A Retrospective Analysis of the Italian Medicines Agency’s Evaluation of Real-World Evidence in Innovativeness Assessments
Author(s)
Diego Civitelli1, Mackenzie Mills, PhD2, Panos Kanavos, BSc, MSc, PhD3;
1LSE, Research Officer, London, United Kingdom, 2Hive, London, United Kingdom, 3The London School of Economics, London, United Kingdom
1LSE, Research Officer, London, United Kingdom, 2Hive, London, United Kingdom, 3The London School of Economics, London, United Kingdom
Presentation Documents
OBJECTIVES: The Italian Medicines Agency (AIFA) assesses the innovativeness of drugs based on unmet need, added clinical benefit, and quality of evidence. The designation provides access to the 1 billion euro Innovative Medicines Fund and faster market access. We investigate the use of Real-World Evidence (RWE) in submissions for innovative status and their appraisal by AIFA.
METHODS: We extracted data from an AIFA database on all Innovativeness Assessments of reimbursed drugs conducted in 2021,2022 and 2023. Unmet need, added clinical benefit, quality of evidence, and certainty of primary endpoint indicators were recorded. Descriptive statistics and tests of statistical association were used to explore how AIFA appraised RWE and potential links to assessment outcomes.
RESULTS: 40 (37 percent) drugs received full innovative status, 27 (25 percent) received conditional status, and 43 (39 percent) were rejected. Randomized studies were used in 76 (69 percent) submissions, and observational studies in 34 (31 percent). Outcomes differed significantly by study design (p=0.005). 20 (59%) submissions using RWE were rejected versus only 23 (30 percent) that provided randomized trials. Additionally, the Quality of Evidence indicator also differed significantly by study design (p = 0.000). 34 (100 percent) submissions that used observational trials received a score of “Low” or “Very low”, as opposed to 16 (21 percent) submissions that provided randomized trials. The Added Clinical Benefit indicator also different significantly by study design (p = 0.001). 10 (29 percent) submissions with observational trials achieved a “Non-quantifiable” score, in contrast to 2 (3 percent) submissions with randomized trials.
CONCLUSIONS: Submissions using RWE were more likely to be rejected by AIFA due to the lower perceived quality of the evidence. However, ethical and feasibility considerations may make randomized trials unviable. Further research is needed to establish the extent to which this is considered in the assessments.
METHODS: We extracted data from an AIFA database on all Innovativeness Assessments of reimbursed drugs conducted in 2021,2022 and 2023. Unmet need, added clinical benefit, quality of evidence, and certainty of primary endpoint indicators were recorded. Descriptive statistics and tests of statistical association were used to explore how AIFA appraised RWE and potential links to assessment outcomes.
RESULTS: 40 (37 percent) drugs received full innovative status, 27 (25 percent) received conditional status, and 43 (39 percent) were rejected. Randomized studies were used in 76 (69 percent) submissions, and observational studies in 34 (31 percent). Outcomes differed significantly by study design (p=0.005). 20 (59%) submissions using RWE were rejected versus only 23 (30 percent) that provided randomized trials. Additionally, the Quality of Evidence indicator also differed significantly by study design (p = 0.000). 34 (100 percent) submissions that used observational trials received a score of “Low” or “Very low”, as opposed to 16 (21 percent) submissions that provided randomized trials. The Added Clinical Benefit indicator also different significantly by study design (p = 0.001). 10 (29 percent) submissions with observational trials achieved a “Non-quantifiable” score, in contrast to 2 (3 percent) submissions with randomized trials.
CONCLUSIONS: Submissions using RWE were more likely to be rejected by AIFA due to the lower perceived quality of the evidence. However, ethical and feasibility considerations may make randomized trials unviable. Further research is needed to establish the extent to which this is considered in the assessments.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
HTA69
Topic
Health Technology Assessment
Topic Subcategory
Decision & Deliberative Processes, Value Frameworks & Dossier Format
Disease
No Additional Disease & Conditions/Specialized Treatment Areas