OBJECTIVES: FDC products provide benefits for patients such as ease, convenience and a single co-payment. However, for FDC superiority vs LDC products is inconclusive and therefore we sought to evaluate existing published evidence on the benefits of FDC formulations.

METHODS: We conducted a SLR on data published (Jan 2001–Dec 2021) comparing FDC and LDC products in: 1) clinical trials, 2) real-world evidence (RWE), 3) health-related quality of life (HRQoL) and 4) health economics. Databases and registries were searched following PRISMA guidelines. Search terms included “fixed or single pill” and “free or loose combination” with related terms along with validated study design filters. Studies were included if medication adherence, compliance, persistence, HRQoL or economic outcomes were reported for FDC and LDC products.

RESULTS: There were 109 original studies identified. All health economic (25 studies) studies favored FDC over LDC: showing dominance, cost savings, and lower healthcare resource use. In the RWE studies, compared with LDC, there was statistically significant higher persistence with FDC in 16/19 studies, higher adherence in 15/20 studies, and higher compliance in 2/4 studies. Of 14 studies evaluating efficacy and adherence/compliance/persistence, 6 (43%) showed a positive correlation between these parameters. In clinical trials, similar adherence (13 studies) and compliance (4 studies) was observed. In the identified HRQoL studies, pill burden was not assessed. Similar HRQoL was observed with both FDC and LDC formulations (one study showed a statistically significant benefit for FDC vs LDC).

CONCLUSIONS: SLRs showed significant benefits of FDC over LDC in terms of cost-effectiveness, cost savings and healthcare resource use. In most (77%) real-world studies, medication adherence, compliance and persistence were significantly improved for FDC vs LDC. RCTs are not appropriate to assess adherence, compliance and persistence as patient behavior differs in trial settings vs the real world.