Paying research participantsPaying research participants

Ayodele S. Jegede, Ayodele S. Jegede, PhD, MHSc.PhD, MHSc.

West African Bioethics Training ProgramWest African Bioethics Training Program

OutlineOutline

ObjectiveObjective Learning outcomeLearning outcome Case studyCase study Payment questionPayment question Concerns Concerns Payment modelsPayment models Case study Case study

Objectives Objectives

To orientate participants to ethical challenges of To orientate participants to ethical challenges of paying research participantspaying research participants

To discus the role of IRB in considering To discus the role of IRB in considering payment for research participants in protocol payment for research participants in protocol reviewreview

Learning OutcomesLearning Outcomes

Participants understand the ethical issues Participants understand the ethical issues involved in paying research participantsinvolved in paying research participants

Participants understand the role expectation of Participants understand the role expectation of IRB in protocol approval regarding payment for IRB in protocol approval regarding payment for research participantsresearch participants

How common is the practice of paying How common is the practice of paying research participants?research participants?

Advertisements in newspapers, the internet, Advertisements in newspapers, the internet, and in hallwaysand in hallways

Most research organizations and academic Most research organizations and academic medical centers pay at least some participants medical centers pay at least some participants (24- 80%*)(24- 80%*)

Paying studies range from short term Paying studies range from short term physiologic studies to long term phase 3 clinical physiologic studies to long term phase 3 clinical trialstrials

*Dickert et al. Annals 2002*Dickert et al. Annals 2002

Table 1. Types of Paying Studies and Types of Subjects

Studies By Studies By Type Of Type Of Subject Subject EnrolledEnrolled Type of Study Type of Study

TotalTotal   Phase Phase

11Phase Phase

22Phase Phase

33Phase Phase

44PhysiologPhysiolog

icicBehavioraBehaviora

ll OtherOther

Studies That Studies That Enrolled Only Enrolled Only Healthy Healthy Subjects Subjects

1616 55 11aa 11bb 3737 3535 1818 113 (24%)113 (24%)

Studies That Studies That Enrolled Only Enrolled Only Patient-Patient-SubjectsSubjects

1010 5252 9797 3535 2121 3939 3232 286 (61%)286 (61%)

Studies That Studies That Enrolled Both Enrolled Both Types Of Types Of Subjects Subjects

00 11 22cc 00 3030 88 2727 68 (15%)68 (15%)

Total Total 26 26 (6%)(6%)

58 58 (12%)(12%)

100 100 (21%)(21%)

36 36 (8%)(8%)

88 (19%)88 (19%) 82 82 (18%)(18%)

77 77 (16%)(16%)

467 467 (100%)(100%)a This phase 3 study was testing a preventive vaccine in uninfected persons

b This phase 4 study was testing a fiber supplement in healthy subjectsc One of these studies was evaluating an intervention to reduce heterosexual transmission of herpes simplex and enrolled both the healthy uninfected partner and the patient with herpes. The other was evaluating an intervention in ADHD and enrolled some healthy children as controls.

Grady et al. Cont. Clinical Trials 2005

Payment in the U.S.Payment in the U.S.

. . Significant variation within and between institutions in Significant variation within and between institutions in

amount of payment for particular procedures, inpatient amount of payment for particular procedures, inpatient days, outpatient visits.days, outpatient visits. Rarely itemized.Rarely itemized. e.g. MRI with contrast 0-$25-$150e.g. MRI with contrast 0-$25-$150

Wide variation in multi-site studies.Wide variation in multi-site studies. Up to $840 difference for the same study.Up to $840 difference for the same study.

Grady et al. Grady et al. Cont. Clinical TrialsCont. Clinical Trials 2005 2005

Payment in Nigeria – no data Payment in Nigeria – no data

Why paying research Why paying research participants? [1]participants? [1] Facilitates RecruitmentFacilitates Recruitment

Helps make participation a revenue-neutral Helps make participation a revenue-neutral experienceexperience

Compensation for time and contributionCompensation for time and contribution

Incentive to overcome barriersIncentive to overcome barriers

Why paying research Why paying research participants? [2]participants? [2]

Money enables participation and can be a sign Money enables participation and can be a sign of respectof respect

““It is reasonable to pay someone for their work. It is reasonable to pay someone for their work. If you gain, If you gain, how much are you gaining? how much are you gaining? How much time does it take? How much time does it take? Time is money. What is the value of time for the Time is money. What is the value of time for the

person in the study?”person in the study?”

