Predictive Evidence Threshold Scaling: Does the Evidence Meet a Confirmatory Standard?

ABSTRACT Making better use of evidence is one of the tenets of modern drug development. This calls for an understanding of the evidential strength of nonconfirmatory evidence relative to a confirmatory standard. Such inferential comparisons can be done via predictive evidence threshold scaling (PETS). Under PETS, the evidence meets a confirmatory standard if the predictive probability of a positive effect reaches the predictive evidence threshold from hypothetical confirmatory data. These probabilities require plausible assumptions about between-trial heterogeneity and potential biases. Two examples are discussed. The first is breakthrough designation, illustrated by a recent Food and Drug Administration approval of crizotinib for the treatment of non-small-cell lung cancer based on phase I and II data. The second is childhood Guillain–Barré syndrome, with sparse children data enriched with adult data. The examples suggest that the evidential strength of nonconfirmatory data can meet a confirmatory standard. This is reassuring for modern drug development, which exploits various types of evidence to inform adaptive licensing decisions. Supplementary materials for this article are available online.