THE NATIONAL ACADEMY OF ENGINEERING

A Alpha Index

This index corresponds to the pages in the original NBAC documents, not the NBAC pages that are included on the Online Ethics Center. To access the original documents go to The NBAC publications. These documents can take a while to download.

A

• AAALAC. See Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC)
• AAAS. See American Association for the Advancement of Science (AAAS)
• AAHRPP. See Association for the Accreditation of Human Research Protection Programs (AAHRPP)
• AAMC. See Association of American Medical Colleges (AAMC)
• Accountability public, of human participants research, oversight system proposal for, xii, 26
• Accreditation organizations, for human participants research, oversight responsibilities of, 27 research ethics competence of institutions/IRBs, measures for demonstrating, vii, xiv, 49 - 50
• ACHRE. See Advisory Committee on Human Radiation Experiments (ACHRE)
• ADAMHA. See Alcohol, Drug Abuse and Mental Health Administration (ADAMHA)
• Adaptability human participants research and, oversight issues, 11 - 12
• Administration for Children and Families, 11, 132, see also Department of Health and Human Services (DHHS)
• Administration on Aging, 11 see also Department of Health and Human Services (DHHS)
• Adverse reactions research, FDA reporting requirements for, 113 - 114, 115, 116 research, FDA reporting requirements for, regulatory text, 213 - 216 research, reporting requirements for local institutions/IRBs, xix - xx, 113 - 114, 115 - 117 research, review requirements for local institutions/IRBs, 114, 115 - 116 See also Drugs and drug testing
• Advisory Committee on Human Radiation Experiments (ACHRE), 45, 46, 99, 124, 156, Final Report, 124 human participants research, recommendations of, 158
• Advocacy organizations, for human participants research, oversight responsibilities of, 27
• Africa vaccine death rates in, 85
• African Americans Tuskegee Syphilis Study, 46, 153, 164
• Agency for Healthcare Research and Quality, 11, 132, see also Department of Health and Human Services (DHHS)
• Agency for International Development (USAID), 11, 132, 205 HIV/AIDS and Pre-Adolescent Awareness Programs in Africa, 5 human participants research, regulations of, 157
• Alabama. See Macon County, Alabama; Tuskegee, Alabama; University of Alabama at Birmingham
• Alcohol, Drug Abuse and Mental Health Administration (ADAMHA), 155
• AMA. See American Medical Association (AMA)
• American Association for the Advancement of Science (AAAS), 47 American Medical Association (AMA), 151 American Psychological Association, 33 Applied Research Ethics National Association, 15, 33 Armed Forces Epidemiological Board, 153
• Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC), 49
• Association for the Accreditation of Human Research Protection Programs (AAHRPP), 49
• Association of American Medical Colleges (AAMC), 15, 46, 60 Association of American Universities, 15 Association of American University Professors, 13
• Assurances of compliance federal agencies practices regarding, listing by agency, 51 research standards compliance by institutions/IRBs, mechanisms for, xiv, 50 - 51 52 See also Compliance; Cooperative Project Assurance (CPA); Federalwide Assurance (FWA); Multiple Project Assurances (MPAs); Single Project Assurances (SPAs)
• Audits institutional, for research standards compliance of institutions/IRBs, xiv, 53
• Auschwitz, Germany interview, face-to-face, risks/potential benefits analysis example, 81
• Australia human participants research, terminology for, 33 research-related injuries, compensation for, 123
• Autonomy human participants research and, ethical principles, 162

B

• Backlar, Patricia, 33
• Balanced Budget Act Act of 1997, 4
• Beecher, Henry, 153
• Behavior psychological experiment on, risk/potential benefits analysis, 82 state law effects on, study of, risks/potential benefits analysis, 81
• Behavioral research prisoners as subjects, protections for, 45 CFR 46, Subpart C, in entirety, 182 - 184 See also Research
• Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research, ii, v, 35, 69, 97, 98, 154 applications of principles, 164 - 167 beneficence, relevance for, 162 - 163, 165 - 167 discussion of principles, 162 - 164 informed consent for, considerations, 164 - 165 justice, relevance for, 163 - 164, 167 research subject selection for, considerations, 167 research v. practice, distinction between, 161 - 162 respect for persons, relevance for, 162, 164 - 165 risks/benefits assessment for, considerations, 165 - 167 text, in entirety, 161 - 167 See also National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (National Commission)
• Beneficence, 71, see also Ethics
• Benefits research, potential, from Belmont Report, 162 - 163, 165 - 167 research, potential, to others, 74 research, potential, to participants, 73 - 74 research, potential, to society, 73 research, potential, types, 73 - 74 research, potential, v. risks, analysis in IRB review process, ii - iv, 79 research, potential, v. risks, analysis of, new technologies effects on, 7 research, potential, v. risks, analysis of, xvi - xvii, 69 - 85, 93 research, potential, v. risks, assessment of, ethical guidelines for, 165 - 167 research, potential, v. risks, balance between, assessment procedure, 78 - 80 research, potential, v. risks, component-based framework for analysis, 76 - 77, 78, 81 - 82 research, potential, v. risks, historical perspective, 75 - 76 research, potential, v. risks, relationship, assessment of, 74 - 75
• Bernard, Claude, 163
• Bioethics Commission. See National Bioethics Advisory Commission (NBAC)
• Biomedical research prisoners as subjects, protections for, 45 CFR 46, Subpart C, in entirety, 182 - 184 see also Research
• Brazil compensation for research-related injuries, 123
• Brooklyn Jewish Chronic Disease Hospital, 152
• Bureau of Census, 5, 10, 39 Disclosure Review Board, 10 Policy Office, 10

C

• California, 3
• See also Los Angeles, California; University of California, Irvine; University of California, Los Angeles; University of California, San Diego; University of California, San Francisco
• Capron, Alexander M., 33
• Cassell, Eric J., 33
• CCIP. See Council for Certification of IRB Professionals (CCIP) CDC. See Centers for Disease Control and Prevention (CDC) Census Bureau. See Bureau of Census
• Center for Molecular Medicine and Immunology research compliance investigations resulting in restrictions/actions, 55
• Centers for Disease Control and Prevention (CDC), 5, 11, 36, 39, 105, 107, 132 research compliance investigations resulting in restrictions/actions, 55 See also Department of Health and Human Services (DHHS)
• Central Intelligence Agency (CIA), 9, 11, 85, 132, 156
• Certificate of Confidentiality, 106, 107
• Certification organizations, for human participants research, oversight responsibilities of, 27 research ethics competence of individuals, measures for demonstrating, vii, xiv, 48 - 49
• 21 CFR 50. See Code of Federal Regulations, Title 21, Part 50 (21 CFR 50)
• 21 CFR 56. See Code of Federal Regulations, Title 21, Part 56 (21 CFR 56)
• 45 CFR 46. See Code of Federal Regulations, Title 45, Part 46 (45 CFR 46)
• Chicago, Illinois. See University of Illinois at Chicago
• Children research involving human participants, possible exemptions from oversight, 39 research participants with vulnerabilities targeted, listing by sponsoring agency, 86 research use of, protections for, 45 CFR 46, Subpart D, in entirety, 184 - 186
• Children's Research Act of 2000, 156
• China human research participants protection, regulations of, 157 research-related injuries, compensation for, 123
• CIA. See Central Intelligence Agency (CIA)
• CIOMS. See Council for International Organizations of Medical Sciences (CIOMS)
• City University of New York research compliance investigations resulting in restrictions/actions, 55
• Clinical trials drug efficacy, risks/potential benefits analysis example, 82 vaccine safety/immunogenicity, risk/potential benefits analysis example, 82 See also Research
• Cloning Human Beings, vii
• Code of Federal Regulations, Title 21, Part 50 (21 CFR 50), 28, 98, 100 human research participants protection, agency regulations, statutory authority for, 205 - 208 human research participants protection, regulations of, 157 Subpart A: General Provisions, for human subjects protection, in entirety, 187 - 189 Subpart B: Informed Consent of Human Subjects, in entirety, 189 - 195 See also Federal regulation
• Code of Federal Regulations, Title 21, Part 56 (21 CFR 56), 28, 53, 87, 98 human research participants protection, regulations of, 157 Subpart A: General Provisions, for IRBs, in entirety, 195 - 198 Subpart B: Organization and Personnel, for IRBs, in entirety, 198 Subpart C: IRB Functions and Operations, in entirety, 198 - 201 Subpart D: Records and Reports, for IRBs, in entirety, 201 Subpart E: Administrative Actions for Noncompliance, for IRBs, in entirety, 201 - 203 See also Federal regulation
• Code of Federal Regulations, Title 45, Part 46 (45 CFR 46), 2, 11, 28, 35, 87, 98, 100 human research participants protection, Common Rule and agency-specific regulations, 157 Subpart A: Federal Policy for Protection of Human Subjects, in entirety, 169 - 179 Subpart B: Additional DHHS Protections Pertaining to Research, Development, and Related Activities Involving Fetuses, Pregnant Women, and Human In Vitro Fertilization, in entirety, 179 - 182 Subpart C: Additional DHHS Protections Pertaining to Biomedical and Behavioral Research Involving Prisoners as Subjects, in entirety, 182 - 184 Subpart D: Additional DHHS Protections for Children Involved as Subjects in Research, in entirety, 184 - 186 See also Federal regulation
• Coercion human participants research, requirements for, 45 CFR 46, Subpart A, 176 - 178 voluntariness of, ethical guidelines from Belmont Report, 165 vulnerability in human participants research, definition of, NBAC recommendation, xvii, 92 vulnerable individuals protection in human participants research and, iv - v, xvii, 9, 11, 85 - 93
• Cognitive ability psychological experiment on, risk/potential benefits analysis example, 82 vulnerability, capacity- and situation-related, in research participants, ethical considerations, 88
• Colleges. See Universities and colleges
• Comments. See Public comments
• Commission. See National Bioethics Advisory Commission (NBAC)
• Commissioned papers. See Papers commissioned
• Common Rule. See Code of Federal Regulations, Title 45, Part 46 (45 CFR 46); Federal Policy for the Protection of Human Subjects (Federal Policy)
• Communication vulnerability, in research participants, ethical considerations, 88
• Communities research involving human participants, consideration of, 7 - 8
• Compensating for Research Injuries, 124
• See also President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research (President's Commission)
• Compensation research-related harm and, current regulatory requirements, 123 - 124 research-related harm and, current situation, 125 research-related harm and, NBAC recommendations, xx, 126 research-related harm and, need for, v, 125 - 126 research-related harm and, previous recommendations for program, 124 - 125 research-related harm and, role of local institutions, xx, 123 - 126
• Competence research ethics, accreditation for institutions/IRBs, vii, xiv, 49 - 50 research ethics, certification of individuals, vii, xiv, 48 - 49 research ethics, measures for demonstrating, xiv, 48 - 50
• Compliance research oversight enforcement weaknesses, 12 - 13 research oversight investigations resulting in restrictions/actions, listing by institution, 54 - 56 research standards and, by institutions/IRBs/investigators, mechanisms for ensuring, xiv, 50 - 58 research standards and, institutional audits for, xiv, 53 research standards and, site inspections by FDA for, xiv, 52 - 53 research standards and, site inspections by other than FDA for, xiv, 53 See also Assurances of compliance; Cooperative Project Assurance (CPA); Federalwide Assurance (FWA); Multiple Project Assurances (MPAs); Single Project Assurances (SPAs)
• Comprehensive Alcohol Abuse and Alcoholism Prevention, Treatment, Rehabilitation Act of 1970, 207
• Confidentiality definition for human participants research, proposed by NBAC, 107 research involving human participants, current regulations on, 104 - 105 research involving human participants, issues for, xviii, 106 - 107 research risk/potential benefit analysis, new technologies effects on, 7 See also Privacy
• Conflict of interest
  • IRB as institutional body and, protection of research participants, xv, 61 - 63, 64
  • IRB composition issues for, protection of research participants, 63 - 64
  • IRB membership and, protection of research participants, xv - xvi, 60 - 61, 63 - 64 research institutions/investigators/IRBs and, managing, NBAC recommendations, xv - xvi, 64 research investigators/IRBs and protection of human participants, measures for managing, xiv - xv, 58 - 60
  See also Ethics
• Congress, U.S. See U.S. Congress
• Consent. See Informed consent
• Consent forms. See Documentation; Informed consent
• Consent process. See Informed consent
• Consumer Product Safety Commission, 11, 132, 205 human participants research, regulations of, 157
• Contract research organizations (CROs), 6, 23, 25
• Cook County Hospital Hektoen Institute for Medical Research research compliance investigations resulting in restrictions/actions, 55
• Cooperative Project Assurance (CPA), 52 See also Assurances of compliance; Compliance; Office for Human Research Protections (OHRP)
• Cooperative research human participants research, and IRB multi-site research studies, 14 range of, summary, 117 review of, by IRBs, foreign models of, 121 - 122 review of, by local IRBs, considerations, 118 - 122 review of, current requirements and problems, xx, 118 See also Research
• Cornell University Medical Center research compliance investigations resulting in restrictions/actions, 55
• Council for Certification of IRB Professionals (CCIP), 48
• Council for International Organizations of Medical Sciences (CIOMS), 123, 215, 216
• Council of Europe, 123
• CPA. See Cooperative Project Assurance (CPA) CROs. See Contract research organizations (CROs) Current Population Survey, 1988, 81

