Faculty Bibliography

PURPOSE: Outcome reporting bias is a well-known fact in clinical research. It's critical since readers believe that published articles are reliable and accurate. METHODS: The need for investigators to register the trials at the start have made it possible to compare the content of the published article with the registered information. RESULTS: Nearly one-third of clinical trials have changed their primary outcome from the time of registration to publication. CONCLUSIONS: Editors should implement measures aimed at preventing outcome reporting bias. To this end, it is proposed that authors, when submitting a manuscript to a journal, should also submit all trial information they have posted on a registry. Authors should comment on the accuracy and completeness of the information provided in the manuscript with respect to that included on the registry. Peer review should only start after the editorial staff has checked the accuracy of the manuscript content with the trial's registered information. This straightforward, although admittedly somewhat demanding exercise for editorial staff, will help ensure the accuracy of published articles and, hence, reduce outcome reporting bias.

As the ability to transplant organs and tissues has grown, the demand for these procedures has increased as well-to the point at which it far exceeds the available supply creating the core ethical challenge for transplantation-rationing. The gap between supply and demand, although large, is worse than it appears to be. There are two key steps to gaining access to a transplant. First, one must gain access to a transplant center. Then, those waiting need to be selected for a transplant. Many potential recipients do not get admitted to a program. They are deemed too old, not of the right nationality, not appropriate for transplant as a result of severe mental impairment, criminal history, drug abuse, or simply because they do not have access to a competent primary care physician who can refer them to a transplant program. There are also financial obstacles to access to transplant waiting lists in the United States and other nations. In many poor nations, those needing transplants simply die because there is no capacity or a very limited capacity to perform transplants. Although the demand for organs now exceeds the supply, resulting in rationing, the size of waiting lists would quickly expand were there to suddenly be an equally large expansion in the number of organs available for transplantation. Still, even with the reality of unavoidable rationing, saving more lives by increasing organ supply is a moral good. Current public policies for obtaining organs from cadavers are not adequate in that they do not produce the number of organs that public polls of persons in the United States indicate people are willing to donate.

The ethical challenges of reporting and managing adverse events (AEs) and serious AEs (SAEs) in the context of mass drug administration (MDA) for the treatment of neglected tropical diseases (NTDs) require reassessment of domestic and international policies on a global scale. Although the World Health Organization has set forth AE/SAE guidelines specifically for NTD MDA that incorporate suspected causality, and recommends that only SAEs get reported in this setting, most regulatory agencies continue to require the reporting of all SAEs exhibiting even a merely temporal relationship to activities associated with an MDA program. This greatly increases the potential for excess "noise" and undue risk aversion and is not only impractical but arguably unethical where huge proportions of populations are being treated for devastating diseases, and no good baseline exists against which to compare possible AE/SAE reports. Other population-specific variables that might change the way drug safety ought to be assessed include differing efficacy rates of a drug, background morbidity/mortality rates of the target disease in question, the growth rate of the incidence of disease, the availability of rescue or salvage therapies, and the willingness of local populations to take risks that other populations might not. The fact that NTDs are controllable and potentially eradicable with well-tolerated, effective, existing drugs might further alter our assessment of MDA safety and AE/SAE tolerability. At the same time, diffuseness of population, communication barriers, lack of resources, and other difficult surveillance challenges may present in NTD-affected settings. These limitations could impair the ability to monitor an MDA programs success, as well as hinder efforts to obtain informed consent or provide rescue therapy. Denying beneficial research interventions and MDA programs intended to benefit millions requires sound ethical justification based on more than the identification of and rote response to AEs and SAEs.

Caplan talks about some ethical concerns against the legalization of physician-assisted suicide. Two main ethical concerns are advanced against the legalization of physician-assisted suicide. The first is that it is not humans' place to decide the time of their death; only God can decide when their time on this planet is over. That argument might persuade some, but it is not a good reason for outlawing physician-assisted suicide. It rests firmly on a foundation of religious belief, which is not a sound basis for public policy. Worse, it runs roughshod over the right to individual self-determination

BACKGROUND: Older patients constitute a growing proportion of U.S. kidney transplant recipients and often have a high burden of comorbidities. A summary measure of health such as functional status might enable transplant professionals to better evaluate and counsel these patients about their prognosis after transplant. METHODS: We linked United Network for Organ Sharing registry data about posttransplantation survival with pretransplantation functional status data (physical function [PF] scale of the Medical Outcomes Study Short Form-36) among individuals undergoing kidney transplant from June 1, 2000 to May 31, 2006. We examined the relationship between survival and functional status with multivariable Cox regression, adjusted for age. Using logistic regression models for 3-year survival, we also estimated the reduction in deaths in the hypothetical scenario that recipients with poor functional status in this cohort experienced modest improvements in function. RESULTS: The cohort comprised 10,875 kidney transplant recipients with a mean age of 50 years; 14% were >/=65. Differences in 3-year mortality between highest and lowest PF groups ranged from 3% among recipients <35 years to 14% among recipients >/=65 years. In multivariable Cox regression, worse PF was associated with higher mortality (hazard ratio, 1.66 for lowest vs. highest PF quartiles; P<0.001). Interactions between PF and age were nonsignificant. We estimated that 11% fewer deaths would occur if kidney transplant recipients with the lowest functional status experienced modest improvements in function. CONCLUSIONS: Across a wide age range, functional status was an independent predictor of posttransplantation survival. Functional status assessment may be a useful tool with which to counsel patients about posttransplantation outcomes.

The Texas Advance Directives Act defines "life-sustaining treatment" as that which "sustains the life of a patient and without which the patient will die." Because Munoz has died, cardiopulmonary or any other form of support is not, and cannot be, "life-sustaining." Lawsuits in Washington state and North Dakota have challenged similar statutes as unconstitutional in that they impose undue burdens on the right to terminate pregnancy, deprive women of liberty without due process in violation of the 14th Amendment, and discriminate on the basis of gender, in violation of the equal protection guarantee of the 4th Amendment

Unlike those in a coma or in a permanent vegetative state like Terri Schiavo, a Florida woman whose family fought unsuccessfully to keep her alive, or Ariel Sharon, the former Israeli prime minister who's been in a coma for eight years, no one recovers from brain death

Deep brain stimulation (DBS) is an efficacious surgical treatment for many conditions, including obsessive-compulsive disorder and treatment-resistant depression. DBS provides a unique opportunity to not only ameliorate disease but also to study mood, cognition, and behavioral effects in the brain. However, there are many ethical questions that must be fully addressed in designing clinical research trials. It is crucial to maintain sound ethical boundaries in this new era so as to permit the proper testing of the potential therapeutic role DBS may play in ameliorating these devastating and frequently treatment-refractory psychiatric disorders. In this review, we focus on the selection of patients for study, informed consent, clinical trial design, DBS in the pediatric population, concerns about intentionally or inadvertently altering an individual's personal identity, potential use of DBS for brain enhancement, direct modification of behavior through neuromodulation, and resource allocation.