Death and organ donation: back to the future.

The practice of transplantation of vital organs from "brain-dead" donors is in a state of theoretical disarray. Although the law and prevailing medical ethics treat patients diagnosed as having irreversible total brain failure as dead, scholars have increasingly challenged the established rationale for regarding these patients as dead. To understand the ethical situation that we now face, it is helpful to revisit the writings of the philosopher Hans Jonas, who forcefully challenged the emerging effort to redefine death in the late 1960s.

Limits to research risks.

Risk-benefit assessment is a routine requirement for research ethics committees that review and oversee biomedical research with human subjects. Nevertheless, it remains unclear how to weigh and balance risks to research participants against the social benefits that flow from generating biomedical knowledge. In this article, we address the question of whether there are any reasonable criteria for defining the limit of permissible risks to individuals who provide informed consent for research participation. We argue against any a priori limit to permissible research risks. However, attention to the uncertainty of potential social benefit that can be derived from any particular study warrants caution in exposing prospective research participants to a substantial likelihood of serious harm.

The search for clarity in communicating research results to study participants.

UNLABELLED: Current guidelines on investigators' responsibilities to communicate research results to study participants may differ on (1) whether investigators should proactively re-contact participants, (2) the type of results to be offered, (3) the need for clinical relevance before disclosure, and (4) the stage of research at which results should be offered. Lack of consistency on these issues, however, does not undermine investigators' obligation to offer to disclose research RESULTS: an obligation rooted firmly in the principle of respect for research participants.

Payment for research participation: a coercive offer?

Payment for research participation has raised ethical concerns, especially with respect to its potential for coercion. We argue that characterising payment for research participation as coercive is misguided, because offers of benefit cannot constitute coercion. In this article we analyse the concept of coercion, refute mistaken conceptions of coercion and explain why the offer of payment for research participation is never coercive but in some cases may produce undue inducement.

Is it ethical to keep interim findings of randomised controlled trials confidential?

Data monitoring committees often are employed to review interim findings of randomised controlled trials. Interim findings are kept confidential until the data monitoring committee finds that they provide sufficiently compelling evidence regarding efficacy, typically because they have crossed the pre-defined statistical boundaries, or they raise serious concerns about safety. While this practice is vital to maintaining the scientific integrity of controlled trials and thereby ensuring their social value, it has been criticised as unethical. Commentators argue that withholding interim findings from research participants is deceptive, inconsistent with valid informed consent, and a violation of respect for participants' autonomy. The present article examines these arguments, focusing specifically on confidential data monitoring for efficacy. This practice need not be deceptive provided its use is disclosed to prospective research participants. In addition, confidential data monitoring does not make research participants worse off than they would be in the clinical setting and represents an acceptable limitation on the options available to prospective research participants. Taken together, these considerations suggest confidential data monitoring, subject to adequate safeguards, is ethically acceptable.

Assessing research risks systematically: the net risks test.

Dual-track assessment directs research ethics committees (RECs) to assess the risks of research interventions based on the unclear distinction between therapeutic and non-therapeutic interventions. The net risks test, in contrast, relies on the clinically familiar method of assessing the risks and benefits of interventions in comparison to the available alternatives and also focuses attention of the RECs on the central challenge of protecting research participants.

Acupuncture trials and informed consent.

Participants are often not informed by investigators who conduct randomised, placebo-controlled acupuncture trials that they may receive a sham acupuncture intervention. Instead, they are told that one or more forms of acupuncture are being compared in the study. This deceptive disclosure practice lacks a compelling methodological rationale and violates the ethical requirement to obtain informed consent. Participants in placebo-controlled acupuncture trials should be provided an accurate disclosure regarding the use of sham acupuncture, consistent with the practice of placebo-controlled drug trials.

A public health perspective on research ethics.

