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Interim Analysis Alpha Spending — SCE Medical Oncology MCQ

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HardClinical Trials & StatisticsInterim Analysis Alpha SpendingSCE Medical Oncology

A phase III trial reports that its primary endpoint (PFS) crossed the pre-specified interim analysis boundary for superiority at the first interim look. The data monitoring committee recommends early reporting. What statistical consideration must be addressed when analysing results at an interim analysis?

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Correct answer: C — The significance threshold at interim analysis must be MORE stringent than the final analysis (using methods such as O'Brien-Fleming, Lan-DeMets alpha-spending function) to control the overall type I error rate at 5% — early stopping for efficacy uses only a fraction of the total alpha

Repeated interim analyses inflate the type I error rate (multiple looks at accumulating data increase the chance of a false positive). Group sequential designs (O'Brien-Fleming, Lan-DeMets alpha-spending function) allocate a small fraction of the total alpha (0.05) to early interim analyses, preserving most of the alpha for the final analysis. For example, with O'Brien-Fleming boundaries, the first interim analysis might require p<0.001, while the final analysis uses p<0.048. This statistical rigour ensures early efficacy claims are robust.

Reference: JRCPTB Curriculum; ICH E9; O'Brien & Fleming Biometrics 1979