Doubly distributing special obligations: what professional practice can learn from parenting.

A traditional ethic of medicine asserts that physicians have special obligations to individual patients with whom they have a clinical relationship. Contemporary trends in US healthcare financing like bundled payments seem to threaten traditional conceptions of special obligations of individual physicians to individual patients because their population-based focus sets a tone that seems to emphasise responsibilities for groups of patients by groups of physicians in an organisation. Prior to undertaking a cogent debate about the fate and normative weight of special obligations and a traditional ethic for contemporary healthcare, we need a deeper examination of what the traditional ethic of special obligations really means. Here we offer a conception of 'doubly distributed' special obligations. Physicians and similarly minded healing professionals abiding by a traditional ethic have always spread their devotion and attention across multiple patients and have shared responsibilities with physician and non-physician colleagues in much the same way devoted parents have frequently distributed their special obligations across multiple children and across multiple parents. By taking up the extended analogy of parent we argue that doubly distributing special obligations need not contradict the possibility of special obligations in restructured collective forms of healthcare delivery and financing.

An Official ATS/AACN/ACCP/ESICM/SCCM Policy Statement: Responding to Requests for Potentially Inappropriate Treatments in Intensive Care Units.

BACKGROUND: There is controversy about how to manage requests by patients or surrogates for treatments that clinicians believe should not be administered. PURPOSE: This multisociety statement provides recommendations to prevent and manage intractable disagreements about the use of such treatments in intensive care units. METHODS: The recommendations were developed using an iterative consensus process, including expert committee development and peer review by designated committees of each of the participating professional societies (American Thoracic Society, American Association for Critical Care Nurses, American College of Chest Physicians, European Society for Intensive Care Medicine, and Society of Critical Care). MAIN RESULTS: The committee recommends: (1) Institutions should implement strategies to prevent intractable treatment conflicts, including proactive communication and early involvement of expert consultants. (2) The term "potentially inappropriate" should be used, rather than futile, to describe treatments that have at least some chance of accomplishing the effect sought by the patient, but clinicians believe that competing ethical considerations justify not providing them. Clinicians should explain and advocate for the treatment plan they believe is appropriate. Conflicts regarding potentially inappropriate treatments that remain intractable despite intensive communication and negotiation should be managed by a fair process of conflict resolution; this process should include hospital review, attempts to find a willing provider at another institution, and opportunity for external review of decisions. When time pressures make it infeasible to complete all steps of the conflict-resolution process and clinicians have a high degree of certainty that the requested treatment is outside accepted practice, they should seek procedural oversight to the extent allowed by the clinical situation and need not provide the requested treatment. (3) Use of the term "futile" should be restricted to the rare situations in which surrogates request interventions that simply cannot accomplish their intended physiologic goal. Clinicians should not provide futile interventions. (4) The medical profession should lead public engagement efforts and advocate for policies and legislation about when life-prolonging technologies should not be used. CONCLUSIONS: The multisociety statement on responding to requests for potentially inappropriate treatments in intensive care units provides guidance for clinicians to prevent and manage disputes in patients with advanced critical illness.

A taxonomy of multinational ethical and methodological standards for clinical trials of therapeutic interventions.

BACKGROUND: If trials of therapeutic interventions are to serve society's interests, they must be of high methodological quality and must satisfy moral commitments to human subjects. The authors set out to develop a clinical-trials compendium in which standards for the ethical treatment of human subjects are integrated with standards for research methods. METHODS: The authors rank-ordered the world's nations and chose the 31 with >700 active trials as of 24 July 2008. Governmental and other authoritative entities of the 31 countries were searched, and 1004 English-language documents containing ethical and/or methodological standards for clinical trials were identified. The authors extracted standards from 144 of those: 50 designated as 'core', 39 addressing trials of invasive procedures and a 5% sample (N=55) of the remainder. As the integrating framework for the standards we developed a coherent taxonomy encompassing all elements of a trial's stages. FINDINGS: Review of the 144 documents yielded nearly 15 000 discrete standards. After duplicates were removed, 5903 substantive standards remained, distributed in the taxonomy as follows: initiation, 1401 standards, 8 divisions; design, 1869 standards, 16 divisions; conduct, 1473 standards, 8 divisions; analysing and reporting results, 997 standards, four divisions; and post-trial standards, 168 standards, 5 divisions. CONCLUSIONS: The overwhelming number of source documents and standards uncovered in this study was not anticipated beforehand and confirms the extraordinary complexity of the clinical trials enterprise. This taxonomy of multinational ethical and methodological standards may help trialists and overseers improve the quality of clinical trials, particularly given the globalisation of clinical research.

