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Experiments in which the treatments are composed of a series of doses of a compound and a zero dose control are often used in animal toxicity studies. A test procedure is proposed to assess trends in the response variable. The notion of a no-statistical-significance-of-trend (NOSTASOT) dose is introduced, and questions of multiplicity of statistical tests(More)
BACKGROUND Rotavirus is a leading cause of childhood gastroenteritis and death worldwide. METHODS We studied healthy infants approximately 6 to 12 weeks old who were randomly assigned to receive three oral doses of live pentavalent human-bovine (WC3 strain) reassortant rotavirus vaccine containing human serotypes G1, G2, G3, G4, and P[8] or placebo at(More)
The increasing complexity of randomized clinical trials and the practice of obtaining a wide variety of measurements from study participants have made the consideration of multiple endpoints a critically important issue in the design, analysis, and interpretation of clinical trials. Failure to consider important outcomes can limit the validity and utility(More)
Clinical adverse experience (AE) data are routinely evaluated using between group P values for every AE encountered within each of several body systems. If the P values are reported and interpreted without multiplicity considerations, there is a potential for an excess of false positive findings. Procedures based on confidence interval estimates of(More)
RNA interference (RNAi) high-throughput screening (HTS) has been hailed as the 2nd genomics wave following the 1st genomics wave of gene expression microarrays and single-nucleotide polymorphism discovery platforms. Following an RNAi HTS, the authors are interested in identifying short interfering RNA (siRNA) hits with large inhibition/activation effects.(More)
Finasteride is a specific 5-alpha-reductase inhibitor that has been shown to reduce prostate size and decrease serum levels of prostate specific antigen (PSA). Among men who received finasteride (5 mg/day) for 12 months in North American clinical trials and in whom prostate cancer was not diagnosed the median percentage change in PSA was -50% (5-95% range:(More)
Developmental and reproductive (DAR) toxicity studies typically include a series of increasing doses of a compound and a zero dose control. Given this framework, Tukey et al. (Biometrics, 41, 295-301, 1985) proposed a procedure (referred to as either the Tukey trend or TCH test procedure) for detecting a nonzero trend in response to increasing doses of the(More)
Kernel densities provide accurate non-parametric estimates of the overlapping coefficient or the proportion of similar responses (PSR) in two populations. Non-parametric estimates avoid strong assumptions on the shape of the populations, such as normality or equal variance, and possess sampling variation approaching that of parametric estimates. We obtain(More)
In multicentre clinical trials using a common protocol, the centres are usually regarded as being a fixed factor, thus allowing any treatment-by-centre interaction to be omitted from the error term for the effect of treatment. However, we feel it necessary to use the treatment-by-centre interaction as the error term if there is substantial evidence that the(More)
BACKGROUND We determined the effect of incorporating the results of eight recently published trials of Hmg CoA reductase inhibitors ("statins") on the conclusions from our previously published meta-analysis regarding the clinical benefit of cholesterol lowering. METHODS AND RESULTS We used the same analytic approach as in our previous investigation,(More)