Identifying Minimum Threshold Level of Trial Crossover Rates Yielding Nonsignificant Overall Survival Benefit Associated with Cancer Treatments: A Systematic Literature Review of HTA Submissions
Crossing‐over rates above approximately 42.7 % in oncology trials typically eliminate significant overall survival (OS) benefit in intention‑to‑treat analyses.
Crossover distortion in oncology trials—when control‑arm patients switch to the experimental treatment—can attenuate intention‑to‑treat overall survival (OS) analyses and obscure the true treatment effect. In a systematic review of HTA submissions from eight major agencies, we examined crossover rates in advanced/metastatic breast, colorectal, gastrointestinal stromal, lung (NSCLC), prostate and renal cancers to identify a threshold that compromises statistical significance. We identified a hypothesis‑generating benchmark of approximately 42.7 % crossover: rates above this threshold were associated with nonsignificant ITT OS, while lower rates preserved significance. The threshold varied modestly with treatment line, crossover type and tumor maturity, but remained a useful context for interpreting OS outcomes in clinical trials.
High crossover rates can mask true treatment benefits, potentially leading to underestimation of efficacy in cost‑effectiveness analyses and misinforming health‑technology assessment decisions. Defining a crossover threshold helps decision-makers discern when OS results are likely to be biased, improving the accuracy of benefit estimations and resource allocation.
Evidence level: Állatkísérletes. Állatmodellben vizsgálták.
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