Index

A

AAHRPP, see Association for the Accreditation of Human Research Protection Programs, Inc.

AAMC, see Association of American Medical Colleges

AAU, see Association of American Universities

Academic research, 37, 58, 183

see also Accreditation

accountability, 50, 54-55, 56-57, 58, 250-252

Association of American Medical Colleges (AAMC), 4(n.3), 62, 118, 183

Association of American Universities (AAU) , 183

ethics education, 60, 62

Federal Demonstration Partnership, 198

funding, 58, 59

liability and compensation, 192

participant-investigator interactions, 113

Research Ethics Review Boards (Research ERBs), 81, 84, 86, 251-252

scientific review, 79, 81

Accountability, general, 2, 5, 27, 38, 48, 50, 51, 175, 249-262

see also Accreditation;

Institutional Review Boards (IRBs);

Liability and compensation;

Research Ethics Review Boards (Research ERBs)

academic research, 50, 54-55, 56-57, 58, 250-252

ethical research culture, 7-8, 18, 23, 38, 54, 60, 61, 69, 117-118, 134, 167-168

human research participant protection programs (HRPPPs), general, 6, 7-8, 30, 44, 48, 50, 54-57, 249-262

pharmaceuticals industry, 55, 252-255

template form to document, 258-262

Accreditation, 2-4 (passim), 8, 15, 17, 21, 23-28, 31, 48, 57, 116, 163, 171-177, 187, 195-196

see also Institutional Review Boards (IRBs);

Research Ethics Review Boards (Research ERBs)

Association for the Accreditation of Human Research Protection Programs (AAHRPP), 4(n.4), 171, 173-175, 176, 232, 245-246

committee study methodology, 42, 231, 232-233, 235

Department of Veterans Affairs (VA), 172-173, 175, 176, 245

education about, 62

human research participant protection programs (HRPPPs), general, 3, 30, 116, 174, 175, 176-177, 193



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Responsible Research: A Systems Approach to Protecting Research Participants Index A AAHRPP, see Association for the Accreditation of Human Research Protection Programs, Inc. AAMC, see Association of American Medical Colleges AAU, see Association of American Universities Academic research, 37, 58, 183 see also Accreditation accountability, 50, 54-55, 56-57, 58, 250-252 Association of American Medical Colleges (AAMC), 4(n.3), 62, 118, 183 Association of American Universities (AAU) , 183 ethics education, 60, 62 Federal Demonstration Partnership, 198 funding, 58, 59 liability and compensation, 192 participant-investigator interactions, 113 Research Ethics Review Boards (Research ERBs), 81, 84, 86, 251-252 scientific review, 79, 81 Accountability, general, 2, 5, 27, 38, 48, 50, 51, 175, 249-262 see also Accreditation; Institutional Review Boards (IRBs); Liability and compensation; Research Ethics Review Boards (Research ERBs) academic research, 50, 54-55, 56-57, 58, 250-252 ethical research culture, 7-8, 18, 23, 38, 54, 60, 61, 69, 117-118, 134, 167-168 human research participant protection programs (HRPPPs), general, 6, 7-8, 30, 44, 48, 50, 54-57, 249-262 pharmaceuticals industry, 55, 252-255 template form to document, 258-262 Accreditation, 2-4 (passim), 8, 15, 17, 21, 23-28, 31, 48, 57, 116, 163, 171-177, 187, 195-196 see also Institutional Review Boards (IRBs); Research Ethics Review Boards (Research ERBs) Association for the Accreditation of Human Research Protection Programs (AAHRPP), 4(n.4), 171, 173-175, 176, 232, 245-246 committee study methodology, 42, 231, 232-233, 235 Department of Veterans Affairs (VA), 172-173, 175, 176, 245 education about, 62 human research participant protection programs (HRPPPs), general, 3, 30, 116, 174, 175, 176-177, 193

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Responsible Research: A Systems Approach to Protecting Research Participants informed consent and, 94 liability and compensation issues, 193 National Committee for Quality Assurance (NCQA), 171, 172-173, 175, 176, 231, 232 non-biomedical research, 245-246 Research Ethics Review Boards (Research ERBs), 104-105, 107 ACHRE, see Advisory Committee on Human Radiation Experiments Adverse event reporting, 15, 16, 37, 47, 59, 68, 103, 148, 149-150, 153, 154, 157-158, 161, 165, 170, 192, 254, 261 Advisory Committee on Human Radiation Experiments (ACHRE), 4(n.8), 119, 213-214 AIDS, see HIV American Association of University Professors, 43 American Medical Association, 118, 206-207 American Society of Gene Therapy (ASGT), 183 Animal studies, 37, 144, 147, 157, 200, 213, 274, 275 Anthrax, 212 Applied Research Ethics National Association (ARENA), 62, 64, 234 Association for the Accreditation of Human Research Protection Programs (AAHRPP), 4(n.4), 171, 173-175, 176, 232, 245-246 Association of American Medical Colleges (AAMC), 4(n.3), 62, 118, 183 Association of American Universities (AAU), 183 Association of Clinical Research Professionals, 183 Association of the British Pharmaceutical Industry, 194 Assurance of Compliance documents, 140 Attitudes and beliefs see also Psychological effects; Public opinion dignity of research participants, 29, 31, 46, 165, 193-194, 238 informed consent, 125-126, 130-131, 132 participants in research, 125-126, 129-133 religious, 97 Audits, 80, 81, 88 committee recommendations, 16, 73, 78, 148-149 defined, 139 Food and Drug Administration (FDA), 69, 73 Research Ethics Review Boards (Research ERBs), 138 Award for Excellence in Human Research Protection, 142 B Bayh-Dole Act, 185 Beaumont, William, 33 Behavioral and social research, see Non-biomedical research Belmont Report, 70, 74-75, 92, 119, 181, 238 Best practices, 61, 106, 107, 163-164, 166, 171, 198 see also Good Clinical Practice (GCP) Biologic license applications, 139 Biomedical Research Alliance of New York (BRANY), 84, 104 Bioterrorism, see Terrorism Britain, see United Kingdom C Center for Drug Evaluation and Research (CDER), 146 Centers for Disease Control and Prevention, 212 Centers for Strategic International Studies, 215 Chief Executive Officers (CEOs), 54, 55, 62, 78, 87, 146, 253 Children, 43 Citizen Advocacy Center, 101, 133, 232 Classified reserach, 213-215 Committee on Human Research Participant Protections (proposed), 199 Common Rule (Federal Policy for the Protection of Human Subjects), 5, 47(n.2), 91, 120, 138, 139, 149, 178, 179, 198, 208, 210, 214, 237, 241-242 see also Institutional Review Boards (IRBs) Compensation for injury, see Liability and compensation Computer applications see also Databases; Internet

