Impact of reducing dosing frequency on adherence to oral therapies: a literature review and meta-analysis

Kunal Srivastava,¹ Anamika Arora,¹ Aditi Kataria,¹ Joseph C Cappelleri,² Alesia Sadosky,³ Andrew M Peterson<sup>4

1</sup>HERON Health PVT, Chandigarh, India; ²Pfizer Inc, Statistics, Groton, CT, USA; ³Pfizer Global Health Economics and Outcomes Research, New York, NY, USA; ⁴Mayes College of Healthcare Business and Policy, University of the Sciences, Philadelphia, PA, USA

Objectives: To assess the impact of reduced frequency of oral therapies from multiple-dosing schedules to a once-daily (OD) dosing schedule on adherence, compliance, persistence, and associated economic impact.
Methods: A meta-analysis was performed based on relevant articles identified from a comprehensive literature review using MEDLINE^® and Embase^®. The review included studies assessing adherence with OD, twice-daily (BID), thrice-daily (TID), and four-times daily (QID) dosing schedules and costs associated with optimal/suboptimal adherence among patients with acute and chronic diseases. Effect estimates across studies were pooled and analyzed using the DerSimonian and Laird random-effect model.
Results: Forty-three studies met inclusion criteria, and meta-analyzable data were available from 13 studies. The overall results indicated that OD schedules were associated with higher adherence rates (odds ratio [OR] 3.07, 95% confidence interval [CI] 1.80–5.23; P < 0.001 for OD versus > OD dosing) and compliance rates (OR 3.50, 95% CI 1.73–7.08; P < 0.001 for OD versus > OD dosing); persistence rates showed the same direction but were not statistically significant (OR 1.43, 95% CI 0.62–3.29; P = 0.405 for OD versus BID dosing). Results for each of the conditions were consistent with those observed overall with respect to showing the benefits of less frequent dosing. From a health economic perspective, higher adherence rates with OD relative to multiple dosing in a number of conditions were consistently associated with corresponding lower costs of health care resources utilization.
Conclusion: Current meta-analyses suggested that across acute and chronic disease states, reducing dosage frequency from multiple dosing to OD dosing may improve adherence to therapies among patients. Improving adherence may result in subsequent decreases in health care costs.

Keywords: compliance, dosage frequency, persistence, random-effect meta-analyses