D

• Data existing, research risks/potential benefits analysis of, example, 81
• Data and Safety Monitoring Board (DSMB), 25, 54, 134 research adverse events reporting requirements for, xix - xx, 113, 115 - 116, 117
• Death research involving deceased individuals, possible exemptions from oversight, 39 - 40
• Deception research informed consent requirements for human participants in, 101
• Decisionmaking capacity mentally impaired research participants and, informed consent and limitations on, 101
• Denmark cooperative research, IRB review models in, 121
• Department of Commerce, 11, 132, 205 human participants research, regulations of, 157
• Department of Defense (DOD), 5, 11, 132, 190, 191, 192, 205 human participants research, regulations of, 157 Secretary, 151 Top Secret policy, 151 - 152
• Department of Education, 9, 11, 39, 85, 104, 107, 132 human participants research, regulations of, 157 human participants research, regulations of, statutory authority for, 205, 206, 208 - 209 Secretary, 206 site inspections to ensure compliance with research standards, 53
• Department of Energy (DOE), 5, 11, 12, 132 human participants research, regulations of, 157 human participants research, regulations of, statutory authority for, 205, 206 Secretary, 206 site inspections to ensure compliance with research standards, 53 See also Nuclear Regulatory Commission (NRC)
• Department of Health and Human Services (DHHS), vi, xiv, 2, 4, 8, 9, 10, 11, 12, 15, 28, 29, 30, 31 - 32, 37, 39, 50, 51, 55, 56, 71, 75, 76, 83, 85, 87, 88, 91, 105, 106, 116, 124, 131, 132, 152, 154, 155, 156 children as research subjects, protections for, 45 CFR 46, Subpart D, in entirety, 184 - 186 Ethics Advisory Board, 155 human participants research, 45 CFR 46, Subpart A, in entirety, 169 - 179 human participants research, regulations of, 157 human participants research, regulations of, statutory authority for, 205, 207 - 208, 209 Office of Inspector General (OIG), 8, 57, 112, 116, 131 Office of the Secretary, 15, 30 pregnant women, fetuses, and in vitro fertilization in research, protections for, 45 CFR 46, Subpart B, in entirety, 179 - 182 prisoners in biomedical/behavioral research, protections for, 45 CFR 46, Subpart C, in entirety, 182 - 184 Secretary, 152, 154, 155, 179, 180, 182, 183, 185, 207, 208 'Standards for Privacy of Individually Identifiable Health Information,' 105 See also Administration for Children and Families; Administration on Aging; Agency for Healthcare Research and Quality; Centers for Disease Control and Prevention (CDC); Department of Health, Education, and Welfare (DHEW), Food and Drug Administration (FDA); Health Care Financing Administration; Health Resources and Services Administration (HRSA); Indian Health Service; National Institutes of Health (NIH); Substance Abuse and Mental Health Services Administration Department of Health, Education, and Welfare (DHEW), 124, 153, 154 Ethics Advisory Board, 124 Medical Malpractice Commission, 124 Secretary, 124 Secretary's Task Force on the Compensation of Injured Research Subjects, 124 'Yellow Book,' 153 See also Department of Health and Human Services (DHHS)
• Department of Housing and Urban Development, 11, 132 human participants research, regulations of, 157 human participants research, regulations of, statutory authority for, 205, 206 Secretary, 206
• Department of Justice, 9, 11, 39, 85, 105, 132 Attorney General, 206 Bureau of Prisons, 9, 208 Federal Prison Industries, Inc., 206 human participants research, regulations of, 157 human participants research, regulations of, statutory authority for, 205, 206, 208
• Department of Labor, 171
• Department of Transportation, 11, 85, 132, 205 Federal Highway Administration, Human Factors Laboratory, 5 human participants research, regulations of, 157 U.S. Coast Guard, 5
• Department of Veterans Affairs (VA), 5, 10, 11, 16, 49, 126, 132 Comprehensive Research Integrity Program, 53 human participants research, regulations of, 157 human participants research, regulations of, statutory authority for, 205, 207, 209 Multi-Assessment Program, 53 Office of Research Compliance and Assurance, 53 Secretary, 207 site inspections to ensure compliance with research standards, 53 Special Inquiry Force Teams, 53
• DHEW. See Department of Health, Education, and Welfare (DHEW)
• DHHS. See Department of Health and Human Services (DHHS)
• Disclosure of information conflict of interest for investigators/IRBs, measures for managing, 59 - 60 human participants research and, ethical guidelines from Belmont Report, 164 - 165 human participants research, requirements for, emphasis on, issues, iv, xvii, 98 - 100 human participants research, requirements for, listing, 99 See also Information; Informed consent
• Diseases and disorders illness, serious, as vulnerability in research participants, ethical considerations, 89 - 90 See also Mental diseases and disorders; Syphilis
• Documentation informed consent requirements for human participants research, discussion of, xviii, 103 - 104
• DOD. See Department of Defense (DOD)
• DOE. See Department of Energy (DOE)
• Drug Abuse Office and Treatment Act of 1972, 207
• Drugs and drug testing efficacy of, clinical trial on, risks/potential benefits analysis example, 82 vaccine, clinical trial on, risk/potential benefits analysis example, 82 research adverse events, FDA reporting requirements for, 113 - 114, 115, 116 See also Adverse reactions; Clinical trials; Vaccines and vaccination
• DSMB. See Data and Safety Monitoring Board (DSMB)
• Duke University, 133 research compliance investigations resulting in restrictions/actions, 56 Medical Center, research compliance investigations resulting in restrictions/actions, 56

E

• Economics. See Investment; Personal finance
• Edgar, H., 9
• Editors scientific, oversight system proposed for human participants research, responsibilities of, 27
• Education disadvantaged persons targeted for research, listing by sponsoring agency, 86 research involving human participants, and IRB needs, 15 research involving human participants, measures needed for, vi - vii, xiii, 45 - 48 research involving human participants, oversight system proposal for, xii, 23
• Eisenberg, J.M., 36
• Ellis, Gary, 119
• Embryos and embryonic materials research involving human participants, possible exemptions from oversight, 39 See also Fetus and fetal tissue; Pregnancy
• Enforcement research involving human participants, protection of, oversight system proposal for, xii, 25 - 26 research involving human participants, protection of, oversight weaknesses, 12 - 13
• Environmental Protection Agency (EPA), 5, 11, 132, 170, 197, 205 human participants research, regulations of, 157
• EPA. See Environmental Protection Agency (EPA)
• Equipoise research, explanation of, 77, 78 See also Clinical trials
• Equivalent protections. See Protections for human participants
• Ethical Advisory Board, 182 research involving pregnant women, fetuses, and in vitro fertilization, requirements for, 45 CFR 46, Subpart B, 180
• Ethical and Policy Issues in International Research: Clinical Trials in Developing Countries, vii
• Ethics accreditation of competence of research institutions/IRBs for, xiv, 49 - 50 benefits, potential, of research to others, 74 benefits, potential, of research to participants, 73 - 74 benefits, potential, of research to society, 73 benefits, potential, of research, types, 73 - 74 certification of competence of research individuals for, xiv, 46, 48 - 49 competence for research, measures for demonstrating, xiv, 48 - 50 compliance with research standards by institutions/IRBs/ investigators, mechanisms for ensuring, xiv, 50 - 58 research equipoise, explanation, 77, 78 risks of harms from research to nonparticipants, 72 - 73 risks of harms from research, types of, 71 - 73 risks, research, minimizing, 73 risks, research, v. potential benefits, analysis of, xvi - xvii, 69 - 85, 93 risks, research, v. potential benefits, balance between, assessment procedure, 78 - 80 risks, research, v. potential benefits, component-based framework for analysis, 76 - 77, 78, 81 - 82 risks, research, v. potential benefits, historical perspective, 75 - 76 risks, research, v. potential benefits, relationship, assessment of, 74 - 75. See also Beneficence; Conflict of interest; Ethics review and review committees; Justice; Protections for human participants; Respect for persons Ethics review and review committees adverse events and, local institutions/IRBs responsibilities, 114, 115 - 116 conflict of interest and IRB institutional role, measures for managing, xv, 61 - 63, 64 conflict of interest and IRB membership/composition, xv - xvi, 60 - 61, 63 - 64 continuing for ongoing research, local institutions responsibilities, xix, 111 - 112, 117 cooperative research, by IRBs, foreign models of, 121 - 122 cooperative research, by local IRBs, alternatives to, 120 - 122 cooperative research, by local IRBs, considerations, 118 - 120 cooperative research, current requirements and problems, xx, 118 cooperative research, role of local IRBs/institutions, xx, 122 human participants research, and IRB multi-site research studies, 14 human participants research, IRB burdens, 13 - 15 human participants research, oversight system proposal, xii, 23 - 24, 28, 30 independent IRBs, emergence of, 6 levels of, oversight system proposal for, vii - viii, xiii, 41 - 42 risk, minimal, research classification, use as sorting mechanism for, 84 risks v. potential benefits of human participants research, analysis in, ii - iv, 79 risks v. potential benefits, analysis in IRB process, 79 risks v. potential benefits, balance between, assessment procedure, 78 - 80 risks v. potential benefits, component-based framework for analysis, 76 - 77, 78, 81 - 82 risks v. potential benefits, component-based framework for analysis, examples, 81 - 82 See also Ethics; Evaluation; Institutional Review Boards (IRBs) Evaluation health services research and, determining oversight coverage, 36 - 37, See also Ethics review and review committees Expert testimony. See Testimony and speakers

