Multivariable and Structural Uncertainty Analyses for Cost-Effectiveness Estimates: Back to the Future

In this commentary, celebrating the 20th anniversary of the journal Value in Health, I present a brief overview and illustration of the evolution over the past 20 years of the methodological literature providing guidelines for multivariable and structural uncertainty analysis for cost-effectiveness estimates. To illustrate the impact of the guidelines for uncertainty analyses, I show how the inclusion of multivariable and structural uncertainty analyses in cost-effectiveness analyses published in Value in Health changed over the past 20 years using publications from 1999/2000, 2007 and 2017. The commentary is organized in three sections: past, focusing on the development and use of methods for multivariable uncertainty analysis; present, focusing on the growing awareness of the need for structural uncertainty analysis, suggested frameworks for structural uncertainty analysis and how it is currently implemented; and future, considering different methods for combining multivariable and structural uncertainty analyses over the next decades. I conclude by suggesting how the continued evolution of uncertainty analyses in published studies and health technology assessment submissions can best take into account an important goal of cost-effectiveness analyses: to provide useful information to decision makers.