Adverse drug events in cost-effectiveness models of pharmacological interventions for diabetes, diabetic retinopathy, and diabetic macular edema: a scoping review.

Objective: The objective of this review was to examine the role of adverse drug events (ADEs) caused by pharmacological interventions in cost-effectiveness models for diabetes mellitus, diabetic retinopathy, and diabetic macular edema.

Introduction: Guidelines for economic evaluation recognize the importance of including ADEs in the analysis, but in practice, consideration of ADEs in cost-effectiveness models seem to be vague. Inadequate inclusion of these harmful outcomes affects the reliability of the results, and the information provided by economic evaluation could be misleading. Reviewing whether and how ADEs are incorporated in cost-effectiveness models is necessary to understand the current practices of economic evaluation.

Inclusion Criteria: Studies included were published between 2011-2022 in English, representing cost-effectiveness analyses using modeling framework for pharmacological interventions in the treatment of diabetes mellitus, diabetic retinopathy, or diabetic macular edema. Other types of analyses and other types of conditions were excluded.

Methods: The databases searched included MEDLINE (PubMed), CINAHL (EBSCOhost), Scopus, Web of Science Core Collection, and NHS Economic Evaluation Database. Gray literature was searched via the National Institute for Health and Care Excellence, European Network for Health Technology Assessment, the National Institute for Health and Care Research, and the International Network of Agencies for Health Technology Assessment. The search was conducted on January 1, 2023. Titles and abstracts were screened for inclusion by 2 independent reviewers. Full-text review was conducted by 3 independent reviewers. A data extraction form was used to extract and analyze the data. Results were presented in tabular format with a narrative summary, and discussed in the context of existing literature and guidelines.

Results: A total of 242 reports were extracted and analyzed in this scoping review. For the included analyses, type 2 diabetes was the most common disease (86%) followed by type 1 diabetes (10%), diabetic macular edema (9%), and diabetic retinopathy (0.4%). The majority of the included analyses used a health care payer perspective (88%) and had a time horizon of 30 years or more (75%). The most common model type was a simulation model (57%), followed by a Markov simulation model (18%). Of the included cost-effectiveness analyses, 26% included ADEs in the modeling, and 13% of the analyses excluded them. Most of the analyses (61%) partly considered ADEs; that is, only 1 or 2 ADEs were included. No difference in overall inclusion of ADEs between the different conditions existed, but the models for diabetic retinopathy and diabetic macular edema more often omitted the ADE-related impact on quality of life compared with the models for diabetes mellitus. Most analyses included ADEs in the models as probabilities (55%) or as a submodel (40%), and the most common source for ADE incidences were clinical trials (65%).

Conclusions: The inclusion of ADEs in cost-effectiveness models is suboptimal. The ADE-related costs were better captured than the ADE-related impact on quality of life, which was most pronounced in the models for diabetic retinopathy and diabetic macular edema. Future research should investigate the potential impact of ADEs on the results, and identify the criteria and policies for practical inclusion of ADEs in economic evaluation.