F

• Family Education Rights and Privacy Act of 1974, 104
• FDA. See Food and Drug Administration (FDA)
• Federal Coordinators Council for Science, Engineering, and Technology, 154
• Federal departments and agencies assurances of compliance, practices regarding, listing by agency, 51 human participants research, Common Rule and agency-specific regulations, 157 human participants research, inconsistencies among, 9, 10 human participants research, independent oversight office proposal for, vi, xii, 28, 30 - 32 human participants research, percent exempt, listing by agency, 11 human participants research, regulations of, statutory authority for, 205 - 211 human participants research, support for FY 1999, listing by agency, 132 human participants research, supported by, size and scope of, 5 vulnerability and human participants targeted in research, listing by agency/vulnerability, 86 See also Federal government; Federal regulation; specific departments and agencies
• Federal Food, Drug, and Cosmetic Act, 29, 187, 190, 195 Kefauver-Harris amendments, 152, 153
• Federal funding for research oversight system for, resources for, viii, xx - xxi, 131, 133 research investment trends, changes in, 4 research involving human participants supported by, size and scope of, 5 research involving human participants, resources for, xx - xxi, 131, 133 research involving human participants, support for FY 1999, listing by agency, 132 See also Federal government; Research funding
• Federal government human research participants protection, activities of, 156 See also Federal departments and agencies; Federal funding for research; Federal legislation; Federal regulation; Public policy; U.S. Congress
• Federal legislation human research participants protection, agency regulations and, statutory authority for, 205 - 211 See also Federal government; Federal regulation; specific legislation; U.S. Congress
• Federal oversight. See Federal regulation; Oversight
• Federal policy. See Federal government; Federal regulation; Public policy
• Federal Policy for the Protection of Human Subjects (Common Rule), 2, 3, 5, 9, 11 - 12, 24, 26, 28, 29, 31, 35, 38, 51, 52, 70 - 71, 76, 113, 118, 135, 155 - 156 Common Rule definition, 154 Common Rule signatories, 159 human participants research, Common Rule and agency-specific regulations, 157 human participants research, inconsistencies among federal agencies, 10 See also Code of Federal Regulations, Title 45, Part 46 (45 CFR 46)
• Federal Register, 10, 39, 154, 170, 174, 179, 182, 183, 184, 191, 199, 202, 205, 206
• Federal regulation, accreditation of competence of research institutions/IRBs, vii, xiv, 49 - 50 adverse research events, FDA reporting requirements, 113 - 114, 115, 116, 213 - 216 adverse research events, reporting requirements for local institutions, xix - xx, 113 - 117 certification of competence of research individuals, vii, xiv, 48 - 49 compliance with research standards by institutions/IRBs/ investigators, mechanisms for ensuring, xiv, 50 - 58 conflict of interest for research IRBs, measures for managing, 60 - 63 cooperative research review, current requirements and problems, xx, 118 cooperative research review, requirements for IRBs, 122 education on human participants protection, measures needed for, vi - vii, xiii, 45 - 48 educational programs for human participants research, oversight system proposal for, xii, 23 human participants research, Common Rule and agency-specific regulations, 157 human participants research, consequences of flawed system, 16 human participants research, current oversight system, challenges for, 8 - 16 human participants research, current protection of, 29 human participants research, defining for oversight coverage determination, xii - xiii, 34 - 42 human participants research, description of, 154, 155 - 156, 157 human participants research, enforcement weaknesses, 12 - 13 human participants research, ethical issues for, future research on, xxi, 134 human participants research, history of, 151 - 154 human participants research, inconsistencies among agencies, 9, 10 human participants research, IRB burdens in, 13 - 15 human participants research, lack of adaptability in, 11 - 12 human participants research, limited scope of, 12 human participants research, oversight independent office proposed for, vi, xii, 28, 30 - 32 human participants research, oversight possible exemptions, 37 - 41 human participants research, oversight system proposal for, xi - xiii, 21 - 42 human participants research, oversight system for, purpose of, i - ii, xi, 2 - 4, 21 - 22 human participants research, oversight system for, resources for, viii, xx - xxi, 131, 133 human participants research, oversight system proposal for enforcement of, xii, 25 - 26 human participants research, oversight system proposal for ethical review of research, xii, 23 - 24 human participants research, oversight system proposal for monitoring, xii, 24 - 25 human participants research, oversight system proposal for National Office for Human Research Oversight for, xii, 28, human participants research, oversight system proposal for policy development through, xii, 23 human participants research, oversight system proposal for public accountability, xii, 26 human participants research, oversight system proposal for unified/comprehensive policy for, v - vi, xii, 28, 30 - 32 human participants research, oversight system proposal for, as dynamic/responsive structure, 134 - 135 human participants research, oversight system proposal for, scope and structure, xii, 26 - 32 human participants research, oversight system proposed for, functions and responsibilities of, xi - xii, 23 - 27 human participants research, percent exempt from, listing by agency, 11 human participants research, procedural v. ethical emphasis, 13 human participants research, protection for, ACHRE recommendations, 158 human participants research, recent government interest in, 156 human participants research, recent initiatives for, 15 - 16 human participants research, report implications for IRBs/ investigators/institutions, 136 - 137 human participants research, report implications for participants, 137 human participants research, report recommendations for, general themes in, 135 informed consent requirements for research participants, deficiencies in, 98 informed consent requirements for research participants, scope/structure of, iv, xvii, 97 - 104 privacy and confidentiality protection for research participants, 104 - 105 research approval by IRBs, current regulations for, 69 - 71 research protocol changes and unanticipated problems, local institutions responsibilities, xix, 112 - 113, 117 research, ongoing, monitoring responsibilities of local institutions, xix, 117 research-related injuries, compensation for, current requirements, v, 123 - 124 review, continuing, of ongoing research, IRBs responsibilities, xix, 117 review, levels of, for human participants research, oversight system proposal for, vii - viii, xiii, 41 - 42 risk, minimal, research classification, definition in, xvi, 80, 83 - 84 risks, research, v. potential benefits, analysis in IRB review process, ii - iv, 79 vulnerability of research participants, current protections for, 85 - 92 vulnerable individuals protection in human participants research, oversight issues, iv - v, 9, 11 See also Federal departments and agencies; Federal government; Federal legislation; Public policy
• Federalwide Assurance (FWA), 52, See also Assurances of compliance; Compliance
• Fetus and fetal tissue research activities on, protections for, 45 CFR 46, Subpart B, in entirety, 179 - 182 research involving human participants, possible exemptions from oversight, 39 research targeting participants with vulnerabilities, listing by sponsoring agency, 86 See also Embryos and embryonic materials; Pregnancy
• Finance. See Investments; Personal finance
• Florida. See Florida State University; University of Florida; University of South Florida
• Florida State University research compliance investigations resulting in restrictions/actions, 54
• Food and Drug Administration (FDA), v, xiv, 2, 3, 4, 7, 9, 10, 11, 12, 15, 25, 26, 27, 28, 29, 32, 38, 50, 57, 59, 71, 98, 106, 120, 121, 126, 132, 152, 153, 154, 156, 170, 171, 187, 188, 191, 192, 193, 194, 203 Bioresearch Monitoring Program, 52, 53 Center for Biologics Evaluation and Research, 215, 216 Center for Drug Evaluation and Research, 215, 216 Commissioner, 202 human participants research, regulations of, 157 human participants research, regulations of, statutory authority for, 210 - 211 IRB functions/operations and, 21 CFR 56, Subpart C, in entirety, 198 - 201 IRB noncompliance with federal regulations and, administrative actions for, 21 CFR 56, Subpart E, in entirety, 201 - 203 IRB records/reports and, 21 CFR 56, Subpart D, in entirety, 201 IRBs and, general provisions for, 21 CFR 56, Subpart A, in entirety, 195 - 198 Office of Clinical Science, 15 research adverse events reporting requirements of, 113 - 114, 115, 116 research adverse events reporting requirements of, regulatory text, 213 - 216 site inspections by, to ensure IRBs compliance with research standards, xiv, 52 - 53 See also Department of Health and Human Services (DHHS)
• Food, Drug, and Cosmetic Act. See Federal Food, Drug, and Cosmetic Act
• Fordham University research compliance investigations resulting in restrictions/actions, 56
• Foreign countries cooperative research, IRB review models in, 121 - 122 See also specific countries
• France research involving human participants, terminology for, 33 research-related injuries, compensation for, 123
• Francis, Leslie, 61
• Friends Research Institute research compliance investigations resulting in restrictions/actions, 56 FWA. See Federalwide Assurance (FWA)

G

• Gelsinger, Jesse, 3
• General Accounting Office, 8
• Germany. See Auschwitz, Germany
• Government funding for research. See Federal funding for research
• Great Britain human research participants, studies on abuses of, 153 See also United Kingdom
• Groups research involving human participants, consideration of, 7 - 8

H

• Harms research involving human participants, oversight of, need for, 2 - 4 research participants vulnerability, current regulatory protections for, 85 - 92 research risks of, for nonparticipants, 72 - 73 research risks of, minimizing, 73 research risks of, types of, 71 - 73 research risks/potential benefits, analysis in IRB review process, 79 research risks/potential benefits, balance between, assessment procedure, 78 - 80 research risks/potential benefits, component-based framework for analysis, 76 - 77, 78, 81 - 82 research risks/potential benefits, historical perspective, 75 - 76 research risks/potential benefits, relationship, assessment of, 74 - 75 research-related, compensation for, current regulatory requirements, 123 - 124 research-related, compensation for, current situation, 125 research-related, compensation for, need for, v, 125 - 126 research-related, compensation for, previous recommendations for program, 124 - 125 research-related, compensation for, role of local institutions, xx, 123 - 126
• Health and Human Services Department. See Department of Health and Human Services (DHHS)
• Health and illness. See Diseases and disorders
• Health care research v. practice of, distinction between, 161 - 162 research v. practice of, distinction between for determining oversight coverage, 34 - 37 See Diseases and disorders; Public health
• Health Care Financing Administration, 5, 11, 132
• See also Department of Health and Human Services (DHHS)
• Health Education and Welfare Task Force, 71
• Health Insurance Portability and Accountability Act of 1996, 105 Health Resources and Services Administration (HRSA), 10, 11, 132 Human Subjects Committee, 10 See also Department of Health and Human Services (DHHS) Health services research oversight system coverage determination, 36 - 37
• See also Research Hippocratic oath, 163 Holm, SÖren, 121
• Hospitals. See Medical centers
• HRSA. See Health Resources and Services Administration (HRSA) Human participants. See Protections for human participants Human Radiation Interagency Working Group, 158 Human Subjects Research Subcommittee, 154

