OBJECTIVES: Health Technology Assessment (HTA) assess the relative therapeutic and economic value of new interventions when comparing to standard-of-care alternatives. When used routinely in clinical practice for an off-label indication, a medicine may be used as a comparator in HTA procedure. This study is aimed at characterizing the frequency of use of off-label comparators and outcomes of reimbursement appraisals in Portugal.

METHODS: INFARMED, I.P. webpage was searched for public reimbursement appraisal reports of medicines published between 2022 and 2023, retrieving the following data: therapeutic indication under assessment, intervention, comparator(s), conclusions of the therapeutic assessment, and reimbursement recommendation. Summaries of Product Characteristics (SmPC) of comparator alternatives were reviewed to identify off-label indications. Descriptive statistics were used for data analyses with Microsoft Excel®.

RESULTS: Of the 109 appraisal reports identified, 28 (26%) used off-label comparators and 81 (74%) used on-label comparators in assessment procedure. Most of the appraisals using off-label comparators (n=27; 96%) issued favorable reimbursement recommendations, with 19 (70%) concluding on the existence of added therapeutic value (ATV) for the intervention under evaluation, and 8 (30%) concluding for therapeutic equivalence between the intervention and the comparators. One (4%) report issued an unfavorable reimbursement recommendation due to the use of inappropriate comparative methods to assess therapeutic value. Of the 81 appraisal reports using on-label comparators, 71 (88%) issued favorable reimbursement recommendations [48 (58%) concluding for ATV and 23 (42%) concluding for therapeutic equivalence]. Ten appraisals issued unfavorable reimbursement recommendations due to methodological limitations (n= 3; 30%) or lack of evidence/valid comparison method (n= 7; 70%) when assessing the therapeutic value.

CONCLUSIONS: The findings from this study suggest that the reimbursement appraisals using off-label comparators do not result in higher rates of unfavorable recommendations. Comparisons with reimbursement appraisals from other countries may be useful to characterize additional practices and identify further conclusions.