Key PointsQuestionWhich methodologic considerations affect drug price inflation estimates, and what may be a better approach to constructing a drug price index?FindingsIn this cross-sectional study of drug price indexes, including a case study of hepatitis C virus medications, a product-level index failed to capture high-cost drugs at launch compared with a class-level index approach. Additionally, adjusting for prescription duration and manufacturer rebates substantially affected inflation rate calculations.MeaningThe findings of this cross-sectional study indicate that although the Inflation Reduction Act prevents prescription drug prices from outpacing the Consumer Price Index, it fails to address new drug launches for specific diseases, which can substantially increase the average cost of treatment for patients.