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Responsible Research: A Systems Approach to Protecting Research Participants personal data protection, 160, 239-240, 261 Research Ethics Review Boards (Research ERBs), education of, 99 Confidentiality and privacy, 4, 6, 40, 138, 156, 159-160, 205, 206, 207-211, 215-216, 256 electronic data protection, 160, 239-240, 261 Health Insurance Portability and Accountability Act (HIPAA) , 159-160, 179, 181-182, 205, 207-211 informed consent and, 119 non-biomedical research, 238, 239-240, 243-244 regulatory issues, general, 159-160, 205-211, 215-216 Research Ethics Review Boards (Research ERBs), 87, 100, 153, 160, 209-211 template form to document, 261 Conflicts of interest, 11, 17-18, 38, 41, 46, 53, 117-118, 132, 162-163, 182-187, 197 accreditation issues, 174 committee study methodology, 41, 42, 232, 235 financial, 2, 6, 10-11, 17, 24, 42, 46, 50, 55, 65, 72, 73-74, 82-83, 117-118, 183-186, 255-256 fraud, 179, 180 human research participant protection programs (HRPPPs), general, 46, 50, 53, 55, 65, 76 informed consent and, 119 institutional, 18, 27, 38, 39, 42, 95, 183, 185-186 National Science Foundation (NSF), 118, 184 non-biomedical research, 238 protocols, 10-11, 66-67, 78, 117, 255-256 recruitment and enrollment of research participants, 117 Research Ethics Review Boards (Research ERBs), 10-11, 18, 24, 72, 74-75, 82-87, 100, 101-102, 105, 118, 162-163, 182, 185-186, 187, 205 scientific, 2, 6, 11, 24, 42, 117 transparency, 65 Consortium to Examine Clinical Research Ethics, 58 Continuing medical education programs, 7, 60-61, 62, 113-116, 150 Continuous quality improvement, 7, 163-170 Contract research organizations (CROs), 48, 60, 85, 105, 147, 148, 178-179, 235, 252-255, 256 Cost factors, 16, 57-59, 235, 243 see also Funding; Liability and compensation ethics reviews, 8, 104 multisite research, 104, 256-257 participants’ medical and rehabilitation services, 47 quality improvement research, 164 Research Ethics Review Boards (Research ERBs), 104-105 Council for International Organizations of Medical Sciences (CIOMS), 34, 188, 189-190 D Data and Safety Monitoring Boards/Data Monitoring Committees (DSMB/ DMCs), 49, 68, 77, 82, 87, 91, 139, 147, 151, 152, 154-157, 158-159, 161, 170, 195, 235, 254, 256, 260-261 funding, 151 Data and safety monitoring, general, 49, 136-161 (passim), 260-261 see also Confidentiality and privacy Food and Drug Administration (FDA), 137, 138, 139-141, 144-150, 151, 152, 156-157, 160, 161 funding, 138 Good Clinical Practice (GCP), 139, 140, 144, 147, 148, 150, 152 human research participant protection programs (HRPPPs), general, 49, 136, 141, 151, 160 informed consent, 141-142, 152, 154, 157 Institutional Review Boards (IRBs), 8, 9, 11, 44, 48, 55, 63(n.9), 71, 103, 136-137, 139, 141-145 (passim), 148, 149, 158-159 National Institutes of Health (NIH), 137, 150-151, 152, 156-157, 161 Office of Human Research Protections (OHRP), 141-143, 148, 150, 151, 159, 160-161

