Mind the Gap! A Multilevel Analysis of Factors Related to Variation in Published Cost-Effectiveness Estimates within and between Countries

Background. Published cost-effectiveness estimates can vary considerably, both within and between countries. Despite extensive discussion, little is known empirically about factors relating to these variations. Objectives. To use multilevel statistical modeling to integrate cost-effectiveness estimates from published economic evalua-tions to investigate potential causes of variation.Methods. Cost-effectiveness studies of statins for cardiovascular dis-ease prevention were identified by systematic review. Esti-mates of incremental costs and effects were extracted from reported base case, sensitivity, and subgroup analyses, with estimates grouped in studies and in countries. Three bivariate models were developed: a cross-classified model to accommodate data from multinational studies, a hierar-chical model with multinational data allocated to a single category at country level, and a hierarchical model excluding multinational data. Covariates at different lev-els were drawn from a long list of factors suggested in the literature. Results. We found 67 studies reporting 2094 cost-effectiveness estimates relating to 23 countries (6 studies reporting for more than 1 country). Data and study-level covariates included patient characteristics, intervention and comparator cost, and some study meth-ods (e.g., discount rates and time horizon). After adjusting for these factors, the proportion of variation attributable to countries was negligible in the cross-classified model but moderate in the hierarchical models (14%–19 % of total variance). Country-level variables that improved the fit of the hierarchical models included measures of income and health care finance, health care resources, and popu-lation risks. Conclusions. Our analysis suggested that vari-ability in published cost-effectiveness estimates is related more to differences in study methods than to differences in national context. Multinational studies were associated with much lower country-level variation than single-country studies. These findings are for a single clinical question and may be atypical. Key words: economic evaluation; transfer-ability; exchangeability; multilevel statistical modeling; sta-tins; cardiovascular disease. (Med Decis Making 2016