To what extent does payment To what extent does payment facilitate recruitment?facilitate recruitment?

Data on survey response ratesData on survey response rates Small amounts of money (e.g. $5) increase Small amounts of money (e.g. $5) increase

response ratesresponse rates Asch et al. Asch et al. Med CareMed Care 1998 1998 Church Church Public Opinion QPublic Opinion Q 1993 1993 Doody et al. Doody et al. Am J EpidemiologyAm J Epidemiology 2003 2003 Ulrich et al. Ulrich et al. Nursing ResearchNursing Research 2005 2005

Data on hypothetical willingness to participateData on hypothetical willingness to participate Money increases willingness to participateMoney increases willingness to participate Halpern et al Halpern et al Arch Int. MedArch Int. Med 2004 2004 Bentley and Thacker Bentley and Thacker J Med EthicsJ Med Ethics 2004 2004

Does money enhance recruitment of Does money enhance recruitment of healthy volunteers?healthy volunteers?

MotivationsMotivations MoneyMoney

>90% of those surveyed said financial compensation was >90% of those surveyed said financial compensation was main motivation for participationmain motivation for participation

e.g. Bigorra and Banos 1990; vanGlederen et al 1993; Hassar et e.g. Bigorra and Banos 1990; vanGlederen et al 1993; Hassar et al. 1977al. 1977

Healthy volunteers also have other motives, Healthy volunteers also have other motives, including curiosity, altruism, sensation seeking, including curiosity, altruism, sensation seeking, knowledge, etc.knowledge, etc.

Does money enhance recruitment of Does money enhance recruitment of patient-subjects for clinical research?patient-subjects for clinical research?

Motivations:Motivations: Hope of personal therapeutic benefitHope of personal therapeutic benefit

Attention by/trust of physicianAttention by/trust of physician

KnowledgeKnowledge

AltruismAltruism

Access to careAccess to care

Why not pay research participants?Why not pay research participants?Ethical concernsEthical concerns

CommodificationCommodification

Skewed sampleSkewed sample

CoercionCoercion

Undue inducementUndue inducement

Skewed sampleSkewed sample

Concern: Money more attractive to lower income Concern: Money more attractive to lower income individualsindividuals

ResultsResults a skewed sample a skewed sample disproportionate burden on the socioeconomically disproportionate burden on the socioeconomically

disadvantageddisadvantaged

DATA???DATA??? Who participates in research?Who participates in research? To what extent are subjects in paid studies different?To what extent are subjects in paid studies different?

Coercion or undue inducement?Coercion or undue inducement?

US Code of Federal Regulations require that informed US Code of Federal Regulations require that informed consent be obtained “under circumstances…that consent be obtained “under circumstances…that minimize the possibility of coercion or undue minimize the possibility of coercion or undue influence”influence”

21CFR.5021CFR.50 45CFR.4645CFR.46

Nigeria National Code of EthicsNigeria National Code of Ethics Social and scientific valueSocial and scientific value Scientific validityScientific validity Fair selection of research participantsFair selection of research participants Risks reductionRisks reduction Peer reviewPeer review Informed consentInformed consent

Pages 37 - 42Pages 37 - 42

Can money be coercive?Can money be coercive?

Coercion is a threat of physical, psychological, Coercion is a threat of physical, psychological, or social harm in order to compel someone to or social harm in order to compel someone to do something, such as participate in research.do something, such as participate in research.

Money is an Money is an offeroffer or an or an opportunityopportunity, and not a , and not a threat of harmthreat of harm..

CoercionCoercion

Used in many different circumstances:Used in many different circumstances: ExpressiveExpressive Non expressiveNon expressive

Often misunderstood as simply meaning Often misunderstood as simply meaning involuntary or under strong influence.involuntary or under strong influence.