Ethical guidelines for conducting clinical trials have historically been based on a perceived therapeutic obligation to treat and benefit the patient-participants. The origins of this ethical framework can be traced to the Hippocratic oath originally written to guide doctors in caring for their patients, where the overriding moral obligation of doctors is strictly to do what is best for the individual patient, irrespective of other social considerations. In contrast, although medicine focuses on the health of the person, public health is concerned with the health of the entire population, and thus, public health ethics is founded on the societal responsibility to protect and promote the health of the population as a whole. From a public health perspective, research ethics should be guided by giving due consideration to the risks and benefits to society in addition to the individual research participants. On the basis of a duty to protect the population as a whole, a fiduciary obligation to realise the social value of the research and the moral responsibility to distribute the benefits and burdens of research fairly across society, how a public health perspective on research ethics results in fundamental re-assessments of the proper course of action for two salient topical issues in research ethics is shown: stopping trials early for reasons of efficacy and the conduct of research on less expensive yet less effective interventions.

Gene therapy ethics and haemophilia: an inevitable therapeutic future?

Haemophilia was recognized early on as an ideal candidate for a gene transfer approach to therapy. In the past decade, gene transfer experimentation in the haemophilias has indeed played an integral role in furthering the science in the global field of gene therapy. However, these expectations have placed haemophilia gene transfer researchers under pressure to succeed in a scientific domain in which successes are infrequent and progress is necessarily slow. These same expectations have also fueled the perception of gene therapy as the inevitable therapeutic goal for the youngest children with haemophilia. In this paper, we will discuss the ethical implications of this perception in light of anticipated benefits, acceptable risk, perceived consumer need and the unknown cost of this intervention. A framework for the future study and therapeutic implementation of gene transfer technology in this specific population is proposed. Public debate on this issue that includes the voices of the intended beneficiaries, especially the parents of the youngest children with haemophilia and the children themselves, is encouraged.

The internal morality of medicine: an evolutionary perspective.

A basic question of medical ethics is whether the norms governing medical practice should be understood as the application of principles and rules of 'the common morality' to medicine or whether some of these norms are 'internal' or 'proper' to medicine. In this article we describe and defend an evolutionary perspective on 'the internal morality of medicine' that is defined in terms of the goals of clinical medicine and a set of duties that constrain medical practice in pursuit of these goals. This perspective is developed by means of a critical examination of the 'essentialist' conception of the internal morality of medicine advocated by Edmund Pellegrino and the critique of internal morality approaches by Robert Veatch and Tom Beauchamp.

A curriculum for teaching psychiatric research bioethics.

Psychiatric research has received intense ethical scrutiny during the past decade. Changes in how studies are designed, reviewed by ethics boards, conducted, and reported in the literature have created a need for a systematic approach to teaching psychiatric research ethics to clinical researchers in training. The purpose of this article is to describe a model curriculum and comprehensive background reading list for training in psychiatric research bioethics. The curriculum was designed as an interactive seminar in a research fellowship program but can be adapted and incorporated into existing medical school and psychiatry residency training curricula. Participants in the seminar provide formal and informal evaluations of each session and the seminar as a whole. The seminar, now in it's third year, has been regularly attended and highly regarded by the NIMH research fellows who have participated. In response to recommendations by the participants, the content and organization of the seminar has been modified. Clinical research is both scientifically and ethically complex. Our initial experience with a formal curriculum in psychiatric research bioethics suggests that this educational activity has been both meaningful and relevant for psychiatrists training to be clinical investigators.

The ethical challenge of infection-inducing challenge experiments.

Challenge experiments that induce infections in healthy volunteers are an important method for initial efficacy testing of candidate vaccines and for study of the pathogenesis of infectious diseases. Although these studies can be conducted safely for selected infectious diseases that are either fully treatable or self-limiting, they raise significant ethical issues. An ethical framework is offered for evaluating infection-inducing challenge experiments, which focuses on the scientific and public health rationale for conducting these studies, the risks that they pose and the ways in which these risks can be minimized, the symptoms experienced by healthy volunteers that may cause discomfort or distress, the exclusion of vulnerable research subjects, the informed consent process, the payment of volunteers, and the use of isolation of volunteers to prevent infection of others.