A Bayesian cost-benefit approach to the determination of sample size in clinical trials. 2008

Takashi Kikuchi, and Hamid Pezeshk, and John Gittins
Centre for Economics and Policy in Health, IMSCaR, University of Wales, Dean Street Building, Dean Street, Bangor, Gwynedd LL57 1UT, U.K. takashi.kikuchi@st-hughs.ox.ac.uk

Current practice for sample size computations in clinical trials is largely based on frequentist or classical methods. These methods have the drawback of requiring a point estimate of the variance of the treatment effect and are based on arbitrary settings of type I and II errors. They also do not directly address the question of achieving the best balance between the cost of the trial and the possible benefits from using the new treatment, and fail to consider the important fact that the number of users depends on the evidence for improvement compared with the current treatment. Our approach, Behavioural Bayes (or BeBay for short), assumes that the number of patients switching to the new medical treatment depends on the strength of the evidence that is provided by clinical trials, and takes a value between zero and the number of potential patients. The better a new treatment, the more the number of patients who want to switch to it and the more the benefit is obtained. We define the optimal sample size to be the sample size that maximizes the expected net benefit resulting from a clinical trial. Gittins and Pezeshk (Drug Inf. Control 2000; 34:355-363; The Statistician 2000; 49(2):177-187) used a simple form of benefit function and assumed paired comparisons between two medical treatments and that the variance of the treatment effect is known. We generalize this setting, by introducing a logistic benefit function, and by extending the more usual unpaired case, without assuming the variance to be known.

UI MeSH Term Description Entries
D009010 Monte Carlo Method In statistics, a technique for numerically approximating the solution of a mathematical problem by studying the distribution of some random variable, often generated by a computer. The name alludes to the randomness characteristic of the games of chance played at the gambling casinos in Monte Carlo. (From Random House Unabridged Dictionary, 2d ed, 1993) Method, Monte Carlo
D002986 Clinical Trials as Topic Works about pre-planned studies of the safety, efficacy, or optimum dosage schedule (if appropriate) of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects. This concept includes clinical trials conducted both in the U.S. and in other countries. Clinical Trial as Topic
D003362 Cost-Benefit Analysis A method of comparing the cost of a program with its expected benefits in dollars (or other currency). The benefit-to-cost ratio is a measure of total return expected per unit of money spent. This analysis generally excludes consideration of factors that are not measured ultimately in economic terms. In contrast a cost effectiveness in general compares cost with qualitative outcomes. Cost and Benefit,Cost-Benefit Data,Benefits and Costs,Cost Benefit,Cost Benefit Analysis,Cost-Utility Analysis,Costs and Benefits,Economic Evaluation,Marginal Analysis,Analyses, Cost Benefit,Analysis, Cost Benefit,Analysis, Cost-Benefit,Analysis, Cost-Utility,Analysis, Marginal,Benefit and Cost,Cost Benefit Analyses,Cost Benefit Data,Cost Utility Analysis,Cost-Benefit Analyses,Cost-Utility Analyses,Data, Cost-Benefit,Economic Evaluations,Evaluation, Economic,Marginal Analyses
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000704 Analysis of Variance A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable. ANOVA,Analysis, Variance,Variance Analysis,Analyses, Variance,Variance Analyses
D001499 Bayes Theorem A theorem in probability theory named for Thomas Bayes (1702-1761). In epidemiology, it is used to obtain the probability of disease in a group of people with some characteristic on the basis of the overall rate of that disease and of the likelihood of that characteristic in healthy and diseased individuals. The most familiar application is in clinical decision analysis where it is used for estimating the probability of a particular diagnosis given the appearance of some symptoms or test result. Bayesian Analysis,Bayesian Estimation,Bayesian Forecast,Bayesian Method,Bayesian Prediction,Analysis, Bayesian,Bayesian Approach,Approach, Bayesian,Approachs, Bayesian,Bayesian Approachs,Estimation, Bayesian,Forecast, Bayesian,Method, Bayesian,Prediction, Bayesian,Theorem, Bayes
D018401 Sample Size The number of units (persons, animals, patients, specified circumstances, etc.) in a population to be studied. The sample size should be big enough to have a high likelihood of detecting a true difference between two groups. (From Wassertheil-Smoller, Biostatistics and Epidemiology, 1990, p95) Sample Sizes,Size, Sample,Sizes, Sample

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