Statistical noise in PD-(L)1 inhibitor trials: unraveling the durable-responder effect

Programmed-death-1/ligand-1 (PD-1(L)1) inhibitors are crucial cancer treatments, with global spending expected to surpass $75 billion by 2026. Multiple versions of these medicines are available, all designed to boost the immune system to fight cancer. We would expect them all to work similarly, but clinical trials show mixed results-some seem effective for certain cancers but not others, without a clear pattern. This article uses simulations (virtual trials) to suggest that these inconsistent results may be due to chance, caused by a small group of patients who respond very well to the treatment. Larger trials or specific analysis methods could help reduce the chance effects and provide more robust data for clinician and patient decision-making.