CRD summary

This review found that fixed-dose combination medications increase medication compliance, compared with free-drug regimens, in patients with chronic conditions. Although the data appear to support these conclusions, they should be interpreted with some degree of caution because of limitations in the search and a failure to assess study quality.

Authors' objectives

To determine the efficacy of fixed-dose combination medications in improving patient compliance with drug regimens.

Searching

MEDLINE was searched from 1966 to November 2005; the search terms were reported. The reference lists of retrieved articles were also examined. The search was limited to studies published in English in peer-reviewed journals.

Study selection

Assessment of study quality

The authors did not state that they assessed validity.

Data extraction

The authors did not state how the data were extracted for the review, or how many reviewers performed the data extraction. The review reported numbers experiencing each outcome in the control and intervention arms of each study, with associated risk ratios (RRs) and 95% confidence intervals (CIs).

Methods of synthesis

Results of the review

Seven studies (n=20,242) reporting 9 comparisons were included: 3 RCTs (n=1,029) and 4 retrospective database analyses (n=19,213), two of which included two subgroup comparisons.

Compliance was significantly higher in patients receiving the fixed-dose combination than in those receiving the free-drug combination (RR for non-compliance 0.74, 95% CI: 0.69, 0.80, p<0.0001; 9 comparisons); the results were similar in studies of patients with hypertension (RR 0.76, 95% CI: 0.71, 0.81 p<0.0001; 4 comparisons, n=17,175). There was moderate evidence of heterogeneity (p=0.07). When the analysis was restricted to the 3 RCTs, the difference between the groups was no longer statistically significant (RR 0.83, 95% CI: 0.64, 1.07). When the meta-analysis was restricted to observational studies, the results were similar to those found when all studies were included, but there was significant heterogeneity (p=0.016). There was no evidence of publication bias for any of the analyses.

In term of efficacy, one RCT of patients with TB reported that sputum conversion at 8 weeks was significantly higher in the fixed-drug combination group (86.6% versus 77.7%, p<0.05). A second RCT reported no significant difference in sputum conversion or radiological improvements. The third RCT assessed treatment failure in patients with HIV and found no significant difference between the groups.

Authors' conclusions

Fixed-dose combinations decrease the risk of medication non-compliance and should be considered as a means of increasing medication compliance in patients with chronic conditions.

CRD commentary

The review question was focused, with inclusion criteria defined for the interventions and outcomes but not for the study design or participants. The search was limited and restricted to fully published studies in English, which might have resulted in some studies being missed. It is not clear whether appropriate procedures were undertaken when selecting studies for inclusion or extracting the data, thus the potential for reviewer bias and error cannot be determined. A formal quality assessment was not conducted, so the reliability of the authors’ conclusions is unclear. Relevant details of the included studies were reported. The studies were combined in a meta-analysis, which appears appropriate, and heterogeneity was evaluated using suitable methods. The authors’ conclusions appear well supported by the data presented, but limitations in the search and a failure to assess study quality mean that they should be interpreted with some degree of caution.

Implications of the review for practice and research

Practice: The authors stated that fixed-dose medication combinations should be considered in patients with chronic diseases in order to increase medication compliance, as this may translate into better clinical outcomes.

Research: The authors stated the need for further studies on the topic of compliance.

Funding

Not stated.

Bibliographic details

Bangalore S, Kamalakkannan G, Parkar S, Messerli F H. Fixed-dose combinations improve medication compliance: a meta-analysis. American Journal of Medicine 2007; 120(8): 713-719. [PubMed: 17679131]

Other publications of related interest

This additional published commentary may also be of interest.

Bergmann JF. Review: fixed dose drug combinations improve medication compliance compared with free-drug regimens. Evid Based Med 2008;13:18.

Indexing Status

Subject indexing assigned by NLM

MeSH

Adult; Aged; Anti-HIV Agents /administration & dosage; Antihypertensive Agents /administration & dosage; Antitubercular Agents /administration & dosage; Chronic Disease /drug therapy; Comorbidity; Diabetes Mellitus /drug therapy /epidemiology; Disease Management; Drug Combinations; HIV Infections /drug therapy; Humans; Hypertension /drug therapy /epidemiology; Hypoglycemic Agents /administration & dosage; Middle Aged; Patient Compliance; Polypharmacy; Tuberculosis /drug therapy

AccessionNumber

12007005994

Database entry date

01/12/2008

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.