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Bertholf, Ph.D. Associate Professor of Pathology Chair, University of Florida IRB-03 MThe Nuremberg TrialseThe International Military Tribunal (1945) The Doctors Trial (1946) The Nuremberg Code (August, 1947)#The Nuremberg CodeEstablished necessity of informed consent Introduced concept of beneficence Introduced the notion of proportionality between risk and benefit $The Declaration of HelsinkiAdopted by the World Medical Association in 1964 Provided guidelines for the conduct of human subjects research Institutional Review Boards  generally accepted scientific principles Distinction between clinical and basic research Placebo controversy.pZZp%The Tuskegee Syphilis StudyPHS initiated syphilis treatment program in 1928 Discovered 35  40% infection rate in Macon County, AL Revised study to observation only Enlisted help of the Tuskegee Institute Terminated in 1972Z&The Belmont Report Drafted by the National Commission for the Protection of Human Subjects in Biomedical and Behavioral Research Final version adopted in 1979 Three sections: Clinical practice vs. research Three guiding principles of ethical research Application of the three principles .ZqZq'Clinical practice vs. researchGWhat is the purpose of the activity? Are results generalizable? Example1  ( ,Three Guiding Principles of Ethical Research+Respect for Individuals Beneficence Justice)!Respect for Individuals$Individuals act as autonomous agents%$*"+#Respect for IndividualsIndividuals act as autonomous agents Individuals who are not capable of acting as autonomous agents are entitled to special protections Minors Mentally incapacitated persons Prisoners(00,$ BeneficenceGuided by two basic principles: Do no harm Maximize benefits and minimize potential harms Risks should be in proportion to potential benefits Research design should ensure valid results < :b :b-%JusticeBenefits and risks of human research should be fairly distributed How do you select human research subjects? Societal allocation of burdens and benefits Equality, need, contribution, effort, merit Social vs. individual justice <mZXZZmX.&The Informed Consent Complete disclosure of all procedures, any foreseeable risks, and any reasonably anticipated benefits Informed consent can be waived only if: The risks are no greater than minimal The research cannot be practically conducted if consent is required Subjects are debriefed, when appropriate*/'The Informed ConsentiProxy consent Intentional/unintentional coercion Information must be presented in a comprehensible manner$jT0(Assessment of Risk/BenefitsgResearch involving brutal or inhumane treatment is never acceptable Risks should be reduced to only those necessary to achieve the objective If there is risk of serious impairment, there must be extraordinary justification If vulnerable populations are used, there must be a specific reason for doing so Relevant risks must be included in the informed consenthZh1)Federal Regulations45 CFR 46 The Common Rule (Part A) Subparts B, C, and D 21 CFR 50 and 56 50 includes rules for clinical trials 56 describes IRB responsibilitiesL .H .HThe Multiple Project AssuranceAny institution conducting federally funded (or regulated) research must provide the OHRP with a legally binding assurance that human research subjects are protected from unnecessary risk. Single or Multiple MPAs are usually approved for 5 years&::"The University of Florida MPAProvides for 4 IRBs: 01-04 (WIRB) Stipulates that all research at UF involving human subjects will be conducted in accordance with federal guidelines $2b,Components of the UF MPA=Institution is guided by the ethical principles in the The Belmont Report Specifies that IRBs will consider: the risks to the subjects, the anticipated benefits to the subjects and others, the importance of the knowledge that may reasonably be expected to result, and the informed consent process to be employed. <mmbBYApplicability of the UF MPABThe UF MPA applies if any of the following conditions are met: the research is sponsored by this institution, or the research is conducted by or under the direction of any employee or agent of this institution in connection with his or her institutional responsibilities, or the research is conducted by or under the direction of any employee or agent of this institution using any property or facility of this institution, or the research involves the use of this institution's non-public information to identify or contact human research subjects or prospective subjects. ?ZZZ?/bbbbbbbBIRB responsibilities^The IRB-03 is administratively responsible to the President of this institution, who has delegated the responsibility to this institution s Vice President for Research. 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