Karine Morin

Surgical “placebo” Controls

ObjectiveTo set ethical guidelines on the use of surgical placebo controls in the design of surgical trials. Background DataEthical concerns recently arose from surgical trials where subjects in the control arm underwent surgical procedures that had the appearance of a therapeutic intervention, but during which the essential therapeutic maneuver was omitted. Although there are ethical guidelines on the use of a placebo in drug trials, little attention has been paid to the use of a surgical placebo control in surgical trials. MethodsThe Council on Ethical and Judicial Affairs developed ethical guidelines based on a wide literature search and consultation with experts. ResultsSurgical placebo controls should be limited to studies of new surgical procedures aimed at treating diseases that are not amenable to other surgical therapies, and are reasonably anticipated to be susceptible to substantial placebo effects. If the standard nonsurgical treatment is efficacious and acceptable to the patient, then it must be offered as part of the study design. ConclusionsSurgical placebo controls should be used only when no other trial design will yield the requisite data and should always be accompanied by a rigorous informed consent process and a careful consideration of the related risks and benefits. The recommended ethical guidelines were adopted as AMA ethics policy and are now incorporated in the AMA’s Code of Medical Ethics.

Guidelines to Prevent Malevolent Use of Biomedical Research

In February 1975, a group of leading scientists, physicians, and policymakers convened at Asilomar, California, to consider the safety of proceeding with recombinant DNA research. The excitement generated by the promise of this new technology was counterbalanced by concerns regarding dangers that might arise from it, including the potential for accidental release of genetically modified organisms into the environment. Guidelines developed at the conference to direct future research endeavors had several consequences. They permitted research to resume, bringing to an end the voluntary moratorium that the National Academy of Sciences (NAS) had instituted several months earlier. They also served to illustrate that the scientific community was capable of self-governance, thereby securing public trust and persuading Congress not to institute legislative restrictions.1 Finally, they underscored the importance of weighing unforeseen risks inherent in some research against potential benefits that may arise from these same endeavors. In February 2000, a second meeting was held at Asilomar, bringing together members from the same groups, including some of the original attendees.2 This meeting was held in honor of the historic event’s 25th anniversary and in recognition of the scientific community’s increasing attention to the potentially harmful applications of biotechnology in general —for example, to facilitate the use of pathogens as deadly weapons.3 Risk of this latter sort that arises not from research per se but from its intentional misapplication for nefarious purposes constitutes the focus of this report. The possibility that scientific research may generate knowledge with the potential for harmful as well as beneficial applications is not new. In recent years, however, it has become imperative to develop parameters within which to address such research, as heightened concerns have arisen from the threat of biochemical terrorism and warfare.

The Physician as Gatekeeper to the Use of Genetic Information in the Criminal Justice System

Cigarette smoking continues to be a leading cause of death in the United States, imposing substantial measurable costs to society. Smoking killed over 440,000 people in the United States each year during the period 1995-1999. If current smoking trends continue, over 5 million people currently younger than 18 will die prematurely from tobacco-related diseases. Increases in excise taxes have been shown to be effective in reducing smoking among youth. However, the adoption of tax increases in any jurisdiction is susceptible to many challenges. Furthermore, smuggling of tobacco products and sales of tobacco products over the Internet threaten the effectiveness of tobacco tax increases. This article discusses the effectiveness of excise tax increases on prevention and reduction of smoking. It also discusses factors that influence the legislative adoption of such increases. Finally, it examines potential threats to the use of tobacco taxes as a prevention tool.

CADAVERIC ORGAN DONATION: ENCOURAGING THE STUDY OF MOTIVATION

Approximately 6,000 patients per year, or 16 per day, with end-stage organ failure die because of the lack of available organs. Each year only 35% to 50% of potential donors consent to donation (1). During the last 20 years, vigorous educational campaigns, both voluntary and legislative, designed to increase organ donation have failed to increase donation rates significantly. The need for organs has grown nearly five times faster than the number of cadaveric donors: the annually compounded rate (1990–2000) of increase in number of patients on waiting lists has averaged 14.1% a year, whereas the rate of increase of donors has averaged 2.9% a year (2). The American Medical Association (AMA) has been concerned about this problem for many years and has developed several policies addressing it in the past decade (3). AMA policy has supported certain forms of financial incentives for cadaveric organ donation since 1993 (Policy E-2.15, AMA Policy Database), but they have never been implemented because federal law prohibits them. AMA policy specifically prohibits payment to living donors (4). Most initiatives to increase organ donation have focused on what motivates or hinders the decision to donate. Programs to improve organ donation rates have been aimed at public and professional groups. These have included widespread educational campaigns aimed at motivating individuals to become donors. They also have included mandated choice legislation, the establishment of the Organ Procurement and Transplantation Network (OPTN), donor card programs, donor registries, and the creation of specialized organ donation teams within hospitals that discuss organ donation with families and patients. Despite these efforts, cadaveric donation rates have remained nearly stable during the past decade. This report encourages the medical and scientific communities to reexamine the motivation for cadaveric organ donation. Building on the work of the Council on Ethical and Judicial Affairs (CEJA) in 1993, which led to Opinion E-2.15, “Financial Incentives for Organ Donation,” this report identifies reasons why ethical objections to financial incentives, for cadaveric organ donation only, should be reexamined. In particular, this report considers the need to study the impact of financial incentives through limited research trials. Such studies would help measure the effect of incentives not only on donation rates but also on public perception of the transplant enterprise and of the meaning of organ donation. For the purposes of this report, donation and procurement of organs are considered completely independent from the allocation of organs. The report neither suggests nor supports any change in the current system of organ distribution, as developed and administered by the United Network for Organ Sharing (UNOS). Even if financial incentives were found to have a positive impact on cadaveric organ donation rates, allocation algorithms developed by the OPTN would continue to govern organ distribution and transplant recipients would continue to be selected according to ethically appropriate criteria related to medical need rather than ability to pay. Physicians have an obligation to hold their patients’ interests paramount and to support access for all patients to medical care (Principles VIII and IX) (5). To discharge these obligations, physicians should participate in efforts to increase organ donation, including education of their patients and the general public regarding the importance of organ donation and promotion of voluntary donation of organs. Beyond educational programs, however, physicians should support innovative approaches to encourage organ donation. Such efforts include encouragement and, if appropriate, participation in the conduct of ethically designed research studies of donor motivation. A potential impetus for cadaveric organ donation that has not been adequately explored (because of federal prohibition) is financial incentives. Such incentives are not intrinsically unethical; AMA policy has supported them since 1993. Whether a particular incentive is ethical or not depends upon the balance of benefits and harms that result, and these are currently unknown because they have never been investigated.

Biodefense: spend, but spend wisely.

*The views expressed in this commentary are those of the authors and do not necessarily represent the views of the American Medical Association.

Safeguards in the use of DNA databanks in genomic research

Genomic research, which uses DNA to identify the gene(s) responsible for complex diseases, relies upon large DNA databases to facilitate population-based research. These databases derive their power from integrating different kinds of information about large samples of individuals: genetic and clinical data and data on health, lifestyle, and environment. Using statistical analysis, the databases can be used to analyze correlations that may enable new therapeutic developments. The use of DNA databanks in genomic research brings new challenges related to the scope of research as well as to the nature and use of the samples and information archived in such databases. This report identifies these issues and considers their relation to the current standard of informed consent in human research.