unjust Inducement
Payment offered
% Willing to
Participate
Low-income
High-income
Payment x income interaction → lower-
income patients preferentially influenced
by money
Low-income
$0

9. Income:
p = 0.70
Payment-by-income
interaction:
p = 0.09
Incentives for RCTs: Unjust inducement?
Halpern SD, et al. Arch Intern Med 2004; 164:801-3.

10. Unjust inducement (kidneys)?
Income:
p = 0.016
Payment-by-income interaction:
p = 0.49
Halpern SD, et al. Ann Intern Med 2010; 152:358-65.

11. Neglecting to
inform about
adverse effects?
Bentley JP, Thacker PG. J Med Ethics 2004; 30: 293-8.

12.  Are higher payments associated with different
judgments of riskiness?
 Are higher payments associated with the amount of
time/effort spent seeking info about risk?
stimulation or (2) blood draws; and offered different
payments ($25, $100, $1000)

13. Riskiness ratings
$25: 2 (0 – 4)
$1000: 3 (1 – 5)
p < 0.05
Cryder et al. Soc Sci Med 2010; 70: 455-64

14. Higher incentives are associated with greater
information seeking
Cryder et al. Soc Sci Med 2010; 70: 455-64

15. R01 CA197332
7/01/15 – 6/30/20
15000
1st consent: Study about attitudes
toward research
Demographics; Economic Well-Being; Research attitudes questionnaire (all patients)
Randomization
Randomization
Patients identified as eligible for RTOG
1308. Patients shown video about trial.
Legend
Primary outcome
Secondary outcomes
Study processes and
parent RCT outcomes
Clinical Outcomes
Assess risk perception and therapeutic misconception
Decision to sign 2nd consent form to enroll in parent RCT (RTOG 1308)
Review (but do not sign) 2nd consent Time spent reviewing 2nd consent form
Assess understanding of basic trial elements (all participants) and perceptions of
coercion ($400 and $1200 arms)
Debriefing about incentives study and payment equalization
IMRTPBT
$1,200$400$0
Semi-structured interviews of patients who do not sign 2nd consent
(selected equally among 3 incentive arms) [HOLD]

16. Outcomes & Recruitment Goals
• Primary Outcome:
– Rate of consent to participate in the parent RCT
• Secondary Outcomes:
– Patients’ research attitudes, motivations to participate or not, attention to
study details and risks, perceptions of research risks, therapeutic
misconceptions, understanding of trial design, and health care system
distrust.
• Target n= 576 – powered to rule out undue/unjust inducements
• 44 months of recruitment
• 3 incentive amounts: $0, 400, 1,200