Exploring the Impact of Heterogeneity in Economic Evaluations: Current Practice and Implications


Komakoma L1, Yi Y2
1Adelphi Values Ltd, Bollington, CHE, UK, 2Adelphi Values Ltd, Bollington, UK

Presentation Documents


Economic evaluation for a target population is usually based on average clinical and economic outcomes. However, real-world patients within one target population are heterogeneous. Failure to accommodate patient heterogeneity in clinical outcomes, health state preferences and/or resource use in economic evaluation can bias cost-effectiveness results, leading to suboptimal reimbursement decisions. This study aims to review updates from the national pharmacoeconomic guidelines (NPGs) on patient heterogeneity. It also explores how heterogeneity issues have been dealt within the NICE Highly Specialized Technology (HST) program for rare diseases.


A targeted literature review of NPGs (n=26) identified updates since January 2013. Updated guidance was extracted based on how guidelines advise to analyze and prespecify the sources of heterogeneity. To assess the current practice of dealing with heterogeneity in rare disease, all NICE HST recommendations were obtained. Data on the manufacturer’s analysis, comments from ERGs and the committee, and final recommendations were extracted.


Since January 2013, 11 of 26 NPGs have been updated, of which six updates had explicit and/or implicit implications on how patient heterogeneity should be addressed. Of these, two expanded on existing guidance and four added new guidance for heterogeneity. Australia has included a checklist that considers the sources of heterogeneity between trials and jurisdictions. All HSTs (n=14) received positive recommendations by NICE. Eight were targeted at a patient subgroup, of which five addressed heterogeneity using a subgroup analysis by the manufacturer.


Updates of NPGs to reflect heterogeneity remain limited and non-explicit. Only Australia has made explicit improvements on their guidance. Whilst the majority of HST submissions have tried to address heterogeneity, the extent of this is limited and often addressed through subgroups. Improving guidance on addressing heterogeneity is increasingly important in optimal resource allocation under constraints, particularly for high cost rare diseases.

Conference/Value in Health Info

2021-11, ISPOR Europe 2021, Copenhagen, Denmark

Value in Health, Volume 24, Issue 12, S2 (December 2021)




Clinical Outcomes, Economic Evaluation, Health Technology Assessment, Methodological & Statistical Research

Topic Subcategory

Clinical Outcomes Assessment, Cost-comparison, Effectiveness, Utility, Benefit Analysis, Decision & Deliberative Processes


Drugs, Rare and Orphan Diseases

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