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Responsible Research: A Systems Approach to Protecting Research Participants Research Ethics Review Boards (Research ERBs), 11, 16, 74, 88, 99, 100, 101, 138, 144, 145-146, 150, 152-154, 157-158, 161 Databases see also Internet quality assurance, 169-170 registries, clinical trials, 14, 22, 197, 201-204 Decisionally impaired persons, 31, 43, 125 Declaration of Helsinki, 32, 33-34 Denmark, 104 Department of Health and Human Services (DHHS)/Health Education and Welfare (DHEW), 38-39, 141, 177, 195, 199-200, 208, 232, 236 see also Food and Drug Administration (FDA); National Institutes of Health (NIH); Office for Human Research Protections (OHRP) compensation for injury, 15, 188, 192 conflicts of interest, 184, 185-186 National Human Research Protections Advisory Committee (NHRPAC), 12, 18-19, 20-22, 39, 199 National Library of Medicine, 14, 201-202 Office of Research Integrity (ORI), 114 Office of the Inspector General (OIG), 4(n.8), 36-37, 68, 141, 143, 180, 203-204 Office of the Secretary, 20-22, 37-39 ongoing review of research, 136-137, 150 Public Health Service, 4(n.7), 79-80, 118, 184, 185(n.20) quality improvement, 17, 69, 164 study at hand, committee charge, 1, 2, 30 Department of Veterans Affairs (VA) accreditation efforts, 172-173, 175, 176, 245 liability and compensation issues, 188 non-biomedical research, 245 Office of Research Compliance and Assurance (ORCA), 166-168 professional education, 114 quality control, 166-168, 171, 172-173 Dignity of participants, 29, 31, 46, 165, 193-194, 238 see also Confidentiality and privacy; Informed consent Drugs, see Pharmaceuticals industry DSMB/DMC, see Data and Safety Monitoring Boards/Data Monitoring Committees E Economic factors see also Cost factors; Financial conflicts of interest; Funding; Liability and compensation; Non-biomedical research; Socioeconomic status genetics research, harm, 35-36 Education and training, see Academic research; Internet; Participant/patient education; Professional education; Public education Emotional factors, see Psychological effects Ethical and Policy Issues in Research Involving Human Participants, 47 Ethical issues, general, 2, 6, 60, 155, 162, 206-208 see also Accountability, general; Confidentiality and privacy; Conflicts of interest; Informed consent; Professional education; Research Ethics Review Boards (Research ERBs) basic principles, 31-32, 56 committee study methodology, 2, 30, 31, 42-43, 235 cultural context of research, 7-8, 18, 23, 38, 54, 60, 61, 69, 117-118, 134, 167-168 historical perspectives, 29-30, 31, 33-34, 45, 99, 100 participant-investigator interactions, 2, 6, 13, 32, 42, 46, 48, 49, 67-68, 103, 108-135 European Convention on Human Rights and Biomedicine, 188 Experimental studies, 32, 34, 36 see also Radiation experiments oversight and data and safety monitoring, 139 participant-investigator interactions, 111-112 F False Claims Act, 179, 181 FDA, see Food and Drug Administration

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Responsible Research: A Systems Approach to Protecting Research Participants Federal Demonstration Partnership, 198 Federal government, general, 3, 4, 38-39, 44, 47, 150, 198-200 see also Funding; Legislation; Regulatory issues; specific departments and agencies academic research, 56-57 accreditation role, 171-172 committee recommendations, 2, 20-22, 44, 148, 198-200 conflicts of interest, 184 financial conflicts of interest, 10-11 liability and compensation, 194 national review system, 2, 3, 18-19, 21, 39, 88-89, 164, 165 certification of professionals, 116-117 professional education efforts, 61, 62 Federal Policy for the Protection of Human Subjects, see Common Rule Federalwide Assurances, 140, 142 Financial conflicts of interest, 2, 6, 10-11, 17, 24, 42, 46, 50, 55, 65, 72, 73-74, 82-83, 117-118, 183-186, 255-256 Food and Drug Administration (FDA), 20-22, 49, 73, 74(n.5), 78, 79, 127, 165, 179, 198, 232 accountability, 55, 57, 251, 252-253 audits, 69, 73 biologic license applications, 139 bioterrorism response drugs, 212, 213 Center for Drug Evaluation and Research (CDER), 146 clinical research, 14, 37, 39, 73, 112, 144, 150, 151, 160, 161, 181, 201-202 computerized data protection, 160 conflicts of interest, 118, 184 financial conflicts of interest, 86 funding, 73, 151, 156 genetics research, 157 inspections by, 69, 144, 145, 150 Investigational Device Exemption (IDE), 158, 258 Investigational New Drug Applications (IND), 112, 140, 146, 152, 157, 158, 201, 212, 251, 253, 255 liability and compensation, 192 multicenter studies, 55, 103 New Drug Applications (NDA), 140 notification, 139 Office for Good Clinical Practice, 39 oversight and data and safety monitoring, 137, 138, 139-141, 144-150, 151, 152, 156-157, 160, 161 Premarket Approval (PMA), 139, 140, 157, 213 professional education, 114, 181 registries, clinical trials, 14, 201-202 Research Ethics Review Boards (Research ERBs), 73, 78, 79, 86, 87, 100, 103, 145-146, 152 Food and Drug Administration Modernization Act of 1997, 14(n.17), 201, 204(n.17) Foreign countries, see International perspectives Fraud, 179, 180 see also Conflicts of interest Freedom of Information Act, 167(n.3) Funding, 2, 6, 8, 20, 21, 23-28, 32, 57-60, 69, 79, 150, 198, 250-252 academic research, 58, 59 Award for Excellence in Human Research Protection, 142(n.5) Committee on Human Research Participant Protections, 199, 236 financial conflicts of interest, 2, 6, 10-11, 17, 24, 42, 46, 50, 55, 65, 72, 73-74, 82-83, 117-118, 183-186, 255-256 Food and Drug Administration (FDA), 73, 151, 156 human research participant programs, general, 23, 44, 52, 53, 54, 57-60 Institutional Review Boards (IRBs), 5, 58, 59, 73 liability and compensation issues, 188, 190 National Institutes of Health (NIH), 58, 59, 60, 79, 128, 151, 156, 161, 169, 251, 252, 255-256 non-biomedical research, 36, 240 oversight and data safety monitoring, 138 peer review and, 78-79 private, 8, 32, 188, 190 quality improvement, 17, 27, 164, 168-169 Research Ethics Review Boards (Research ERBs), 78-79, 105-106 terrorism response, 211

