Institutional Review Board for Institutional Review Board for Human Research (IRB)Human Research (IRB)

Human Subject ProtectionsHuman Subject Protections

Susan Sonne, PharmD, BCPPSusan Sonne, PharmD, BCPP

Chair, MUSC IRB IIChair, MUSC IRB II

Nuremberg CodeNuremberg Code

first major control on research in any nation

prescribed 1948 as part of trial of a Nazi Physician

willfully harmful research on unwilling human subjects

Jewish Chronic Disease Hospital Jewish Chronic Disease Hospital StudyStudy

• July 1963

• Injection of live cancer cells into 22 patients

• No written consent

• Some verbally informed – “involved in experiment”

Never told being given live cancer cells

• Guilty of fraud, deceit, unprofessional conduct

The Declaration of HelsinkiThe Declaration of Helsinki

Produced 1961, adapted 1964

Informed consent = ethical research

Basis for FDA policy

Willowbrook State SchoolWillowbrook State School

Study began 1956

Institution for “mentally defective” children

Study designed to contribute to understanding etiology of infectious hepatitis and test effects of gamma globulin in preventing disease.

First subjects fed extracts of infected stool

Public attention 1971

National Research Act of 1974National Research Act of 1974

Created National commission for the protection of Human Subjects of Biomedical and Behavioral research.

Charge was to:

Identify basic ethical principles that should underlie conduct of biomedical and behavioral research involving human subjects

More specifically, considerMore specifically, consider

Boundaries between research and practice

Role of assessment of risk-benefit

Selection of subjects

Nature and definition of informed consent

Result was 1976 Belmont report

Good Clinical Practice

Why have this training?

The Tuskegee Syphilis StudyThe Tuskegee Syphilis Study

1932 to 19721932 to 1972 399 African American 399 African American

Males were denied Males were denied treatment for syphilistreatment for syphilis

Study conducted by Study conducted by U.S. Public Health U.S. Public Health ServiceService

From President ClintonFrom President Clinton

"Although these regulations [Protection of Human Subjects, Code "Although these regulations [Protection of Human Subjects, Code of Federal Regulations, Title 45, Part 46} provide the framework for of Federal Regulations, Title 45, Part 46} provide the framework for protecting human subjects in research, we must exercise constant protecting human subjects in research, we must exercise constant care and ensure that these regulations are strictly enforced by care and ensure that these regulations are strictly enforced by departments and agencies. Therefore, I direct each department and departments and agencies. Therefore, I direct each department and agency of Government to review present practices to assure agency of Government to review present practices to assure compliance with the Federal Policy for the Protection of Human compliance with the Federal Policy for the Protection of Human Subjects and to cease immediately sponsoring or conducting any Subjects and to cease immediately sponsoring or conducting any experiments involving humans that do not fully comply with the experiments involving humans that do not fully comply with the Federal Policy." -Bill Clinton, 1994 Federal Policy." -Bill Clinton, 1994

““The people who ran the study at Tuskegee diminished the stature The people who ran the study at Tuskegee diminished the stature of man by abandoning the most basic ethical precepts. They forgot of man by abandoning the most basic ethical precepts. They forgot their pledge to heal and repair. They had the power to heal the their pledge to heal and repair. They had the power to heal the survivors and all the others and they did not. Today, all we can do survivors and all the others and they did not. Today, all we can do is apologize….” – Bill Clinton, 1997is apologize….” – Bill Clinton, 1997

OHRP SuspensionsOHRP Suspensions

During the last 6-7 years, OHRP has During the last 6-7 years, OHRP has suspended all human research at the suspended all human research at the following institutions:following institutions:– University of Illinois, Chicago CampusUniversity of Illinois, Chicago Campus– University of ColoradoUniversity of Colorado– Duke UniversityDuke University– Johns HopkinsJohns Hopkins– University of PennsylvaniaUniversity of Pennsylvania– And othersAnd others

General Rule for Human Subject General Rule for Human Subject ProtectionProtection

Any element of research?

Yes

Undergo review

IRB PurposeIRB Purpose

To protect the rights and welfare of human To protect the rights and welfare of human research subjectsresearch subjects

Authority to approve, require modification Authority to approve, require modification and disapprove any research involving and disapprove any research involving human subjectshuman subjects

Institutional Review BoardInstitutional Review Board• responsible to verify

1. Safety

2. Integrity

3. Human rights

4. Public reassurance

5. Scientific content

The Belmont ReportThe Belmont Report

3 Basic Principles for Protection of Human Subjects:3 Basic Principles for Protection of Human Subjects:– RespectRespect

voluntary informed consentvoluntary informed consent privacyprivacy protections for vulnerable populations protections for vulnerable populations

– BeneficenceBeneficence– JusticeJustice

BeneficenceBeneficence

Persons treated in an ethical manner

Protecting them from harm

Helping to secure their well being

JusticeJustice

• Who ought to receive the benefits of research and bear the burden of research?

• Equals ought to be treated equally

• Fairness in distribution

• What is deserved

Criteria for ApprovalCriteria for Approval

Risks are minimizedRisks are minimized Reasonable risk:benefit ratio Reasonable risk:benefit ratio Equitable selection of subjectsEquitable selection of subjects Informed consent obtained appropriatelyInformed consent obtained appropriately Informed consent adequately documentedInformed consent adequately documented Monitor data to insure safetyMonitor data to insure safety Protect confidentialityProtect confidentiality No coercionNo coercion

Informed Consent• Essential to ethical conduct of clinical

investigation

• Potential subject chooses whether or not they will participate

• Obtained after full information is given and understood

• Explanation of study objective, potential benefits, risks, inconveniences, subject’s rights and responsibilities

Informed Consent–Introduction –Purpose of the Study–Procedures–Potential Risks and Discomforts–Anticipated Benefits to Subjects–Anticipated Benefits to Society–Alternative to Participation–Emergency Care and Compensation for Injury–Payment for Participation–Financial Obligation–Privacy and Confidentiality–Participation and Withdrawal–Rights of Research Subjects–Signatures

•Protecting Participants•Implementing Study•Reporting Accurately

The Mountain of Responsibility

Investigator Obligations• Conducts a clinical investigation

• Responsible for

All procedures conducted

All data collected

• May delegate work in conducting study but they retain responsibility

Investigators – and by delegation all study staff responsibilities

• To protect the rights of participants• To obtain informed consent from each

participant• To keep specific records and issue

specific orders• To assure that the IRB is provided

information for initial and continuing review of the study

Useful Regulatory/Policy MaterialUseful Regulatory/Policy Material

MUSC IRBMUSC IRB http://research.musc.edu/ori/irb/homehttp://research.musc.edu/ori/irb/home Office for Human Research ProtectionsOffice for Human Research Protections http://www.hhs.gov/ohrp/http://www.hhs.gov/ohrp/ Food & Drug AdministrationFood & Drug Administration http://www.fda.gov/oc/ohrt/irbs/default.htmhttp://www.fda.gov/oc/ohrt/irbs/default.htm