Sensitivity of Cost-Effectiveness to Inclusion of Adverse Drug Events: A Scoping Review of Economic Models of Pharmacological Interventions for Diabetes, Diabetic Retinopathy, and Diabetic Macular Edema.

Purpose: Incorporation of adverse drug events (ADEs) is suboptimal in economic evaluation, and thus the information provided by it may be inaccurate. Better guidance on incorporating ADEs into economic evaluation prompts for exploring whether the results are sensitive to ADEs. Methods: This scoping review explored 242 cost-effectiveness models for pharmacological interventions for type 1 (T1DM) and 2 diabetes (T2DM), diabetic retinopathy (DR), and diabetic macular edema (DME), in relation to the type of ADEs included in the models (if any), whether the results were sensitive to the ADEs, and what could explain their potential impact. Results: Of the analyses partly or completely including ADEs, 62% examined their impact on the results, with half of them (50%) reporting ADE-related sensitivity. The models included common to very common ADEs, and some rare but severe ones. The main reasons for excluding ADEs were low incidence (13%) and no reporting in clinical trials (13%). Many analyses reported no reason for the exclusion (53%). The analyses for T1DM and DR or DME included more severe ADEs and reported a higher ADE-related sensitivity compared to the analyses of T2DM (76,2%, 77.8%, and 46.4%, respectively). Higher incidence of ADEs (60,0%) and time trade off method (72,2%) were associated with higher ADE-related sensitivity (72,2%). Conclusion: Incidence, condition, and the measure of utility were associated with the results being sensitive to ADEs. ADEs are an important outcome for the results of economic evaluation and better guidance on their inclusion and exclusion is needed.