Institutional Review Board Institutional Review Board (IRB)(IRB)

What is our Purpose and Role for What is our Purpose and Role for

Ethical ResearchEthical Research

Historical Development of Historical Development of the IRBthe IRB

Nuremberg CodeNuremberg Code

War Crime Trials StandardsWar Crime Trials StandardsVoluntary consent/withdrawal at any timeVoluntary consent/withdrawal at any timeDegree of risk not outweighed by human Degree of risk not outweighed by human

importanceimportanceExperimental design to protectExperimental design to protectTermination of experiment at any stage if Termination of experiment at any stage if

continuation is likely to result in injury, continuation is likely to result in injury, disability, or deathdisability, or death

Declaration of HelsinkiDeclaration of Helsinki

Adopted June 1964Adopted June 1964Biomedical Research to ImproveBiomedical Research to Improve

DiagnosticDiagnosticTherapeutic andTherapeutic andProphylactic proceduresProphylactic procedures

Improve UnderstandingImprove UnderstandingEtiology andEtiology andPathogenesis of diseasePathogenesis of disease

Belmont ReportBelmont Report

Adopted April 18, 1979 ethical principles Adopted April 18, 1979 ethical principles and guidelines for the protection of human and guidelines for the protection of human subjectssubjects

Three basic (primary) ethical principlesThree basic (primary) ethical principlesRespect for persons (Autonomy)Respect for persons (Autonomy)Beneficience—treated in an ethical mannerBeneficience—treated in an ethical mannerJusticeJustice

Respect for PersonsRespect for Persons

Persons should be treated as autonomous Persons should be treated as autonomous agentsagents

persons with diminished autonomy are persons with diminished autonomy are entitled to protectionentitled to protection

BeneficenceBeneficence

Do no harmDo no harmMaximize possible benefits and minimize Maximize possible benefits and minimize

possible harms possible harms sometimes research subjects are not direct sometimes research subjects are not direct

beneficiariesbeneficiaries

JusticeJustice Developed from the Tuskegee syphilis studies of the 1940s, Developed from the Tuskegee syphilis studies of the 1940s,

whereby rural black men were denied effective treatment to whereby rural black men were denied effective treatment to chart the untreated course of the disease even though it was chart the untreated course of the disease even though it was not confined to that populationnot confined to that population

Who ought to receive the benefits of research and bear its Who ought to receive the benefits of research and bear its burdens? Benefits and burdens of research to be distributed burdens? Benefits and burdens of research to be distributed fairlyfairly

Mentally retarded children housed at the Willowbrook State Mentally retarded children housed at the Willowbrook State School in Staten Island, New York, were intentionally given School in Staten Island, New York, were intentionally given hepatitis in an attempt to track the development of the viral hepatitis in an attempt to track the development of the viral infection. The study began in 1956 and lasted for 14 years. infection. The study began in 1956 and lasted for 14 years. The researcher also wanted to determine the effectiveness The researcher also wanted to determine the effectiveness of gamma globulin injections as protection against hepatitis.  of gamma globulin injections as protection against hepatitis.  They justified their deliberate infections and exposures by They justified their deliberate infections and exposures by claiming that given that there was a high rate of infection in claiming that given that there was a high rate of infection in the institution it was practically inevitable that the children the institution it was practically inevitable that the children would become infected would become infected

Federal RegulationsFederal Regulations

HHS Title 45 CFR 46 The Protection of HHS Title 45 CFR 46 The Protection of Human SubjectsHuman SubjectsOffice of Human Research Protections Office of Human Research Protections

(OHRP)(OHRP)Common RuleCommon Rule

FDA Title 21 CFR 50, 54, 56, 312, 314 FDA Title 21 CFR 50, 54, 56, 312, 314 International Committee on Harmonisation International Committee on Harmonisation

(ICH) Guidelines(ICH) GuidelinesGood Clinical PracticeGood Clinical Practice

IRB MakeupIRB Makeup

Minimum of 5 membersMinimum of 5 membersAt least one community memberAt least one community member

Varying backgrounds Varying backgrounds Scientific and Non-scientificScientific and Non-scientific

Sufficiently qualified through experience Sufficiently qualified through experience and expertise and expertise Meet the needs of studies reviewedMeet the needs of studies reviewed

Must be nondiscriminatoryMust be nondiscriminatory

45 CFR 46.11145 CFR 46.111Criteria for IRB Approval of Research

(a) In order to approve research covered by this policy the IRB shall determine that all of the following requirements are satisfied: (1) Risks to subjects are minimized: (i) By using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risk, and (ii) whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes.

(2) Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result. In evaluating risks and benefits, the IRB should consider only those risks and benefits that may result from the research (as distinguished from risks and benefits of therapies subjects would receive even if not participating in the research). The IRB should not consider possible long-range effects of applying knowledge gained in the research (for example, the possible effects of the research on public policy) as among those research risks that fall within the purview of its responsibility.

45 CFR 46.11145 CFR 46.111Criteria for IRB Approval of Research

(3) Selection of subjects is equitable. In making this assessment the IRB should take into account the purposes of the research and the setting in which the research will be conducted and should be particularly cognizant of the special problems of research involving vulnerable populations, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons.

(4) Informed consent will be sought from each prospective subject or the subject's legally authorized representative, in accordance with, and to the extent required by §46.116.

(5) Informed consent will be appropriately documented, in accordance with, and to the extent required by §46.117.

45 CFR 46.11145 CFR 46.111Criteria for IRB Approval of Research

(6) When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects.

(7) When appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data.

(b) When some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons, additional safeguards have been included in the study to protect the rights and welfare of these subjects.

Questions?Questions?