Clinical Evidence Quality in Appraisals of Drugs for Rare Diseases in England and Germany
Author(s)
Lea Wiedmann, MSc, John Cairns, MPhil, Ellen Nolte, PhD.
Department of Health Services Research and Policy, London School of Hygiene & Tropical Medicine, London, United Kingdom.
Department of Health Services Research and Policy, London School of Hygiene & Tropical Medicine, London, United Kingdom.
OBJECTIVES: Health technology assessment (HTA) processes for rare disease treatments (RDTs) differ between England and Germany. However, systematic comparisons of the quality of clinical evidence in RDT appraisals are lacking. This study analysed clinical evidence quality characteristics in RDT appraisals in England and Germany, two countries with well-established HTA processes but different evaluation methods and pathways.
METHODS: We analysed appraisals between 2011 to 2023 by systematically extracting data from appraisals for clinical evidence quality characteristics (availability of alternative treatments, design of the main study, use of indirect treatment comparisons, applicability, risk of bias, and maturity of survival data). We used Kappa scores to measure the level of agreement, calculated the proportion of appraisals for which there was agreement or disagreement, and highlighted similarities and differences in approaches.
RESULTS: We analysed 102 medicine-indication pairs. We found a high level of agreement between HTA agencies on the design of the main study which was an RCT in 64.7% of appraisals in each country. There was also strong agreement on the maturity of survival data. The main difference was in the consideration of whether the main study was applicable to clinical practice, with 40.2% of appraisals without agreement on the applicability. We also found no agreement on the risk of bias in 41.3% of appraisals in which the main study was the same RCT. Further, in Germany, the proportion of appraisals that did not include an alternative treatment was higher than in England (57.8% vs 43.1%). In England, there was a higher number of appraisals that used indirect treatment comparisons compared to Germany (50% vs 6.9%).
CONCLUSIONS: While clinical evidence in RDT appraisals was to some extent similar in England and Germany, how it was evaluated varied in some areas. Sharing experiences between stakeholders across countries is important to avoid fragmentation of HTA outcomes and patient access.
METHODS: We analysed appraisals between 2011 to 2023 by systematically extracting data from appraisals for clinical evidence quality characteristics (availability of alternative treatments, design of the main study, use of indirect treatment comparisons, applicability, risk of bias, and maturity of survival data). We used Kappa scores to measure the level of agreement, calculated the proportion of appraisals for which there was agreement or disagreement, and highlighted similarities and differences in approaches.
RESULTS: We analysed 102 medicine-indication pairs. We found a high level of agreement between HTA agencies on the design of the main study which was an RCT in 64.7% of appraisals in each country. There was also strong agreement on the maturity of survival data. The main difference was in the consideration of whether the main study was applicable to clinical practice, with 40.2% of appraisals without agreement on the applicability. We also found no agreement on the risk of bias in 41.3% of appraisals in which the main study was the same RCT. Further, in Germany, the proportion of appraisals that did not include an alternative treatment was higher than in England (57.8% vs 43.1%). In England, there was a higher number of appraisals that used indirect treatment comparisons compared to Germany (50% vs 6.9%).
CONCLUSIONS: While clinical evidence in RDT appraisals was to some extent similar in England and Germany, how it was evaluated varied in some areas. Sharing experiences between stakeholders across countries is important to avoid fragmentation of HTA outcomes and patient access.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
HTA76
Topic
Clinical Outcomes, Health Policy & Regulatory, Health Technology Assessment
Topic Subcategory
Decision & Deliberative Processes
Disease
Rare & Orphan Diseases