Authors: Ezekiel J. Emanuel (Editor), John D. Arras (Editor), Jonathan D. Moreno (Editor), Robert A. Crouch
ISBN-13: 9780801878138, ISBN-10: 0801878136
Format: Paperback
Publisher: Johns Hopkins University Press
Date Published: February 2004
Edition: 1st Edition
Ezekiel J. Emanuel, M.D., Ph.D., is Chair of the Department of Clinical Bioethics at the Warren G. Magnuson Clinical Center at the National Institutes of Health. Robert A. Crouch, M.A., is an Assistant Professor in the Biomedical Ethics Unit and the Department of Social Studies of Medicine at McGill University. John D. Arras, Ph.D., is Porterfield Professor of Biomedical Ethics and Professor of Philosophy at the University of Virginia. Jonathan D. Moreno, Ph.D., is Director of the Center for Biomedical Ethics at the University of Virginia. Christine Grady, R.N., Ph.D., is Head, Section on Human Subjects Research in the Department of Clinical Bioethics at the National Institutes of Health.
"Many of the chapters easily deserve to be required reading... Most of the readings that have been chosen for the book can lay claim to being classics. They represent sophisticated thinking on various topics." -- Bulletin of the World Health Organization
"This book provides excellent matieral on a broad variety of ethical topics in clinical research." -- Quality Assurance Journal
All investigators funded by the National Institutes of Health are now required to receive training about the ethics of clinical research. Based on a course taught by the editors at NIH, Ethical and Regulatory Aspects of Clinical Research is the first book designed to help investigators meet this new requirement. The book begins with the history of human subjects research and guidelines instituted since World War II. It then covers various stages and components of the clinical trial process.
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 |