I

• ICH. See International Conference on Harmonization (ICH) IDE. See Investigational device exemption (IDE) Illinois. See University of Illinois at Chicago Illness. See Diseases and disorders Immunogenicity vaccine safety clinical trial, risk/potential benefits analysis example, 82
• Implementing Human Research Regulations, 155
• See also President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research (President's Commission) IND. See Investigational new drug application (IND) Independent bodies IRBs, emergence of, 6 human participants research, oversight office proposed for, vi, xii, 28, 30 - 32 India research-related injuries, compensation for, 123 Indian Health Service, 11, 132 See also Department of Health and Human Services (DHHS) Inducement. See Coercion Influence. See Coercion Information revelation of, about others, research involving human participants, 39 See also Disclosure of information; Informed consent Informed consent comprehension for, ethical guidelines from Belmont Report, 165 deficiencies in current requirements for, 98 documentation requirements for, discussion of, xviii, 103 - 104 human participants research and, ethical guidelines from Belmont Report, 164 - 165 human participants research, requirements for, 21 CFR 50, Subpart B, in entirety, 189 - 195 human participants research, requirements for, 45 CFR 46, Subpart A, 176 - 178 mentally impaired research participants and, requirements for, 101 process, emphasis on, discussion of, iv, xvii, 98 - 101 processes for various research settings, 100 - 101 recommendations of NBAC on, xvii, xviii, 98, 101, 102, 103, 104 voluntariness of, ethical guidelines from Belmont Report, 165 voluntary, requirements for research participants, scope/ structure of, 97 - 104 waiver of requirements for, discussion, xvii - xviii, 101 - 103 See also Disclosure of information; Information
• Injuries. See Harms
• Inspections. See Site inspections
• Institute of Medicine (IOM), 36, 49, 107
• Institutional Review Boards (IRBs), xi, xvi, xvii, xviii, 1, 10, 13, 22, 31, 32, 37, 39, 53, 58, 59, 71, 72, 73, 80, 83, 85, 87, 90, 91, 92, 97, 98, 99, 100, 101, 104, 105, 106, 107, 155, 158 accreditation of competence for research ethics, measures for demonstrating, vii, xiv, 49 - 50 adverse events reporting requirements for, xx, 117 adverse events review, requirements for, xix, xx, 114, 115 - 116, 117 adverse events, FDA reporting requirements for, regulatory text, 213 - 216 assurances of compliance for research standards by, xiv, 50 - 51, 52 audits, institutional, for research standards compliance by, xiv, 53 children as research subjects, protections for, requirements for, 45 CFR 46, Subpart D, 184 competence in research ethics, measures for demonstrating, xiv, 48 - 50 compliance oversight investigations resulting in restrictions/actions to MPAs, listing by institution, 54 - 56 compliance with research standards by, mechanisms for ensuring, xiv, 50 - 53 compliance with research standards of, by investigators, monitoring for verification, xiv, 57 - 58 composition of and conflict of interest, issues for, 63 - 64 conflict of interest and institutional role of, measures for managing, xv, 61 - 63, 64 conflict of interest and, measures for managing, xv - xvi, 64 cooperative research local review by, alternatives to, 120 - 122 cooperative research local review by, pros/cons, 118 - 119, 119 - 120 cooperative research review by, foreign models of, 121 - 122 cooperative research review role of, xx, 122 cooperative research review, current requirements and problems, xx, 118 education on human participants protection, measures needed for, vi - vii, xiii, 45 - 48 educational needs on human participants research, 15 functions/operations of, requirements for, 21 CFR 56, Subpart C, in entirety, 198 - 201 human participants research, current oversight burdens of, 13 - 15 human participants research, general provisions for, 21 CFR 56, Subpart A, in entirety, 195 - 198 human participants research, proposed oversight system, and ethical review, xii, 23 - 24 human participants research, proposed oversight system, and enforcement of requirements, xii, 25 - 26 human participants research, proposed oversight system, and functions/responsibilities of, xi - xii, 23 - 27 human participants research, proposed oversight system, and monitoring, xii, 24 - 25 human participants research, report implications for, 136 - 137 human participants research, requirements for, 45 CFR 46, Subpart A, 173 - 176 human participants research, resources for, 131, 133 human participants research, responsibilities of, issues concerning, xix - xx, 111 - 126 human participants research, revised oversight system, as dynamic/responsive structure, 134 - 135 independent, emergence of, 6 informed consent documentation requirements of, xviii, 104 informed consent requirements of, waiver of, xviii, 102, 103 membership and conflict of interest, measures for managing, xv - xvi, 60 - 61, 64 monitoring of ongoing research, responsibilities of, xix - xx, 111 - 117 multi-site research studies, and human participants, 14 noncompliance with federal regulations by, administrative actions for, 21 CFR 56, Subpart E, in entirety, 201 - 203 organization/personnel of, requirements for, 21 CFR 56, Subpart B, in entirety, 198 pregnant women, fetuses, and in vitro fertilization, research protections for, requirements for, 45 CFR 46, Subpart B, 180 prisoners in biomedical/behavioral research, protections for, requirements for, 45 CFR 46, Subpart C, 182 - 183 protocol changes and unanticipated problems, local institutions responsibilities, xix, 112 - 113, 117 records/reports of, requirements for, 21 CFR 56, Subpart D, in entirety, 201 research approval by, current regulations for, 69 - 71 research risks v. potential benefits analysis, xvi - xvii, 69 - 85, 93 research risks v. potential benefits, component-based framework for analysis, 76 - 77, 78, 81 - 82 research risks v. potential benefits, component-based framework for analysis, examples, 81 - 82 research risks v. potential benefits, relationship, assessment of, 74 - 75 review process for research of, 79 review, continuing, of ongoing research, responsibilities of, xix, 117 review, levels of, for human participants research, oversight system proposal for, xiii, 41 - 42 risk, minimal, for human research participants, review of, oversight proposal, 24 risk, minimal, research classification, use as sorting mechanism for review, 84 risks v. potential benefits of human participants research, analysis in review process, ii - iv, 79 site inspections by FDA to ensure compliance with research standards, xiv, 52 - 53 vulnerability of research participants, evaluation of, xvii, 85 - 93 See also Ethics review and review committees
• Internal Revenue Service (IRS), 34, 40
• International Conference on Harmonization (ICH), 123 Internet, 7 Interventions. See Health care
• Interviews face-to-face, research risks/potential benefits analysis example, 81
• Investigational device exemption (IDE), 193
• Investigational new drug application (IND), 190, 191, 193 adverse research events, FDA reporting requirements for, regulatory text, 213 - 216
• Investigators accreditation for competence of, measures for demonstrating, xiv, 49 - 50 certification of competence of research individuals, vii, xiv,
• 48 - 49 compliance with research standards by, monitoring for verification, xiv, 57 - 58 conflict of interest for, measures for managing, xiv - xv, 58 - 60 education on human participants research, measures needed for, vi - vii, xiii, 45 - 48 human participants research, report implications for IRBs/ investigators/institutions, 136 - 137 monitoring of ongoing research, local institutions responsibilities, xix, 117 oversight system, proposed, functions and responsibilities of, 26 oversight system, proposed, monitoring, xii, 24 - 25 oversight system, proposed, enforcement of requirements, xii,
• 25 - 26 recommendations of NBAC for, xiv, xv - xvi, xiii, xix, 47 - 48, 50, 64, 117 See also Research
• Investment research, changes in trends in, 4
• In Vitro fertilization (IVF) research activities involving, protections for, 45 CFR 46, Subpart B, in entirety, 179 - 182
• IOM. See Institute of Medicine (IOM) IRBs. See Institutional Review Boards (IRBs) IRS. See Internal Revenue Service (IRS)

J

• Joint United Nations Programme on HIV/AIDS (UNAIDS), 33, 123
• Jonas, Hans, i, ii
• Justice human research participants protection and, from Belmont Report, 163ñ164 human research participants selection and relevance, from Belmont Report, 167 individual, and human research participants selection, 167 social, and human research participants selection, 167

L

• Languages, German, interview, face-to-face, risks/potential benefits analysis example, 81 Hebrew, interview, face-to-face, risks/potential benefits analysis example, 81
• Levine, Robert J., 75
• Local entities adverse events reporting requirements for, xix - xx, 113 - 117 adverse events review, requirements for, 114, 115 - 116 compensation for research-related injuries, role of, xx, 123 - 126 cooperative research review, by, alternatives to, 120 - 122 cooperative research review, by, considerations, 118 - 120 cooperative research review, role of, 122 human participants research responsibilities of, issues concerning, xix - xx, 111 - 126 monitoring of ongoing research, responsibilities of, xixñxx, 111 - 117
• Los Angeles, California, 119 See also California

M

• Macon County, Alabama, 153
• Massachusetts Eye and Ear Infirmary research compliance investigations resulting in restrictions/actions, 54
• Maternity. See Pregnancy
• Maryland, 56
• See also University of Maryland, Baltimore Medicaid, 5 Medical care. See Health care
• Medical centers academic, and research universities, stresses on, 4, 6
• Medical devices research adverse events, FDA reporting requirements, 114, 115
• Medical interventions/treatment. See Health care
• Medical University of South Carolina research compliance investigations resulting in restrictions/actions, 54
• Memorial-Sloan Kettering Cancer Center research compliance investigations resulting in restrictions/actions, 54
• Mental diseases and disorders vulnerable persons targeted for research, listing by sponsoring agency, 86 See Diseases and disorders
• Milgram, S., 71
• Minnesota. See University of Minnesota
• Monitoring human research participants protection, local institutions responsibilities for, xix - xx, 111 - 117 human research participants protection, oversight enforcement weaknesses, 12 - 13 human research participants protection, oversight proposal for, xii, 24 - 25 research standards compliance by investigators, verification of, xiv, 57 - 58
• Moreno, Jonathan, 9, 22
• MPAs. See Multiple Project Assurances (MPAs)
• Mt. Sinai School of Medicine research compliance investigations resulting in restrictions/actions, 56
• Multiple Project Assurances (MPAs), 8, 14, 46, 52, 118 compliance investigations by OPRR resulting in restrictions/actions to, listing by institution, 54 - 56 See also Assurances of compliance; Compliance; Office for Human Research Protections (OHRP)
• Multi-site research. See Cooperative research