Traditional knowledge and intellectual property.

Biotechnological inventions are sometimes based upon the traditional knowledge of indigenous communities about the beneficial properties of plants and animals. Some institutions have adopted the uniqueness of traditional knowledge approach, which maintains that the indigenous communities have sui generis rights to a share of the profits from these inventions. Others have adopted the protection of inventive steps approach, which maintains that the inventors are entitled to the full profits from the invention if it involves a non-obvious and novel inventive step. The article analyzes this debate at the Convention on Biological Diversity, at the World Intellectual Property Organization, and at the World Trade Organization. It concludes that the adherents of the uniqueness of traditional knowledge approach have not justified their claims.

Intellectual property, state sovereignty, and biotechnology.

The issue of biopiracy has attracted considerable attention in recent years. The Convention on Biological Diversity adopted a principle of state sovereignty over biological resources and the genetic information contained within those resources to address this issue. It is argued that this principle has not been adequately justified and that there are other solutions to the issue of biopiracy, based on different theories of justice, that deserve greater consideration. These alternatives include the common heritage of mankind principle and the global commons principle.

A controlled trial of arthroscopic surgery for osteoarthritis of the knee.

BACKGROUND: Many patients report symptomatic relief after undergoing arthroscopy of the knee for osteoarthritis, but it is unclear how the procedure achieves this result. We conducted a randomized, placebo-controlled trial to evaluate the efficacy of arthroscopy for osteoarthritis of the knee. METHODS: A total of 180 patients with osteoarthritis of the knee were randomly assigned to receive arthroscopic débridement, arthroscopic lavage, or placebo surgery. Patients in the placebo group received skin incisions and underwent a simulated débridement without insertion of the arthroscope. Patients and assessors of outcome were blinded to the treatment-group assignment. Outcomes were assessed at multiple points over a 24-month period with the use of five self-reported scores--three on scales for pain and two on scales for function--and one objective test of walking and stair climbing. A total of 165 patients completed the trial. RESULTS: At no point did either of the intervention groups report less pain or better function than the placebo group. For example, mean (+/-SD) scores on the Knee-Specific Pain Scale (range, 0 to 100, with higher scores indicating more severe pain) were similar in the placebo, lavage, and débridement groups: 48.9+/-21.9, 54.8+/-19.8, and 51.7+/-22.4, respectively, at one year (P=0.14 for the comparison between placebo and lavage; P=0.51 for the comparison between placebo and débridement) and 51.6+/-23.7, 53.7+/-23.7, and 51.4+/-23.2, respectively, at two years (P=0.64 and P=0.96, respectively). Furthermore, the 95 percent confidence intervals for the differences between the placebo group and the intervention groups exclude any clinically meaningful difference. CONCLUSIONS: In this controlled trial involving patients with osteoarthritis of the knee, the outcomes after arthroscopic lavage or arthroscopic débridement were no better than those after a placebo procedure.

Intellectual property and biotechnology: the European debate.

The European patent system allows for the introduction of moral issues into decisions about the granting of patents. This feature has greatly impacted European debates about the patenting of biotechnology. This essay explores the European experience, in both the European Union and the European Patent Organization. It argues that there has been great confusion surrounding these issues primarily because the Europeans have not developed a general theory about when exclusion from patentability is the best social mechanism for dealing with morally offensive technologies.

Intellectual property and biotechnology: the U.S. internal experience--Part II.

Continuing the discussion begun in the March 2006 issue of the Kennedy Institute of Ethics Journal, this paper further documents the failure of the United States to adequately consider possible modifications in the traditional robust system of intellectual property rights as applied to biotechnology. It discusses concrete suggestions for alternative disclosure requirements, for exemptions for research tools, and for improved access to clinical advances. In each of these cases, the modifications might be more responsive to the full set of relevant values.

Intellectual property and biotechnology: the U.S. internal experience--Part I.

In the development of biotechnology in the United States, many questions were raised about the appropriateness of applying to this area a traditional robust system of intellectual property rights. Despite these hesitations, the U.S. rejected suggested modifications. This was a mistake, and there is a need to develop a modified system that promotes more of the relevant ethical values.

Is the use of placebo controls ethically permissible in clinical trials of agents intended to reduce fractures in osteoporosis?

