Placebo-controlled trials are held by many, including regulators at agencies like the United States Food and Drug Administration, to be the gold standard in the assessment of new medical interventions. Yet the use of placebo controls in clinical trials has been the focus of considerable controversy. In this two-part article, we challenge a number of common beliefs concerning the value of placebo controls. Part I critiques statistical and other scientific justifications for the use of placebo controls in clinical research. The (...) continued use of placebo controls in clinical trials on diseases for which accepted treatment exists raises equally important ethical, legal, and regulatory issues for which various justifications have been given. Defense of this practice relies on normative as well as empirical myths.In their attack on the prevailing use of placebo controls, Kenneth Rothman and Karin Michels emphasize that this practice stands in violation of the World Medical Association's guidelines on the ethics of human experimentation, most commonly known as the Helsinki Declaration. (shrink)

The use of statistics in medical research has been compared to a religion: it has its high priests, supplicants, and orthodoxy. Although the comparison may be more unfair to religion than to research, a useful lesson can nonetheless be drawn: the practice of clinical research may benefit—as does the spirit—from critical self-examination. Arguably, no aspect of the conduct of clinical trials is currently more controversial—and thus in as dire need of critical examination—than the use of placebo controls. The ethical and (...) scientific controversies associated with placebo-controlled trials, never far below the surface, have once again seized public attention. Clearly, concern about these issues within the professional community runs deep and wide, as evidenced by the volume of response generated by Kenneth Rothman and Karin Michels's recent Critique. Criticisms of the use of placebo controls in clinical research are scattered through the literatureo; our objective is to present the case against placebos in a compendious form that takes account of scientific and statistical as well as normative issues. (shrink)

The use of statistics in medical research has been compared to a religion: it has its high priests, supplicants, and orthodoxy. Although the comparison may be more unfair to religion than to research, a useful lesson can nonetheless be drawn: the practice of clinical research may benefit—as does the spirit—from critical self-examination. Arguably, no aspect of the conduct of clinical trials is currently more controversial—and thus in as dire need of critical examination—than the use of placebo controls. The ethical and (...) scientific controversies associated with placebo-controlled trials, never far below the surface, have once again seized public attention. Clearly, concern about these issues within the professional community runs deep and wide, as evidenced by the volume of response generated by Kenneth Rothman and Karin Michels's recent Critique. Criticisms of the use of placebo controls in clinical research are scattered through the literatureo; our objective is to present the case against placebos in a compendious form that takes account of scientific and statistical as well as normative issues. (shrink)

The revelation that data obtained for the US-based National Surgical Adjuvant Breast and Bowel Project (NSABP) from subjects enrolled at Hôpital Saint-Luc in Montreal was falsified has eroded public trust in research. Institutions can educate researchers and help prevent unethical research practices by establishing procedures to monitor research involving human subjects. Research monitoring encompasses four categories of activity: annual reviews of continuing research, monitoring of informed consent, monitoring of adherence to approved protocols and monitoring of the integrity of data. The (...) authors describe characteristics of research projects that may call for monitoring procedures in each category. The form taken by such monitoring depends on the nature of the protocol. Although appropriate research monitoring requires substantial investment of personnel and financial resources, it is required under guidelines regulating research involving human subjects in Canada. Research monitoring is a step forward in re-establishing public confidence in medical research. (shrink)

The voluntary and informed consent of subjects has been the central focus of concern in research reviews, overshadowing the importance of all other considerations. The Nuremberg Code, with its rights-based protection of the subject's autonomy above all else, made it difficult to justify research with no intended benefit when subjects are incompetent to make a valid informed choice to participate. Subsequent codes providing for research with incompetent subjects followed the lead of Nuremberg, substituting the informed authorization of a proxy for (...) the informed consent of the subject. (shrink)

The continuous pursuit and support of medical research on both a societal and individual level is frequently presupposed as laudable, or even obligatory. However, some critics have challenged the assumption that medical research ought to be conducted. These critics reject claims that there is a moral obligation to pursue research, and that medical research may always be justifiable given adequate safeguards and regulations. We align ourselves with critics of the research imperative to the extent that we believe that medical research (...) may only be an imperfect obligation, grounded in the principle of beneficence. Our central purpose in this article, however, is not to advance an original argument concerning the .. (shrink)