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Responsible Research: A Systems Approach to Protecting Research Participants G GCP, see Good Clinical Practice Gelsinger, Jesse, 37-38, 236(n.1) General Accounting Office (GAO), 4(n.8), 182 General Clinical Research Center (GCRC), 251 Genetics research, 35-36, 37-38, 148, 236(n.1) Food and Drug Administration (FDA) oversight, 157 National Institutes of Health (NIH) oversight, 151 Research Ethics Review Boards (Research ERBs), 88 Germany, 189 Good Clinical Practice (GCP), 50, 55, 88, 154 oversight and data and safety monitoring, 139, 140, 144, 147, 148, 150, 152 professional education, 61, 114 Government role, see Federal government, general; Legislation; Regulatory issues; State government Greenwall Foundation, 236 Guidelines for Good Clinical Practice, see Good Clinical Practice (GCP) H Health Insurance Portability and Accountability Act (HIPAA), 4(n.5), 95, 159-160, 179, 181-182, 205, 207-211 Historical perspectives, 29-30, 31, 33-34, 37, 73 conflicts of interest, 183 continuing review of research, 143 ethical issues, general, 29-30, 31, 33-34, 45, 99, 100 ethics education, 63, 97, 99, 100 informed consent, 120-121, 134 journal articles, 203, 206-207 liability and compensation, 189-191, 192 monitoring and oversight, 141 HIV, 43, 131, 202(n.8) Human research participant protection programs (HRPPPs), general, 1-2, 45-69, 141, 162-196 see also Institutional Review Boards (IRBs); Research Ethics Review Boards (Research ERBs) accountability, 6, 7-8, 30, 44, 48, 50, 54-57, 249-262 accreditation issues, 3, 30, 116, 174, 175, 176-177, 193 committee recommendations, 6, 9, 11, 12, 19-28, 44, 47, 54, 197-216 committee study at hand, methodology, 1, 3, 4, 30, 42, 231-236 conflicts of interest, 46, 50, 53, 55, 65, 76 data safety and monitoring plans, 49, 136, 141, 151, 160 definitional issues, 48-52 ethical research culture, 7-8, 18, 23, 38, 54, 60, 61, 69, 117-118, 134, 167-168 funding, 23, 44, 52, 53, 54, 57-60 participant-investigator interactions, 2, 6, 13, 32, 42, 46, 48, 49, 67-68, 103, 108-135, 157 protocols, 1-2, 6, 46, 49-51, 53, 56, 59, 65, 66-67, 68, 69, 76, 108-109, 136, 151, 162, 249-262 quality improvement, 17, 163, 168-171 Research Ethics Review Boards (Research ERBs), 9, 72, 102 risk classification, 90 Human Research Protections Acts, 47(n.2) I Incidence of research injuries, 21, 191 Incompetent participants, see Decisionally impaired persons Informed consent, 2, 29, 38, 40, 42, 53, 67-68, 119-128, 130, 135, 141, 162, 181-182 accreditation and, 94 attitudes and beliefs about, 125-126, 130-131, 132 basic principles of research, 31, 32, 46, 206-207 bioterrorism response drugs, 212 committee recommendations, 13, 24, 25, 92, 120, 130 committee study methodology, 3, 31, 235

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Responsible Research: A Systems Approach to Protecting Research Participants Common Rule (Federal Policy for the Protection of Human Subjects), 5, 47(n.2), 91, 120, 138, 139, 149, 178, 179, 198, 208, 210, 214, 237, 241-242 community consent, 127-128 confidentiality and, 119 conflicts of interest, 83, 184, 187 consent forms, 64, 92-94, 103, 119, 121-122, 123-126, 130-131, 154, 181, 187 decisionally impaired persons, 31, 43, 125 disclosure documents, 93 financial conflicts of interest, 83 genetics research, 37 historical perspectives, 120-121, 134 Institutional Review Boards (IRBs), 38, 39-40, 92, 119-120, 123, 240-242 language issues, 124, 125 non-biomedical research, 36, 238, 240-242 oversight and data and safety monitoring, 141-142, 152, 154, 157 participant-investigator interactions, 2, 6, 13, 32, 42, 46, 48, 49, 67-68, 103, 108-135, 157 physician’s role, 120, 121, 125 professional education, 108-109, 119-120 protocols, 40, 93, 94, 108-111, 119-120, 125, 128 race/ethnicity of participant, 125 regulatory issues, general, 94-95, 121, 141-142 risk-appropriate safety monitoring, 93, 94, 122, 123 standardization, other, 110 video presentations, 94, 124, 126, 154 Inspections, 69, 144, 145, 148, 150 Institutional Review Boards (IRBs), 2, 3, 5, 6, 8-9, 36-37, 39-40, 48, 53, 70-74, 103, 141, 142, 184, 209, 215, 236 see also Accreditation; Research Ethics Review Boards (Research ERBs) academic research, 81, 84, 232 committee recommendations, 8-12, 60, 71, 110(n.3), 200 committee study methodology, 2, 3, 31, 232, 234, 235 Common Rule (Federal Policy for the Protection of Human Subjects), 5, 47(n.2), 91, 120, 138, 139, 149, 178, 179, 198, 208, 210, 214, 237, 241-242 continuing review, 143 education of members, 38, 60, 62, 63-64, 70, 114, 116 financial conflicts of interest, 55, 72, 73-74, 82, 86 funding, 5, 58, 59, 73 informed consent, 38, 39-40, 92, 119-120, 123, 240-242 membership, 38, 95-96 multicenter studies, 12, 39, 55, 215 national system, 19, 39 non-biomedical research, 36, 43, 237-238, 239, 240-247 oversight and data and safety monitoring, 8, 9, 11, 44, 48, 55, 63(n.9), 71, 103, 136-137, 139, 141-145 (passim), 148, 149, 158-159 protocols, 5, 9, 38, 39, 56, 58, 63, 66-67, 73-74, 80-81, 88-89, 119-120, 239, 240 public transparency, 64, 65 quality improvement/compliance, 68-69, 173 Research Ethics Review Boards (Research ERBs) renamed as, 9, 24, 71-72, 110-111(n.3), 136(n.1), 162(n.1), 201(n.5), 249(n.1) risk classification, 68, 89-90 taxonomy of, 165 Institutional Review Boards: A Time for Reform, 37 Interdisciplinary approaches, see Multidisciplinary approaches International Conference on Harmonisation, 50, 93(n.20), 189 oversight and data and safety monitoring, 151 professional education, 114 International Organization for Standardization, 210 International perspectives, 42-43, 50, 100, 129 see also Terrorism compensation for injury, 15, 188 confidentiality and privacy, 210