How Common is Coercion?How Common is Coercion?

Coercion is rare in researchCoercion is rare in research

InmateInmate whose care and treatment might be whose care and treatment might be compromised for refusing participation.compromised for refusing participation.

Patient may participate in a study run by his or her Patient may participate in a study run by his or her physician because of the fear or reality that care is physician because of the fear or reality that care is contingent on participation.contingent on participation.

Is payment coercive?Is payment coercive?

What is undue inducement? What is undue inducement? (influence)(influence)

An offer one cannot refuseAn offer one cannot refuse

A controlling and irresistible influenceA controlling and irresistible influence

Strong enough to compel someone to Strong enough to compel someone to participate against their interestsparticipate against their interests

Why worry about undue inducement in Why worry about undue inducement in research?research?

An inducement is undue if it is “…so attractive An inducement is undue if it is “…so attractive [that it] can blind prospective subjects to [that it] can blind prospective subjects to potential risks or impair their ability to exercise potential risks or impair their ability to exercise proper judgment” proper judgment”

[or] “prompt them to lie or conceal information [or] “prompt them to lie or conceal information that would disqualify them from enrolling--or that would disqualify them from enrolling--or continuing--in research”continuing--in research”

Official IRB Guidebook OHRPOfficial IRB Guidebook OHRP

Do financial incentives blind prospective Do financial incentives blind prospective subjects to research risks?subjects to research risks?

If risks are judged acceptable – is this a misplaced If risks are judged acceptable – is this a misplaced worry?worry?

Will subjects be asked to accept the same risks Will subjects be asked to accept the same risks without financial incentive?without financial incentive?

Understanding of risks can be evaluated during the Understanding of risks can be evaluated during the process of informed consentprocess of informed consent

Limited data suggest payment does not obscure Limited data suggest payment does not obscure risk perception risk perception (eg. Bentley and Thacker 2004)(eg. Bentley and Thacker 2004)

Do financial incentives impair Do financial incentives impair judgment?judgment?

VoluntaryVoluntary decisions are motivated by various decisions are motivated by various factors, often including but not limited to moneyfactors, often including but not limited to money

Money is one factor in research decisions of Money is one factor in research decisions of some participantssome participants

Most participants Most participants (75%)(75%) in one study thought in one study thought $500 could impair the judgment of others, but $500 could impair the judgment of others, but fewer fewer (20%)(20%) that it would impair their own that it would impair their own judgment.judgment.

Casarett et al. Casarett et al. J Gen Intern. MedJ Gen Intern. Med. 2002. 2002

Should bother about undue Should bother about undue Inducement?Inducement?

An excessively An excessively attractiveattractive offer that leads offer that leads people to exercise people to exercise poor judgmentpoor judgment about about research participation that involves a research participation that involves a risk of risk of serious harmserious harm..

IRBs should not approve studies that IRBs should not approve studies that expose subjects to risk of serious harmexpose subjects to risk of serious harm

Payment cannot be undue inducement in an Payment cannot be undue inducement in an appropriately approved studyappropriately approved studyEmanuel, Emanuel, J Law Med EthicsJ Law Med Ethics. 2004.. 2004.

Undue InducementUndue Inducement

Concern about undue inducement Concern about undue inducement misdirected in a study with little risk. misdirected in a study with little risk.

Concerns about payment obviating Concerns about payment obviating voluntariness are counter-intuitive.voluntariness are counter-intuitive.

Concerns about problems with consent Concerns about problems with consent argue for improving the consent process.argue for improving the consent process.

Emanuel, Emanuel, J Law Med EthicsJ Law Med Ethics. 2004. 2004

Undue inducementUndue inducement

““I’ll know it when I see it”I’ll know it when I see it” Decisions left to Decisions left to

investigators and IRBsinvestigators and IRBs Caution at the ends of Caution at the ends of

the risk spectrum or in the risk spectrum or in settings where subjects settings where subjects might have values that might have values that conflict with the conflict with the researchresearch..

