Evaluation of Progression Free Survival as a surrogate for Overall Survival for prostate cancer treatment: Software development

Abstract

In clinical trials, the determination of the true endpoint or the effect of a new therapy on the true endpoint may be difficult, requiring an expensive, invasive or uncomfortable procedure. In some trials, however, the main endpoint of interest (true endpoint), for example death, is rare and/or takes a long period of time to reach. In such trials, there would be benefit in finding a more proximate endpoint (surrogate endpoint) to determine more quickly the effect of an intervention (Ellenberg et al. 1989).

The validation and evaluation of a surrogate endpoints needs to be assessed at both the patient and the trial-level (Burzykowski et al 2005). The individual-level surrogacy, measures the association between the potential surrogate endpoint and the true endpoint after adjusting for treatment effects on both true and surrogate endpoints. On the other hand, the trial-level surrogacy, describes how well one can predict the treatment effect on the true clinical endpoint in a future trial based on the observed association between the treatment effects on the surrogate and true endpoints observed in previous trials (Buyse et al. 2000). Unfortunately, standard software to perform analysis to validate surrogate endpoints is lacking. To that end, we developed a user friendly SAS macro to automate such an analysis. We demonstrate the usage and capacities of the software implementation using a clinical trial data set with two failure time endpoints.