Daniel NelsonDirector, Office of Human Research Ethics

Professor of Social Medicine, Adjunct Professor of PediatricsUniversity of North Carolina - Chapel Hill

EVOLVING PROTECTIONS FOR HUMAN RESEARCH SUBJECTS

…or…What’s an “IRB” and why should you care?

Presentation for IBD Patient Governance CommitteeFebruary 4, 2014

But research is a good thing… why do research subjects

need “protection?”

Concerns for protecting subjects grew out of a long

history in which people were abused in the name of science

Celsus, 1st century AD

“It is not cruel to inflict on a few criminals sufferings which may benefit multitudes of innocent people through all centuries.”

Informed consent “contract” used by Maj. Walter Reed for yellow fever transmission experiments in Cuba, signed 26 Nov 1900(duplicate in Spanish)

Courtesy of Col. Arthur Anderson, U.S. Army

Nazi Medical Experiments During WWII

15 of 23 guilty, 7 hanged, 5 life sentences

Case No. 1 of the Nuremberg Military Tribunal U.S.A. vs. Karl Brandt et al.Dec 9, 1946 - Aug 20, 1947

NUREMBERG CODE1947

• Voluntary informed consent absolutely essential• Research should yield useful results• Base research on prior work• Avoid physical and mental suffering• No expectation of death or disabling injury• Risk must be outweighed by importance• Subjects must be protected from injury• Qualified scientists, adequate facilities• Subject free to stop at any time• Investigator must be ready to withdraw subject

“Before IRBs, the only consent required was that of a researcher's department head. The Nuremberg Code was ignored in practice. As I look back on it, the interpretation of these codes was that they were necessary for barbarians, but not for fine upstanding people... In this prestigious unit we had a very strong obligation to behave in a civilized manner.”

Dr. William Silverman, Columbia pediatrician, on the postwar mentality (ACHRE interviews)

Willowbrook State School Staten Island, 1956-1963

• Institutionalized children• Deliberate infection with hepatitis A• Coercive recruitment through restricted admission

• RationalizationIntroducing Jerry Rivers, 1971

“Tuskegee Syphilis Study” Conducted by US-PHS in Rural Alabama

1932-1972

Syphilis Expose

Philadelphia Inquirer, 1972

“Sometimes, with the best of intentions, scientists and public officials… working for the benefit of us all, forget that people are people. They concentrate so totally on plans and programs, experiments, statistics- on abstractions- that people become objects, symbols on paper, figures in a mathematical formula…”

Atlanta Constitution, July 27, 1972

US National Research ActJuly, 1974

Established National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (1974-1978) The Belmont Report (1979)

Code of Federal Regulations (1981) Institutional Review Boards (IRBs) Informed consent

Public Law 93-348

THE BELMONT REPORTEthical Principles and Guidelines for the

Protection of Human Subjects of Research

Respect for PersonsBeneficence

Justice

National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, 1979

Translating Ethical Principles Into Regulations

Translating Ethics into Regulations“The Twin Pillars of Protection”

Rights and Welfare of Human Subjects

Informed Consent

Independent Review

WHAT IS AN IRB?Institutional Review Board

Independent review of proposed research, to protect the rights and welfare of participants

At least 5 members, not all men, not all women (UNC IRBs have 10-25 members)

Not all members of one profession Diversity Expertise appropriate to the research At least one scientist, one non-scientist At least one member not otherwise affiliated

with the institution

WHAT IS AN “IRB?”Institutional Review Board

• 5 IRB committees at UNC-Chapel Hill• Social and Behavioral Sciences• Biomedical Sciences (x4)

• Members include 80 faculty, staff and community representatives

• Oversee approx 4000 active research studies

What does an IRB do when it reviews a research study?

• Risks minimized• Balance of risks and benefits• Equitable selection of subjects• Informed consent• Monitoring plan for safety• Privacy and confidentiality• Additional safeguards for vulnerable

populations

Informed Consent

INFORMED CONSENT• Obtaining consent is a PROCESS in which...

• investigator discloses all relevant information• potential subject has opportunity to ask

questions• investigator answers questions• subject signs a consent form

• The consent form is a permanent record of...• information conveyed• subject’s willingness to participate

What Questions Should You Ask Before Participating in a Research Study?

• What is the study about?• Who put this study together?• Who is going to be in this study?• What will I get out of this study?• What are the possible risks?

• How will I be protected from harm?• What do I have to do in this study?• What will happen after the study is over?

Our National System for Protecting Research

Subjects has Come Under

Scrutiny

Current Challenges and Opportunities • Continuing legacy of Tuskegee• Storing specimens and data for future unspecified research• Genetic testing• Return of results to participants

• Research results?• Incidental findings?

• Data sharing data security• Waiver of consent• Community engagement • Study design issues

• Multisite research• “Standard of Care” research• Cluster randomized trials