Clinical trials are the key mechanism for testing efficacy of cancer therapy. While results from clinical trials have high internal validity, generalizability is limited due to strict criteria for inclusion and exclusion (i.e., eligibility criteria). Indeed, eligibility criteria are designed to protect the safety of trial participants by excluding those expected to have low efficacy or high toxicity from the treatment under investigation. However, if overly restrictive, eligibility criteria can also result in narrow populations that do not reflect the general population treated in routine practice. Recent analyses of cancer clinical trial data have shown that eligibility criteria have become increasingly restrictive, ranging from 16 to 32 exclusion criteria per trial, over time. Therefore, it is not surprising that <5% of US adult patients with cancer participate in clinical trials, and those who do are often younger and healthier than patients seen in clinical practice. These differences raise serious concern that the “efficacy” of cancer therapies reported in published clinical trials provides incomplete evidence of their “effectiveness” when administered to patients in routine care
