Ethics and Regulation of Clinical Research

Ethics and Regulation of Clinical Research: Second Edition

Robert J. Levine
Copyright Date: 1986
Published by: Yale University Press
Pages: 480
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  • Book Info
    Ethics and Regulation of Clinical Research
    Book Description:

    The use of human subjects in medical and scientific research has given rise to troubling ethical questions. How should human subjects be selected for experiments? What should they be told about the research in which they are involved? How can their privacy be protected? When is it permissible to deceive them? How do we deal with subjects such as children, fetuses, and the mentally infirm, for whom informed consent is impossible? In this book, Dr. Robert J. Levine reviews federal regulations, ethical analysis, and case studies in an attempt to answer these questions. His book is an essential reference for everyone-members of institutional review boards, scientists, philosophers, lawyers-addressing the ethical issues involved."[Levine's] experience as a clinician, IRB chairman, writer and editor of a journal devoted exclusively to issues faced by IRBS makes him uniquely qualified to bring together the legal, ethical, and practical dimensions. . . [The book] is sophisticated but readable. . . [and] should be on every IRB administrator's desk and in every medical ethics library."-Norman Fost, M.D.,The New England Journal of Medicine"Levine. . . is one of the foremost historians of contemporary clinical science. . . . His book is at once a guide to primary sources for the history of clinical research in the late twentieth century and a pioneering secondary source about that history."-Daniel M. Fox,Bulletin of the History of Medicine"You will be charmed by the [book's] elegance and lucidity and. . . persuaded of its relevance to doctors in any country."-Alex Paton,British Medical Journal"Should be of wide interest to those keen to see advances in medical research brought into general medical practice."-Gilbert Omenn,Issues in Science and Technology

    eISBN: 978-0-300-16349-0
    Subjects: Business, General Science

Table of Contents

  1. Front Matter
    (pp. i-vi)
  2. Table of Contents
    (pp. vii-viii)
  3. Preface to the First Edition, Abridged and Edited
    (pp. ix-xiv)
    Robert J. Levine
  4. Preface to the Second Edition
    (pp. xv-xviii)
  5. Acknowledgments
    (pp. xix-xx)
    Robert J. Levine
  6. Chapter 1 Basic Concepts and Definitions
    (pp. 1-18)

    In the twentieth century discourse on law and ethics, men and women, not the Lord, are building a Tower of Babel. They are doing this not by creating diverse languages, but rather by confounding the meanings of words and phrases within the English language. While most are doing this inadvertently, some are doing it deliberately.

    I shall now identify some of the more common obfuscations. Stipulated definitions often create serious misunderstandings. Consider, for example, the word “fetus.” All dictionaries I have consulted provide a more or less definite gestational age at which the product of human conception is first called...

  7. Chapter 2 Ethical Norms and Procedures
    (pp. 19-36)

    An ethical norm is a statement that actions of a certain type ought (or ought not) to be done. If reasons are supplied for these behavioral prescriptions (or proscriptions), they are that these acts are right (or wrong). Statements of ethical norms commonly include the words “should” or “ought,” but in some cases there are stronger terms such as “must” or “forbidden.” A typical statement of an ethical norm is: research should be conducted only by scientifically qualified persons. The behavior-prescribing statements contained in the various codes and regulations on research involving human subjects may be regarded as variants of...

  8. Chapter 3 Balance of Harms and Benefits
    (pp. 37-66)

    The terms “risk” and “benefit” clearly are not parallel constructions. Risk entails prediction of some future occurrence of harm. Risk may be expressed in terms of probability that a certain harm will occur. The harm or injury itself may be evaluated quantitatively; e.g., it may be described as either a large or small harm. The meaning of such constructions as “small risk” is unclear; it might mean either a small probability of an unspecified amount of harm or an unspecified probability of a small amount of harm.

    By contrast, the term “benefit” has no intrinsic connotations of prediction or probability....

  9. Chapter 4 Selection of Subjects
    (pp. 67-94)

    In its report on Institutional Review Boards (IRBs) (527), the Commission recommended that the IRB shall determine that: “… selection of subjects is equitable…” (Recommendation 4B). The brief commentary on this recommendation elaborates, “The proposed involvement of hospitalized patients, other institutionalized persons, or disproportionate numbers of racial or ethnic minorities or persons of low socioeconomic status should be justified.” The reaction of the Department of Health and Human Services (DHHS) is reflected in its substantially identical Section 46.111a(3).

    This requirement is derived from the principle ofjustice, which requires equitable distribution of both the burdens and the benefits of research....

  10. Chapter 5 Informed Consent
    (pp. 95-154)

    Thus began the critical commentary on the doctrine of informed consent. Subsequently, a massive literature on this topic has accumulated with a conspicuous crescendo during the past 40 years. I do not intend to provide a comprehensive survey. In 1979, William Woodward announced the availability of a bibliography of over 4000 references to publications on informed consent (738); by now I suppose the number has at least doubled.

    The empirical literature on informed consent is, in general, characterized by many flaws; some of the more common ones are discussed in the Section on Comprehension. Specific errors are noted in passing...

  11. Chapter 6 Compensation for Research-induced Injury
    (pp. 155-162)

    In 1982, the President’s Commission concluded its deliberations onCompensating for Research Injurieswith these statements (570):

    A social policy experiment is needed to see whether compensation programs might provide a feasible means further to reduce the risk of unremedied injury to subjects and to avoid the occurrence of events that might needlessly tarnish the reputation of research.

