76 research outputs found

    A surplus of positive trials: weighing biases and reconsidering equipoise

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    In this issue, Fries and Krishnan raise provocative new ideas to explain the surfeit of positive industry sponsored trials evaluating new drugs. They suggest that these trials were designed after so much preliminary work that they were bound to be positive (design bias) and that this violates clinical equipoise, which they characterize as an antiquated concept that should be replaced by a focus on subject autonomy in decision making and expected value for all treatments in a trial. We contend that publication bias, more than design bias, could account for the remarkably high prevalence of positive presented trials. Furthermore, even if all new drugs were efficacious, given the likelihood of type 2 errors, not all trials would be positive. We also suggest that clinical equipoise is a nuanced concept dependent on the existence of controversy about the relative value of two treatments being compared. If there were no controversy, then trials would be both unnecessary and unethical. The proposed idea of positive expected value is intriguing, but in the real world such clearly determinable values do not exist. Neither is it clear how investigators and sponsors, who are invested in the success of a proposed therapy, would (or whether they should) develop such a formula

    Gift Giving to Biobanks

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    We agree with Mark Rothstein\u27s goal of giving tissue donors control over their donated tissues. But we think using the research model as the basis for attaining this goal, while widely employed and accepted, should be abandoned. The research regulations were originally adopted to deal with interventions on living human beings, not on the tissue of human beings. The Nuremberg Code (a reaction to concentration camp experiments), the Willowbrook experiment, the Tuskegee syphilis experiment, and the other examples of the abuse of research subjects that provided the rationale for regulating research on human subjects clearly had nothing to do with research on their tissues. The regulations were directed at protecting the safety and welfare of the living human beings who are being intervened upon by researchers. Moreover, most of the concern over tissue collection has little, if anything, to do with research. For example, the creation of a tissue repository, regardless of the Office for Human Research Protections (OHRP 1997) position and guidance, is not research at all. There is no hypothesis, no methodology, no statistical design, and so forth. It is a mere warehouse of tissues, and all the tissue could be discarded without anyone ever doing anything to them resembling research. Nonetheless, the fact that tissue banking per se is not research doesn\u27t mean that there should be no rules for the donation of tissue to tissue banks. But rules for the donation of tissue to banks should not be dictated by inapt research regulations

    The Genetic Privacy Act: A Proposal for National Legislation

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    Privacy is a major issue in medical law, and genetics is a major force in contemporary medical science. Nonetheless, the combination of these two fields has only recently been seen as central to both individual rights and medical progress. Disclosures in June of 1996 that White House officials had wrongly acquired and read FBI files of raw background checks of prominent Republicans reminded Americans that there is no such thing as a completely secure and secret file of personal information. Had these files contained DNA profiles or samples, they would have supplied additional information about the unsuspecting individuals-information that could be used against the individuals without their knowledge. In late June 1996, Senator Pete V. Domenici (R-N.M.) introduced S.1898, the Genetic Confidentiality and Nondiscrimination Act of 1996 (GCNA), which was based in large part on the proposed Genetic Privacy Act of 1995 (GPA) drafted by the authors.\u27 This article outlines the purpose and provisions of the GPA. Along the way, it highlights some of the differences between the GPA and the GCNA

    Scientific Research with Children: Legal Incapacity and Proxy Consent

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    Before an investigator can use any person as a subject in biomedical or behavioral research, he must obtain that person\u27s informed consent. This consent must be voluntary, competent, and understanding.1 There are two questions that arise in regard to experimentation on children. First, is a child legally capable of giving an informed and understanding consent? Second, do parents have the legal capacity to consent to the performance of research on their children? This article will attempt to answer both of these questions

    Amici for Appellees: Brief for Bioethicists for Privacy as Amicus Curiae Supporting Appelles Brief for Bioethicists for Privacy as Amicus Curiae Supporting Appellees

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    Amicus is an ad hoc group of 57 philosophers, theologians, attorneys and physicians .. .who teach medical ethics to medical students and physicians. The members believe that permitting competent adults to make important, personal medical decisions in consultation with their physician is a fundamental principle of medical ethics, and that the doctor-patient relationship deserves the constitutional protection the Court has afforded it under the right of privacy

    Early indicators of exposure to biological threat agents using host gene profiles in peripheral blood mononuclear cells

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    <p>Abstract</p> <p>Background</p> <p>Effective prophylaxis and treatment for infections caused by biological threat agents (BTA) rely upon early diagnosis and rapid initiation of therapy. Most methods for identifying pathogens in body fluids and tissues require that the pathogen proliferate to detectable and dangerous levels, thereby delaying diagnosis and treatment, especially during the prelatent stages when symptoms for most BTA are indistinguishable flu-like signs.</p> <p>Methods</p> <p>To detect exposures to the various pathogens more rapidly, especially during these early stages, we evaluated a suite of host responses to biological threat agents using global gene expression profiling on complementary DNA arrays.</p> <p>Results</p> <p>We found that certain gene expression patterns were unique to each pathogen and that other gene changes occurred in response to multiple agents, perhaps relating to the eventual course of illness. Nonhuman primates were exposed to some pathogens and the <it>in vitro</it> and <it>in vivo</it> findings were compared. We found major gene expression changes at the earliest times tested post exposure to aerosolized <it>B. anthracis </it>spores and 30 min post exposure to a bacterial toxin.</p> <p>Conclusion</p> <p>Host gene expression patterns have the potential to serve as diagnostic markers or predict the course of impending illness and may lead to new stage-appropriate therapeutic strategies to ameliorate the devastating effects of exposure to biothreat agents.</p

    Dynamic Gene Expression in the Human Cerebral Cortex Distinguishes Children from Adults

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    In comparison with other primate species, humans have an extended juvenile period during which the brain is more plastic. In the current study we sought to examine gene expression in the cerebral cortex during development in the context of this adaptive plasticity. We introduce an approach designed to discriminate genes with variable as opposed to uniform patterns of gene expression and found that greater inter-individual variance is observed among children than among adults. For the 337 transcripts that show this pattern, we found a significant overrepresentation of genes annotated to the immune system process (pFDR≅0). Moreover, genes known to be important in neuronal function, such as brain-derived neurotrophic factor (BDNF), are included among the genes more variably expressed in childhood. We propose that the developmental period of heightened childhood neuronal plasticity is characterized by more dynamic patterns of gene expression in the cerebral cortex compared to adulthood when the brain is less plastic. That an overabundance of these genes are annotated to the immune system suggests that the functions of these genes can be thought of not only in the context of antigen processing and presentation, but also in the context of nervous system development

    Should smokers be refused surgery?

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