Human Subject Protection Judith Birk IRB Health / Behavioral Sciences

What is Research? A systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge 45CFR46.102(d)

Who is a Human Subject? A living individual about whom an investigator (whether professional or a student) conducting research obtains data through intervention or interaction with the individual, or private information 45CFR46.102(f)

What is an Intervention? Physical procedures (like a blood draw) and manipulations of the subject or the subject’s environment that are performed for research purposes

Interaction? Communication or interpersonal contact between the investigator and subject

Private Information? (part 1) -Information about a behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place

Private Information (part 2) …and information which has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public

Private Information (part 3) Private information must be individually identifiable in order for obtaining the information to constitute research involving human subjects

Historical Events Nuremberg Doctors Trial of 1946 –23 defendants (20 physicians) charged with murder in the name of medical science –15 found guilty –7 sentenced to death

Nuremberg Vacuum chamber: 40% mortality Cold water immersion: 30% Traumatic amputations: 50% Chemical warfare agent testing: 25%

International Codes of Research Ethics Nuremberg Code 1947 Declaration of Helsinki 1964

“Tuskegee Study of Untreated Syphilis in the Negro Male” Predecessor of CDC designed the study to demonstrate the need to establish syphilis treatment programs in 1932 Study would investigate the effects of the untreated disease on a short term basis Penicillin was accepted as treatment in 1943 Lack of treatment revealed by the Associated Press in 1972

US Response National Research Act 1974 –National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research The Belmont Report US Code of Federal Regulations –Title 21 Food and Drugs –Title 45 Part 46 (Common Rule)

Belmont Report Respect for persons Beneficence Distributive Justice

Respect for Persons Individuals should be treated autonomously Their informed consent should be freely given

Beneficence Do no harm Maximize possible benefits and minimize the risks

Distributive Justice Equitable selection of research subjects

Informed Consent A process, not just a document –Informed –Understood –Voluntary

Elements of Informed Consent It is research What are the reasonably foreseeable risks Are there benefits Alternative treatments or procedures Record confidentiality If more than minimal risk will there be treatment or compensation of/for any harms

Elements… Who has information and can help Participation is voluntary and it is okay to stop

Role of the IRB Review and approve research involving human subjects Conduct continuing review/oversight Informed consent Risk/benefit Vulnerable subjects Other special considerations

IRB Structure/Types of Review Convened (Full) Board Expedited Exempt

IRB Review Process Initiate a complete, thoughtful application –Informed consent, supporting documents, permissions Administrative review Convened board or Chair review Administrative follow-up Repeat bullets 3 and 4 as necessary Final approval Notification provided

Staying in Compliance Don’t initiate research before obtaining IRB approval Renew ongoing proposals each year in a timely fashion (not fashionably late…) Stay within the approved scope of the project Submit modifications to the IRB before initiating the change to the research Report Adverse Events

Common Pitfalls Letting an active project lapse in approval Failing to get approval in the first place (there are no retroactive approvals) Exceeding the scope of the approval Using materials which are not IRB approved

Oversight Federal –OHRP (Office of Human Research Protections) –FDA Local –IRB (Institutional Review Boards)

What do these have in common? Duke University Rush-Presbyterian Chicago Johns Hopkins University of Colorado Virginia Commonwealth University of Pennsylvania

What do IRBs Worry About? Informed consent Well, I think I understand this -- you only want me to umhh, well, what was that thing you said…

Worries Coercion Gee, I’m not sure about this, but I could really use the $1300 they’re offering me.

And More Worries Risk/Benefit Let’s see, you’re saying that I only need to wear a blindfold and walk across this 5 lane highway - right? Well, you ARE the scientist, you must know what you are doing.

The Best Solutions Just ask –Your faculty mentor –The IRB