Medication Adherence with Fixed-Dose Versus Free-Equivalent Combination Therapies: Systematic Review and Meta-Analysis

OBJECTIVES: We conducted a large-scale meta-analysis and subgroup analysis to compare the effect of fixed-dose combination (FDC) therapy with that of free-equivalent combination (FEC) therapy on medication adherence.

METHODS: Studies were identified by searching Web of Science, PubMed, Cochrane Library, ScienceDirect, and Embase. The primary assessed outcomes were the medication possession ratio (MPR) and proportion of days covered (PDC) exceeding 80% or their corresponding average estimate. The search results were independently screened and reviewed by two authors. The results were extracted and pooled in a meta-analysis using a random effects model. The quality of the cohort studies was assessed using the Newcastle-Ottawa scale.

RESULTS: Of the 1,814 screened studies, 61 met the predefined inclusion criteria. The meta-analysis of the results showed that compared to FEC, FDC significantly improved the medication compliance of patients by 1.30 times [95% confidence interval (CI):1.24–1.37, p < 0.00001]. The mean difference in medication adherence between FDC and FEC was 0.10 (95% CI: 0.06–0.14, p < 0.00001). Subgroup analyses were performed for studies that reported adherence outcomes according to disease type and period of evaluation.

CONCLUSIONS: Analysis of the assessed parameters for the intention-to-treat and subgroup populations suggests that FDC can improve adherence to treatment and its advantages over FEC diminish over time. It is recommended to extend the use of fixed-dose combination therapy to more diseases to improve patient compliance.