Table A1.
Summary of the systematic reviews and meta-analyses (n = 17) regarding the medical condition in focus, study aim, number and design of included studies, and main results.
| Author, Reference, Year of Publication, Study Design | Medical Condition or Disease in Focus | Study Aim | Number and Design of Studies Included | Main Results |
|---|---|---|---|---|
| Various diseases (n = 1) | ||||
| Van Galen et al. [29], 2014 Systematic review and meta-analysis |
HIV (n = 2), tuberculosis (n = 3), hypertension (n = 1) | To summarize and synthesize existing evidence from RCTs about the effect on adherence to FDCT versus the same drugs administered as separate pills | 6 RCTs | Administering drugs as FDC increased the likelihood of optimal adherence (OR 1.33 (95% CI, 1.03–1.71)); however, the difference was statistically significant only for HIV. Other diseases only showed the same trend. |
| Bangalore et al. [13], 2007 Meta-analysis |
Tuberculosis (n = 2), hypertension (n = 4), DMII (n = 2), HIV (n = 1) | To evaluate the effect of FDCT on patient adherence to medication | 9: 3 RCTs, 6 retrospective database analyses | Utilizing FDC resulted in 26% decrease in the risk of non-compliance compared to the free-drug therapy (RR: 0.74; 95% CI: 0.69–0.80; p < 0.0001). |
| Hypertension (n = 5) | ||||
| Kawalec et al. [25], 2018 Systematic review with meta-analysis and narrative synthesis |
Hypertension | To present an up-to-date evaluation of the effectiveness of FDCs and free equivalent combinations in management of hypertension and to get more accurate results by using a stratified meta-analysis | Whole systematic review: 26 clinical studies, 2 systematic reviews Meta-analysis: 12; 11 retrospective cohort studies, 1 nonrandomized trial (assessing adherence) |
FDC were shown to be associated with an improvement in adherence in comparison to free equivalent combination therapy; e.g., meta-analysis of 4 cohort studies showed an increased adherence with FDCT in the average MPR by 13.1% (95% CIs: 8.9%–17.2%, p < 0.001). |
| Du et al. [14], 2018 Meta-analysis |
Hypertension | To assess the effect of FDCT on medication adherence in comparison to free-equivalent combination therapies in management of hypertension | 7 (assessing adherence): 6 retrospective studies, 1 prospective study | FDCT was associated with higher medication adherence than free equivalent combination therapies; mean difference was 14.92% (95% CIs: 7.38%–22.46%). |
| Sherrill et al. [15], 2011 Meta-analysis |
Hypertension | To compare healthcare resource use costs, adherence, and persistence between groups of patients on single-pill and free-equivalent combination therapies | 7 retrospective studies (assessing adherence) | The average MPR was 8% higher in the patient group to prior antihypertensives and 14% higher in experienced FDCT patient group, compared with corresponding free-equivalent combination group. |
| Gupta et al. [16], 2009 Meta-analysis |
Hypertension | To compare compliance, persistence, blood pressure control, and safety between FDCTs and free-drug combinations | 5 (assessing adherence): 2 RCTs, 3 retrospective cohort studies | The use of FDCT was associated with significantly better compliance (OR: 1.21, 95% CIs: 1.03–1.43; p = 0.02). |
| Mallat et al. [26], 2016 Systematic review and meta-analysis |
Essential arterial hypertension | To compare the effects of FDCT and free combination therapy with blood pressure lowering agents in the management of essential hypertension | 3 RCTs (assessing adherence) | Two articles reported no difference in adherence between groups, one article showed increased adherence in FDCT group. |
| CVD (n = 2) | ||||
| Selak et al. [17], 2018 Meta-analysis |
CVD | To assess the impact of FDCT on achieving the 2016 European Society of Cardiology guideline targets for blood pressure, low-density lipoprotein, cholesterol, and antiplatelet therapy | 3 RCTs | No difference was observed between groups in antiplatelet adherence (96% vs. 96%, RR: 1.00, 95% CIs: 0.98–1.01). |
| Bahiru et al. [21], 2017 Systematic review |
