Ethical and Regulatory Aspects of Clinical Research: Readings and Commentary Book

	Preface
	Acknowledgments and Permissions
	Commonly Used Acronyms
	Frequently Cited Research Regulations, Guidelines, and Reports
	List of Contributors
Pt. I	Scandals and Tragedies of Research with Human Participants: Nuremberg, the Jewish Chronic Disease Hospital, Beecher, and Tuskegee	1
1	U.S. Medical Researchers, the Nuremberg Doctors Trial, and the Nuremberg Code: A Review of Findings of the Advisory Committee on Human Radiation Experiments	7
2	The Jewish Chronic Disease Hospital Case	11
3	Ethics and Clinical Research	16
4	Racism and Research: The Case of the Tuskegee Syphilis Study	20
Pt. II	Ethical and Regulatory Guidance for Research with Humans	25
5	The Nuremberg Code	29
6	The Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects	30
7	The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research	33
8	The Common Rule, Title 45 (Public Welfare), Code of Federal Regulations, Part 46 (Protection of Human Subjects), Subparts A-D	39
9	The International Ethical Guidelines for Biomedical Research Involving Human Subjects	56
10	The ICH Harmonised Tripartite Guideline - Guideline for Good Clinical Practice (ICH-GCP Guideline)	80
Pt. III	The Ethics of Clinical Trial Design	95
Sect. 1	The Distinction between Research and Treatment	103
11	Research and Practice	103
12	Demarcating Research and Treatment: A Systematic Approach for the Analysis of the Ethics of Clinical Research	107
Sect. 2	The Ethics of Randomized Clinical Trials: Clinical Equipoise	113
13	Of Mice but Not Men: Problems of the Randomized Clinical Trial	113
14	Equipoise and the Ethics of Clinical Research	117
15	Randomized Controlled Trials: Lessons from ECMO	121
Sect. 3	The Role of Placebos in Clinical Research
16	The Continuing Unethical Use of Placebo Controls	127
17	Placebo-Controlled Trials and the Logic of Clinical Purpose	130
18	Placebo-Controlled Trials and Active-Control Trials in the Evaluation of New Treatments, Part 1: Ethical and Scientific Issues	137
19	The Ethics of Placebo-Controlled Trials: A Middle Ground	140
Sect. 4	The Ethics of Phase I Research	144
20	On the Nature and Ethics of Phase I Clinical Trials of Cancer Chemotherapies	144
21	The Changing Landscape of Human Experimentation: Nuremberg, Helsinki, and Beyond	146
Pt. IV	The Ethics of Research Participant Recruitment	151
Sect. 1	Justifications for the Recruitment of Research Participants	155
22	Philosophical Reflections on Experimenting with Human Subjects	155
23	Experimentation on Trial: Why Should One Take Part in Medical Research?	161
Sect. 2	Access to Research	166
24	Wanted: Single, White Male for Medical Research	166
25	Why Should We Include Women and Minorities in Randomized Controlled Trials?	171
26	The Duty to Exlude: Excluding People at Undue Risk from Research	175
Sect. 3	Payment of Research Participants	179
27	What's the Price of a Research Subject? Approaches to Payment for Research Participation	179
28	Justice for the Professional Guinea Pig	183
29	Paying People to Participate in Research: Why Not?	185
Pt. V	Informed Consent in Research	189
30	Consent Issues in Human Research	197
31	Informed (But Uneducated) Consent	202
32	A Moral Theory of Informed Consent	203
33	Is Informed Consent Always Necessary for Randomized, Controlled Trials?	207
34	Human Experimentation and Human Rights	210
35	Subject Interview Study	213
36	False Hopes and Best Data: Consent to Research and the Therapeutic Misconception	216
37	"Therapeutic Misconception" and "Recruiting Doublespeak" in the Informed Consent Process	221
Pt. VI	Clinical Research with Special Populations	225
Sect. 1	People with Cognitive Impairments	229
38	Research Involving Persons with Mental Disorders That May Affect Decisionmaking Capacity	229
39	Are Research Ethics Bad for Our Mental Health?	234
40	Caring about Risks: Are Severely Depressed Patients Competent to Consent to Research?	237
Sect. 2	Children	240
41	The NIH Trials of Growth Hormone for Short Stature	240
42	In loco parentis: Minimal Risk as an Ethical Threshold for Research upon Children	247
43	Minors' Assent, Consent, or Dissent to Medical Research	252
Sect. 3	Captive Populations: Soldiers, Prisoners, Students	258
44	Convenient and Captive Populations	258
45	Medical Experimentation on Prisoners	262
46	Students, Grades, and Informed Consent	266
47	Against Special Protections for Medical Students	270
