The value of information and optimal clinical trial design.

Traditional sample size calculations for randomized clinical trials depend on somewhat arbitrarily chosen factors, such as type I and II errors. Type I error, the probability of rejecting the null hypothesis of no difference when it is true, is most often set to 0.05, regardless of the cost of such an error. In addition, the traditional use of 0.2 for the type II error means that the money and effort spent on the trial will be wasted 20 per cent of the time, even when the true treatment difference is equal to the smallest clinically important one and, again, will not reflect the cost of making such an error. An effectiveness trial (otherwise known as a pragmatic trial or management trial) is essentially an effort to inform decision-making, i.e. should treatment be adopted over standard? As such, a decision theoretic approach will lead to an optimal sample size determination. Using incremental net benefit and the theory of the expected value of information, and taking a societal perspective, it is shown how to determine the sample size that maximizes the difference between the cost of doing the trial and the value of the information gained from the results. The methods are illustrated using examples from oncology and obstetrics. Copyright 2005 John Wiley & Sons, Ltd.