Atherosclerotic CVD | To study the effect of FDC therapy on all-cause mortality, fatal and non-fatal ASCVD events, adverse events, blood pressure, lipids, adherence, discontinuation rates, health-related quality of life and costs | 4 RCTs (assessing adherence) | FDC therapy improved adherence by 44% (26% to 65%) compared with usual care. |
| Webster et al. [18], 2016 Meta-analysis |
CVD | To compare FDCT with usual care in patients with CVD or at high risk | 3 RCTs | Participants in the FDC group had higher adherence than patients with usual care (80% vs. 50%, RR: 1.58; 95% CIs: 1.32–1.90; p < 0.001). |
| Diabetes (n = 2) | ||||
| Han et al. [28], 2012 Systematic review and meta-analysis |
DMII | To compare effects of FDCs and dual therapy of antihyperglycemic agents on glycemic control and adherence |
8 cohort studies (assessing adherence) | Five comparisons FDC versus dual therapy cohorts showed significantly higher MPR with FDC (MD = 8.6% (95% CIs: 1.6–15.6); p = 0.0162). Three comparisons showed results for patients who switched from dual therapy to FDC or stayed on dual therapy, with higher MPR for patients who switched to FDC (MD = 5.0% (95% CIs: 3.1–6.8); p < 0.0001). |
| Hutchins et al. [22], 2011 Systematic review |
DMII | To evaluate adherence, patient-reported outcomes, costs, resource use and cost effectiveness between FDCT and LDCT | 8 cohort studies (assessing adherence) | Adherence was improved with using FDCT instead of LDCT. |
| HIV (n = 4) | ||||
| Altice et al. [27], 2019 Systematic review and meta-analysis |
HIV | To study the relationship between single or multiple tablet regimens and treatment adherence and viral suppression | Whole systematic review: 11 prospective or retrospective non-randomized studies (assessing adherence); 10 full texts and one conference abstract Meta-analysis: 8; 7 full texts and one conference abstract |
Polypills were associated with higher treatment adherence than multipill therapy in 10 studies: a 63% greater likelihood of achieving ≥95% adherence (95% CIs: 1.52–1.74; p < 0.001) and a 43% increase in the likelihood of achieving ≥90% adherence (95% CIs: 1.21–1.69; p < 0.001). |
| Clay et al. [24], 2018 Systematic review, meta-analysis |
HIV | To compare single-pill to multi-tablet regimens in HIV treatment by using published data | Reporting on adherence: 30, but only 8 observational studies reported quantifiable data and were included in the meta-analysis. | Patients utilizing single-pill regimens were significantly more adherent (OR: 1.96, p < 0.001). |
| Clay et al. [20], 2015 Meta-analysis |
HIV | To compare patient adherence and clinical and economic outcomes of FDCT and multipill therapy regimens | Reporting on adherence: 20; but only 5 having quantifiable or analyzable data for meta-analysis: 4 observational studies, 1 economic models-based study. | Patients on FDCT were more adherent than patients on multipill therapy regimen of any frequency (OR: 2.37, 95% CIs: 1.68–3.35; p < 0.001; 4 studies). |
| Ramjan et al. [19], 2014 Meta-analysis |
HIV | To compare the advantages of FDC antiretroviral therapy to separate pill therapy regimens for patients and programs | Reporting on adherence: 10, but only 7 included in the quantitative analysis: 5 RCTs and 2 retrospective cohort studies. | RCTs showed better adherence in FDCT group than in separate pill regimens (RR: 1.10, 95% CIs: 0.98–1.22); observational studies showed the same trend (RR: 1.17, 95% CIs: 1.07–1.28). |
| Tuberculosis (n = 1) | ||||
| Albanna et al. [23], 2013 Systematic review and meta-analysis |
Tuberculosis | To assess different aspects of management of tuberculosis using FDC or free combination treatment | 5 RCTs (assessing adherence) | None of the studies favored FDCT. |
FDCT, fixed-dose combination therapy; FDC, fixed-dose combination; RCT, randomized controlled trial; MPR, medication possession ratio; MD, mean difference; CVD, cardiovascular disease; ASCVD, atherosclerotic CVD; HIV, human immunodeficiency virus; DMII, diabetes mellitus type II; CI, confidence interval; OR, odds ratio; RR, relative risk.