Is Consent to Research Necessary in Comparative Effectiveness Trials?

Collin O’Neil, PhD

Department of Philosophy

Lehman College, City University of New York

MEDICRES CONGRESS 2014

Types of Randomized Controlled Trials

• Placebo-controlled

– Investigational Therapy versus Placebo

• Active-controlled

– Investigational Therapy versus Proven

Therapy

– Proven Therapy versus Proven Therapy

Comparative Effectiveness Trials (CETs)

• Why are they important?

– Improve clinical decision-making

– Lower health care costs

– Incentivize pharma to make more

socially productive R&D investments

Recent Argument

• Comparative effectiveness trials count as human

subjects research

• But Robert Truog, Ruth Faden, Nancy Kass, and

others have argued that some of these trials are so

close to standard clinical care that:

– No need for IRB review

– No need for written consent

– No need to inform patients they are involved in research

Consent• We have a general right to bodily

integrity

– A right against bodily interventions

• The function of consent is to waive

rights

• But consent is not always successful

or “valid.”

Consent

• To be successful (or “valid”), consent

must be adequately informed

– Consent is adequately informed only if the

consent is not based on ignorance or mistake

• I.e, when it is not the case that the subject would

not have consented had they been better informed

Consent

• Can consent to the interventions in

comparative effectiveness trials be

adequately informed when the

subject is ignorant of the fact there is

a research purpose behind them?

Clinical Care Expectations

• Non-maleficence: no risks or burdens

except those necessary to prevent

greater harm to the patient

• Beneficence: the patient will be offered

whatever available treatment is, in the

physician’s judgment, best for the patient

• Non-maleficence

– Some CETs involve non-therapeutic interventions

• E.g., blood draws for purely research purposes

• Beneficence

– Some CETs randomize between X and Y even

when in the physician’s judgment, X or Y would

be better for the patient

CETs may disappoint these expectations

Problem• If the patient does not know they are

involved in research, they will

assume these clinical care

expectations are satisfied

–When this assumption is mistaken, their

consent will often be based on this

mistake, and so invalid

But not all CETs disappoint these expectations

• Consider a trial that:

– Involves no non-therapeutic

interventions

– Randomizes patients only with physician

assent

• Will their consent to the interventions be

valid, even though they have not been

informed they are involved in research

rather than standard clinical care?

– The care they are receiving in the trial is in

no respect inferior to the care they would

receive in standard clinical care

• But the research purpose itself might

matter to them, even if it does not

compromise the care they receive

–May have conscientious objections to

serving certain research goals

–May be suspicious of research

Best Candidate

• No non-therapeutic interventions

• Randomized only with physician

assent

• Uncontroversial research goal

• Patient population unlikely to be

mistrustful of research

• In this trial, although the patients are

unaware of the research purpose, their

consent is not based on this ignorance

• Is that enough to secure the validity of

their consent to the interventions?

• In order to successfully waive a

certain right, one needs to waive it

intentionally

• So one needs to know which right or

right one needs to waive

• There is a general right of bodily integrity, a

right against bodily interventions

• But there are two distinct types of rights of

bodily integrity

– A right against being intervened upon for one’s

own benefit

– A right against being intervened upon for the

benefit of others

• To successfully waive the right against

being intervened upon for the benefit of

others, one must know this is the right

one needs to waive

• And one can know this is the right one

needs to waive only if one is informed of

the research purpose

• Respecting the rights of subjects in CETs always

requires that the research purpose be disclosed

• But disclosure is not required for all kinds of

research

– Research that merely collects data on outcomes of

clinical care

– Research on samples or specimens originally

extracted for therapeutic purposes

• Why the reluctance to disclose the

research purpose?

– Not impossible

– Not even difficult

• The main worries (I suspect) are that, if the

research purpose is disclosed, there will be

insufficient or imbalanced enrollment

– These are not legitimate reasons for not

disclosing the research purpose

– But there may be other ways to avoid

enrollment problems

• The requirement to obtain research consent

requires only that the patient not be

randomized if they refuse

– It is commonly assumed that, if they refuse

randomization, they must be offered the treatment

of their choice

– But this requirement says nothing about what they

should be offered if they refuse

Proposal

• Make it a condition on their receiving

any treatment at all at the hospital

that they accept randomization

• Potential objection: coercive?

• Consent is coerced only if obtained

by threatening to otherwise withhold

something they have a prior right to

– NIH Clinical Center

– Private Hospitals

Conclusion

• However, at public hospitals, like the VA,

conditioning treatment on their

acceptance of randomization may be

coercive

– Their patients do have a prior right to

treatment from the VA

• Patient education is the key here