To give valid informed consent to participate in clinical research, potential participants should understand the risks, potential benefits, procedures, and alternatives. Potential participants also should understand that they are being invited to participate in research. Yet it is unclear what potential participants need to understand to satisfy this particular requirement. As a result, it is unclear what additional information investigators should disclose about the research; and it is also unclear when failures of understanding in this respect undermine the validity of (...) potential participants' informed consent. An analysis of individuals' interests suggests that potential participants need to understand three additional facts to understand that they are being invited to participate in research: 1) research contribution: those who enroll in the study will be contributing to a project designed to gather generalizable knowledge to benefit others in the future; 2) research relationship: the investigators will rely on participants' efforts to gather the generalizable knowledge to benefit others; and 3) research impact: the extent to which participating in the study will alter what participants do and what happens to them. (shrink)

Medical research is widely thought to have a fundamentally therapeutic orientation, in spite of the fact that clinical research is thought to be ethically distinct from medical care. We need an entirely new conception of clinical research ethics—one that looks to science instead of the doctor‐patient relationship.

: Medical research is widely thought to have a fundamentally therapeutic orientation, in spite of the fact that clinical research is thought to be ethically distinct from medical care. We need an entirely new conception of clinical research ethics—one that looks to science instead of the doctor-patient relationship.

This new edition of Charles Fried's Medical Experimentation includes a general introduction by Franklin Miller and the late Alan Wertheimer, a reprint of the 1974 text, an in-depth analysis by Harvard Law School scholars I. Glenn Cohen and D. James Greiner, and a new essay by Fried reflecting on the original text and how it applies to the contemporary landscape of medicine and medical experimentation.

: As clinicians, researchers, bioethicists, and members of society, we face a number of moral dilemmas concerning randomized clinical trials. How we manage the starting and stopping of such trials—how we conceptualize what evidence is sufficient for these decisions—has implications for both our obligations to trial participants and for the nature and security of the resultant medical knowledge. One view of how this is to be done, "clinical equipoise," recently has been given an extended defense by Paul Miller and Charles (...) Weijer in their article "Rehabilitating Equipoise." The present paper critiques this position and Miller and Weijer's defense of it. I argue that their attempted rehabilitation fails. Their analysis suffers from a number of confusions, as well as a failure to make crucial distinctions, adequately to clarify key concepts, or to think through exactly what needs to be established to justify their claim. We are left with little reason to uphold the clinical equipoise criterion. (shrink)

The doctrine of informed consent, borrowed from the law of torts, cannot be readily transplanted into therapeutic settings. The broader, as yet unrealized, idea of informed consent, which suggests that parties must make decisions jointly, should guide interactions between physicians and patients or investigators and subjects.

: When may a physician legitimately offer enrollment in a randomized clinical trial (RCT) to her patient? Two answers to this question have had a profound impact on the research ethics literature. Equipoise, as originated by Charles Fried, which we term Fried's equipoise (FE), stipulates that a physician may offer trial enrollment to her patient only when the physician is genuinely uncertain as to the preferred treatment. Clinical equipoise (CE), originated by Benjamin Freedman, requires that there exist a state of (...) honest, professional disagreement in the community of expert practitioners as to the preferred treatment. FE and CE are widely understood as competing concepts. We argue that FE and CE offer separable and, in themselves, incomplete justifications for the conduct of clinical trials. FE articulates conditions under which the fiduciary duties of physician to patient may be upheld in the conduct of research. CE sets out a standard for the social approval of research by institutional review boards. Viewed in this way, FE and CE are not necessarily competing notions, but rather address complementary moral concerns. (shrink)

A predominant ethical view holds that physician‐investigators should conduct their research with therapeutic intent. And since a physician offering a therapy wouldn't prescribe second‐rate treatments, the experimental intervention and the best proven therapy should appear equally effective. "Clinical equipoise" is necessary. But this perspective is flawed. The ethics of research and of therapy are fundamentally different, and clinical equipoise should be abandoned.

Most people know precious little about the risks and benefits of participating in a clinical trial--a medical research study involving some innovative treatment for a medical problem. Yet millions of people each year participate anyway. Patients at Risk explains the reality: that our current system intentionally hides much of the information people need to make the right choice about whether to participate. Witness the following scenarios: -Hundreds of patients with colon cancer undergo a new form of keyhole surgery at leading (...) cancer centersnever -Tens of thousands of women at high risk of developing breast cancer are asked to participate in a major research study. They are told about the option of having both breasts surgically removed but not told about the option of taking a standard osteoporosis pill that might cut the risk of getting breast cancer by one-half or more. Patients at Risk written by two nationally prominent experts, is the first book to reveal the secrets that many in the research establishment have fought long and hard to keep from patients. It shows why options not commonly knownincluding getting a new treatment outside of a research studycan often be the best choice. It explains how patients can make good decisions even if there is only limited information about a treatments effect. And it does this through the eye-opening stories of what is happening daily to thousands of people. Day after day, we are learning how little we know about what really works. Headlines regularly announce that a previously unquestioned treatmenthormone replacement therapy, drugs such as Vioxx or Celebrexmay now be much riskier than we thought. The latest book in a surge of recent books criticizing the medical establishment (but the first to look at clinical trials specifically), Patients at Risk helps to empower patients to survive in a world of medical uncertainty, and makes positive recommendations for systemic reform. (shrink)

: Challenging the interpretation of Charles Fried's use of "equipoise" presented by Paul Miller and Charles Weijer in a recent issue of the Kennedy Institute of Ethics Journal , this commentary argues that Fried was in no way promoting the concept of equipoise. In fact, his key point was that patients have a right to know and to make their own decisions about participation in clinical trials, regardless of equipoise, however it is defined.

An apparent ethical dilemma arises when physicians consider enrolling their patients in randomized clinical trials. Suppose that a randomized clinical trial comparing two treatments is in progress, and a physician has an opinion about which treatment is better. The physician has a duty to promote the patient's best medical interests and therefore seems to be obliged to advise the patient to receive the treatment that the physician prefers. This duty creates a barrier to the enrollment of patients in randomized clinical (...) trials.1-10 Two strategies are often used to resolve the dilemma in favor of enrolling patients in clinical trials. (shrink)

In the 1950s, estimates of the incidence of depression were fifty people per million; today the estimate is 100,000 per million. What was once defined as “anxiety” and treated with tranquilizers in the wake of the crisis of benzodiazipine dependence and the development of selective serotonin reuptake inhibitors became “depression.” And as SSRIs have been shown to be effective for treating other nervous conditions, such as panic disorder, estimates of their frequency have increased markedly as well. Disease increasingly means whatever (...) we have a reimbursable treatment for. (shrink)