H o l l y F e r n a n d e z L y n c h , J . D . , M . B i o e t h i c s E x e c u t i v e D i r e c t o r , P e t r i e - F l o m C e n t e r f o r H e a l t h L a w P o l i c y ,

B i o t e c h n o l o g y , a n d B i o e t h i c s , H a r v a r d L a w S c h o o l F a c u l t y , C e n t e r f o r B i o e t h i c s , H a r v a r d M e d i c a l S c h o o l

E m i l y L a r g e n t , J . D . , P h . D . , R . N .

R e s e a r c h A s s o c i a t e , P e t r i e - F l o m C e n t e r f o r H e a l t h L a w P o l i c y , B i o t e c h n o l o g y , a n d B i o e t h i c s , H a r v a r d L a w S c h o o l

D e c e m b e r 9 , 2 0 1 6

PAYING RESEARCH PARTICIPANTS: CONSIDERATIONS AT BOTH ENDS

OF THE SPECTRUM

Disclaimer This work was conducted with support from Harvard Catalyst, the Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award UL1 TR001102) and financial contributions from Harvard University and its affiliated academic healthcare centers. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centers, or the National Institutes of Health.

Recap: What Do We Know?

• Paying participants is common • US regulations focus on coercion

and undue influence • Confusion around those terms • Most attention to high payment

• Several different ways to conceptualize paying participants – what are we paying for?

Overview

• Assessing high payment • Assessing low payment • How to balance both ends of the

spectrum – what should we really worry about?

• Spoiler alert: Low payment is an ethical concern, too.

Concerns about high payment: COERCION

• Proposed definitions: B has no reasonable alternative but to accept

A’s proposal A threatens to make B worse off (i.e., physical,

psychological, or social harm) in order to obtain compliance

A threatens to violate B’s rights or not fulfill an obligation to B in order to obtain compliance AND B has no reasonable alternative

Concerns about high payment: COERCION

• Coercion requires a threat • Payment is an offer, not a threat • So, payment cannot coerce Coercion is possible in research, but not due to

payment

Concerns about high payment: UNDUE INFLUENCE

Distinct from mere inducement, which is not an ethical concern Doing something you would not do but for the

payment is not per se problematic Must be undue Proposed definitions: A makes B a “coercive offer” A offers B an excessive or improper reward A offers B an excessive reward that produces bad

judgment and entails risk of harm (inducing decision unreasonably against B’s interests)

Concerns about high payment: UNDUE INFLUENCE

Payment could cause undue influence But IRB review should generally protect

against it IRB risk/benefit determination occurs

independent of payment offers IRB approval means that participation is a

reasonable choice for the target population Doesn’t have to be best interests – just not

unreasonably against interests NB: Concern about payment may be proxy for concern about risk-

benefit ratio of study

Concerns about high payment: UNDUE INFLUENCE

Caveat: IRB review is not complete protection Reviewing for target population as a whole,

rather than for individuals Participation might still be unreasonable for

certain individuals: some characteristic that they are aware of that the IRB didn’t or couldn’t consider that makes participation an unreasonable choice

Concerns about high payment: UNDUE INFLUENCE

Distinguishing unreasonable v. rational but unfortunate choices?

Protect few by limiting payment for all? Not necessarily a “safe” choice… And no clear threshold applicable for all

participants

Concerns about high payment: DECEPTIVE PARTICIPANTS

High payment may cause subjects to lie or conceal info that might disqualify them from enrollment Might be unduly influenced Might be damaging to scientific integrity/value of

the study Is limiting payment the only solution? Is deception more likely in certain types of studies?

Concerns about low payment: RECRUITMENT ISSUES

Low recruitment is an ethical problem Assuming research is important and/or any

subjects are already exposed to risks/burdens Higher payment may: Enroll more diverse participant population Increase likelihood of study completion

(enrollment and continuation) Although higher payment won’t be a panacea Other reasons for not participating Budget issues

Concerns about low payment: EXPLOITATION

Exploitation = taking unfair advantage One party insufficiently benefits or assumes

unfair share of burdens relative to other party May be consensual and mutually beneficial Not a “deal breaker” – but should be avoided

Takeaways Offers of payment are never coercive IRB approval protects most participants against undue

influence BUT not all Choice 1: Should we level-down, just in case?

High payment may lead to deception in some cases Choice 2: Is reducing payment the only lever?

Payment can help with recruitment Not always, or completely – so does this outweigh concerns

about undue inducement or deception? Low payment risks exploitation of participants who have few

alternatives Is exploitation an equivalent concern to undue inducement?

Balance concern about high and low payment by asking what is FAIR

New Approach: Fair Payment

Possible considerations: Risks, burdens, and benefits of research Opportunity costs/alternatives Social value Non-research contexts – relevant? Others?

Thank You

Case Study

2016: 6 subjects hospitalized—one pronounced brain-dead—after a “serious accident” in French Phase I trial

BIA 10-2474, novel compound designed to treat “anxiety and motor disorders associated with Parkinson’s disease, and chronic pain in people with cancer and other conditions”

Each participant paid €1,900 (about $2,060) “including travel expenses; in return, they agreed to stay at [the testing] facility in Rennes [France] for 2 weeks, swallow a drug on 10 consecutive days, undergo extensive medical tests, and provide at least 40 blood samples”

Was the payment unduly influential/ethically problematic?