Substantial progress has been made in developing treatments that reduce the risk of fractures in osteoporosis. However, available treatments are only partially effective, they are not widely used, and there is need to search for more effective means of fracture prevention. Currently known effective means of reducing fractures were found using randomized placebo-controlled trials. The use of placebo controls in clinical trials has been a subject of significant controversy in recent years. The Declaration of Helsinki revision of October 2000 caused great concern among clinical investigators about the future use of placebo controls if known effective therapeutic agents are available. A working group of ethicists, clinical trial design experts, and clinical investigators examined the current state of knowledge of osteoporosis treatment and trials. They concluded that if placebo controls put subjects at substantial risk of serious outcomes, they are not ethically permissible. Placebo controls in osteoporosis trials with fracture as the measured outcome are permissible only under narrowly defined conditions. Placebo controls may be used if competent, well-informed patients refuse approved therapies for sound reasons, there is a reasonable basis for substantial disagreement or lack of consensus among professionals about whether approved treatments are better than placebos, or subjects are refractory to known effective agents. Active control trials are permissible and desirable if they can be designed and conducted in ways that overcome the interpretive difficulties often associated with such trials.

Pharmacogenetic challenges for the health care system.

Pharmacogenetics--the effect of genotype on drug response--holds the promise of safer and more effective drug therapy. Genetic tests would be routinely given to patients prior to prescription of a drug, with therapeutic decisions based on the patient's drug-response profile. This paper examines the operational changes and the ethical, legal, and policy challenges that pharmacogenetic medicine poses for key actors in the health care system. Adaptation by drug companies, regulatory agencies, physicians, patients, insurers, and public funding agencies will be necessary to integrate pharmacogenetic medicine into health care.

Pharmacogenetics: ethical issues and policy options.

Pharmacogenetics offers the prospect of an era of safer and more effective drugs, as well as more individualized use of drug therapies. Before the benefits of pharmacogenetics can be realized, the ethical issues that arise in research and clinical application of pharmacogenetic technologies must be addressed. The ethical issues raised by pharmacogenetics can be addressed under six headings: (1) regulatory oversight, (2) confidentiality and privacy, (3) informed consent, (4) availability of drugs, (5) access, and (6) clinicians' changing responsibilities in the era of pharmacogenetic medicine. We analyze each of these categories of ethical issues and provide policy approaches for addressing them.

Ethical dilemmas surrounding the use of ventricular assist devices in supporting patients with end-stage organ dysfunction.

Successful practice of cardiovascular medicine requires familiarity with the complex ethical issues that accompany therapeutic innovation and diffusion. Even as technologies transition from experimental to standard care, challenges remain. Mechanical circulatory support devices, for instance, are increasingly conceptualized as conventional therapies. Despite this, or perhaps because of it, the ethical issues surrounding the use of these devices in patients with end-stage organ dysfunction are becoming increasingly apparent. In this paper, we provide an introduction to ethical considerations related to the use of ventricular assist devices (VADs) in end-stage organ failure, focusing on three stages or decision points: initiation, continued use, and deactivation. Our goal is not to exhaustively resolve these dilemmas but to illustrate how ethical considerations relate to decision making.

Are surgical trials with negative results being interpreted correctly?

BACKGROUND: Many published accounts of clinical trials report no differences between the treatment arms, while being underpowered to find differences. This study determined how the authors of these reports interpreted their findings. STUDY DESIGN: We examined 54 reports of surgical trials chosen randomly from a database of 110 influential trials conducted in 2008. Seven that reported having adequate statistical power (ß ≥ 0.9) were excluded from further analysis, as were the 32 that reported significant differences between the treatment arms. We examined the remaining 15 to see whether the authors interpreted their negative findings appropriately. Appropriate interpretations discussed the lack of power and/or called for larger studies. RESULTS: Three of the 7 trials that did not report an a priori power calculation offered inappropriate interpretations, as did 3 of the 8 trials that reported an a priori power < 0.90. However, we examined only a modest number of trial reports from 1 year. CONCLUSIONS: Negative findings in underpowered trials were often interpreted as showing the equivalence of the treatment arms with no discussion of the issue of being underpowered. This may lead clinicians to accept new treatments that have not been validated.

Conflicts among multinational ethical and scientific standards for clinical trials of therapeutic interventions.

Utilizing a sorted compendium of international clinical trial standards, investigators identified 15 conflicts among ethical and methodological guidance. Analysis distinguishes interpretational issues, lack of clarity, and contradiction as factors to be addressed if international trial guidance is to be improved.