Statistics in medicine
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Statistics in medicine · Oct 1998
Comparative StudyPropensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group.
In observational studies, investigators have no control over the treatment assignment. The treated and non-treated (that is, control) groups may have large differences on their observed covariates, and these differences can lead to biased estimates of treatment effects. Even traditional covariance analysis adjustments may be inadequate to eliminate this bias. ⋯ In order to estimate the propensity score, one must model the distribution of the treatment indicator variable given the observed covariates. Once estimated the propensity score can be used to reduce bias through matching, stratification (subclassification), regression adjustment, or some combination of all three. In this tutorial we discuss the uses of propensity score methods for bias reduction, give references to the literature and illustrate the uses through applied examples.
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Statistics in medicine · Sep 1998
Comparative StudyUsing prior information to allocate significance levels for multiple endpoints.
We maximize power in a replicated clinical trial involving multiple endpoints by adjusting the individual significance levels for each hypothesis, using preliminary data to obtain the optimal adjustments. The levels are constrained to control the familywise error rate. ⋯ Sample size requirements for the replicate study are given. Intuitive principles such as downweighting insignificant variables from a preliminary study and giving primary endpoints more emphasis are justifiable within the conceptual framework.
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Statistics in medicine · Jul 1998
Comparative StudyAn evaluation of phase I cancer clinical trial designs.
Phase I clinical trials are designed to identify an appropriate dose for experimentation in phase II and III studies. I present the results from a simulation study to evaluate the performance of nine phase I designs involving the standard design, the two-stage modified Storer's design, the two-stage Korn's design, the one-stage modified continual reassessment method (CRM) designs, and the two-stage modified CRM designs. ⋯ The one-stage modified CRM II and III designs require much fewer numbers of cohorts than do the two-stage modified CRM II and III designs. The one-stage modified CRM II and III designs avoid the criticisms of the original CRM by reducing the average number of cohorts and toxicity incidences, while estimating the MTD more accurately than does the standard design.
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Statistics in medicine · Jul 1998
Some extensions and applications of a Bayesian strategy for monitoring multiple outcomes in clinical trials.
We present some practical extensions and applications of a strategy proposed by Thall, Simon and Estey for designing and monitoring single-arm clinical trials with multiple outcomes. We show by application how the strategy may be applied to construct designs for phase IIA activity trials and phase II equivalence trials. We also show how it may be extended to incorporate the use of mixture priors in settings where a Dirichlet distribution does not adequately quantify prior experience, randomized phase II selection trials involving two or more experimental treatments, and trials with group-sequential monitoring for applications involving multiple institutions.