CIOMS International Ethical GuidelinesCIOMS International Ethical Guidelines

Subjects may be paid for inconvenience and time Subjects may be paid for inconvenience and time spent, and should be reimbursed for expenses spent, and should be reimbursed for expenses incurred, in connection with their participation in incurred, in connection with their participation in research; they may also receive free medical services. research; they may also receive free medical services. However, the payments should not be so large or the However, the payments should not be so large or the medical services so extensive as to induce medical services so extensive as to induce prospective subjects to consent to participate in the prospective subjects to consent to participate in the research against their better judgment ("undue research against their better judgment ("undue inducement").inducement").

Models for paying research Models for paying research participantsparticipants

Market modelMarket model

Wage payment modelWage payment model

Reimbursement modelReimbursement model

Appreciation modelAppreciation model

Models of paymentModels of payment

MarketMarket Wage PaymentWage Payment ReimbursementReimbursement

JustificationJustification Incentives to Incentives to facilitate facilitate recruitmentrecruitment

Compensation Compensation for time, effort, for time, effort, uncomfortable uncomfortable proceduresprocedures

Participation Participation should be revenue should be revenue neutralneutral

ApproachApproach Escalate Escalate payment to payment to meet meet recruitment recruitment

StandardizedStandardized

wage-like wage-like paymentspayments

Reimbursement of Reimbursement of out-of-pocket out-of-pocket expensesexpenses

Dickert, N and Grady, C. (1999) NEJM 341(3):198-203

Wage Payment ModelWage Payment Model

Participation in research requires little skill but Participation in research requires little skill but takes time, effort, and endurance takes time, effort, and endurance

Payment should be based on a wage scale Payment should be based on a wage scale similar to other unskilled jobssimilar to other unskilled jobs

Pay a standardized hourly “wage”, perhaps Pay a standardized hourly “wage”, perhaps augmented by pay for particularly augmented by pay for particularly uncomfortable procedures or added uncomfortable procedures or added inconvenienceinconvenience

Advantages of Wage PaymentAdvantages of Wage Payment

Greatly reduces the potential for undue Greatly reduces the potential for undue inducementinducement

Provides valuable standardization across Provides valuable standardization across studiesstudies

Adheres to the principle of justice by paying Adheres to the principle of justice by paying similar individuals similar amountssimilar individuals similar amounts

Does/should who you are paying Does/should who you are paying matter?matter?

Patient subjects Patient subjects

ChildrenChildren

Payment to research subjectsPayment to research subjects

Common perception- Only healthy subjects in Common perception- Only healthy subjects in research are paid, patient-subjects are notresearch are paid, patient-subjects are not

Why might patient subjects be viewed Why might patient subjects be viewed differently?differently? They may benefit from the researchThey may benefit from the research They are especially vulnerableThey are especially vulnerable

Patient-Subjects and Healthy Patient-Subjects and Healthy SubjectsSubjects

These common perceptions appear not to be true:These common perceptions appear not to be true: 75% of paying protocols included ‘patient-subjects’ 75% of paying protocols included ‘patient-subjects’

and paid all or some of themand paid all or some of them 64% of those studies offered a prospect of 64% of those studies offered a prospect of

therapeutic benefit to the patient-subjectstherapeutic benefit to the patient-subjects And, patient subjects are often asked to participate And, patient subjects are often asked to participate

in research or research procedures that offer no in research or research procedures that offer no prospect of benefitprospect of benefit

Grady et al. Grady et al. Cont. Clinical TrialsCont. Clinical Trials 2005 2005

Are patient-subjects more vulnerable?Are patient-subjects more vulnerable?

Special vulnerability of patientsSpecial vulnerability of patients ““Therapeutic misconception”Therapeutic misconception”

Payment could reduce or eliminate itPayment could reduce or eliminate it

Power differential Power differential Payment could make it easier to refusePayment could make it easier to refuse

Benatar 2001Benatar 2001

Need dataNeed data

Patient subjectsPatient subjects

For studies with a prospect of benefit, For studies with a prospect of benefit, payment may be unnecessary as an payment may be unnecessary as an incentive; incentive; but it does not follow that but it does not follow that payment is unethical.payment is unethical.

