Composite endpoints in health technology assessment: Part 2 – expanding the evidence base with a framework for best modeling practice

The first paper of this two-part series critically examined the role of composite endpoints in health technology assessments (HTAs) and outlined strategies for determining whether to employ the composite estimate of treatment effect or disaggregate into the component endpoints of the composite and apply separate treatment effects within a modeling framework. In this second paper, we expand the discussion beyond a pivotal trial and consider the way in which additional evidence from the same indication for different drugs in the same class, or the same drug for different indications, could be employed within HTAs. We offer a continuation of the case study of dapagliflozin for the treatment of heart failure with preserved or mildly reduced ejection fraction, where the evidence base was expanded to consider empagliflozin for the same indication, as well as both dapagliflozin and empagliflozin for heart failure with reduced ejection fraction. We conclude that, where there are multiple drugs in the same class and/or multiple indications for a class of drugs, HTAs should consider the exchangeability of the information that comes from additional evidence beyond the pivotal registration study. Further, we show how consideration of this additional evidence can support the decision concerning whether to disaggregate the components of a composite endpoint or employ the treatment effect from the composite for each endpoint.