The Ethics of Research with Human Subjects: Protecting People, Advancing Science, Promoting Trust

320 Pages·2018·2.822 MB·English

by  David B. Resnik (auth.)

International Library of Ethics, Law, and the New Medicine 74
David B. Resnik
The Ethics
of Research
with Human
Subjects
Protecting People, Advancing Science,
Promoting Trust
International Library of Ethics, Law,
and the New Medicine
Volume 74
Series editors
David N. Weisstub, University of Montreal Fac. Medicine, Montreal, QC, Canada
Dennis R. Cooley, North Dakota State University, History, Philosophy, and
Religious Studies, Fargo, ND, USA
Founded by
Thomasine Kimbrough Kushner, Berkely, USA
David C. Thomasma, Dordrecht, The Netherlands
David N. Weisstub, Montreal, Canada
The book series International Library of Ethics, Law and the New Medicine
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More information about this series at http://www.springer.com/series/6224
David B. Resnik
The Ethics of Research with
Human Subjects
Protecting People, Advancing Science,
Promoting Trust
David B. Resnik
National Institutes of Health
National Institute of Environmental Health Sciences
Research Triangle Park, NC, USA
This is a U.S. government work and its text is not subject to copyright protection in the
United States; however, its text may be subject to foreign copyright protection.
ISSN 1567-8008 ISSN 2351-955X (electronic)
International Library of Ethics, Law, and the New Medicine
ISBN 978-3-319-68755-1 ISBN 978-3-319-68756-8 (eBook)
https://doi.org/10.1007/978-3-319-68756-8
Library of Congress Control Number: 2017958835
© Springer International Publishing AG (outside the USA) 2018
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The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
This book is dedicated to my late wife, Susan
Preston Resnik, whose love, companionship,
support, beauty, and kindness I will greatly
miss.
Acknowledgements
I would like to thank the following people for reading drafts of the manuscript and
providing helpful comments: Bruce Androphy, Jessica Berg, Linda Birnbaum, Kyle
Brunner, Michael Fessler, Symma Finn, Vanessa Flores, Stavros Garantziotis,
Brandon Konecny, Amy McGuire, Mark Miller, Liam O’Fallon, Henry Richardson,
Adil Shamoo, Elise Smith, Devin Sullivan, Paul Wade, Joshua Warmack, and David
Wendler. This research was supported by the intramural program of the National
Institute of Environmental Health Sciences (NIEHS), National Institutes of Health
(NIH). It does not represent the views of the NIEHS, NIH, or US government.
vii
Contents
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.1 Perinatal HIV Prevention Trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.2 The SUPPORT Study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
1.3 Hospital Quality Improvement Research . . . . . . . . . . . . . . . . . . . . . . 6
1.4 Henrietta Lacks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
1.5 The Facebook Study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
1.6 Overview of This Book . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
2 Historical Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
2.1 Research with Human Subjects Before World War II . . . . . . . . . . . . 16
2.2 Research with Human Subjects During World War II . . . . . . . . . . . . 21
2.3 Research with Human Subjects After World War II . . . . . . . . . . . . . 22
2.4 The Belmont Report . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
2.5 The U.S. Federal Regulations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
2.6 Continuing Scandals and Controversies . . . . . . . . . . . . . . . . . . . . . . 34
2.7 Concerns About Integrity in Biomedical Research . . . . . . . . . . . . . . 39
2.8 Jesse Gelsinger’s Death . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
2.9 Concerns About Research on Human Biosamples . . . . . . . . . . . . . . . 43
2.10 Conclusion: Human Research Regulations and Guidelines
in Historical Context . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
3 Moral Theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
3.1 What Is a Moral Theory? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
3.2 Moral Subjectivism and Relativism . . . . . . . . . . . . . . . . . . . . . . . . . . 57
3.3 Classifying Moral Theories . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
3.4 Divine Command Theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
3.5 Virtue Ethics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
3.6 Natural Law Theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
3.7 Utilitarianism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
3.8 Kantianism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
3.9 Natural Rights Theories . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
3.10 Pluralistic Theories . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
3.11 Conclusion: Toward a Decision-Making Framework . . . . . . . . . . . . 84
ix
x Contents
4 Trust as a Foundation for Research with Human Subjects . . . . . . . . 87
4.1 What Is Trust? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
4.2 Trust in Research Involving Research with Human Subjects . . . . . . 89
4.3 Trust as a Foundation for the Ethics of Research with Human
Subjects: Some Alternative Views . . . . . . . . . . . . . . . . . . . . . . . . . . . 92
4.4 Trust as a Foundation for the Ethics of Research with Human
Subjects: My View . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
4.5 Promoting Trust in Research with Human Subjects . . . . . . . . . . . . . 98
4.6 The Relationship Between Moral Principles and Research
Regulations and Guidelines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
4.7 The Role of Trust in Resolving Ethical Dilemmas in Research
with Human Subjects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
