Ethical issues in selection of research subjects

Bernard Lo, M.D.

July 28, 2001

Is it care rather than research?

Potentially life-saving intervention

Liver transplant is standard care in

other clinical settings

Transplant may be available outside

trial

Different selection priorities

In clinical care Well-being of individual patient paramount Priority to those in greatest medical urgency

In research Benefits/risks uncertain Generalizable knowledge also a goal Priority to most appropriate to answer research

question

What is the research question?

Proof of concept

Generalizability

Proof of concept

Is intervention efficacious in optimal

circumstances?

Negative study is definitive

Positive study needs follow-up in

broader population

Generalizability

Is intervention effective in ordinary

practice?

Need larger sample size

Positive study is definitive

Negative study may be due to selection

Subject selection for different research questions

If proof of concept Select those with best prognosis after Tx Exclude those with poorer or uncertain

prognosis

If generalizability Select those representative of population

Risk to health care workers?

Persons with high viral titers whose

liver disease precludes HAART

If no resistance, likely to respond to

HAART after Tx

Risk to health care workers?

Needlesticks during operation

Risk to HCWs is greater if higher titer

Ethical obligation to provide standard

care, even at risk to self, but not

experimental care?

Characteristics of ethical dilemma

Strong arguments for different

positions

Reasonable people may disagree

Should HIV+ persons be given a scarce resource?

How should scarce organs be allocated?

Bernard Lo, M.D.

July 29, 2001

Reaction to Mickey Mantle

“With each crack of the bat, Mickey

Mantle allowed us to dream. For one

moment forget about everything else.”

Reaction to Mickey Mantle

“Had my sister been a start baseball

player perhaps she would be alive

today… Unfortunately, her only claim

to fame was that she was a loving wife

and mother.”

Reaction to Mickey Mantle

“I have lost three relatives to liver failure

… None were given the preferential

treatment he received… My only hope

is that he doesn’t take advantage of his

brand-new liver and revert to his old

ways.”

Principles of “fair” allocation

Those with greatest medical urgency

Those most likely to benefit Exclude those unlikely to benefit

Those with greatest medical urgency

Rescue those in greatest need Probability of death Likelihood of good outcome after Tx

Those most likely to benefit

Help the greatest number of patients

Groups with similar outcomes should

have similar priority Need outcomes data

Arguments over data, not principle

May conflict with medical urgency

Exclude those unlikely to benefit

Medical Too sick: sepsis, other organ failure Too healthy: survive without Tx

Poor adherence Active substance abuse Poor social support Possibility of bias

Principles of “fair” allocation

Those with greatest medical urgency

Those most likely to benefit Exclude those unlikely to benefit

Those who waited longest

Exclude those who cannot pay

Those who are “unworthy”?

Favor those who are “worthy”?

Past contributions to society

Future contributions to society

Traditional social/cultural values

Exclude those who are “unworthy”?

Behaviors that lead to illness

Groups stigmatized or marginalized

Public willingness to donate organs

History of early renal dialysis