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When patients in a trial's control arm are allowed to switch to the experimental drug after their cancer progresses. It is fair to patients but blurs the survival comparison, because the control group has now had the drug too.
Crossover is common in trials of drugs already approved elsewhere or clearly active (imatinib in GIST, osimertinib in FLAURA, 177Lu-PSMA in VISION and PSMAfore, where 84% of controls crossed over) and explains why such trials often show large progression-free survival gains but little or no overall survival difference. Statistical corrections (rank-preserving structural failure time, inverse probability of censoring weighting) estimate what survival would have been without crossover but rely on assumptions and are treated cautiously by regulators, who may still demand an OS trend. In regulatory debates, crossover cuts both ways: it can hide a true survival benefit or excuse its absence.
Shares Surrogate endpoint, Surrogate endpoint validation: which stand-ins have earned trust, Why trials fail: underpowered, wrong endpoint, control arm drift, subgroup fishing, crossover, Progression-free survival (PFS).
Shares N-of-1 trial, Estimands and intercurrent events (ICH E9(R1)), Clinical equipoise, Kaplan-Meier curve, censoring and proportional hazards.
Shares Kaplan-Meier curve, censoring and proportional hazards, Hazard ratio (HR), Progression-free survival (PFS), Overall survival (OS).
Shares Kaplan-Meier curve, censoring and proportional hazards, Hazard ratio (HR), Progression-free survival (PFS), Overall survival (OS).
Shares Surrogate endpoint, Surrogate endpoint validation: which stand-ins have earned trust, Hazard ratio (HR), Progression-free survival (PFS).
Shares Kaplan-Meier curve, censoring and proportional hazards, Hazard ratio (HR), Progression-free survival (PFS), Overall survival (OS).
Shares Control arm and comparator (investigator's choice), Estimands and intercurrent events (ICH E9(R1)), Why trials fail: underpowered, wrong endpoint, control arm drift, subgroup fishing, crossover.
Shares N-of-1 trial, Control arm and comparator (investigator's choice), Clinical equipoise.