    Accordingly, the Commission recommends that the Secretary of Health and Human Services conduct a small-scale experiment in which several institutions would receive Federal support over 3 to 5 years for the administrative and insurance costs of providing compensation on a nonfault basis...

  12. Chapter 7 Privacy and Confidentiality
    (pp. 163-184)

    Privacy is “the freedom of the individual to pick and choose for himself the time and circumstances under which, and most importantly, the extent to which, his attitudes, beliefs, behavior and opinions are to be shared with or withheld from others” (349). Because this is the definition used in this chapter, some matters considered under the rubric of privacy by the law are excluded, e.g., the right to abortion and contraception. In general, in clinical research we do not condone intrusions into individuals’ privacy without their informed consent (Chapter 5). When an informed person allows an investigator into his or...

  13. Chapter 8 Randomized Clinical Trials
    (pp. 185-212)

    The randomized clinical trial (RCT) is a device used to compare the efficacy and safety of two or more interventions or regimens. The RCT was designed primarily to test new drugs (294); however, over the last 20 years, as its popularity has increased, it has been applied to the study of old drugs, vaccinations, surgical interventions, and even social innovations such as multiphasic screening. The RCT has four main elements. 1) It is “controlled,” i.e., one part of the subject population receives a therapy that is being tested while another part, as similar as possible in all important respects, receives...

  14. Chapter 9 Deception
    (pp. 213-234)

    Sissela Bok provides the definition of “deception” as it is used in this book (66, p. 13): “When we undertake to deceive others intentionally, we communicate messages meant to mislead them, meant to make them believe what we ourselves do not believe. We can do so through gesture, through disguise, by means of action or inaction, even through silence.” Bok views deception as a large category, of which lying is a subset defined as “any intentional deceptive message which isstated.”

    Research methods dependent upon deceiving subjects are used very commonly by social and behavioral scientists. Deceptive strategies seem particularly...

  15. Chapter 10 Children
    (pp. 235-256)

    When the Department of Health, Education, and Welfare (DHEW) published its first proposals to develop regulations providing additional protections for especially vulnerable populations of research subjects, it designated them as persons having “limited capacities to consent” (181). The choice of this label for the special populations highlights the nature of the fundamental problem in justifying their use as research subjects. Because the Nuremberg Code identifies voluntary consent as absolutely essential, it is clearly problematic to involve subjects who lack free power of choice (e.g., prisoners), the legal capacity to consent (e.g., children), or the ability to comprehend (e.g., the mentally...

  16. Chapter 11 Those Institutionalized as Mentally Infirm
    (pp. 257-276)

    Proposals to do research involving as subjects those institutionalized as mentally infirm present a very complicated array of ethical issues. Much of the literature on the ethics of research involving those institutionalized as mentally infirm tends to see the problems as extremely similar to, if not identical with, those presented by proposals to do research involving children (371, 373). Consequently, as we shall see, the Commission’s recommendations for these two classes of subjects are similar in many respects. There are some important differences. 1) There is a problem in defining a class of persons as “those institutionalized as mentally infirm.”...

  17. Chapter 12 Prisoners
    (pp. 277-296)

    “Ladies and Gentlemen: You are in a place where death at random is a way of life. We have noticed that the only place in this prison that people don’t die is in the research unit. Just what is it that you think you are protecting us from?” This is the statement of an inmate to representatives of the Commission during their site visit to the Jackson State Prison in Michigan on November 14, 1975.

    The use of prisoners as research subjects presents two special and, perhaps, intractable ethical problems (524, pp. 5–13). 1) Are prisoners “so situated as...

  18. Chapter 13 The Fetus and the Embryo
    (pp. 297-320)

    In the past two decades, one of the most controversial issues in the American political arena has been the ethical and legal permissibility of abortion. Although a discussion of these matters is beyond the scope of this book, I shall comment briefly on its relevance to considerations of research involving the fetus. It is worth noting that the Commission was established by Congress in the year following theRoe v. Wadedecision in which the United States Supreme Court established the right of women to secure abortions. Subsequently, there have been a variety of bills and Constitutional Amendments introduced in...

  19. Chapter 14 The Institutional Review Board
    (pp. 321-364)

    In 1803, Thomas Percival wrote what is generally regarded as the first authoritative statement that, before proceeding with therapeutic innovation, a physician ought to consult with peers (564).

    Whenever cases occur, attended with circumstances not heretofore observed, or in which the ordinary modes of practice have been attempted without success, it is for the public good, and in a special degree advantageous for the poor (who, being the most numerous class of society, are the greatest beneficiaries of the healing art) that new remedies and new methods of chirurgical treatment should be devised. But in the accomplishment of the salutary...

  20. References
    (pp. 365-392)
  21. Appendix l Department of Health and Human Services Rules and Regulations 45 CFR 46
    (pp. 393-412)
  22. Appendix 2 Food and Drug Administration Rules and Regulations
    (pp. 413-424)
  23. Appendix 3 The Nuremberg Code
    (pp. 425-426)
  24. Appendix 4 World Medical Association Declaration of Helsinki: Recommendations Guiding Medical Doctors in Biomedical Research Involving Human Subjects
    (pp. 427-430)
  25. Appendix 5 Leo Szilard’s Ten Commandments
    (pp. 431-432)
  26. Index
    (pp. 433-452)