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Responsible Research: A Systems Approach to Protecting Research Participants Council for International Organizations of Medical Sciences (CIOMS), 34, 188, 189-190 Declaration of Helsinki, 32, 33-34, 62, 188 European Convention on Human Rights and Biomedicine , 188 multisite research, 104 Nuremburg Code, 32, 33, 62 Internet accreditation, 172 confidentiality and privacy, 208(n.13) continuing review of research, 143(n.6) Federalwide Assurance agreement (FWA), 142(n.3) gene therapy, 236(n.1) investigational drug studies (FDA), 146 professional education, 60, 113-114, 115(n.6), 134, 198 protocol accountability, 249-250 public education, 65 registries, clinical trials, 14(n.16), 202(n.7, n.9), 201-204 Investigational Device Exemption (IDE), 158, 258 Investigational New Drug Applications (IND), 112, 140, 146, 152, 157, 158, 201, 212, 251, 253, 255 IRBs, see Institutional Review Boards J Journal articles, 158, 163, 168, 197, 203, 206-207, 235 L Legal issues, see also Confidentiality and privacy; Conflicts of interest; Informed consent; Legislation; Liability and compensation; Regulatory issues fraud, 179, 180 Legislation, 20-22, 47-48 see also Regulatory issues Bayh-Dole Act, 185 False Claims Act, 179, 181 Food and Drug Administration Modernization Act, 14(n.17), 201, 204(n.11) Freedom of Information Act, 167(n.3) Health Insurance Portability and Accountability Act (HIPAA), 4(n.5), 95, 159-160, 179, 181-182, 205, 207-211 Human Research Protections Acts, 47(n.2) National Childhood Vaccine Compensation Injury Act, 194 Patent and Trademark Law Amendment Act , 185(n.19) proposed/recommended, 4(n.6), 6, 47 Public Health Service Act, 4(n.7), 185(n.20) Research Revitalization Act, 47(n.2) state-level, 47-48, 65 Liability and compensation, 2, 14-15, 27, 42, 163, 178, 179-181, 188-195, 254-255 academic research, 192 accreditation and, 193 funding and, 188, 190 historical perspectives, 189-191, 192 informed consent forms, 93(n.20), 120-122 National Institutes of Health (NIH), 188, 194 Research Ethics Review Boards (Research ERBs), 88, 104, 194-195 transparency, 65 Litigation, see Liability and compensation Longitudinal studies, 241(n.8) protocol review, 46 taxonomy of, 165 M Marrett, Cora, 236-248 Maryland, 48, 65 Mass media, 3, 15, 37 Medicaid, 180 Medicare, 35, 179, 180, 203, 208(n.16) MedWatch, 149 Mentoring, 60, 81, 113, 114-115 Methodology, see Research methodology Minority groups, see Race/ethnicity Monitoring, 40, 81, 104, 136-161 (passim), 235 see also Oversight, general; Quality control; Risk-appropriate safety monitoring

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Responsible Research: A Systems Approach to Protecting Research Participants adverse event reporting, 15, 16, 37, 47, 59, 68, 103, 148, 149-150, 153, 154, 157-158, 161, 165, 170, 192, 254, 261 continuing review, general, 3, 31, 32, 46, 49, 59, 63, 90, 91, 139, 143, 251-252, 254 Data and Safety Monitoring Boards/ Data Monitoring Committees (DSMB/DMC), 49, 68, 77, 82, 87, 91, 139, 147, 151, 152, 154-157, 158-159, 161, 170, 195, 235, 254, 256, 260-261 funding, 151 data and safety monitoring, general, 49, 136-161 (passim), 260-261 defined, 140 historical perspectives, 141 informed consent, 137, 152, 154 inspections, 69, 144, 145, 148, 150 internal, 16, 48, 78, 138, 149, 163 protocols, 5, 40, 137, 152, 154 Research Ethics Review Boards (Research ERBs), 74, 88, 99, 100, 101, 144, 152-154, 251-252, 254, 256 template forms to document, 260-261 Multicenter Academic Clinical Research Organization (MACRO), 84, 104 Multicenter research, 3, 7, 12, 25, 31, 37, 102, 215, 235 accountability, 50, 55, 56, 255-257 cost factors, 104, 256-257 Institutional Review Boards (IRBs), 12, 39, 55, 215 oversight, 142 Research Ethics Review Boards (Research ERBs), 12, 102-104 Multidisciplinary approaches national system review, 19, 21 oversight and data and safety monitoring, 139 risk classification, 89 Multiple Project Assurances (MPAs), 142 N National Bioethics Advisory Commission (NBAC), 4, 38, 47, 74, 89-90, 96, 103, 116, 119, 128, 184, 232 continuing review of research, 137-138, 143, 149 National Center for Health Statistics (NCHS), 241(n.8) National Childhood Vaccine Compensation Injury Act, 194 National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, 4(n.8), 31, 119, 143 National Committee for Quality Assurance (NCQA), 4(n.4), 171, 172-173, 175, 176, 231, 232 National Health Interview Survey, 241(n.8) National Human Research Protections Advisory Committee (NHRPAC), 12, 18-19, 20-22, 39, 106, 119, 199-200, 232 National Institutes of Health (NIH), 20-22, 38-39, 50, 73, 82, 201-202, 256-257 see also Office for Human Research Protections (OHRP) accreditation role, 166 committee study methodology, 232, 234 community involvement, 128 funding, 58, 59, 60, 79, 128, 151, 156, 161, 169, 251, 252, 255-256 genetics research, 151 informed consent, 128, 134 liability and compensation issues, 188, 194 Office for Protection from Research Risks (OPRR), 37, 38, 75-76, 142, 199, 200, 232 oversight and data and safety monitoring, 137, 150-151, 152, 156-157, 161 peer review, 79-80 professional education efforts, 99, 114 public education, 127 National Library of Medicine (NLM), 14, 201-202 National Science Foundation (NSF), 58, 80 conflicts of interest, 118, 184 non-biomedical research, 238 New Drug Application (NDA), 140 Investigational New Drug Applications (IND), 112, 140, 146, 152, 157, 158, 201, 212, 251, 253, 255 New Zealand, 189 Non-biomedical research, 36, 43, 63, 90, 106, 236-248 accreditation, 245-246 confidentiality issues, 238, 239-240, 243-244

