Modelling the consequences of a reduction in alcohol consumption among patients with alcohol dependence based on real-life observational data.

BACKGROUND: Most available pharmacotherapies for alcohol-dependent patients target abstinence; however, reduced alcohol consumption may be a more realistic goal. Using randomized clinical trial (RCT) data, a previous microsimulation model evaluated the clinical relevance of reduced consumption in terms of avoided alcohol-attributable events. Using real-life observational data, the current analysis aimed to adapt the model and confirm previous findings about the clinical relevance of reduced alcohol consumption. METHODS: Based on the prospective observational CONTROL study, evaluating daily alcohol consumption among alcohol-dependent patients, the model predicted the probability of drinking any alcohol during a given day. Predicted daily alcohol consumption was simulated in a hypothetical sample of 200,000 patients observed over a year. Individual total alcohol consumption (TAC) and number of heavy drinking days (HDD) were derived. Using published risk equations, probabilities of alcohol-attributable adverse health events (e.g., hospitalizations or death) corresponding to simulated consumptions were computed, and aggregated for categories of patients defined by HDDs and TAC (expressed per 100,000 patient-years). Sensitivity analyses tested model robustness. RESULTS: Shifting from >220 HDDs per year to 120-140 HDDs and shifting from 36,000-39,000 g TAC per year (120-130 g/day) to 15,000-18,000 g TAC per year (50-60 g/day) impacted substantially on the incidence of events (14,588 and 6148 events avoided per 100,000 patient-years, respectively). Results were robust to sensitivity analyses. CONCLUSIONS: This study corroborates the previous microsimulation modeling approach and, using real-life data, confirms RCT-based findings that reduced alcohol consumption is a relevant objective for consideration in alcohol dependence management to improve public health.

Cost-Effectiveness of Mirabegron Compared with Antimuscarinic Agents for the Treatment of Adults with Overactive Bladder in the United Kingdom.

BACKGROUND: Mirabegron, a first-in-class selective oral ß3-adrenoceptor agonist, has similar efficacy to most antimuscarinic agents and a lower incidence of dry mouth in patients with overactive bladder (OAB). OBJECTIVES: To evaluate the cost-effectiveness of mirabegron 50 mg compared with oral antimuscarinic agents in adults with OAB from a UK National Health Service perspective. METHODS: A Markov model including health states for symptom severity, treatment status, and adverse events was developed. Cycle length was 1 month, and the time horizon was 5 years. Antimuscarinic comparators were tolterodine extended release, solifenacin, fesoterodine, oxybutynin extended release and immediate release (IR), darifenacin, and trospium chloride modified release. Transition probabilities for symptom severity levels and adverse events were estimated from a mirabegron trial and a mixed treatment comparison. Estimates for other inputs were obtained from published literature or expert opinion. Quality-adjusted life-years (QALYs) and total health care costs, including costs of drug acquisition, physician visits, incontinence pad use, and botox injections, were modeled. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: Base-case incremental cost-effectiveness ratios ranged from £367 (vs. solifenacin 10 mg) to £15,593 (vs. oxybutynin IR 10 mg) per QALY gained. Probabilistic sensitivity analyses showed that at a willingness-to-pay threshold of £20,000/QALY gained, the probability of mirabegron 50 mg being cost-effective ranged from 70.2% versus oxybutynin IR 10 mg to 97.8% versus darifenacin 15 mg. A limitation of our analysis is the uncertainty due to the lack of direct comparisons of mirabegron with other agents; a mixed treatment comparison using rigorous methodology provided the data for the analysis, but the studies involved showed heterogeneity. CONCLUSIONS: Mirabegron 50 mg appears to be cost-effective compared with standard oral antimuscarinic agents for the treatment of adults with OAB from a UK National Health Service perspective.

Expected cost effectiveness of high-dose trivalent influenza vaccine in US seniors.

OBJECTIVES: Seniors are particularly vulnerable to complications resulting from influenza infection. Numerous influenza vaccines are available to immunize US seniors, and practitioners must decide which product to use. Options include trivalent and quadrivalent standard-dose inactivated influenza vaccines (IIV3 and IIV4 respectively), as well as a high-dose IIV3 (HD). Our research examines the public health impact, budget impact, and cost-utility of HD versus IIV3 and IIV4 for immunization of US seniors 65 years of age and older. METHODS: Our model was based on US influenza-related health outcome data. Health care costs and vaccine prices were obtained from the Centers for Medicare and Medicaid Services. Efficacies of IIV3 and IIV4 were estimated from various meta-analyses of IIV3 efficacy. The results of a head-to-head randomized controlled trial of HD vs. IIV3 were used to estimate relative efficacy of HD. Conservatively, herd protection was not considered. RESULTS: Compared to IIV3, HD would avert 195,958 cases of influenza, 22,567 influenza-related hospitalizations, and 5423 influenza-related deaths among US seniors. HD generates 29,023 more Quality Adjusted Life Years (QALYs) and a net societal budget impact of $154 million. The Incremental Cost Effectiveness Ratio (ICER) for this comparison is $5299/QALY. 71% of the probabilistic sensitivity analysis (PSA) simulations were <$100,000/QALY. Compared to IIV4, HD would avert 169,257 cases of influenza, 21,222 hospitalizations and 5212 deaths. HD generates 27,718 more QALYs and a net societal budget impact of -$17 million and as such dominates IIV4. For this comparison, 81% of PSA simulations were <$100,000/QALY. CONCLUSIONS: HD is expected to achieve significant reductions in influenza-related morbidity and mortality. Further, HD is a cost effective alternative to both IIV3 and IIV4 in seniors. Our conclusions were robust in the face of sensitivity analyses.