Ethical issues in clinical research

Bernard Lo, M.D.

August 24, 2011

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Conflicts of interest

None

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Outline of session

Historical background

IRB review

Informed consent

Research misconduct

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STD transmission research 1946-8

Intentionally infected subjects with syphilis, GC, chancroid

Female sex workers Males directly innoculated

Prisoners, patients in mental hospitals

In Guatemala

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STD studies 1946-8

Intentionally infected subjects with

syphilis, GC, chandroid Female sex workers inoculated on cervix Males directly inoculated into skin or

urethra

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STD studies 1946-8

Study carried out in Guatemala

Subjects were prisoners, residents of

mental asylums

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STD studies 1946-8

Most but not all treated with penicillin One subject died of status epilepticus

US government involved: NIH, PHS,

Surgeon General

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Senior PHS official

“I am a bit, in fact more than a bit, leery

of the experiment with the insane

people. They can not give consent, do

not know what is going on, and if some

goody organization got wind of the

work, they would raise a lot of smoke”

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Fundamental ethical tension in research

Primary goal is generalizable

knowledge, benefit to society

Participants experience risks but

benefit to others

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Ethical violations

1. Serious harm to participants Deliberately cause harm

2. No informed consent

3. Unfair selection of participants Take advantage of vulnerable population

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Regulations respond to scandal

1. Beneficence Risks must be acceptable in light of benefits Risks must be minimized Independent IRB must approve study

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Regulations respond to scandal

2. Respect for persons Informed and voluntary consent Not capable of consent (children, adults

who lack decision-making capacity)

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Regulations respond to Tuskegee

3. Justice Equitable selection of subjects Protections for vulnerable subjects

Federal regulations

1. Risks acceptable in light of benefits

2. Informed and voluntary consent

3. IRB review and approval

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Questions?

Do you need IRB review?

Just give out questionnaires?

Just review medical records?

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Only need IRB review if

Participants identifiable OR

Interact with participants OR

Questionnaire covers sensitive topics

Ask IRB staff

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Do you need IRB review?

Student project that will not be

published? “It’s not research”

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Do you need IRB review?

Can’t get IRB approval before study

begins

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What is research misconduct?

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Bone growth factors

Recombinant human bone

morphogenetic protein-2

13 early trials claimed no

complications compared to controls

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Bone growth factors

Serious adverse events actually 10%-

50% Male sterility, infection, bone loss and

unwanted bone growth

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Bone growth factors

Original studies were sponsored by

manufacturer

Authors received up to $12-$16 million

in payments from company

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Federal definition of research misconduct

Fabrication

Falsification

Plagiarism

Must be intentional

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Research misconduct excludes

Unintentional “honest” error

Sloppiness, incompetence, laziness

Differences of opinion or interpretation

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Research misconduct excludes

Lack of IRB approval

Lack of informed consent

Financial mismanagement

Discrimination

Poor mentoring

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Federal definition of misconduct

Legal requirements set a minimum

standard

Ethical and professional standards

may be higher

How do people respond to plagiarism?

Using computer programs, identify 212

pairs of similar articles

Survey to authors, journal editors of

these articles

Science 2009; 323; 1293.

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Individual response to misconduct

“It is my understanding that copying

someone else’s description virtually

word-for-word is considered a

compliment to the person whose words

were copied.”

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Individual response to misconduct

“I have no idea why the pieces are

similar, except that I am sure I do not

have a good enough memory to have

allowed me to ‘copy’ his piece.”

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Consequences of research misconduct

Suspension of federal grant

Debarment from future grants

Institutional penalties Termination of employment

Civil and criminal liability

Questions?

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Take home points

IRB review and informed consent

essential

Don’t plagiarize, fabricate, falsify data

Ask if you’re uncertain or concerned

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