Surrogate endpoint trials: Benefit and pitfalls for clinical decision making

Ideally clinicians should base their treatment decisions on results from randomised controlled trials which include patient-important outcomes, such as quality of life, prevented disease events or death. Conducting such trials often involves large sample sizes and extended follow-up periods. Therefore, researchers have aimed to conduct trials with surrogate endpoints by substituting patient-important outcomes in order to reduce sample size and observation time. Surrogate endpoints are outcomes that substitute for direct measures of how a patient feels, functions, or survives. In many countries drugs are approved based on data from surrogate endpoint trials. Recently, a controversy evolved on the reliability of results generated from these trials driven by unanticipated side effects or severe toxicity leading to the withdrawal of drugs that were solely approved based on evidence from surrogate endpoint trials. We present some recent examples and criteria how clinicians can critically evaluate the validity of claims by experts or the pharmaceutical industry in regard to the expected patients' benefit from drugs approved by results from surrogate endpoint trials.