No Head-to-Head Trial? Simulate the Missing Arms

Establishing efficacy relative to placebo is no longer sufficient for payers to agree to cover new interventions. Evidence from comparisons of competing interventions is increasingly important, although head-to-head studies are seldom available to inform decisions. In this article, we describe the simulated treatment comparison (STC) approach to incorporating ‘missing arms’ into an existing trial. This approach yields a simulated head-to-head trial and can address many of the differences among source trials. It provides inputs for economic models and can inform decision makers until actual trial data are available.

A simulation is constructed to replicate an index trial, including enrolment, randomization and follow-up of patients. The simulation is driven by predictive equations derived from the index trial. Separate data for the comparators are used to calibrate the index equations to reflect the alternative interventions. The simulation is used to add the missing arms to the index trial and estimate the results that would have been obtained in a head-to-head trial. The STC can also be used to estimate results in various settings and populations and to explore variations in the trial design. An STC offers a way to derive comparative effectiveness in the absence of direct trial evidence and a platform to test design features that may help in planning future head-to-head studies.