wendler fair subject selection

8/8/2019 Wendler Fair Subject Selection

1/47

Fair Subject Selection

David Wendler

Department of Bioethics

NIH Clinical Center


2/47

Disclaimer

The opinions expressed are my own.They do not reflect any position or policyof the National Institutes of Health, Public

Health Service, or Department of Healthand Human Services.


3/47

Three Aspects of Subject Selection

1.Selection: determining which groups ofindividuals are eligible

2.Recruitment: actively approachingindividuals in the eligible groups

3.Retention: retaining eligible subjects


4/47

Goals

Selection, Recruitment, and Retention should:

1. Distribute burdens and benefits fairly

2. Ensure social value of research

3. Enhance scientific validity

4. Minimize risks to subjects

5. Maximize benefits to subjects6. Protect the vulnerable


5/47

Potential Conflicts

In some cases, these different goals mayconflict.

For instance, minimizing risks to subjectsmay decrease the social value of the

research.


6/47

Tradeoffs

In cases of conflict, investigators, ethicsreview committees, and sponsors must

balance the competing goals.


7/47

Subject Selection

Subject selection involves determiningwhich subjects may enroll in the research.

Subject selection is determined by thestudys inclusion/exclusion criteria.


8/47

Research as a Benefit

Exclusion without a good reason may beunfair or discriminatory.

People are clamoring for access to clinicaltrials...demanding they, and others like

them, are owed such as a matter ofjustice. (Levine, 1994)


9/47

Fairness

To ensure fairness, begin by assumingeveryone is eligible.

Exclude individuals from this pool onlywith good reason.


10/47

Priority of Science

The scientific goals of the study should bethe primary consideration in determiningwho can enroll.

This involves ensuring the value of the

study and enhancing its validity.


11/47

Ensuring Value

Exclude individuals not suitable foranswering the scientific question.

For instance, individuals with conditionsthat make it impossible to assess the drugbeing tested (e.g. brain tumors).


12/47

Enhancing Validity

Also exclude individuals who cannotsatisfy the protocol requirements.

For instance, subjects who cannot (or donot) make the required clinic visits.


13/47

Minimize Physical Risks

To minimize risks, exclude individuals whowould face significantly higher risks.

Individuals with poor kidney functionmight be excluded from a phase II studyof a drug with renal clearance.


14/47

Maximize Benefits

Select subjects who are more likely tobenefit from participation.

A study of a new anti-HIV drug mightfocus on individuals with low CD4 counts.


15/47

Protecting the Vulnerable

There is an order of preference inselecting subjects, for instance, adultsbefore children. (Belmont Report)

Exclude vulnerable subjects unless theirparticipation is needed for scientific

reasons. (CIOMS

)


16/47

Vulnerable Subjects

In general, vulnerable subjects are thosewho are significantly less able to protecttheir own interests.

In the context of clinical research,

vulnerable subjects typically are those notable to give voluntary informed consent.


17/47

Address Vulnerability First

In some cases, it is possible to addressindividuals vulnerability withoutexcluding them.

Individuals who do not understandEnglish are vulnerable (in the US), but

this vulnerability can be addressed bytranslators and translated documents.


18/47

Subjects Who Cant Consent

Exclude individuals unable to consent,unless there is a compelling reason to

enroll them.

Scientific necessity is the most obvious

reason to enroll those who cannotconsent.


19/47

Lower Risks?

Should individuals who cannot consent beenrolled when they face significantly lowerrisks than individuals who can consent?

For example: a phase I study that can be

conducted with relatively low risks inchildren or high risks in adults.


20/47

The Prospect of Benefit

Should subjects who cannot consent beexcluded from trials that offer potentialclinical benefit?

Should an individual unable to consent beenrolled in a phase II study of a new

chemotherapy, if the study could equallywell be completed with individuals whocan consent?


21/47

The Justification?

In some cases, enrollment may be inriskier subjects (e.g. individuals withpoor kidney function) best interests.

Thus, a general exclusion of these

subjects cannot be justified on thegrounds that it protects them.


22/47

Research vs. Clinical Care

It is important to distinguish research fromclinical care.

Excluding riskier subjects minimizes theaggregate risks of research.

Applies to moral (cant consent) as well asphysical risks (renal clearance example)?


23/47

Additional Safeguards

Informed consent is a primary researchsafeguard.

Hence, when enrollment of subjectsunable to consent is justified, the study

should include additional safeguards toprotect them.