Some authors argue that the ethics of medical care and the ethics of research differ, and that it is a mistake to conflate the two. They propose “that medical research and medical treatment are two distinct forms of activities, governed by different ethical principles.” This raises the question of whether physicians who are also clinical investigators may separate their role as physician from that of researcher when they are involved in clinical trials, thereby avoiding the obligations required in the physician-patient (...) relationship. Miller and Brody suggest that medical training is to blame for what they believe is the physicians’ tendency to confound the obligations of research and practice. “Physician-investigators, after all, went to medical school” they explain. They believe that considering research with patients outside the ethical framework of the physician-patient relationship may be “difficult and threatening” to physicians who have “psychological needs” to consider the ethical obligations flowing from their relationship with their patients. (shrink)

Some authors argue that the ethics of medical care and the ethics of research differ, and that it is a mistake to conflate the two. They propose “that medical research and medical treatment are two distinct forms of activities, governed by different ethical principles.” This raises the question of whether physicians who are also clinical investigators may separate their role as physician from that of researcher when they are involved in clinical trials, thereby avoiding the obligations required in the physician-patient (...) relationship. Miller and Brody suggest that medical training is to blame for what they believe is the physicians’ tendency to confound the obligations of research and practice. “Physician-investigators, after all, went to medical school” they explain. They believe that considering research with patients outside the ethical framework of the physician-patient relationship may be “difficult and threatening” to physicians who have “psychological needs” to consider the ethical obligations flowing from their relationship with their patients. (shrink)

Advances in medicine depend not only on the generation of information but also on its dissemination. Clinically relevant data must be transmitted to the practitioners who will use it. Health care professionals in North America are aware of their ethical and legal obligations to inform patients adequately concerning interventions and treatments so that they may make informed choices about medical care. This obligation has been well described and defined by the courts and in the literature of medicine, ethics, and law. (...) But do investigators and others who are responsible for disseminating information have any obligation to divulge adequately the results of clinical trials to practitioners so that the latter might offer the choice of appropriate care to their patients? Can incomplete disclosure of trial outcomes result in harm to patients? If this is the case, what possible avenues are available to avoid such harm? (shrink)

Advances in medicine depend not only on the generation of information but also on its dissemination. Clinically relevant data must be transmitted to the practitioners who will use it. Health care professionals in North America are aware of their ethical and legal obligations to inform patients adequately concerning interventions and treatments so that they may make informed choices about medical care. This obligation has been well described and defined by the courts and in the literature of medicine, ethics, and law. (...) But do investigators and others who are responsible for disseminating information have any obligation to divulge adequately the results of clinical trials to practitioners so that the latter might offer the choice of appropriate care to their patients? Can incomplete disclosure of trial outcomes result in harm to patients? If this is the case, what possible avenues are available to avoid such harm? (shrink)

This article reviews four areas of pediatric research in which we have identified questionable levels of allowable risk, exceeding those foreseen by the Commission. They are the following: the categorization of increasingly risky interventions as minimal risk in a variety of protocols; the increasing number of applications for federal panel review of research not otherwise approvable because of higher projected risk levels; research on asymptomatic at risk children; and the inclusion of children and adolescents in placebo-controlled trials for participants of (...) all ages without performing subgroup analysis. While embracing the imperative to include children in research is an encouraging step towards providing the pediatric population with effective medical care and finally eradicating the therapeutic orphan, we must ensure that this research does not become overly permissive. (shrink)

Over the past several decades, geneticists have succeeded in identifying the genetic mutations associated with disease. New strategies for treatment, including gene transfer and gene therapy, are under development. Although genetic science has been welcomed for its potential to predict and treat disease, interventions may become ethically objectionable if they threaten to alter characteristics that are distinctively human. Before we can determine whether or not a genetic technique carries this risk, we must clarify what it means to be “human”. This (...) paper inquires how “humanness” has been defined within various academic fields. The views of several legal theoreists, scientists, bioethicists, psychologists, philosophers and anthropologists whose works seem to best reflect how “humanness” is understood in their respective fields of study are considered. Our survey attempts to chart a path for a more detailed study on the meaning of “humanness” in the future. (shrink)