Nuremberg Code

Nuremberg Code

• Nuremberg Code

• Declaration of Helsinki

• Public becomes more aware of potential research ethics problems in U.S. funded/conducted studies

• Jewish Chronic Disease Hospital
• Henry Beecher 1966 NEJM article
• Tuskegee study

• Tuskegee Ad Hoc panel convened 1972

Beneficence:

• Beneficence:

• duty to protect the welfare of participants

• Respect for persons

• duty to respect autonomous persons, their choices, and their information
• Out of respect, duty to protect those less than fully autonomous

• Justice

• Duty to distribute benefits and burdens fairly

Risks/benefits: to individuals and communities

• Risks/benefits: to individuals and communities

• Physical
• Psychological
• Social

• Considerations when assessing risk:

• Nature of risk
• Likelihood of risk
• Severity/magnitude of harm
• Permanence/reversibility of harm

Valid design? Valid findings? If not, no benefit

• Valid design? Valid findings? If not, no benefit
• Sufficient sample size?
• Is randomization appropriate?
• Are placebos appropriate?
• Surrogate markers vs. clinical endpoints?
• Often can change design to reduce risk

Requires we go through informed consent process

• Requires we go through informed consent process

• Requires we provide additional protection for persons who cannot consent themselves

• Requires we respect privacy and maintain confidentiality

Disclosure

• Disclosure

• Understanding

• Voluntariness

• Capacity (competence)

Average reading level >8th grade (numerous studies)

• Average reading level >8th grade (numerous studies)

• 65 approved forms: avg. 15th grade (Hammerschmidt and Keane 1992)

• Ann Landers columns avg 7.7 grade
• Reader’s Digest avg 9.95 grade readability
• IRB review never improved by >1 grade level

• IRBs’ own boilerplate often >8th grade

• (Paasche-Orlow et al 2003)

Appelbaum: “therapeutic misconception”

• Appelbaum: “therapeutic misconception”

• 69% didn’t know how random assignment had been made
• 32% thought they were in group best for therapeutic needs
• 44% did not know some patients who wanted tx would not get it
• 39% did not understand MD would not know which tx they received

• Riecken and Ravich

• 28% didn’t know they were in study, despite having just signed consent form

Shortening form (Epstein 1969)

• Shortening form (Epstein 1969)

• Overall comprehension: 67% vs. 35%

• Lowering readability level (Young 1990)

• Purpose: 77% vs. 44%; Side effects: 72% vs. 58%

• More sections, headings, lay language (Bjorn 1999)

• Randomization: 26% vs. 42%

• Corrected feedback or verbalization

• Quiz and correct wrong answers (Taub 1984)
• Verbalization of surgical risks (Wadey 1997)

Fair selection of individuals

• Fair selection of individuals

• Fair selection of populations

• Opposite is exploitation

Overall research portfolio

• Overall research portfolio

• What diseases do we study?
• Who gets them? How many people? Which groups?
• Fair distribution of who benefits from overall research?

• Which population do we pick for individual studies?

• Is study particularly relevant to THEM?
• If not, is there a fair distribution/broad inclusion?

• What happens after study is over?

• Access to successful intervention?
• Does fairness require this?

IRB must review studies for adherence to ethics principles, including:

• IRB must review studies for adherence to ethics principles, including:

• Review risk/benefit; risks minimized
• Review consent elements/procedures and documentation
• Review proper selection of subjects

• 1991: adopted by 17 US federal agencies as “Common Rule”

Think through ethics issues for your project – minimize harms, choose populations fairly, develop respectful procedures

• Think through ethics issues for your project – minimize harms, choose populations fairly, develop respectful procedures

• Submit protocol to IRB, submit annual reviews to IRB, submit changes to IRB, submit adverse or unanticipated events to IRB

• Maintain records (with IRB, with subjects)

• Honesty and integrity as an investigator

You must follow regulations

• You must follow regulations

• You must be thoughtful about the ethics of your studies

• If you’re lucky, these will happen at the same time