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Crossover Adjustment RPSFT — SCE Medical Oncology MCQ

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HardClinical Trials & StatisticsCrossover Adjustment RPSFTSCE Medical Oncology

A researcher is asked to explain the concept of 'crossover adjustment' in oncology trials. A trial allowed control-arm patients to cross over to the experimental drug at progression. The unadjusted OS analysis shows HR 0.85 (p=0.08). After crossover adjustment using RPSFT method, the adjusted HR is 0.70 (p=0.01). What happened?

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Correct answer: D — Crossover dilutes the OS benefit by giving control patients the experimental drug at progression; statistical adjustment methods (RPSFT, IPCW) estimate the 'true' treatment effect had crossover not occurred — the adjusted HR better represents the drug's OS benefit for regulatory and reimbursement decisions

When control patients cross over to the experimental arm at progression, the subsequent survival benefit they receive dilutes the ITT OS difference. Two statistical methods adjust for this: RPSFT (rank preserving structural failure time — adjusts survival times) and IPCW (inverse probability of censoring weights — adjusts for informative censoring at crossover). These methods estimate the 'counterfactual' OS had crossover not occurred. NICE explicitly considers crossover-adjusted OS analyses in technology appraisals when ITT OS is confounded by high crossover rates.

Reference: JRCPTB Curriculum; NICE Methods Guide; Latimer et al Med Decis Making 2014