ObjectivesTo 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.MethodsA 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.ResultsForty-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.ConclusionCurrent 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.

Symptomatic COPD is associated with a substantial economic burden. The HRQoL of patients with symptomatic COPD is, in general, low and influenced by dyspnoea.

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VMP and MPT seem more effective than MP, VMP was superior to MPT regarding response criteria and AEs. Our results may best be confirmed by a head-to-head trial of VMP vs. MPT.

Objectives: A systematic literature review was undertaken with quantitative analysis, including meta-analysis and Bucher-adjusted indirect treatment comparisons (ITCs), to evaluate efficacy, safety, and tolerability of dabrafenib and trametinib monotherapy versus other first-line metastatic melanoma (MM) treatments. Methods: Embase ® , MEDLINE ® , CCTR, and key conferences were searched through October 2012 for relevant randomized controlled trials. Using a random-effects network meta-analysis, dabrafenib and trametinib were compared directly versus dacarbazine (DTIC) and indirectly versus ipilimumab plus DTIC, temozolomide, and vemurafenib. A Rank Preserving Structural Failure Time Method was used to adjust overall survival (OS) estimates in studies that allowed treatment crossover upon progression. Results: Forty-eight studies (147 publications) met the inclusion criteria; five (2462 patients) contributed to the metaanalysis. Both dabrafenib and trametinib showed a significant reduction in risk of progression directly versus DTIC and indirectly versus ipilimumab plus DTIC and temozolomide; comparable progression-free survival (PFS) indirectly versus vemurafenib; and lower risk of death directly versus DTIC and indirectly versus ipilimumab plus DTIC and vemurafenib (not significant). Dabrafenib demonstrated a significantly reduced risk of treatment discontinuations (due to any cause and to adverse events [AEs]), significantly fewer grade 3/4 AEs versus ipilimumab plus DTIC, and a significantly lower risk of grade 3/4 hematologic AEs (leukopenia, neutropenia, and thrombocytopenia) versus temozolomide. Dabrafenib showed significantly fewer dose interruptions/modifications (risk ratio [RR]=0.18; 95% CI=0.12-0.28; p<0.001) and a significantly lower incidence of photosensitivity (RR=0.05; 95% CI=0.01-0.19; p<0.001) versus vemurafenib. Conclusions: ITCs of dabrafenib or trametinib in treatment-naïve MM patients showed significantly better PFS directly versus DTIC and indirectly versus ipilimumab plus DTIC and temozolomide, with efficacy comparable with that of vemurafenib. Dabrafenib showed important differences in tolerability and safety versus vemurafenib. Results require cautious interpretation given methodological assumptions and immature OS data for dabrafenib and trametinib. Headto-head studies remain the gold standard for comparing treatments.