Presentation (CTI)

OBJECTIVES: To examine factors influencing approval and reimbursement of fixed-dose combinations (FDCs) for non-communicable diseases (NCDs) across four HTA agencies (SMC, HAS, G-BA, CDA) from 2014-2024. The analysis covered clinical and economic evidence, stakeholder perspectives, and implementation factors for FDCs targeting diabetes mellitus (DM), asthma, chronic obstructive pulmonary disease (COPD), and cardiovascular diseases (CVDs).
METHODS: Comparative systematic review of 84 HTA reports for 41 FDCs used the HTA-Hive database, analysing clinical, economic, and implementation considerations. Statistical analyses assessed associations between reimbursement outcomes and factors like disease area and HTA agency. Two scenarios were examined: (1) FDCs replacing monotherapies, and (2) FDCs introducing novel therapeutic advancements. A qualitative thematic analysis explored convergent and divergent decision drivers across agencies. NICE was excluded due to insufficient reports on FDCs (n=1).
RESULTS: Chi-square test (χ²=19.91, df=6, p≈0.003) revealed a significant association between HTA outcome and disease area. Post-hoc analysis indicated asthma FDCs were granted full listing more often (+2.24), while DM FDCs were granted it less frequently (-2.35). No significant differences arose between novel FDCs (n=19) and those replacing monotherapies (n=65), though novel combinations received higher clinical benefit ratings and higher pricing. Cost, disease control, severity, treatment history, and biomarkers positively influenced decisions. Agencies require robust efficacy and clinical benefits (favouring cost-effectiveness) yet diverge on comparator choice, surrogate endpoints, and thresholds for “added benefit”. Overdosing inflexibility and insufficient benefit led to two rejections, and no agency explicitly addressed patient adherence or polypharmacy.
CONCLUSIONS: FDCs demonstrate favourable value over monotherapies, provided they deliver tangible clinical outcomes and cost savings. Reimbursement decisions are tied to pricing considerations and tend to favour innovative FDCs that show clear added benefits. Though HTA agencies converge on requiring robust efficacy and clinical relevance, variations remain in comparator choice and “added benefit” criteria. Addressing patient adherence and polypharmacy could strengthen FDC value demonstrations.