To what risks may children participating in research be subjected? Institutional review boards can stand surrogate for parents by filtering out studies whose risk is unacceptably high.

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)

Duty and Healing positions ethical issues commonly encountered in clinical situations within Jewish law. The concept of duty is significant in exploring bioethical issues, and this book presents an authentic and non-parochial Jewish approach to bioethics, while it includes critiques of both current secular and Jewish literatures. Among the issues the book explores are the role of family in medical decision-making, the question of informed consent as a personal religious duty, and the responsibilities of caretakers. The exploration of contemporary ethical (...) problems in healthcare through the lens of traditional sources in Jewish law is an indispensable guide of moral knowledge. (shrink)

There is the world of ideas and the world of practice; the French are often for sup pressing the one and the English the other; but neither is to be suppressed. -Matthew Arnold The Function of Criticism at the Present Time From its inception, bioethics has confronted the need to reconcile theory and practice. At first the confrontation was purely intellectual, as writers on ethical theory (within phi losophy, theology, or other humanistic disciplines) turned their attention to topics from the (...) world of medical practice. Recently the confrontation has grown more intense. The ap pointment of clinical ethicists in hospitals and other health care settings is an accelerating trend in North America. Concomitantly, those institutions involved in training peo ple in clinical ethics have added organized exposure to the world of practice, in the form of placement requirements, to the normal academic course load. In common with other dis ciplines, bioethics has begun to see clinical training as a con dition of didactic theory and apprenticeship. (shrink)

In summary, the usual elements of a typical health care ethics consultation note might reasonably accommodate the needs and expectations of relevant parties, and would therefore include: 1. identification of the relevant ethical issues, questions, or dilemmas; 2. reference to any relevant facts--medical, nursing, social, psychological, spiritual, legal, political, etc.; 3. a prioritized list of recommendations to improve coordinated care; 4. a clear and concise articulation of relevant arguments, wtih specific reference to the list of recommendations as well as to (...) the institution's overall ethos; 5. a contextual statement, identifying the perceived degree of consensus or support for the recommendations and conclusions, as well as any inherent agendas. (shrink)

OBJECTIVE: Pilot study to characterize treatment differences between patients treated in clinical trials and those treated in a clinical setting. Previous studies have shown higher survival rates for participants in trials of cancer therapy. This difference is observed even after rates are adjusted for important covariates such as age and stage of disease. DESIGN: Retrospective chart review. SETTING: Oncology outpatient department in a tertiary care hospital. PATIENTS: Ninety women 18 to 70 years of age with early-stage breast cancer who were (...) diagnosed in 1990. Fifty-one of the women were treated through clinical trials and 39 were treated outside of clinical trials. OUTCOME MEASURES: Number of blood tests, telephone calls, clinic visits and imaging procedures as well as intensity of chemotherapy and use of radiation therapy. The age of the patient and the stage of disease were important covariates. RESULTS: After the analysis was controlled for patient age and stage of disease, patients treated through a clinical trial were more likely to receive standard-dose chemotherapy (p = 0.020, 95% confidence interval 1.20 to 200.73) and more frequent blood tests (p < 0.001, 95% confidence interval 1.02 to 1.13) than other patients treated in the clinic. CONCLUSIONS: Our results provide a plausible mechanism for the observed survival advantage for participants in clinical trials in oncology. Further study is called for. If these results are confirmed, they have important implications for informed consent to participate in clinical trials and for clinical practice. (shrink)

Too often, caregivers and ethicists misunderstand the motivations of adult children who are involved in the care of their parents. They sometimes fail to appreciate the ways in which adult children may be trying to carry out their filial obligations toward a parent, obligations dictated by their religious commitments. Exploring these obligations within the Jewish tradition can help to illuminate these issues and provide an alternative to a rights‐based framework in which to reason about them.

