Clinical trials : journal of the Society for Clinical Trials
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There has been tremendous progress over the last decade in the development of health products--drugs, vaccines, and diagnostics--for neglected diseases. There are now dozens of candidate products in the pipeline. ⋯ Realizing the promise of the neglected disease product pipeline will require not only increased funding for large-scale clinical trials and capacity building, but also greater attention to how these trials and their regulatory pathways can be improved to reduce unnecessary costs, delays, and risks to trial subjects. We propose a two-prong strategy: (1) adaptation and adoption of emerging research on 'sensible guidelines' for reducing large-scale, randomized clinical trial costs to the demands of the neglected disease product pipeline and (2) regional approaches to regulation and ethical review of clinical trials for health products for neglected diseases.
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The current practice for seeking genomically favorable patients in randomized controlled clinical trials using genomic convenience samples. ⋯ Complete ascertainment of genomic samples in a randomized controlled trial should be the first step to explore if a favorable genomic patient subgroup suggests a treatment effect when there is no clear prior knowledge and understanding about how the mechanism of a drug target affects the clinical outcome of interest. When stratified randomization based on genomic biomarker status cannot be implemented in designing a pharmacogenomics confirmatory clinical trial, if there is one genomic biomarker prognostic for clinical response, as a general rule of thumb, a sample size of at least 100 patients may be needed to be considered for the lower prevalence genomic subgroup to minimize the chance of an imbalance of 20% or more difference in the prevalence of the genomic marker. The sample size may need to be at least 150, 350, and 1350, respectively, if an imbalance of 15%, 10% and 5% difference is of concern.
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Recently, the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial published 7-year complete prostate cancer mortality results, which showed no benefit of screening with prostate specific antigen (PSA) and digital rectal examination (DRE). An issue of concern was the substantial level of 'contamination', or use of PSA and DRE in control arm men. ⋯ Use of prostate screening by control arm men was substantial, but also substantially less than in screened arm men. Detailed quantitative analyses of screening use across arms are critical for understanding current and future findings from the prostate component of PLCO.