Just Plain Wrong

This chapter will give examples of particular clinical trial designs that are fundamentally flawed. Each example will illustrate a fairly common practice. The first example is a futility rule that aims to stop accrual to a single-arm trial early if the interim data show that it is unlikely the experimental treatment provides at least a specified level of anti-disease activity. The rule is given in terms of progression-free survival time. An alternative, much more sound, and reliable futility monitoring rule that accounts for each patient’s complete time-to-event follow-up data will be presented. The second example will show how the routine practice of defining patient evaluability can lead one astray when estimating treatment effects, by misrepresenting the actual patient outcomes. The next two examples pertain to the problems of incompletely or vaguely specified safety monitoring rules. The final example shows what can go wrong when one ignores fundamental experimental design issues, including bias and confounding, when evaluating and comparing multiple treatments. As an alternative approach, the family of randomized select-and-test designs will be presented.