Journal of biopharmaceutical statistics
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In areas such as oncology, two-stage designs are often preferred as compared to one-stage designs due to the ability to stop the trial early when faced with evidence of lack of sufficient efficacy and the associated sample size savings. We present exact two-stage designs based on Barnard's exact test for differences in proportions and compare the designs to those proposed by Kepner ( 2010 ) and Jung ( 2010 ). In addition, we present tables of decision rules under a variety of assumed realities for use in trial planning. The procedure is recommended for use due to the substantial sample size savings experienced.
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While randomized, well-controlled, clinical trials have been viewed as the gold standard in the evaluation of medical products, including drugs, biological products, and medical devices, it is not uncommon for safety assessment to be performed using observational studies, for ethical or practical reasons. In observational studies, various biases could be introduced in every stage and aspect of study, and consequently the resulting statistical inference may carry a lower level of scientific assurance, compared to randomized trials. To ensure the objectivity of study design and interpretability of the results, it is critical to address the challenges of such studies. In this paper, we share regulatory considerations on the prospective design of observational studies to address safety issues using propensity score methodology.
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The International Conference for Harmonization (ICH) has released regulatory guidelines for pharmaceutical development. In the document ICH Q8, the design space of a process is presented as the set of factor settings providing satisfactory results. However, ICH Q8 does not propose any practical methodology to define, derive, and compute design space. ⋯ This Bayesian framework was then extended to the multicriteria setting to estimate the predictive probability that several critical quality attributes will be jointly achieved in the future use of an analytical method. An example based on a high-performance liquid chromatography (HPLC) method is given. For this example, a constrained sampling scheme was applied to ensure the modeled responses have desirable properties.
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Comparative Study
Homogeneity test of difference between two correlated proportions in stratified matched-pair studies.
Stratified matched-pair studies are often designed for adjusting stratification factors in modern medical researches. This article investigates a homogeneity test of differences between two correlated proportions in stratified matched-pair studies. ⋯ Empirical results show that (1) the likelihood ratio statistic is robust, while the score statistic and the modified score statistic are conservative in some cases of our considered settings; (2) the likelihood ratio statistic and the score statistic with the bootstrap method and the MaxT procedure behave satisfactorily in the sense that their type I error rates are close to the pre-given significance level; and (3) the derived sample size formulas are rather accurate. A real example from a clinical laboratory study is used to illustrate the proposed methodologies.