Evaluation of progression free survival as surrogate endpoint for overall survival for prostate cancer treatment

Abstract

In some clinical research, the endpoint of greatest relevance to inferences concerning therapeutic efficacy is frequently not practical or even feasible to measure. Sometimes the determination of the true endpoint is difficult, requiring an expensive, invasive or uncomfortable procedure. In some trials, however, the main endpoint of interest, 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 to determine more quickly the effect of an intervention. In this report, a meta-analytic approach was used to validate progression free survival as a surrogate for Overall Survival. Firstly the logarithm of both endpoints were assumed to be normally distributed and fixed effects models were applied to them. Secondly both endpoints were considered as failure time and appropriate methods were applied. In all cases, the individual and trial level surrogacy estimates were too low to be useful. It was