4.8 Objections to My View . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
4.9 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110
5 Informed Consent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
5.1 Trust and Informed Consent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
5.2 The Elements of Consent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
5.3 Disclosure Standards . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
5.4 Documentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
5.5 Consent by Parties Other than the Subject . . . . . . . . . . . . . . . . . . . . . 122
5.6 Research Without Consent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
5.7 Opt-Out Consent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130
5.8 General Consent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
5.9 Deception in Research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
5.10 Assent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
5.11 Payment for Research Participation . . . . . . . . . . . . . . . . . . . . . . . . . . 136
5.12 The Right to Withdraw . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
5.13 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
6 Privacy and Confidentiality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
6.1 Privacy, Confidentiality, and Trust . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
6.2 Sharing and Publishing Data and Samples . . . . . . . . . . . . . . . . . . . . 152
6.3 Justifiable Breaches of Privacy and Confidentiality . . . . . . . . . . . . . . 155
6.4 Harm to Self . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155
6.5 Harm to Others . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156
6.6 Suspected Abuse/Neglect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 158
6.7 Communicable Disease Reporting . . . . . . . . . . . . . . . . . . . . . . . . . . . 159
6.8 Informing Family Members About Genetic Diseases . . . . . . . . . . . . 160
6.9 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162
7 Risks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165
7.1 What Is Risk? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165
7.2 Types of Risk Related to Research Participation . . . . . . . . . . . . . . . . 166
7.3 Risk and Trust . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 166
7.4 Assessing Risk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167
Contents xi
7.5 Minimizing Risk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169
7.6 Minimal Risk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171
7.7 Research on Healthy Volunteers . . . . . . . . . . . . . . . . . . . . . . . . . . . . 176
7.8 Phase I Trials on Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 180
7.9 Randomized Controlled Trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181
7.10 Placebo-Controlled Trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183
7.11 Risks to Researchers and Third Parties . . . . . . . . . . . . . . . . . . . . . . . 186
7.12 Compensation for Research-Related Injuries . . . . . . . . . . . . . . . . . . 188
7.13 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 190
8 Benefits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193
8.1 What Are Benefits? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193
8.2 What Are the Benefits of Research? . . . . . . . . . . . . . . . . . . . . . . . . . 194
8.3 What Is the Relationship Between Research Design
and Benefits? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 194
8.4 Sources of Special Duties of Beneficence . . . . . . . . . . . . . . . . . . . . . 195
8.5 Disclosing Individual Research Results to Human Subjects . . . . . . . 195
8.6 Ancillary Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201
8.7 Post-trial Access to Medications . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204
8.8 Benefits in Placebo-Controlled Clinical Trials . . . . . . . . . . . . . . . . . 209
8.9 Fair Benefits to Host Communities and Nations . . . . . . . . . . . . . . . . 211
8.10 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213
9 Vulnerable Subjects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215
9.1 Who or What Is a Vulnerable Subject? . . . . . . . . . . . . . . . . . . . . . . . 216
9.2 Research Involving Children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 220
9.3 Research Involving Adults with Mental Disabilities or Diseases
that Impair Decision-Making . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227
9.4 Research Involving Pregnant Women . . . . . . . . . . . . . . . . . . . . . . . . 230
9.5 Conclusion: Protection vs. Access . . . . . . . . . . . . . . . . . . . . . . . . . . . 232
10 Research Integrity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235
10.1 The Importance of Integrity in Research with Human
Subjects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235
10.2 Misconduct in Research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 238
10.3 Noncompliance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 240
10.4 Whistleblowing in Research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 241
10.5 Preventing Misconduct and Noncompliance . . . . . . . . . . . . . . . . . . 242
10.6 Conflict of Interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243
10.7 Data Suppression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 250
10.8 Dealing with Conflicts of Interest in Research . . . . . . . . . . . . . . . . 252
10.9 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 256
11 Regulatory Reform . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 257
11.1 Institutional Review Boards: A Time for Reform . . . . . . . . . . . . . . 257
11.2 Risk-Based Review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259
11.3 IRB Mission Creep . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259