Considerations for Design and Data Analysis of Noninferiority/Superiority Cardiovascular Trials.

The Food and Drug Administration (FDA) guidance for evaluating cardiovascular (CV) risk in new antidiabetic therapies to treat type 2 diabetes released in December 2008 recommends that sponsors conduct appropriate data analysis to rule out CV safety concerns for drugs treating type 2 diabetes. CV trials of antidiabetic drugs and drugs of other indications for chronic conditions are usually large-scale/long-term trials and can be designed as adaptive noninferiority/superiority trials. In these trials, treatment effect may not manifest immediately after patients take study medication and there will be a dilution in treatment effect after treatment discontinuation. These factors should be taken into account for more precise planning of study sample size and timeline. In this paper, we first derive closed-form formulas for the number of events and total exposure as functions of many other trial parameters. We then outline some considerations for the design of an adaptive noninferiority/superiority CV trial based on ideas of other authors. We also use an example to illustrate the application of the methods. [ABSTRACT FROM AUTHOR]