A Systematic Review of Economic Modeling Challenges and Proposed Solutions for Rare Disease Technologies: An HTAi RDIG Initiative
Author(s)
Jyotirmoy Sarker, MPharm, MBA, MBiotech1, Farzana Malik, PhD2, Abhirup Dutta Majumdar, MS3, Lea Wiedmann, MSc4, Persefoni Kritikou, PhD5, Khashayar Azimpour, PhD, MD6, Madhusubramanian Muthukumar, MSc7, Martina Garau, BA, MSc8.
1Pharmacy Systems, Outcomes and Policy, University of Illinois Chicago, Chicago, IL, USA, 2Cogience, London, United Kingdom, 3PharmaQuant Insights Private Limited, Kolkata, India, 4London School of Hygiene and Tropical Medicine (LSHTM), London, United Kingdom, 5HCD Economics, Athens, Greece, 6Chiesi, Notre Dame Ile Perrot, QC, Canada, 7Alira Health, London, United Kingdom, 8Office of Health Economics, London, United Kingdom.
1Pharmacy Systems, Outcomes and Policy, University of Illinois Chicago, Chicago, IL, USA, 2Cogience, London, United Kingdom, 3PharmaQuant Insights Private Limited, Kolkata, India, 4London School of Hygiene and Tropical Medicine (LSHTM), London, United Kingdom, 5HCD Economics, Athens, Greece, 6Chiesi, Notre Dame Ile Perrot, QC, Canada, 7Alira Health, London, United Kingdom, 8Office of Health Economics, London, United Kingdom.
OBJECTIVES: Rare diseases present distinct challenges for health technology assessment (HTA) due to limited evidence, small patient populations, and substantial population heterogeneity. The Health Technology Assessment international (HTAi) society’s Rare Diseases Interest Group (RDIG) is conducting a systematic literature review to identify novel approaches or adaptations in economic evaluation methods to address these challenges. This work presents initial findings from that review.
METHODS: We searched Ovid (MEDLINE, Embase), the Cost-Effectiveness Analysis Registry, and the Pediatric Economic Database Evaluation for studies published from 2018 onward. We also reviewed HTA websites (NICE, ICER, PBAC, CADTH, SMC, IQWiG). Two reviewers independently screened titles/abstracts and full texts, and a third reviewer resolved disagreements. A predefined template for data extraction was used. The review was registered in PROSPERO (CRD42024522132), and we followed the PRISMA 2020 and CADTH PRESS guidelines.
RESULTS: The initial search yielded 1314 records. After screening, 124 full-text articles were assessed for eligibility, and 23 studies were included in the final synthesis. Among the methodological challenges related to input and outcome parameters were limited natural history data, small sample sizes, lack of head-to-head trial data, reliance on single-arm designs, and heterogeneity or imbalance in trial populations, affecting representativeness and comparability. Additional challenges in modeling rare pediatric diseases included age restrictions on utility measures, difficulty collecting quality-of-life data outside trials, limited published health related quality-of-life data, and uncertainty from sparse data and poorly understood disease trajectories. While a few studies applied approaches such as customized matching, utility and hazard mapping, survival curve reconstruction, and expert elicitation, the application of novel methods remains limited.
CONCLUSIONS: While the methodological challenges of economic evaluation for rare disease technologies are widely acknowledged, our review highlights a gap between awareness and implementation of methodological innovation.
METHODS: We searched Ovid (MEDLINE, Embase), the Cost-Effectiveness Analysis Registry, and the Pediatric Economic Database Evaluation for studies published from 2018 onward. We also reviewed HTA websites (NICE, ICER, PBAC, CADTH, SMC, IQWiG). Two reviewers independently screened titles/abstracts and full texts, and a third reviewer resolved disagreements. A predefined template for data extraction was used. The review was registered in PROSPERO (CRD42024522132), and we followed the PRISMA 2020 and CADTH PRESS guidelines.
RESULTS: The initial search yielded 1314 records. After screening, 124 full-text articles were assessed for eligibility, and 23 studies were included in the final synthesis. Among the methodological challenges related to input and outcome parameters were limited natural history data, small sample sizes, lack of head-to-head trial data, reliance on single-arm designs, and heterogeneity or imbalance in trial populations, affecting representativeness and comparability. Additional challenges in modeling rare pediatric diseases included age restrictions on utility measures, difficulty collecting quality-of-life data outside trials, limited published health related quality-of-life data, and uncertainty from sparse data and poorly understood disease trajectories. While a few studies applied approaches such as customized matching, utility and hazard mapping, survival curve reconstruction, and expert elicitation, the application of novel methods remains limited.
CONCLUSIONS: While the methodological challenges of economic evaluation for rare disease technologies are widely acknowledged, our review highlights a gap between awareness and implementation of methodological innovation.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
P42
Topic
Economic Evaluation, Health Technology Assessment
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, Rare & Orphan Diseases