Real-world validity of randomized controlled phase III trials

Clinical trials are fundamental for therapeutic advances in GBM and according to the National Comprehensive Cancer Network, the best management of a cancer patient is in a trial. However, by current trial inclusion and exclusion criteria, only a selected group of patients can be considered eligible for trials. This bias not only restricts patients from receiving the best care, but also makes it difficult to extrapolate trial results to a real-world population.

Using the Cancer Registry of Norway and the Brain Tumor Database at Oslo University Hospital, we tracked all patients within a well-defined geographical area with newly diagnosed GBM during the years 2012-2017. Based on data from these registries and the medical records, the patients were evaluated for trial eligibility according to criteria employed in recent phase III trials for GBM.

Here, we estimated the proportion of GBM patients who did not fulfill eligibility criteria for trial participation and compared the characteristics of patients considered trial participants to those excluded. We found that approximately 60% of patients were ineligible for trials. These patients were older, had worse performance status, received less treatment and had worse survival. This implies that the current trial landscape inadequately reflects the population, and that generalizability of trials results into clinical practice carries considerable uncertainty.