24/47

Sufficient Evidence

Adults no longer able to consent should beenrolled only with sufficient evidence thatit is consistent with their preferences and

interests.

What about adults who were nevercompetent?


25/47

Surrogates

Subjects unable to consent should beenrolled only with the permission of anappropriate surrogate.

Are health care surrogates sufficient forresearch purposes (evidence that those

close to us are bad predictors of ourpreferences)?


26/47

Subject Recruitment

Subject recruitment involves activeattempts to enroll specific individuals or

groups within the pool of eligible subjects.


27/47

Finding the Right Community

In many cases, the choice of communitiesfrom which to recruit is determined by

institution location.


28/47

Selecting a Community

In other cases, investigators have a choiceof possible communities.

In these cases, the principles of subjectselection apply in deciding which

community to select.


29/47

Goals of Selection and Recruitment

1. Distribute burdens and benefits fairly2. Ensure social value

3. Enhance scientific validity

4. Minimize harm

5. Maximize benefit

6. Protect the vulnerable


30/47

Declaration of Helsinki -2008

Medical research involving adisadvantaged or vulnerable populationor community is only justified if the

research is responsive to the healthneeds and priorities of this population orcommunity and if there is a reasonable

likelihood that this population orcommunity stands to benefit from theresults of the research.


31/47

Social Value/Community Benefit

To what extent must communities benefitfrom research involvement?

To what extent must the communitybenefit specifically from the research

results?


32/47

Community vs. Individual Benefit

Should the requirement of benefit be

added to the conditions on selection ofindividual (vulnerable) subjects?


33/47

The Need to Recruit

According to a 2007 survey by CenterWatch, over 70% of clinical trials aredelayed due to difficulty enrolling a

sufficient number of subjects.

To be ethical, clinical trials needs to recruit

a sufficient number of subjects to obtainvalid data.


34/47

The Ethics of Recruitment

This provides an ethical reason to recruitand retain subjects.

Yet, recruiting and retaining researchsubjects raises important ethical issues.


35/47

Recruitment

Targeted recruitment

Inviting referrals from colleagues/clinicians

Advertising

Inviting ones own patients


36/47

Recruitment for good reasons

Do not focus recruitment on individualswho are (or appear to be?) vulnerable

Ensure subjects are recruited for reasonsof science, not compromised position.

(Belmont Report)


37/47

Incentives to Enroll Subjects

Investigators are under considerablepressure to recruit subjects, sometimesreceiving financial incentives. (US Inspector General2000)

Physicians receive payments for referringtheir patients to trials.


38/47

Concerns about Incentives

Do incentives to refer patients pose aconflict of interest?

To what extent might use of incentivesencourage investigators to enrollriskier/inappropriate subjects?


39/47

Advertising

What effect does advertising have onrecruitment?

Does advertising affect consent?

May benefits be advertised?

Must risks be advertised?


40/47

IRBs and AdvertisingThe IRB should review the methods and

material that investigators propose to useto recruit subjects.

Ads should not claim that investigationalinterventions are safe or effective.

IRB should evaluate the relative size oftype used and other visual effects.

www.fda.gov/oc/ohrt/irbs/toc4.html#recruiting


41/47

Ads in Real Life: Bar Coaster

Research Subjects Wanted

Earn $50-$1295

Call555-555-5555

Daves Research Institute


42/47

Proposed T.V. Ad Thumping music; Tie-dye colors on screen.

Attention alcohol Usersyou are a candidatefor a new research study being done at DavesInstitute.

We are enrolling men and women, 18-40, tostudy the effects of alcohol on the brain.

This study pays up to 3500 dollars and includesroom and board. Call today.


43/47

Effect of Ads

Do advertisements affect which groupsenroll?

Does advertising affect understanding?

Does it affect motivations (does itmatter?)


44/47

Payment

What role should payment play inrecruiting research subjects?

Is it acceptable to advertise payment?


45/47

Concerns

Some argue that payment may coerceindividuals.

Others worry that payment may representan undue inducement.


46/47

The Real World

Data suggest that many problemsrecruiting subjects trace to mundane,practical concerns: awareness of studies,

transportation, parking, child care.

Clinical trials should take these concernsinto account.


47/47

Retaining Subjects

To collect valid data, recruited subjectsneed to be retained.

Future research is needed on ways toretain subjects and encourage them tocontinue to participate withoutundermining their right to withdraw.

wendler fair subject selection

Documents