Benefits, challenges and obstacles of adaptive clinical trial designs

In recent years, the use of adaptive design methods in pharmaceutical/clinical research and development has become popular due to its flexibility and efficiency for identifying potential signals of clinical benefit of the test treatment under investigation. The flexibility and efficiency, however, increase the risk of operational biases with resulting decrease in the accuracy and reliability for assessing the treatment effect of the test treatment under investigation. In its recent draft guidance, the United States Food and Drug Administration (FDA) expresses regulatory concern of controlling the overall type I error rate at a pre-specified level of significance for a clinical trial utilizing adaptive design. The FDA classifies adaptive designs into categories of well-understood and less well-understood designs. For those less well-understood adaptive designs such as adaptive dose finding designs and two-stage phase I/II (or phase II/III) seamless adaptive designs, statistical methods are not well established and hence should be used with caution. In practice, misuse of adaptive design methods in clinical trials is a concern to both clinical scientists and regulatory agencies. It is suggested that the escalating momentum for the use of adaptive design methods in clinical trials be slowed in order to allow time for development of appropriate statistical methodologies

Common Weeds of the Yard and Garden

This guide is meant to serve as a means of identifying common weeds in the home landscape and supplying enough information for readers to make educated decisions about their properties

Crossing the Rubicon: Investigating Congressional Oversight of the Intelligence Community

There is a common narrative among researchers and experts that congressional bipartisanship among intelligence overseers is decreasing and effectiveness is increasingly degraded. The Senate Select Committee on Intelligence has historically demonstrated strong bipartisanship as a result of its organization and leaders. Changing trends among committee membership and voting since the committee’s inception suggests the environment is shifting. There is evidence of modest increases in partisan membership and increasingly divided “yea” votes by committee members on significant national security legislation. However, examining open hearing dialogue suggests its necessary to maintain a more nuanced perspective of oversight partisanship and effectiveness. In the cyber domain, the Senate Select Committee on Intelligence demonstrates strong public advocacy and actively addresses constitutional adherence by the Intelligence Community. The committee does not however, effectively provide the Intelligence Community important strategic guidance. Despite shortfalls, public perceptions of intelligence oversight are generally positive. Public opinion among informed respondent’s supports “hands-on” intelligence oversight with an understanding of the secrecy required by intelligence overseers. Respondents recognize the negative effects of partisanship and reinforce the significance of existing oversight institutions. There is support for some changes in intelligence oversight to improve effectiveness, but no indication respondents believe the system is in need of major change. Crossing the Rubicon explores each of these important intelligence oversight issues with objective and methodical analysis. The research provides academics and legislators unique data regarding a critical government function. Intelligence oversight has a responsibility to ensure American ideals are protected and the Intelligence Community operates effectively within prescribed boundaries

Risk factors for cytomegalovirus retinitis among individuals with HIV and low CD4 count in northern Thailand

Abstract withdrawn from publication