Pt. VII	Special Topics in Research Ethics	273
Sect. 1	Genetics Research	285
48	Structuring the Review of Human Genetics Protocols: Gene Localization and Identification Studies	285
49	Structuring the Review of Human Genetics Protocols, Part II: Diagnostic and Screening Studies	291
50	Structuring the Review of Human Genetics Protocols, Part III: Gene Therapy Studies	297
51	Protecting the Privacy of Family Members in Survey and Pedigree Research	302
Sect. 2	Stored Human Biological Specimens	305
52	Statement on Informed Consent for Genetic Research	305
53	Informed Consent for Genetic Research on Stored Tissue Samples	308
54	Use of Human Tissues in Research: Clarifying Clinician and Researcher Roles and Information Flows	311
Sect. 3	Human Embryos and Stem Cells	313
55	Report of the Human Embryo Research Panel, Volume 1	313
56	The Inhuman Use of Human Beings: A Statement on Embryo Research	317
57	Ethical Issues in Human Stem Cell Research	319
58	Creating Embryos for Research: On Weighing Symbolic Costs	325
Sect. 4	Drug Challenge and Drug Washout Studies	329
59	Drug-Free Research in Schizophrenia: An Overview of the Controversy	329
60	Psychiatric Symptom-Provoking Studies: An Ethical Appraisal	332
Sect. 5	Research with Communities	335
61	A Model Agreement for Genetic Research in Socially Identifiable Populations	335
62	Groups as Gatekeepers to Genomic Research: Conceptually Confusing, Morally Hazardous, and Practically Useless	337
63	Protecting Communities in Research: Current Guidelines and Limits of Extrapolation	340
64	Protecting Communities in Biomedical Research	342
Sect. 6	International Research	343
65	Unethical Trials of Interventions to Reduce Perinatal Transmission of the Human Immunodeficiency Virus in Developing Countries	343
66	Human Rights and Maternal-Fetal HIV Transmission Prevention Trials in Africa	346
67	AZT Trials and Tribulations	348
68	Fair Benefits for Research in Developing Countries	354
69	Ethical Imperialism? Ethics in International Collaborative Clinical Research	356
70	Ethics Are Local: Engaging Cross-Cultural Variation in the Ethics for Clinical Research	358
71	Ethical and Regulatory Challenges in a Randomized Control Trial of Adjuvant Treatment for Breast Cancer in Vietnam	363
Pt. VIII	The Behavior of Clinical Investigators: Conflicts of Interest	369
72	Understanding Financial Conflicts of Interest	375
73	Finder's Fees for Research Subjects	377
74	Conflicts of Interests and the Validity of Clinical Trials	378
75	In Whose Best Interest? Breaching the Academic-Industrial Wall	382
Pt. IX	Scientific Misconduct	385
Sect. 1	Altering Data: Fraud, Fabrication, and Falsification	393
76	Pressure to Publish and Fraud in Science	393
77	Science, Statistics, and Deception	395
78	Data Torturing	397
79	Preventing Scientific Misconduct	399
Sect. 2	Rules of Authorship	403
80	When Authorship Fails: A Proposal to Make Contributors Accountable	403
Sect. 3	Problems in the Publication of Research Methods and Findings	411
81	Underreporting Research Is Scientific Misconduct	411
82	The CONSORT Statement: Revised Recommendations for Improving the Quality of Reports of Parallel-Group Randomized Trials	414
Pt. X	Challenges to the Institutional Review Board System	419
83	Monitoring Clinical Research: An Obligation Unfulfilled	425
84	Ethics Review for Sale? Conflict of Interest and Commercial Research Review Boards	429
85	The Institutional Review Board and Beyond: Future Challenges to the Ethics of Human Experimentation	436
86	A Central Institutional Review Board for Multi-institutional Trials	441
	Appendixes: Informed Consent Forms	445
App. A	Phase I Treatment of Adults with Recurrent Supratentorial High-Grade Glioma with Gliadel Wafers Plus Temodar	447
App. B	A Phase I Study of Intra-arterial Onyx-015 for Squamous Cell Cancer of the Head and Neck	451
App. C	Cohort-Varying Information Insert for Form for Consent to Participate in a Phase I Study	459
App. D	Nitric Oxide Inhalation Therapy for Myocardial Ischemia in Patients with Coronary Artery Disease	460
App. E	Double-Blind Drug Crossover and Withdrawal Project	468
App. F	Information and Consent Letter for Hemochromatosis Study	471
App. G	National Action Plan on Breast Cancer (NAPBC) Consent Form for Use of Tissue for Research	474
App. H	Patient Written Consent Form for Review of Medical Records	476
App. I	A Descriptive Study of the Views and Experiences of Persons Involved in a Measles Vaccine Study	478
	Index	479