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Responsible Research: A Systems Approach to Protecting Research Participants conflicts of interest, 238 funding, 36, 240 informed consent, 36, 238, 240-242 Institutional Review Boards (IRBs), 36, 43, 237-238, 239, 240-247 National Science Foundation (NSF), 238 observational studies, 32, 35, 36, 237 regulatory issues, general, 43, 242-244 Nuremburg Code, 32, 33, 62 O Observational studies, 32, 35, 36, 237 see also Non-biomedical research Office for Good Clinical Practice, 39 Office for Human Research Protections (OHRP), 7, 12, 18-19, 20-22, 37, 38, 39, 50, 57, 198 committee study methodology, 215, 232, 234 financial conflicts of interest, 86 informed consent, 141-142 non-biomedical research, 238-246 (passim) oversight and data and safety monitoring, 141-143, 148, 150, 151, 159, 160-161 professional education efforts, 61, 160-161 quality improvement (QI), 165, 166-168 Research Ethics Review Boards (Research ERBs), 86, 87, 89, 92, 106 risk classification, 92 Office for Protection from Research Risks (OPRR), 37, 38, 75-76, 142, 199, 200, 232 Office of General Counsel, 50 Office of Research Compliance and Assurance (ORCA), 166-168 Office of Research Integrity (ORI), 114 Office of the Inspector General (DHHS), 4(n.8), 36-37, 68, 141, 143, 180, 203-204 OHRP Compliance Data by Institution, by Determination Letters Issues, and by Site-Visited Institution October 1998 to December 2001, 232 Ombudsman programs, 49, 68, 154 Oversight, general, 1, 2, 13, 38, 136-161 (passim), 197 see also Accreditation; Data and safety monitoring; Monitoring; Quality control; Regulatory issues continuing review, general, 3, 31, 32, 46, 49, 59, 63, 90, 91, 143 definitional issues, 29(n.1), 139-140 federal human research participant protection programs (HRPPPs), 6, 18, 19, 42, 44, 47, 48, 52, 56, 90, 136-137 Food and Drug Administration (FDA), 137, 138, 139-141, 144-150, 151, 152, 156-157, 160, 161 funding, 138 Good Clinical Practice (GCP), 139, 140, 144, 147, 148, 150, 152 historical perspectives, 141 informed consent, 141-142, 152, 154, 157 inspections, 69, 144, 145, 148, 150 internal, 16, 48, 78, 138, 149, 163 Institutional Review Boards (IRBs), 8, 9, 11, 44, 48, 55, 63(n.9), 71, 103, 136-137, 139, 141-145 (passim), 148, 149, 158-159 multicenter studies, 35, 90 National Institutes of Health (NIH), 137, 150-151, 152, 156-157, 161 non-biomedical research, 36, 43 Office for Human Research Protections (OHRP), 141-143, 148, 150, 151, 159, 160-161 participant-investigator interaction, 108, 131, 134 professional education, 7, 61, 63(n.9), 66, 107 protocols, 5, 40, 137, 138 Research Ethics Review Boards (Research ERBs), 11, 16, 74, 88, 99, 100, 101, 138, 144, 145-146, 150, 152-154, 157-158, 161 Ovieto Convention, 188 P Participant/patient education, 2, 31, 64, 126, 130, 131, 150, 200-204 see also Informed consent; Public education dignity of participants, 29, 31, 46, 165, 193-194