N

• NAS. See National Academy of Sciences (NAS)
• NASA. See National Aeronautics and Space Administration (NASA)
• National Academy of Sciences (NAS), 47
• National Aeronautics and Space Administration (NASA), 5, 11, 132, 205 human participants research, regulations of, 157
• National Bioethics Advisory Commission (NBAC), ii, xi, xviii, 1, 5, 7, 16, 21, 22, 24, 26, 30, 31, 32, 33, 34, 35, 38, 39, 41, 45, 46, 47, 48, 52, 53, 60, 63, 71, 72, 75, 76, 84, 85, 92, 97, 99, 100, 101, 102, 103, 104, 106, 107, 116, 117, 119, 123, 125, 131, 133 accreditation of competence of research institutions/IRBs, recommendations, xiv, 50 adverse events reporting requirements for, recommendations, xx, 117 certification of competence of research individuals, recommendations, xiv, 48 - 49 compensation for research-related injuries, recommendations, xx, 126 compliance with research standards by institutions/IRBs/ investigators, ensuring, recommendations, xiv, 58 confidentiality for research participants, proposed definition for, 107 confidentiality for research participants, recommendation, xviii, 107 conflict of interest and investigators/IRBs/institutions, recommendations, xv - xvi, 64 cooperative research review, requirements for, recommendations, xx, 122 education on research ethics and human participants protection, education on, recommendations, xiii, 47 - 48 human participants research, defining for oversight coverage determination, recommendations, xii, 40 human participants research, ethical and policy issues in, recommendations summary, xi - xxi human participants research, ethical issues for, future research recommendations, xxi, 134 human participants research, report recommendations for, general themes in, 135 human participants research, resources for, recommendations, xx - xxi, 133 human participants research, revised oversight system for, scope/structure, recommendations, xii, 28, 30 human participants research, unified/comprehensive federal policy for, recommendations, xii, 30 informed consent documentation requirements for human participants, recommendation, xviii, 104 informed consent requirements for human participants, previous recommendations on, 98 informed consent requirements for human participants, process emphasis, recommendations, xvii, 101 informed consent requirements for human participants, waiver of, recommendations, xviii, 102, 103 IRB membership/composition and conflict of interest, recommendations, xv - xvi, 64 monitoring of ongoing research, local institutions responsibilities, recommendations, xix, 117 National Office for Human Research Oversight creation, recommendations, xii, 28, 30 privacy for research participants, proposed definition for, 106 privacy for research participants, recommendation, xviii, 107 research protocol changes and unanticipated problems, local institutions role, recommendations, xix, 117 research risks v. potential benefits, analysis of, recommendations, xvi - xvii, 77, 85 review, continuing, of ongoing research, IRBs responsibilities, recommendations, xix, 117 review, levels of, for human participants research, oversight proposal for, recommendations, xiii, 41 - 42 risk, minimal, of research, federal policy on, recommendation, xvi - xvii, 85 vulnerability of research participants, definition of, recommendation, xvii, 92
• National Cancer Institute (NCI), 121
• National Center for Educational Statistics Confidentiality Statute, 105, 107
• National Center for Health Statistics, 39
• National Commission. See National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (National Commission)
• National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (National Commission), i, 34, 35, 45, 50, 57, 58, 62, 83, 112, 118, 120, 124, 131, 153 - 154, 155, 161, 207, Institutional Review Boards, 76 Research Involving Children, 75 Research on the Fetus, 75 Research Involving Prisoners, 75 research risks/potential benefits, historical perspective, 75 - 76, See also Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research
• National Heart, Lung, and Blood Institute, 7 - 8
• National Human Experimentation Board, 153
• National Institutes of Health (NIH), 3, 7, 10, 11, 15, 28, 30, 46, 48, 113, 116, 118, 131, 132, 133, 151, 152, 153, 155, 170, 172, 174 Clinical Center, 34, 151, 152 Director, 152, 208 Division of Research Grants, 50, 152 Institutional Relations Branch, 152 Office of Extramural Research, 8 Reducing Regulatory Burden, 133 research compliance investigations by OPRR resulting in restrictions/actions to MPAs, 54 See also Department of Health and Human Services (DHHS); Office for Protection from Research Risks (OPRR)
• National Office for Human Research Oversight (NOHRO), 40, 84 advantages v. disadvantages of, 30 - 31 creation of, vi, xii, 28, 30 - 32 operating mode of, 31 - 32 private sector research, regulation of, 32
• National Research Act. See Public Law 93 - 348
• National Science Foundation (NSF), 5, 11, 53, 132, 205 Directorate of Social, Behavioral and Economic Sciences, 5 human participants research, regulations of, 157 Office of Inspector General, 53 site inspections to ensure compliance with research standards, 53
• Nazis, 34, 81, 151, 164
• NBAC. See National Bioethics Advisory Commission (NBAC)
• NCI. See National Cancer Institute (NCI)
• Netherlands research-related injuries, compensation for, 123
• New York City, 3
• See also City University of New York
• New York State, 153
• See also State University of New York
• New York Times, 153
• National Bioethics Advisory Commission
• New Zealand research-related injuries, compensation for, 123
• NIH. See National Institutes of Health (NIH)
• NOHRO. See National Office for Human Research Oversight (NOHRO)
• NRC. See Nuclear Regulatory Commission (NRC)
• NSF. See National Science Foundation (NSF)
• Nuclear Regulatory Commission (NRC), 31 See also Department of Energy (DOE)
• Nuremberg Code, 151, 152, 161 Nuremberg Military Tribunal, 151 Nuremberg War Crime Trials, ii, 161

O

• 'Obedience to Authority' experiments, 71
• Office for Human Research Protections (OHRP), 8, 9, 10, 12, 13, 15 - 16, 28, 30, 31 - 32, 49, 52, 58, 61, 62 - 63, 100, 121, 124, 133, 152 'Common Findings and Guidance,' 13 site inspections to ensure compliance with research standards, 53 See also Cooperative Project Assurance (CPA); Multiple Project Assurances (MPAs); Office for Protection from Research Risks (OPRR); Single Project Assurances (SPAs)
• Office for Protection from Research Risks (OPRR), 3, 8, 10, 14, 15, 30, 46, 58, 83, 102, 119, 121, 133, 152, 154, 170, 172, 174 compliance investigations of, resulting in restrictions/actions to MPAs, listing by institution, 54 - 56 IRB Guidebook, 70 OPRR Reports, 154 site inspections to ensure compliance with research standards, 53 See also National Institutes of Health (NIH); Office for Human Research Protections (OHRP)
• Office of Government Ethics (OGE), 31 See also Office of Personnel Management (OPM)
• Office of Personnel Management (OPM), 31 See also Office of Government Ethics (OGE)
• Office of Science and Technology Policy (OSTP), xi, 1, 155 human participants research, regulations of, 157 See also White House
• Office of Special Education and Rehabilitative Services human participants research, regulations of, statutory authority for, 209
• Office of the President
• Committee on Science, National Science and Technology Council, 154 See also President of the U.S.
• OGE. See Office of Government Ethics (OGE)
• Opinion. See Public opinion
• OHRP. See Office for Human Research Protections (OHRP)
• OPM. See Office of Personnel Management (OPM)
• OPRR. See Office for Protection from Research Risks (OPRR)
• OSTP. See Office of Science and Technology Policy (OSTP)
• Oversight accreditation of competence of research institutions/IRBs, vii, xiv, 49 - 50 adverse research events, FDA reporting requirements, 113 - 114, 115, 116, 213 - 216 adverse research events, reporting requirements for local institutions, xix - xx, 113 - 117 biomedical/behavioral research, prisoners in, and, 45 CFR 46, Subpart C, in entirety, 182 - 184 certification of competence of research individuals, vii, xiv, 48 - 49 children as research subjects, 45 CFR 46, Subpart D, in entirety, 184 - 186 compliance with research standards by institutions/IRBs/ investigators, mechanisms for ensuring, xiv, 50 - 58 conflict of interest for research IRBs, measures for managing, 60 - 63 cooperative research review, current requirements and problems, xx, 118 cooperative research review, requirements for IRBs, 122 education on human participants protection, measures needed for, vi - vii, xiii, 45 - 48 educational programs for human participants research, proposal for, xii, 23 health services research/program evaluation, determining coverage, 36 - 37 human participants research, Common Rule and agency-specific regulations, 157 human participants research, consequences of flawed system, 16 human participants research, current protection of, 29 human participants research, current system, challenges for, 8 - 16 human participants research, current system, description of, 154, 155 - 156, 157 human participants research, current system, enforcement weaknesses, 12 - 13 human participants research, current system, IRB burdens, 13 - 15 human participants research, current system, lack of adaptability of, 11 - 12 human participants research, current system, limited scope of, 12 human participants research, current system, procedural v. ethical emphasis of, 13 human participants research, defining for coverage determination, xii - xiii, 34 - 42 human participants research, ethical issues for, future research on, xxi, 134 human participants research, exemptions possible, 37 - 41 human participants research, federal agency regulations and, statutory authority for, 205 - 211 human participants research, federal regulations on, 21 CFR 50, Subpart A, in entirety, 187 - 189, human participants research, federal regulations on, 45 CFR 46, Subpart A, in entirety, 169 - 179 human participants research, flawed, for, consequences, 16 human participants research, history of, 151 - 154 human participants research, inconsistencies among agencies, 9, 10 human participants research, percent exempt from, listing by agency, 11 human participants research, possible exemptions from, 37 - 41 human participants research, proposal for, independent office, vi, xii, 28, 30 - 32 human participants research, proposed system for, independent office for, vi, xii, 28, 30 - 32 human participants research, proposed system, functions/responsibilities of all parties, xi - xii, 23 - 27 human participants research, proposed system, as dynamic/responsive structure, 134 - 135 human participants research, proposed system, educational programs for all parties, xii, 23 human participants research, proposed system, enforcement of, xii, 25 - 26 human participants research, proposed system, ethical review of research, vii - viii, xii, 23 - 24 human participants research, proposed system, functions and responsibilities of, xi - xii, 23 - 27 human participants research, proposed system, monitoring for, xii, 24 - 25 human participants research, proposed system, National Office for Human Research Oversight for, xii, 28, 30 - 32 human participants research, proposed system, overview of, xi - xiii, 21 - 42 human participants research, proposed system, policy development through regulations/guidance, xii, 23 human participants research, proposed system, public accountability of, xii, 26 human participants research, proposed system, recommendations for, general themes in, 135 human participants research, proposed system, resources for, viii, xx - xxi, 131, 133 human participants research, proposed system, scope and structure, vii, xii, 26 - 32 human participants research, proposed system, unified/ comprehensive policy for, v - vi, xii, 28, 30 - 32 human participants research, protection for, ACHRE recommendations, 158 human participants research, purpose of, i - ii, xi, 2 - 4, 21 - 22 human participants research, recent government interest in, 156 human participants research, recent initiatives for, 15 - 16 human participants research, report implications for IRBs/ investigators/institutions, 136 - 137 human participants research, report implications for participants, 137 human participants research, report recommendations for, general themes in, 135 human participants research, resources for, viii, xx - xxi, 131, 133, informed consent for human participants research, 21 CFR 50, Subpart B, in entirety, 189 - 195 informed consent requirements for research participants, deficiencies in, 98 informed consent requirements for research participants, scope/structure of, iv, xvii, 97 - 104 IRB approval for research, current regulations for, 69 - 71 IRB functions/operations for human participants research, 21 CFR 56, Subpart C, in entirety, 198 - 201 IRB noncompliance for human participants research, 21 CFR 56, Subpart E, in entirety, 201 - 203 IRB organization/personnel and human participants research, 21 CFR 56, Subpart B, in entirety, 198 IRB records/reports and human participants research, 21 CFR 56, Subpart D, in entirety, 201 IRBs and, general provisions for, 21 CFR 56, Subpart A, in entirety, 195 - 198 medical practice v. research, distinction for determining coverage, 34 - 37 pregnant women, fetuses, and in vitro fertilization in research, 45 CFR 46, Subpart B, in entirety, 179 - 182 prisoners in biomedical/behavioral research and, 45 CFR 46, Subpart C, in entirety, 182 - 184 privacy and confidentiality protection for research participants, 104 - 105 research protocol changes and unanticipated problems, local institutions responsibilities, xix, 112 - 113, 117 research, ongoing, monitoring responsibilities of local institutions, xix, 117 research-related injuries, compensation for, current requirements, v, 123 - 124 review for, levels of, proposal for, vii - viii, xiii, 41 - 42 review, continuing, of ongoing research, IRBs responsibilities, xix, 117 review, levels of, for human participants research, proposal for, vii - viii, xiii, 41 - 42 risk, minimal, research classification, definition in, xvi, 80, 83 - 84 risks, research, v. potential benefits, analysis in IRB review process, ii - iv, 79 vulnerability and human participants research, issues, iv - v, 9, 11 vulnerability of research participants, current protections for, 85 - 92. See also Federal regulation; Public policy

