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 framewo...