Developing an evidence-based methodological framework to systematically compare HTA coverage decisions: A mixed methods study.

Health Technology Assessment (HTA) often results in different coverage recommendations across countries for a same medicine despite similar methodological approaches. This paper develops and pilots a methodological framework that systematically identifies the reasons for these differences using an exploratory sequential mixed methods research design. The study countries were England, Scotland, Sweden and France. The methodological framework was built around three stages of the HTA process: (a) evidence, (b) its interpretation, and (c) its influence on the final recommendation; and was applied to two orphan medicinal products. The criteria accounted for at each stage were qualitatively analyzed through thematic analysis. Piloting the framework for two medicines, eight trials, 43 clinical endpoints and seven economic models were coded 155 times. Eighteen different uncertainties about this evidence were coded 28 times, 56% of which pertained to evidence commonly appraised and 44% to evidence considered by only some agencies. The poor agreement in interpreting this evidence (κ=0.183) was partly explained by stakeholder input (ns=48 times), or by agency-specific risk (nu=28 uncertainties) and value preferences (noc=62 "other considerations"), derived through correspondence analysis. Accounting for variability at each stage of the process can be achieved by codifying its existence and quantifying its impact through the application of this framework. The transferability of this framework to other disease areas, medicines and countries is ensured by its iterative and flexible nature, and detailed description.