P

• Papers commissioned human research participants protection, ethical and policy issues, 225 - 226
• Participants. See Protections for human participants Peckman, Steven, 119 Pennsylvania. See University of Pennsylvania
• Personal finance disadvantaged persons targeted for research, listing by sponsoring agency, 86 vulnerability in research participants, considerations, 90
• Personnel human participants research, resources for, xx - xxi, 131, 133 human participants research, federal support for FY 1999, listing by agency, 132
• Phillips, D.F., 9
• PHS. See Public Health Service (PHS) P.L. 93 - 348. See Public Law 93 - 348 Policy. See Public policy
• Postal service questionnaire, mail, for study of state law effects on behavior, risks/potential benefits analysis example, 81
• Practice of health care/medicine. See Health care
• Pregnancy research activities on, protections for, 45 CFR 46, Subpart B, in entirety, 179 - 182 vulnerable persons targeted for research, listing by sponsoring agency, 86 See also Embryos and embryonic materials; Fetus and fetal tissue
• President of the U.S., 190, 191 Memorandum of, 11 See also Office of the President
• President's Commission. See President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research (President's Commission)
• President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research (President's Commission), i, v, xx, 45 - 46, 50 - 51, 52, 57 - 58, 112, 124, 126, 154
• See alsoCompensating for Research Injuries; Implementing Human Research Regulations
• PRIM&R. See Public Responsibility in Medicine and Research (PRIM&R)
• Prisoners biomedical/behavioral research subjects, protections for, 45 CFR 46, Subpart C, in entirety, 182 - 184 vulnerable persons targeted for research, listing by sponsoring agency, 86
• Privacy definition for human research participants proposed by NBAC, 106 research participants protection, current regulations on, 104 - 105 research participants protection, issues for, xviii, 106 - 107 research participants protection, NBAC recommendation, xviii, 107 See also Confidentiality
• Private sector research involving human participants, recommendations of President's Commission, 155 research involving human participants sponsored by, proposed regulation by NOHRO, 32
• Professional societies human participants research, proposed oversight system for, responsibilities of, 27 research ethics and human participants research, programs in, measures needed for, xiii, 48
• Protection of Pupil Rights Amendment, 104 - 105
• Protections for human participants accreditation of competence for institutions/IRBs, vii, xiv, 49 - 50 adverse events FDA reporting requirements for, 113 - 114, 115, 213 - 216 adverse events reporting requirements for local institutions, xix - xx, 113 - 117 adverse events review, requirements for local institutions/IRBs, 114, 115 - 116 beneficence, relevance for, from Belmont Report, 162 - 163, 165 - 167 benefits, potential, to others, 74 benefits, potential, to participants, 73 - 74 benefits, potential, to society, 73 benefits, potential, types, 73 - 74 biomedical/behavioral, prisoners in, and, 45 CFR 46, Subpart C, in entirety, 182 - 184 certification of competence of individuals, vii, xiv, 48 - 49 children as subjects, 45 CFR 46, Subpart D, in entirety, 184 - 186 communities/groups and, consideration of, 7 - 8 compensation for research-related injuries, current situation, 123 - 125 compensation for research-related injuries, need for, v, 125 - 126 compensation for research-related injuries, previous recommendations for program, 124 - 125 compensation for research-related injuries, role of local institutions, xx, 123 - 126 competence for, measures for demonstrating, xiv, 48 - 50 compliance investigations by OPRR resulting in restrictions/actions to MPAs, listing by institution, 54 - 56 compliance with standards by institutions/IRBs/investigators, mechanisms for ensuring, xiv, 50 - 58 conflict of interest for investigators, measures for managing, xiv - xv, 58 - 60 conflict of interest for IRBs, measures for managing, xv, 60 - 64 cooperative research review, by IRBs, foreign models of, 121 - 122 cooperative research review, by local IRBs, alternatives to, 120 - 122 cooperative research review, by local IRBs, considerations, 118 - 120 cooperative research review, current requirements and problems, xx, 118 cooperative research review, role of local IRBs/institutions, 122, defining for oversight coverage determination, xii - xiii, 34 - 42 education on, measures needed for, vi - vii, xiii, 45 - 48 ethical and policy issues for, papers commissioned on, 225 - 226 ethical and policy issues for, public comments on, 217 - 220 ethical and policy issues for, testimony, public/expert, on, 221 - 223 ethical issues for, future research on, xxi, 133 - 134 ethical principles/guidelines for, Belmont Report text in entirety, 161 - 167 federal agency regulations for, statutory authority for, 205 - 211 federal agency support for FY 1999, listing by agency, 132 federal protection for, 29 federal regulations of Common Rule and specific agencies, 157 federal regulations on, 21 CFR 50, Subpart A, in entirety, 187 - 189 federal regulations on, 45 CFR 46, Subpart A, in entirety, 169 - 179 federal regulations on, exemptions from, percent listing by agency, 11 federal regulations on, inconsistent interpretation/implementation by agencies, 9, 10 federally supported research, size and scope of, 5 government recent interest in, 156 health services research/program evaluation, determining oversight coverage, 36 - 37 informed consent disclosure requirements for, emphasis on, issues, xvii, 98 - 100 informed consent disclosure requirements for, listing, 99 informed consent documentation requirements for, discussion of, xviii, 103 - 104 informed consent for, 21 CFR 50, Subpart B, in entirety, 189 - 195 informed consent for, ethical considerations, from Belmont Report, 164 - 165 informed consent process for, emphasis on, discussion of, iv, xvii, 98 - 101 informed consent requirements for, deficiencies in, 98 informed consent requirements for, scope/structure of, 97 - 104 informed consent requirements for, waiver of, discussion, xvii - xviii, 101 - 103 IRB functions/operations and, 21 CFR 56, Subpart C, in entirety, 198 - 201 IRB noncompliance with regulations, actions for, 21 CFR 56, Subpart E, in entirety, 201 - 203 IRB organization/personnel and, 21 CFR 56, Subpart B, in entirety, 198 IRB records/reports and, 21 CFR 56, Subpart D, in entirety, 201 IRB research review process, 79 IRB research studies approval, current regulations for, 69 - 71 IRBs and, general provisions for, 21 CFR 56, Subpart A, in entirety, 195 - 198 justice and participants selection, ethical guidelines from Belmont Report, 167 justice, relevance for, from Belmont Report, 163 - 164, 167 local institutions and IRBs responsibilities for, issues for, xix - xx, 111 - 126 medical practice v., distinction for determining oversight coverage, 34 - 37 mentally impaired research participants and informed consent, requirements for, 101 moderate protectionism, explanation, 22 monitoring of ongoing research, local institutions responsibilities, xix - xx, 111 - 117 oversight of, need for, i - ii, 2 - 4 oversight office, independent, proposed for, vi, xii, 28, 30 - 32 oversight system for, purpose of, xi, 21 - 22 oversight system proposed for, as dynamic / responsive structure, 134 - 135 oversight system proposed for, educational programs for all parties, xii, 23 oversight system proposed for, enforcement of requirements, xii, 25 - 26 oversight system proposed for, ethical review of research, vii - viii, xii, 23 - 24 oversight system proposed for, functions/responsibilities of all parties, xi - xii, 23 - 27 oversight system proposed for, monitoring, xii, 24 - 25 oversight system proposed for, need for unified/comprehensive federal policy for, v - vi, xii, 28, 30 - 32 oversight system proposed for, overview of, xi - xiii, 21 - 42 oversight system proposed for, policy development through regulations/guidance, xii, 23 oversight system proposed for, public accountability for, xii, 26 oversight system proposed for, recommendations for, general themes in, 135 oversight system proposed for, resources for, viii, xx - xxi, 131, 133 oversight system proposed for, scope and structure, vii, xii, 26 - 32 oversight system, current, challenges for, 8 - 16 oversight system, current, description, 154, 155 - 156, 157 oversight system, current, enforcement weaknesses of, 12 - 13 oversight system, current, IRB burdens, 13 - 15 oversight system, current, lack of adaptability of, 11 - 12 oversight system, current, limited scope of, 12 oversight system, current, procedural v. ethical emphasis of, 13 oversight system, exemptions possible, 37 - 41 oversight system, flawed, for, consequences, 16 oversight system, history of, 151 - 154 oversight system, recent initiatives for, 15 - 16 pregnant women, fetuses, and in vitro fertilization and, 45 CFR 46, Subpart B, in entirety, 179 - 182 prisoners in biomedical/behavioral research and, 45 CFR 46, Subpart C, in entirety, 182 - 184 privacy and confidentiality for, current regulations on, 104 - 105 protocol changes and unanticipated problems, local institutions responsibilities, xix, 112 - 113, 117 public perspectives about research participation, changes in, 6 - 7 recommendations of ACHRE for, 158 recommendations of NBAC for, xi - xxi, 28, 30, 40, 41 - 42, 47 - 49, 50, 64, 77, 85, 92, 98, 101, 102, 103, 104, 117, 122, 124 - 126, 133, 134 report implications for, 137 respect for persons, relevance for, from Belmont Report, ii, 162, 164 - 165 review for, levels of, oversight system proposal for, vii - viii, xiii, 41 - 42 review, continuing, IRBs responsibilities, xix, 117 risk, minimal, classification, definition in federal regulations, xvi, 80, 83 - 84 risk, minimal, classification, use as sorting mechanism for IRB review, 84 risk, minimizing, 73 risks of harms, to nonparticipants, 72 - 73 risks of harms, types of, 71 - 73 risks v. potential benefits analysis for, ethical considerations, from Belmont Report, 165 - 167 risks v. potential benefits analysis for, new technologies effects on, 7 risks v. potential benefits analysis for, xvi - xvii, 69 - 85, 93 risks v. potential benefits analysis in IRB review process, ii - iv, 79 risks v. potential benefits, balance between, assessment procedure, 78 - 80 risks v. potential benefits, component-based framework for analysis, 76 - 77, 78, 81 - 82 risks v. potential benefits, component-based framework for analysis, examples, 81 - 82 risks v. potential benefits, historical perspective, 75 - 76 risks v. potential benefits, relationship, assessment of, 74 - 75 selection of, ethical considerations, from Belmont Report, 167 strong protectionism, explanation, 22 terminology for, 32 - 33 vulnerability and, current regulatory protections for, 85 - 92 vulnerability and, definition of, xvii, 92 vulnerability and, evaluation of, xvii, 85 - 93 vulnerability and, minimal risk and, 92 vulnerability and, oversight issues, iv - v, 9, 11 vulnerability, cognitive/communicative, and, considerations, 88 vulnerability, deferential, and, considerations, 89 vulnerability, economic, and, considerations, 90 vulnerability, institutional, and, considerations, 88 - 89 vulnerability, medical, and, considerations, 89 - 90 vulnerability, participants targeted in research, listing by sponsoring agency/vulnerability, 86 vulnerability, social, and, considerations, 90 - 91 weak protectionism, explanation, 22 See also Research
• Psychology experiment to study human cognition/behavior, risk/potential benefits analysis example, 82
• Public accountability to, for research involving human participants, oversight system proposal, xii, 26 See also Public comments; Public health; Public opinion; Public policy
• Public comments human participants research, ethical and policy issues, 217 - 220 See also Testimony and speakers
• Public health activities, v. research involving human participants, distinction for determining oversight coverage, 35 - 36 See also Health care
• Public Health Service (PHS), 124, 152
• 'Policy for Clinical Investigations with Human Subjects,' 152 See also Tuskegee Syphilis Study; Tuskegee Syphilis Study Ad Hoc Advisory Panel
• Public Health Service Act, 29, 105, 106, 187, 188, 189, 196, 197
• Public Law 93 - 348, 153 - 154, 207
• Public opinion research participation and, changing perspectives, 6 - 7
• Public policy, research events, reporting requirements for, NBAC recommendations, xx, 117 conflict of interest and IRB membership/composition, NBAC recommendations, xv - xvi, 64 conflict of interest for research investigators/IRBs/institutions, NBAC recommendations, xv - xvi, 64 education for human participants research, NBAC recommendations, xiii, 47 - 48 human participants research, defining for oversight coverage, NBAC recommendations, xii, 40 human participants research, ethical principles/guidelines for, Belmont Report text in entirety, 161 - 167 human participants research, issues for, NBAC recommendations summary, xi - xxi human participants research, issues for, papers commissioned on, 225 - 226 human participants research, issues for, public comments on, 217 - 220 human participants research, issues for, testimony, public/expert, on, 221 - 223 human participants research, oversight system proposed for, development through regulations/guidance, xii, 23 human participants research, oversight system proposed for, independent office for, vi, xii, 28, 30 - 32 human participants research, oversight system proposed for, National Office for Human Research Oversight for, vi, xii, 28, 30 - 32 human participants research, oversight system proposed for, scope/structure of, NBAC recommendations, xii, 28, 30 human participants research, oversight system proposed for, unified/comprehensive policy for, v - vi, xii, 28, 30 - 32 human participants research, report implications for IRBs/ investigators/institutions, 136 - 137 human participants research, report implications for participants, 137 review, continuing, of ongoing research, IRBs responsibilities, NBAC recommendations, xix, 117 review, levels of, for human participants research, NBAC recommendations, xiii, 41 - 42, risk, minimal, of research, and, NBAC recommendation, xvi - xvii, 85 risks, research, v. potential benefits, analysis of, NBAC recommendations, xvi - xvii, 77, 85 vulnerability of research participants, definition of, NBAC recommendation, xvii, 92 See also Federal government; Federal regulation
• Public Responsibility in Medicine and Research (PRIM&R), 15, 33, 46
• Public testimony. See Testimony and speakers
• Publishers scientific, and human participants research, oversight responsibilities proposed for, 27

