Evaluating the dependence of a non-leaky intervention's partial efficacy on a categorical mark (1206.6701v2)

Abstract: We address discrete-marks survival analysis, also known as categorical sieve analysis, for a setting of a randomized placebo-controlled treatment intervention to prevent infection by a pathogen to which multiple exposures are possible, with a finite number of types of "failure". In particular, we address the case of interventions that are partially efficacious due to a combination of failure-type-dependent efficacy and subject-dependent efficacy, for an intervention that is "non-leaky" (where "leaky" interventions are those for which each exposure event has a chance of resulting in a "failure" outcome, so multiple exposures to pathogens of a single type increase the chance of failure). We introduce the notion of some-or-none interventions, which are completely effective only against some of the failure types, and are completely ineffective against the others. Under conditions of no intervention-induced failures, we introduce a framework and Bayesian and frequentist methods to detect and quantify the extent to which an intervention's partial efficacy is attributable to uneven efficacy across the failure types rather than to incomplete "take" of the intervention. These new methods provide more power than existing methods to detect sieve effects when the conditions hold. We demonstrate the new framework and methods with simulation results and new analyses of genomic signatures of HIV-1 vaccine effects in the STEP and RV144 vaccine efficacy trials.