We studied changes in eligibility criteria--the largest impediment to patient accrual--in two samples of clinical trials. Trials from the NSABP (National Surgical Adjuvant Breast and Bowel Program) and POG (Pediatric Oncology Group) were analyzed. After eliminating duplications, the criteria in each protocol were enumerated and classified according to a novel schema. NSABP trials contained significantly more criteria than POG trials, and added precision criteria (making study populations homogeneous) at a faster rate than POG studies. The difference between NSABP studies (explanatory (...) trials) and POG studies (pragmatic trials) suggest that large numbers of eligibility criteria are not necessary for quality studies. We recommend that: (1) the inclusion/exclusion criteria distinction be abandoned; (2) eligibility criteria be explicitly justified; (3) the need for each criterion be assessed when new trials are planned; (4) criteria in phase III trials restricting patient accrual be minimized; and (5) further research be done to assess the impact of criteria on generalizability. (shrink)

In contrast to attempts that have been made to measure the clarity of reporting of the methods of clinical trials in journal articles, we report here an attempt to measure the accuracy of methods reporting. We focus in this article on eligibility criteria as a test case for the reporting of clinical trial methods. We examined the reporting of eligibility criteria in the protocol, methods paper (if applicable), journal article, and Clinical Alert for articles appearing in print between January 1988 (...) and September 1994 for which a Clinical Alert had been issued. Eligibility criteria were further classified into five categories in order to examine the content of information loss, if any. On average, 82% of protocol eligibility criteria were reported in methods papers. Journal articles and Clinical Alerts fared somewhat worse: 63% of criteria were reported in journal articles, 19% in Clinical Alerts. In all three categories of medical communication, the reporting of criteria that defined the study disease tended to be complete; reporting of criteria relating to trial precision, patient safety, legal and ethical concerns, and administrative considerations, was not complete. We found that criteria for clinical trial eligibility are frequently under-reported in medical communications. Moreover, some of the criteria omitted are of considerable clinical importance. We suggest that in the design phase of clinical trials, proposed eligibility criteria be scrutinized closely. Those criteria that survive this scrutiny and that have clinical import must be reported upon fully and accurately when communicating trial results. (shrink)

OBJECTIVE: To investigate whether eligibility criteria that exclude the elderly, persons with psychiatric disease, and persons with substance abuse problems from participation in randomized controlled trials (RCTs) are subjective and hence a source of variability in enrolment decisions and investigator uncertainty. DESIGN: Survey questionnaire. PARTICIPANTS: Cancer investigators from the United States and Canada. INTERVENTIONS: Investigators were presented with clinical vignettes from 3 patient categories--eligible, ineligible and uncertain--for each of 5 eligibility criteria--3 subjective and 2 objective--and were asked whether they would (...) enrol the patient in a trial and how sure they were of this decision. Demographic characteristics of the investigators were also collected. OUTCOME MEASURES: The difference in enrolment decisions between subjective and objective criteria, and the difference in the certainty associated with these decisions. RESULTS: Of 365 questionnaires sent out, 224 usable ones were returned. Compared with the objective criteria, the subjective criteria were associated with more variable enrolment decisions (p = 0.07 for the "eligible" scenario and p = 0.0001 for the "ineligible" and "uncertain" scenarios), and investigators were less sure about the decisions they made (p = 0.0001 for all scenarios). Demographic characteristics of the investigators failed to explain the observed differences. CONCLUSIONS: Subjective eligibility criteria may interfere with the conduct and interpretation of RCTs and, therefore, their use ought to be justified explicitly in the study protocol. RCT designers, funding agencies and research ethics boards have an important role in reviewing eligibility criteria for their necessity. (shrink)

This paper is an attempt to achieve a moral understanding of recombinant DNA technology through an examination of the Biblical ban on the cross-breeding of species, as that ban was understood by traditional Jewish commentators. By paying close attention to the concept of natural law which some of those commentators employed in this connection, a nuanced response to the modern moral problem can be developed, which is immune to the standard arguments employed against those who rely upon natural law.

As more AIDS patients seek access to nonvalidated therapies, Authorized Investigational Units can preserve the integrity of clinical trials, protect patients' interests, and enhance clinicians' flexibility.

A common difficulty with the application of theories of justice to the allocation of medical resources is the assumption that one perspective is primary, whether that privileged perspective be that of the practitioner, on the one hand, or policy analyst on the other. By a discussion of three theories — those of Ramsey, Childress, and Joseph Fletcher — I attempt to show that these perspectives must be treated as related. As a result, values and ethics expressed in micro-allocation should be (...) uniform with those of macro-allocation. This point has implications for such issues as substance and procedure in just decision, the role of the political process in medical allocation, and the definition of health and health services. (shrink)