Q

• Questionnaires mail, study of effects of state law on behavior, risks/potential benefits analysis example, 81

R

• Reactions. See Adverse reactions
• Recommendations accreditation of competence of research institutions/IRBs, measures for demonstrating, xiv, 50 adverse events reporting requirements for, xx, 117 certification of competence of research individuals, measures for demonstrating, xiv, 48 - 49 compensation for research-related injuries, xx, 124 - 125, 126 compliance with research standards by institutions/IRBs/ investigators, mechanisms for ensuring, xiv, 58 confidentiality protection for research participants, xviii, 107 conflict of interest and investigators/IRBs/institutions, measures for managing, xv - xvi, 64 cooperative research review, requirements for, xx, 122 education on research ethics and human participants, measures needed for, xiii, 47 - 48 human participants research, ACHRE recommendations, 158 human participants research, defining for oversight coverage determination, xii, 40 human participants research, ethical and policy issues in, summary of, xi - xxi human participants research, ethical issues for, future research on, xxi, 134 human participants research, general themes in, 135 human participants research, oversight proposal for unified/comprehensive federal policy for, xii, 30 human participants research, oversight system proposal for, scope and structure, xii, 28, 30 human participants research, proposal for National Office for Human Research Oversight, xii, 28, 30 human participants research, resources for, xx - xxi, 133 informed consent documentation requirements for human participants, xviii, 104 informed consent requirements for human participants, waiver of, xviii, 102, 103 informed consent requirements for human participants, xvii, 98, 101 IRB membership/composition and conflict of interest, measures for managing, xv - xvi, 64 monitoring of ongoing research, local institutions responsibilities, xix, 117 privacy protection for research participants, xviii, 107 research protocol changes and unanticipated problems, local institutions responsibilities, xix, 117 research risks, v. potential benefits, analysis of, xvi - xvii, 77, 85 review, continuing, of ongoing research, IRBs responsibilities, xix, 117 review, levels of for human participants research, oversight system proposal for, xiii, 41 - 42 risk, minimal, of research, Federal policy on, xvi - xvii, 85 vulnerability of research participants, definition of, xvii, 92
• Regulation. See Federal government; Federal regulation; Oversight; Research regulations
• Reporting requirements adverse research events and, xix - xx, 113 - 117 adverse research events, FDA, 113 - 114, 115, 213 - 216 research protocol changes and unanticipated problems, local institutions responsibilities, xix, 112 - 113, 117
• Research adverse events, FDA reporting requirements for, regulatory text, 213 - 216 assurances of compliance for institutions/IRBs, xiv, 50 - 51, 52 audits, institutional, for standards compliance by institutions/IRBs, xiv, 53 benefits, potential, to others, 74 benefits, potential, to participants, 73 - 74 benefits, potential, to society, 73 benefits, potential, types, 73 - 74 communities/groups consideration for, 7 - 8 compliance with standards by institutions/IRBs/investigators, mechanisms for ensuring, xiv, 50 - 58 conduct of, current factors influencing, 4, 6 - 8 equipoise of, explanation, 77, 78 ethical issues for, future research on, xxi, 133 - 134 informed consent processes for various settings, 100 - 101 injuries from, compensation for, current regulatory requirements, 123 - 124 injuries from, compensation for, current situation, 125 injuries from, compensation for, need for, v, 125 - 126 injuries from, compensation for, previous recommendations for program, 124 - 125 injuries from, compensation for, role of local institutions, xx, 123 - 126 IRB approval for studies, current regulations for, 69 - 71 IRB review process, 79 observational study of effects of state law on behavior, risks/potential benefits analysis example, 81 participation in, changing public perspectives about, 6 - 7 practice v., distinction between, from Belmont Report, 161 - 162 pregnant women, fetuses, and in vitro fertilization in, protections for, 45 CFR 46, Subpart B, in entirety, 179 - 182 risk of harms to nonparticipants, 72 - 73 risk of harms, minimizing, 73 risk of harms, types of, 71 - 73 risks v. potential benefits, analysis in IRB review process, 79 risks v. potential benefits, balance between, assessment procedure, 78 - 80 risks v. potential benefits, component-based framework for analysis, 76 - 77, 78, 81 - 82 risks v. potential benefits, component-based framework for analysis, examples, 81 - 82 risks v. potential benefits, historical perspective, 75 - 76 risks v. potential benefits, relationship, assessment of, 74 - 75 site inspections by FDA to ensure IRBs compliance with standards, xiv, 52 - 53 site inspections to ensure compliance with standards, xiv, 53 universities for, and academic medical centers, stresses on, 4, 6 value of, summary, 1 - 2 See also Behavioral research; Biomedical research; Clinical trials; Cooperative research; Health services research; Investigators; Protections for human participants; Research documents; Research funding; Research institutions; Research regulations; Science and technology; Sponsors
• Research design. See Equipoise; Research
• Research documents IRB records/reports requirements, 21 CFR 56, Subpart D, in entirety, 201. See also Research
• Researchers. See Investigators
• Research funding academic medical centers and research universities, stresses on, 4, 6 human participants protection, federal support for FY 1999, listing by agency, 132 human participants protection, resources for, viii, xx - xxi, 131, 133 investment trends for, changes in, 4 See also Federal funding for research; Research
• Research institutions accreditation for research ethics competence, measures for demonstrating, vii, xiv, 49 - 50 adverse events FDA reporting requirements, 113 - 114, 115 adverse events reporting requirements for, xix - xx, 113 - 117 adverse events review, requirements for, 114, 115 - 116 assurances of compliance for research standards, xiv, 50 - 51, 52 audits, institutional, for research standards compliance by, xiv, 53 compensation for research-related injuries, role of, xx, 123 - 126 compliance oversight investigations resulting in restrictions/actions to MPAs, listing by institution, 54 - 56 compliance with research standards by, mechanisms for ensuring, xiv, 50 - 53 conflict of interest for, measures for managing, xiv - xv, 58 - 64, cooperative research review by local IRBs, alternatives to, 120 - 122 cooperative research review by local IRBs, considerations, 118 - 120 cooperative research review, current requirements and problems, xx, 118 cooperative research review, role of local IRBs/institutions, 122 education on human participants protection, measures needed for, vi - vii, xiii, 45 - 48 human participants research responsibilities of local institutions, issues concerning, xix - xx, 111 - 126 human participants research, report implications for IRBs/ investigators/institutions, 136 - 137 monitoring of ongoing research, local institutions responsibilities, xix - xx, 111 - 117 oversight system, proposed, for human participants research, functions and responsibilities of, 26 - 27 oversight system, proposed, for human participants research, monitoring, xii, 24 - 25 oversight system, proposed, for human participants research, enforcement of requirements, xii, 25 - 26 protocol changes and unanticipated problems, reporting requirements for, xix, 112 - 113, 117 site inspections to ensure compliance with research standards, xiv, 53 See also Research
• Research Involving Persons with Mental Disorders That May Affect Decisionmaking Capacity, vii
• Research regulations accreditation of competence of institutions/IRBs, vii, xiv, 49 - 50 adverse events, FDA reporting requirements, 113 - 114, 115, 116, 213 - 216 adverse events, reporting requirements for local institutions, xix - xx, 113 - 117 biomedical/behavioral, prisoners in, and, 45 CFR 46, Subpart C, in entirety, 182 - 184 certification of competence of individuals, vii, xiv, 48 - 49 children as subjects, 45 CFR 46, Subpart D, in entirety, 184 - 186 compliance with standards by institutions/IRBs/investigators, mechanisms for ensuring, xiv, 50 - 58 conflict of interest for IRBs, measures for managing, 60 - 63 cooperative review, current requirements and problems, xx, 118 cooperative review, requirements for IRBs, 122 education on human participants protection, measures needed for, vi - vii, xiii, 45 - 48 educational programs on human participants protection, oversight system proposal for, xii, 23 human participants, Common Rule and agency-specific regulations, 157 human participants, consequences of flawed system, 16 human participants, current oversight system, challenges for, 8 - 16 human participants, current protection of, 29 human participants, defining for oversight coverage determination, xii - xiii, 34 - 42 human participants, description of, 154, 155 - 156, 157 human participants, enforcement weaknesses, 12 - 13 human participants, ethical issues for, future research on, xxi, 134 human participants, federal regulations on, 21 CFR 50, Subpart A, in entirety, 187 - 189 human participants, federal regulations on, 45 CFR 46, Subpart A, in entirety, 169 - 179 human participants, history of, 151 - 154 human participants, inconsistencies among agencies, 9, 10 human participants, IRB burdens in, 13 - 15 human participants, lack of adaptability in, 11 - 12 human participants, limited scope of, 12 human participants, oversight independent office proposed for, vi, xii, 28, 30 - 32 human participants, oversight possible exemptions, 37 - 41 human participants, oversight system proposal for, xi - xiii, 21 - 42 human participants, oversight system for, purpose of, i - ii, xi, 2 - 4, 21 - 22 human participants, oversight system for, resources for, viii, xx - xxi, 131, 133 human participants, oversight system proposal for enforcement of, xii, 25 - 26 human participants, oversight system proposal for ethical review of research, xii, 23 - 24 human participants, oversight system proposal for monitoring, xii, 24 - 25 human participants, oversight system proposal for National Office for Human Research Oversight for, xii, 28, 30 - 32 human participants, oversight system proposal for policy development through, xii, 23 human participants, oversight system proposal for public accountability, xii, 26 human participants, oversight system proposal for unified/ comprehensive policy for, v - vi, xii, 28, 30 - 32 human participants, oversight system proposal for, as dynamic/responsive structure, 134 - 135 human participants, oversight system proposal for, scope and structure, xii, 26 - 32 human participants, oversight system proposed for, functions and responsibilities of, xi - xii, 23 - 27 human participants, percent exempt from, listing by agency, 11 human participants, procedural v. ethical emphasis, 13 human participants, protection for, ACHRE recommendations, 158 human participants, recent government interest in, 156 human participants, recent initiatives for, 15 - 16 human participants, report implications for IRBs/investigators/ institutions, 136 - 137 human participants, report implications for participants, 137 human participants, report recommendations for, general themes in, 135 informed consent for human participants, 21 CFR 50, Subpart B, in entirety, 189 - 195 informed consent requirements for participants, deficiencies in, 98, informed consent requirements for participants, scope/structure of, iv, xvii, 97 - 104 injuries, compensation for, current requirements, v, 123 - 124 IRB approval, current regulations for, 69 - 71 IRB functions/operations for human participants, 21 CFR 56, Subpart C, in entirety, 198 - 201 IRB noncompliance for human participants, actions for, 21 CFR 56, Subpart E, in entirety, 201 - 203 IRB organization/personnel and human participants, 21 CFR 56, Subpart B, in entirety, 198 IRB records/reports and human participants, 21 CFR 56, Subpart D, in entirety, 201 IRBs and, general provisions for, 21 CFR 56, Subpart A, in entirety, 195 - 198 ongoing, monitoring responsibilities of local institutions, xix, 117 pregnant women, fetuses, and in vitro fertilization and, 45 CFR 46, Subpart B, in entirety, 179 - 182 prisoners in biomedical/behavioral research and, 45 CFR 46, Subpart C, in entirety, 182 - 184 privacy and confidentiality protection for participants, 104 - 105 protocol changes and unanticipated problems, local institutions responsibilities, xix, 112 - 113, 117 review, continuing, IRBs responsibilities, xix, 117 review, levels of, for human participants, oversight system proposal for, vii - viii, xiii, 41 - 42 risk, minimal, classification, definition in, xvi, 80, 83 - 84 risks v. potential benefits, analysis in IRB review process, ii - iv, 79 vulnerability of participants, current protections for, 85 - 92 vulnerable participants protection, oversight issues, iv - v, 9, 11. See also Research
• Research review. See Ethics review and review committees; Institutional Review Boards (IRBs)
• Resources human participants research, federal support for FY 1999, listing by agency, 132 human participants research oversight system and, viii, xx - xxi, 131, 133
• Respect for persons research participants informed consent and, ethical guidelines from Belmont Report, 164 - 165 research participants protection and, from Belmont Report, ii, 162, 164 - 165. See also Ethics
• Review bodies. See Ethics review and review committees; Institutional Review Boards (IRBs)
• Risks informed consent requirements for research participants and, xviii, 102, 103 levels of, review for, oversight system proposal for, vii - viii, xiii, 41 - 42 minimal, of research, Federal policy on, NBAC recommendation, xvi - xvii, 85 minimal, research classification, definition in federal regulations, xvi, 80, 83 - 84 minimal, research classification, use as sorting mechanism for IRB review, 84 minimal, research involving no more than for human participants, IRB review of, oversight proposal, 24 minimal, use related to vulnerability of research participants, 92 research, for nonparticipants, 72 - 73 research, for participants, minimizing, 73 research, for participants, types of, 71 - 73 research, v. potential benefits, analysis in IRB review process, ii - iv, 79 research, v. potential benefits, analysis of, new technologies effects on, 7 research, v. potential benefits, analysis of, xvi - xvii, 69 - 85, 93 research, v. potential benefits, assessment for protection of participants, ethical guidelines, 165 - 167 research, v. potential benefits, balance between, assessment procedure, 78 - 80 research, v. potential benefits, component-based framework for analysis, 76 - 77, 78, 81 - 82 research, v. potential benefits, component-based framework for analysis, examples, 81 - 82 research, v. potential benefits, historical perspective, 75 - 76 research, v. potential benefits, relationship, assessment of, 74 - 75 Rothman, D.J., 9
• Rush Presbyterian St. Lukes Medical Center research compliance investigations resulting in restrictions/actions, 56