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Responsible Research: A Systems Approach to Protecting Research Participants general principles of research, 46 participant-investigator interactions, 2, 6, 13, 32, 42, 46, 48, 49, 67-68, 103, 108-135, 138 transparency, 7, 13-14, 52, 64-66 Patent and Trademark Law Amendment Act, 185(n.19) Peer review, 73, 78-80, 110, 158 Percival, Thomas, 33 Pharmaceutical Research and Manufacturers of America (PhRMA), 62 Pharmaceuticals industry, 14, 34-35, 50, 78, 112, 194 see also Food and Drug Administration (FDA) accountability, 55, 252-255 bioterrorism, response, 22, 28, 88, 197, 211-215 vaccines, 194, 211-212 Physicians, 35, 78, 94, 98, 113, 130, 149, 180, 249, 252 informed consent, 120, 121, 125 oversight and data and safety monitoring, 139 Premarket approval (FDA), 139, 140, 157, 213 Preserving Public Trust: Accreditation and Human Research Participation, 3, 30, 48, 116, 164, 171, 173(n.10), 175, 231 President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research, 4(n.8), 38, 119 Privacy, see Confidentiality and privacy Professional associations and societies, general, 3, 183, 240 see also specific associations and societies Professional education, 31, 81, 108, 133-135, 174, 181, 198 accreditation, education about, 62 certification, 63, 96, 101, 113-114, 115-117, 133 computer data, personal data protection, 160 continuing medical education programs, 7, 60-61, 62, 113-116, 150 Department of Veterans Affairs (VA), 114 ethics, 2, 7-8, 52, 53, 60-64, 70, 113-117, 142, 147, 180 Food and Drug Administration (FDA), 114, 181 Good Clinical Practice (GCP), 61, 114 informed consent, 108-109, 119-120 Institutional Review Boards (IRBs), 38, 60, 62, 63-64, 70, 114, 116 Internet-based, 60, 113-114, 115(n.6), 134, 198 journal articles, 158, 163, 168, 197, 203, 206-207, 235 mentoring, 60, 81, 113, 114-115 National Institutes of Health (NIH), 99, 114 non-biomedical research, 246 participant-investigator interactions, 108, 110, 112-117, 133 informed consent, 108-109, 119-120 pathophysiology and pharmacology, 150 quality monitoring, 170, 172 recruitment and enrollment of participants, 108-109 regulatory issues, general, 61, 62, 114, 115 Research Ethics Review Boards (Research ERBs), 88, 99-101, 106, 115-116, 133, 134, 150, 181 computer applications, 99 template form to document, 261 Project LEAD, 101, 134, 232 Protocols, 1-2, 6, 25, 32, 40, 41, 42, 46, 68, 70, 72-107, 154, 170, 251, 255-256 see also Scientific review access to, stakeholders, 13-14 conflicts of interest, 10-11, 66-67, 78, 117, 255-256 definitional issues, 49-51 financial conflicts of interest, 10-11 human research participant protection programs (HRPPPs), general, 1-2, 6, 46, 49-51, 53, 56, 59, 65, 66-67, 68, 69, 76, 108-109, 136, 151, 162, 249-262 informed consent, 40, 93, 94, 108-111, 119-120, 125, 128 Institutional Review Boards (IRBs), 5, 9, 38, 39, 56, 58, 63, 66-67, 73-74, 80-81, 88-89, 119-120, 239, 240 non-biomedical research, 238

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Responsible Research: A Systems Approach to Protecting Research Participants participant-investigator interactions, 2, 6, 13, 32, 42, 46, 48, 49, 67-68, 103, 108-113 professional education, 61, 108-109, 134-135 Research Ethics Review Boards (Research ERBs), 72-77, 78, 79, 82-84, 87, 93, 95, 98, 100, 101-104, 110, 112, 118, 128, 135, 152-153, 253-254 standard operating procedures, 139, 140, 152, 154 template forms to document, 258-261 Psychological effects, 165, 193-194 see also Attitudes and beliefs dignity of participants, 29, 31, 46, 165, 193-194 genetics research, 35-36 non-biomedical research, 237 Public education, 13-14, 23, 64, 131, 200-204 see also Participant/patient education committee study methodology, access to, 234-235 mass media, 3, 15, 37 registries, clinical trials, 14, 22, 197, 201-204 transparency, 7, 13-14, 52, 64-66, 69, 127-128, 234-235 Public Health Service, 79-80 conflicts of interest, 118, 184 Public Health Service Act, 4(n.7) Public opinion, 14-15, 39, 215 mass media, 3, 15, 37 participant-investigator interactions, 110, 130, 133 Research Ethics Review Boards (Research ERBs), 88 Public Responsibility in Medicine and Research (PRIM&R), 62, 63-64, 99, 231 PXE International, 232 Q Quality control see also Accreditation; Good Clinical Practice (GCP); Regulatory issues; Standards assurance, 2, 6, 42, 49, 53, 68-69, 88, 166-173 (passim), 181, 195 best practices, 61, 106, 107, 163-164, 166, 171, 198 cultural context of research, 7-8, 18, 23, 38, 54, 60, 61, 69, 117-118, 134, 167-168 Department of Veterans Affairs (VA), 166-168, 171, 172-173 funding, 17, 27, 164, 168-169 human research participant protection programs (HRPPPs), general, 17, 163, 168-171 improvement (QI), 2, 6, 7, 8, 16, 17, 31, 42, 49, 68-69, 88, 94, 116, 142-143, 194, 195 continuous, 7, 163-170, 173-174 informed consent, 94, 126-127, 164 Institutional Review Boards (IRBs), 68-69, 173 Office for Human Research Protection (OHRP), 165, 166-168 peer review, 73, 78-80, 110, 158 professional education, 170, 172 Research Ethics Review Boards (Research ERBs), 88, 167, 168, 170, 194 R Race/ethnicity, 100, 125 Radiation experiments Advisory Committee on Human Radiation Experiments (ACHRE), 4(n.8), 119, 213-214 informed consent, 213, 214 Research Ethics Review Boards (Research ERBs), 88 RAND Corporation, 215 Recruitment and enrollment of participants, 41, 51, 77, 95 see also Informed consent conflicts of interest, 117 professional education, 108-109 Research Ethics Review Boards (Research ERBs), 75, 81, 87, 154 template forms to document, 260 Registries, clinical trials, 14, 22, 197, 201-202 Regulatory issues, 4, 5, 20-28, 34, 39, 45, 47-48, 53, 56-57, 68, 89, 92, 103, 118, 129, 138-142, 235