In contrast, In contrast, it may be unfair not to it may be unfair not to compensate or reimburse all subjects for compensate or reimburse all subjects for similar contributions or expensessimilar contributions or expenses

ChildrenChildren

Worry: Children do not provide their own consent. Worry: Children do not provide their own consent. Money could sway parental decision making.Money could sway parental decision making.

Yet, research can involve cost and inconvenience to Yet, research can involve cost and inconvenience to parents. parents.

And, risk to children in research is carefully evaluated And, risk to children in research is carefully evaluated and limited.and limited.

Should children and/or their parents receive Should children and/or their parents receive money or other payment as reimbursement, money or other payment as reimbursement, compensation, appreciation, or incentive??compensation, appreciation, or incentive??

ChildrenChildren

Some support for at least reimbursing Some support for at least reimbursing expenses of parentsexpenses of parents

Some argue compensation for contribution Some argue compensation for contribution should go to the children should go to the children

Child’s age mattersChild’s age matters

Need more dataNeed more data

Forms of PaymentForms of Payment

Payment may come in several forms:Payment may come in several forms:

MoneyMoney GiftsGifts Free careFree care Travel vouchersTravel vouchers Gift certificatesGift certificates

Determinants of Payment DecisionDeterminants of Payment Decision

The nature of the study, including study risks The nature of the study, including study risks and budgetand budget

The nature of participant contributions and The nature of participant contributions and vulnerabilitiesvulnerabilities

Institutional or organizational guidelinesInstitutional or organizational guidelines

Local societal and cultural normsLocal societal and cultural norms

Practical considerationsPractical considerations

Proposal submitted to the IRB should Proposal submitted to the IRB should describe rationale for payment, describe rationale for payment, how the mount was calculated, how the mount was calculated, how payment will be madehow payment will be made when payment will be made.when payment will be made.

NoteNote

IRBs do not consider payment a benefit to IRBs do not consider payment a benefit to offset research risks when deciding to offset research risks when deciding to approve a studyapprove a study

Issues for further Issues for further discussiondiscussion How does payment affect recruitment?How does payment affect recruitment? What trade-offs do participants make?What trade-offs do participants make? To what extent do people participate in studies To what extent do people participate in studies

they find objectionable or against their they find objectionable or against their interests?interests?

What are and what determines the What are and what determines the sociodemographics of research participants?sociodemographics of research participants?

Case 1Case 1

Phase 2 study of a new anti-anxiety drug for Phase 2 study of a new anti-anxiety drug for those with high levels of stress on a validated those with high levels of stress on a validated screening instrument, no current anti-anxiety screening instrument, no current anti-anxiety drugs, and no significant medical problems. drugs, and no significant medical problems.

Involves several blood draws, physical exams, Involves several blood draws, physical exams, and hour-long interviews over the course of six and hour-long interviews over the course of six months. months.

Participants will be paid N1000 on completion Participants will be paid N1000 on completion of the study. of the study.

Case 2Case 2

Comparison of a long-lasting formulation of an Comparison of a long-lasting formulation of an antihypertensive drug and the standard version antihypertensive drug and the standard version to see if the new version improves adherence. to see if the new version improves adherence.

The participants are already taking the standard The participants are already taking the standard formulation and there are no additional risks. formulation and there are no additional risks.

They will be paid N500 each visit for a blood They will be paid N500 each visit for a blood pressure check and other basic tests.pressure check and other basic tests.

Case 3Case 3

Study of neurophysiologic correlates of Study of neurophysiologic correlates of anesthesia in healthy volunteersanesthesia in healthy volunteers

EEG, serial bloods, and multiple diagnostic EEG, serial bloods, and multiple diagnostic tests after the administration of different tests after the administration of different anesthetics at each of 4 or 5 clinic visitsanesthetics at each of 4 or 5 clinic visits

Compensation offered is pro-rated by visit, with Compensation offered is pro-rated by visit, with total about N4000total about N4000

To pay or not to pay?To pay or not to pay?

acknowledgementacknowledgement

Christine Grady, Ethical and practical considerations of paying Christine Grady, Ethical and practical considerations of paying research participants Department of Clinical Bioethics, Clinical research participants Department of Clinical Bioethics, Clinical Center/NIHCenter/NIH

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