S

• Safeguards. See Protections for human participants
• Sanctions administrative action, for IRB noncompliance, 21 CFR 56, Subpart E, in entirety, 201 - 203 human research participants protection, oversight enforcement weaknesses, 12 - 13 research compliance investigations resulting in restrictions/actions to MPAs, listing by institution, 54 - 56
• Science and technology - IRB scientists membership and conflict of interest, measures for managing, xv, 62 - 63, 64 technologies, new, challenges to research risk/potential benefit analysis, 7 See also Research
• Scripps Clinic and Research Foundation, Scripps Research Institute research compliance investigations resulting in restrictions/actions, 56
• Senate Committee on Governmental Affairs, 8 Senate Labor and Public Welfare Committee, 153 Shannon, James, 152
• Single Project Assurances (SPAs), 14, 52, 55, 56 See also Assurances of compliance; Compliance; Office for Human Research Protections (OHRP)
• Site inspections compliance investigations by OPRR resulting in restrictions/actions to MPAs, listing by institution, 54 - 56 compliance with research standards by IRBs, FDA, xiv, 52 - 53 compliance with research standards, site inspections to ensure, xiv, 53 directed (for cause), of FDA, 53 surveillance (routine), of FDA, 53
• Site Management Organizations (SMOs), 6
• SMOs. See Site Management Organizations (SMOs)
• Social position vulnerability of research participants, considerations, 90 - 91
• Social Security Act, 10
• Social Security Administration (SSA), 9, 10, 11, 85, 132, 156 human participants research, regulations of, 157
• South Africa research-related injuries, compensation for, 123
• South Carolina. See Medical University of South Carolina
• SPAs. See Single Project Assurances (SPAs)
• Sponsors accreditation of competence in research ethics, NBAC recommendations, xiv, 50 education on research ethics and human participants protection, NBAC recommendations, xiii, 47 - 48 human participants research, proposed oversight system, functions and responsibilities of, 27 human participants research, proposed oversight system, monitoring, xii, 24 - 25 research conflict of interest for institutions/IRBs/investigators, NBAC recommendations, xv, 64 research, ongoing, monitoring of, local institutions responsibilities, NBAC recommendations, xix, 117 vulnerability, participants targeted in research, listing by sponsoring agency, 86 See also Research
• SSA. See Social Security Administration (SSA)
• State Children's Health Insurance Program, 5
• State laws behavior effects of state law, observational study of, risks/ potential benefits analysis example, 81
• State regulation human participants research, oversight system proposed for, responsibilities of, 27
• State University of New York College of Optometry, research compliance investigations resulting in restrictions/actions, 54
• St. Jude Children's Research Hospital research compliance investigations resulting in restrictions/actions, 56
• Subordination deferential vulnerability in research participants, considerations, 89 institutional vulnerability in research participants, considerations, 88 - 89
• Substance Abuse and Mental Health Services Administration, 5, 11, 132 See also Department of Health and Human Services (DHHS)
• Substantive standard of informed consent. See Informed consent,
• Syphilis, 46, 153, 164

T

• Technology. See Science and technology
• Terminology research involving human participants, discussion, 32 - 33
• Testimony and speakers human research participants protection, issues for, testimony, public/expert, on, 221 - 223 See also Public comments
• Translation. See Languages Treatment. See Health care Trials. See Clinical trials Tuskegee, Alabama, 153, 164
• Tuskegee Syphilis Study, 46, 153, 164
• Tuskegee Syphilis Study Ad Hoc Advisory Panel, 125, 153 Final Report, 124 See also Public Health Service (PHS)

U

• Uganda human participants research, terminology for, 33 research-related injuries, compensation for, 123
• UNAIDS. See Joint United Nations Programme on HIV/AIDS (UNAIDS)
• Undue influence. See Coercion
• United Kingdom cooperative research, IRB review models in, 121 human participants research, terminology for, 33 research-related injuries, compensation for, 123 See also Great Britain
• United Nations (UN). See Joint United Nations Programme on HIV/AIDS (UNAIDS)
• United Nations Programme on HIV/AIDS. See Joint United Nations Programme on HIV/AIDS (UNAIDS)
• Universities and colleges research, and academic medical centers, stresses on, 4, 6 research ethics and human participants protection, programs in, measures needed for, xiii, 48 See also specific universities and colleges
• University of Alabama at Birmingham research compliance investigations resulting in restrictions/actions, 56
• University of California, Irvine research compliance investigations resulting in restrictions/actions, 55
• University of California, Los Angeles research compliance investigations resulting in restrictions/actions, 54, 55
• University of California, San Diego research compliance investigations resulting in restrictions/actions, 54,
• University of California, San Francisco research compliance investigations resulting in restrictions/actions, 54
• University of Florida research compliance investigations resulting in restrictions/actions, 54
• University of Illinois at Chicago research compliance investigations resulting in restrictions/actions, 56
• University of Maryland, Baltimore research compliance investigations resulting in restrictions/actions, 55,
• University of Minnesota Department of Surgery, research compliance investigations resulting in restrictions/actions, 54
• University of Pennsylvania, 3
• University of Rochester, 3 research compliance investigations resulting in restrictions/actions, 55
• University of South Florida, 3 - 4
• University of Virginia research compliance investigations resulting in restrictions/actions, 55
• USAID. See Agency for International Development (USAID)
• U.S. Congress, 7, 27, 31, 42, 52, 125, 134, 155, 156 human participants research, interest in, 156 human participants research, oversight system proposed for, responsibilities of, 27
• U.S. Department of Agriculture (USDA), 205 Food Safety and Inspection Service, 170, 197 human participants research, regulations of, 157
• U.S. district courts, 11,
• U.S. government. See Federal government; Federal regulation; Public policy; U.S. Congress
• U.S. Public Health Service Act. See Public Health Service Act

V

• VA. See Department of Veterans Affairs (VA)
• Vaccines and vaccination safety/immunogenicity, clinical trial on, risks/potential benefits analysis example, 82 See also Drugs and drug testing
• Vanderpool, Harold, Y., 22, 97
• Verification compliance with research standards by investigators, monitoring for, xiv, 57 - 58
• Veterans Affairs, Greater Los Angeles Health Care System research compliance investigations resulting in restrictions/actions, 56 See also Veterans Affairs Medical Center, West Los Angeles
• Veterans Affairs Medical Center, West Los Angeles research compliance investigations resulting in restrictions/actions, 55 See also Veterans Affairs, Greater Los Angeles Health Care System
• Virginia. See University of Virginia; Virginia Commonwealth University
• Virginia Commonwealth University research compliance investigations resulting in restrictions/actions, 56
• Voluntary consent. See Coercion; Informed consent
• Vulnerability cognitive/communicative, in research participants, considerations, 88 deferential, in research participants, considerations, 89 economic, in research participants, considerations, 90 institutional, in research participants, considerations, 88 - 89 medical, in research participants, considerations, 89 - 90 research participants protection and, current regulatory protections for, 85 - 92 research participants protection and, definition of, NBAC recommendation, xvii, 92 research participants protection and, evaluation of, xvii, 85 - 93 research participants protection and, oversight issues for, iv - v, 9, 11 research participants protection and, use of minimal risk and, 92 research participants targeted for, listing by sponsoring agency/vulnerability, 86 research participants, aligning protections with, considerations, 91 - 92 social, in research participants, considerations, 90 - 91

W

• Waivers informed consent requirements and, discussion, xvii - xviii, 101 - 103 informed consent requirements and, NBAC previous recommendations, 102 informed consent requirements and, NBAC recommendation, xviii, 103
• Wayne State University research compliance investigations resulting in restrictions/actions, 55
• Weijer, Charles, 76
• Western Carolina Center research compliance investigations resulting in restrictions/actions, 55
• West Virginia University research compliance investigations resulting in restrictions/actions, 54
• White House, xi, 1, 154 See also Office of Science and Technology Policy (OSTP)
• Willowbrook State School for the Retarded, 153
• Wilson, Charles, 151
• Women. See Pregnancy World Medical Assembly Declaration, 170
• World War II, 161

National Academy of Engineering

500 Fifth Street, NWWashington, DC 20001T. 202.334.3200F. 202.334.2290