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Responsible Research: A Systems Approach to Protecting Research Participants see also Accreditation; Food and Drug Administration (FDA); Institutional Review Boards (IRBs); Health Information Portability and Accountability Act (HIPAA) Legislation; Office for Human Research Protections (OHRP); Research Ethics Review Boards (Research ERBs); Standards academic research, 50 Assurance of Compliance documents, 140 Belmont Report, 70, 74-75, 92, 119, 181, 238 Common Rule (Federal Policy for the Protection of Human Subjects), 5 confidentiality and privacy, 159-160, 205-211, 215-216 continuing review of research, 139, 143 exempt research and expedited review, 43, 90, 91, 112, 160, 176, 209, 238, 242-244 Federal Demonstration Partnership, 198 informed consent, 94-95, 121, 141-142 non-biomedical research, 43, 242-244 professional education about, 61, 62, 114, 115 risk-appropriate safety monitoring, 11, 68, 89 Religious factors, 97 Research Ethics Review Boards (Research ERBs), 9-12, 23-28, 70-88, 91-107, 176, 177-178, 179, 196, 201 academic research, 81, 84, 86, 251-252 accreditation, 104-105, 107 audits, 138 certification of members, 101, 115 commercial, 79, 80, 85-86, 88 committee recommendations, 9, 11, 23-28, 71, 72, 96, 98, 102, 106, 138, 144, 162, 182 confidentiality and privacy, 87, 100, 153, 160, 209-211 conflicts of interest, 10-11, 18, 24, 72, 74-75, 82-87, 100, 101-102, 105, 118, 162-163, 182, 185-186, 187, 205 cost factors, 104-105 financial conflicts of interest, 10-11, 74-75, 82-83, 85-86 Food and Drug Administration (FDA), 73, 78, 79, 86, 87, 100, 103, 145-146, 152 funding, 78-79, 105-106 genetics research, 88 historical perspectives, 88, 104, 194-195 human research participant protection programs (HRPPPs), 84 informed consent, 92-95, 100, 103, 123-124, 127, 128, 133, 134-135, 157-158, 181, 204 Institutional Review Boards (IRBs) renamed as, 9, 24, 71-72, 110-111(n.3), 136(n.1), 162(n.1), 201(n.5), 249(n.1) membership, qualifications, and voting, 95-101 multicenter research, 12, 102-104 Office for Human Research Protection (OHRP), 86, 87, 89, 92, 106 oversight and data and safety monitoring, 11, 16, 74, 88, 99, 100, 101, 138, 144, 145-146, 150, 152-154, 157-158, 161 participant-investigator interactions, 110-111, 112 professional education, 88, 99-101, 106, 115-116, 133, 134, 150, 181 computer applications, 99 protocols, 72-77, 78, 79, 82-84, 87, 93, 95, 98, 100, 101-104, 110, 112, 118, 128, 135, 152-153, 253-254 quality control, general, 88, 167, 168, 170, 194 radiation experiments, 88 recruitment and enrollment of research participants, 75, 81, 87, 154 registries, clinical trials, 14, 204 risk-appropriate safety monitoring, 87, 90-92, 100, 107, 178, 196 Research methodology, 16, 100, 132 see also Longitudinal studies; Protocols; Scientific review bias, 46, 47, 76, 83, 111 committee study at hand, 2-4, 5, 30-31, 40-44, 231-235, 236 experimental studies, 32, 34, 36, 111-112, 139 non-biomedical research, 36, 236-247 observational studies, 32, 35-36, 237

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Responsible Research: A Systems Approach to Protecting Research Participants risk stratification, 91 sampling, 16, 45, 66, 73, 76, 90, 112, 164, 170 Research Revitalization Act, 47(n.2) Resource needs, see Funding Risk-appropriate safety monitoring, 2, 8, 9, 11, 20, 26, 31, 32, 40, 42, 49, 55, 56, 66, 68, 136, 154-155, 178, 235, 261 classification of risk, 16, 20, 89-92, 107 Data and Safety Monitoring Boards/ Data Monitoring Committees (DSMB/DMC), 49, 68, 77, 82, 87, 91, 139, 147, 151, 152, 154-157, 158-159, 161, 170, 195, 235, 254, 256, 260-261 informed consent and, 93, 94, 122, 123 participant-investigator interactions, 110 regulatory issues, general, 11, 68, 89 Research Ethics Review Boards (Research ERBs), 87, 90-92, 100, 107, 178, 196 transparency, 66 Risk stratification, 75-76, 90-92, 107 S Sampling, 16, 45, 66, 73, 76, 90, 112, 164, 170 SBES research, see Non-biomedical research Scientific review, 76-81, 155 academic research, 79, 81 conflicts of interest, 2, 6, 11, 24, 42, 117 peer review, 73, 78-80 Research Ethics Review Boards (Research ERBs)/Institutional Review Boards (IRBs), 72, 73, 75-76, 77, 87, 95, 97, 98, 100, 101-102 Single Project Assurances (SPAs), 142 Smallpox, 211-212 Social and behavioral research, see Non-biomedical research Socioeconomic status, 43 Spanish, 189 Standard operating procedures, 139, 140, 152, 154 Standards, 2, 17, 46-47, 79-80, 88, 161, 163, 168-169 see also Accreditation; Good Clinical Practice (GCP); Protocols; Quality control; Regulatory issues academic research, 50 best practices, 61, 106, 107, 163-164, 166, 171, 198 certification of professionals, 63, 96, 101, 113-114, 115-117, 133 conflicts of interest, 18 cost factors, 236 Project LEAD, 101, 134, 232 reporting, 148, 149-150 State government, 47-48, 65 T Terrorism, 22, 28, 197, 211-215 informed consent, 212 Research Ethics Review Boards (Research ERBs), 88 Transparency, 7, 13-14, 52, 64-66 U United Kingdom, 71, 104, 189-190, 206 V Vaccines, 194, 211-215 Veterans, see Department of Veterans Affairs (VA) Video presentations, informed consent, 94, 124, 126, 154 W World Wide Web, see Internet