OBJECTIVES: In 1993, the US Public Health Service convened the First Panel on Cost-Effectiveness in Health and Medicine, which concluded that decision-makers should consider both health and cost impacts when choosing among competing technologies. An important feature of economic analysis is how it captures heterogeneity (i.e., ‘diversity in character or content’). In particular, the dominant practice of performing economic evaluations at mean values can lead to sub-optimal decisions. Unfortunately, guidelines are vague on methods, key academic underpinnings are spread across the literature, and methods papers focus primarily on the European setting. Our aim was to fill this gap by performing an integrative review of heterogeneity in guidelines and the methodology literature to provide best practice recommendations for the US setting.

METHODS: We performed an integrative review of modeling guidelines and used PubMed to search for “patient heterogeneity” AND “economic evaluation” AND “cost-effectiveness” in the English language. All materials until November 1, 2021 were considered for inclusion independently by study authors (and discrepancies resolved). Methodological studies were subject to forward and backward citation searches. Qualifying studies and guidelines were reviewed and US-focused recommendations developed.

RESULTS: Forty-six methodological studies, 31 model taxonomy studies, and 8 best practice recommendations were chosen. Best practice guidelines are vague on methods. Several methodological studies provide more detail, including guidance on how appropriate subgroups should be identified. Most studies focus on patient heterogeneity; less is written on other types of heterogeneity important primarily for the US. For example, insurance coverage heterogeneity and individual risk preferences were identified and incorporated in the broader framework.

CONCLUSION: Properly accounting for heterogeneity is essential for economic analysis and analyses that short shrift its consideration result in sub-optimal decisions. By synthesizing the existing literature and guidelines and tailoring to the US setting, a broader framework including heterogeneity can improve economic analyses.