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

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 <i>predictive evidence threshold scaling</i> (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.