Statistics in medicine
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Statistics in medicine · Apr 2007
Individualizing drug dosage by using a random intercept linear model.
An algorithm for drug dosage individualization is proposed. The algorithm assumes a random intercept linear model for the log of trough-plasma-concentration-to-dosage ratio of the drug at steady-state, and aims at determining an optimum dosage for producing a trough steady-state plasma concentration within a target concentration range. The minimum number of algorithm steps necessary to find the optimum dosage is computed. Computations are illustrated for clozapine, an antipsychotic drug used to treat patients with severe schizophrenia.
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Statistics in medicine · Mar 2007
A score test for overdispersion in zero-inflated poisson mixed regression model.
Count data with extra zeros are common in many medical applications. The zero-inflated Poisson (ZIP) regression model is useful to analyse such data. For hierarchical or correlated count data where the observations are either clustered or represent repeated outcomes from individual subjects, a class of ZIP mixed regression models may be appropriate. ⋯ Sampling distribution and power of the test statistic are evaluated by simulation studies. The results show that the test statistic performs satisfactorily under a wide range of conditions. The test procedure is applied to pancreas disorder length of stay that comprised mainly same-day separations and simultaneous prolonged hospitalizations.
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Statistics in medicine · Feb 2007
Comparative StudyA comparison of the ability of different propensity score models to balance measured variables between treated and untreated subjects: a Monte Carlo study.
The propensity score--the probability of exposure to a specific treatment conditional on observed variables--is increasingly being used in observational studies. Creating strata in which subjects are matched on the propensity score allows one to balance measured variables between treated and untreated subjects. There is an ongoing controversy in the literature as to which variables to include in the propensity score model. ⋯ Reduction in bias was marginally greater for the first two propensity score models than for the last two propensity score models when stratification on the quintiles of the propensity score model was employed. Furthermore, omitting a confounding variable from the propensity score model resulted in biased estimation of the treatment effect. Finally, the mean squared error for estimating a null treatment effect was lower when either of the first two propensity scores was used compared to when either of the last two propensity score models was used.
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Statistics in medicine · Jan 2007
ReviewA 25-year review of sequential methodology in clinical studies.
This paper explores the theoretical developments and subsequent uptake of sequential methodology in clinical studies in the 25 years since Statistics in Medicine was launched. The review examines the contributions which have been made to all four phases into which clinical trials are traditionally classified and highlights major statistical advancements, together with assessing application of the techniques. The vast majority of work has been in the setting of phase III clinical trials and so emphasis will be placed here. Finally, comments are given indicating how the subject area may develop in the future.
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One type of pharmacokinetic/pharmacodynamic (PK/PD) relationship that is used to characterize the therapeutic action of a drug is the relationship between some univariate summary of the plasma-concentration-versus-time profile and the drug effect on a response outcome. Operationally, such a relationship may be observed in a large clinical trial where randomly sampled patients are randomized to different values of the concentration summary. If, under such conditions, the relationship between concentration and effect does not depend on the dose needed to attain the target concentration, such a relationship will be called a true PK/PD relationship. ⋯ We show that diagnostics for confounding can be devised under reasonable assumptions. We then apply these diagnostics to PK/PD assessments of adults and children on oxcarbazepine adjunctive therapy. It was necessary to demonstrate the similarity of the true PK/PD relationships of adults and children on adjunctive therapy in order to support the approval of oxcarbazepine monotherapy in children by a bridging argument.