Systematic review with meta-analysis: high prevalence and cost of continued aminosalicylate use in patients with ulcerative colitis escalated to immunosuppressive and biological therapies.

BACKGROUND: Aminosalicylates are the most frequently prescribed treatment for ulcerative colitis (UC). In the absence of empirical evidence, clinicians are uncertain whether to continue aminosalicylates in patients with UC after escalating therapy. AIMS: To quantify concomitant aminosalicylate use in UC randomised clinical trials (RCTs), identify factors associated with their use, and estimate treatment costs of concomitant aminosalicylate therapy. METHODS: MEDLINE, Embase, and CENTRAL were searched from inception to 1 March 2017 for placebo-controlled RCTs of immunosuppressants, biologics, or oral small molecules in adults with UC. The proportion of patients prescribed concomitant aminosalicylates at trial entry was pooled using a random-effects model. Meta-regression was performed to assess trial-level factors associated with aminosalicylate use. Treatment costs were estimated using 2018 formulary data from five Canadian provinces. RESULTS: Thirty-two trials were included (23 induction only, nine induction, and maintenance trials). The pooled proportion of patients co-prescribed aminosalicylates was 80.7% (95% CI 75.5%-85.1%), with considerable observed heterogeneity (I2  = 95%). In univariable meta-regression, aminosalicylate use was not associated with trial design, setting, year of publication, disease severity, disease duration, or drug class. The estimated direct annual treatment cost of concomitant aminosalicylates is ~$20 million for the Canadian UC population, assuming conservative estimates of UC prevalence, aminosalicylate use and dose, and the lowest cost formulation. CONCLUSIONS: Approximately 80% of UC patients entering clinical trials of immunosuppressants, biologics, or oral small molecules continue to use aminosalicylates. An RCT is needed to inform the benefits and harms of continuing vs stopping aminosalicylates in patients escalating therapy.

Anticoagulation Therapy for Atrial Fibrillation in Patients With Alzheimer's Disease.

Background and Purpose- Direct oral anticoagulants (DOACs) are safer, at least equally efficacious, and cost-effective compared to warfarin for stroke prevention in atrial fibrillation (AF) but they remain underused, particularly in demented patients. We estimated the cost-effectiveness of DOACs compared with warfarin in patients with AF and Alzheimer's disease (AD). Methods- We constructed a microsimulation model to estimate the lifetime costs, quality-adjusted life-years (QALYs), and cost-effectiveness of anticoagulation therapy (adjusted-dose warfarin and various DOACs) in 70-year-old patients with AF and AD from a US societal perspective. We stratified patient cohorts based on stage of AD and care setting. Model parameters were estimated from secondary sources. Health benefits were measured in the number of acute health events, life-years, and QALYs gained. We classified alternatives as cost-effective using a willingness-to-pay threshold of $100 000 per QALY gained. Results- For patients with AF and AD, compared with warfarin, DOACs increase costs but also increase QALYs by reducing the risk of stroke. For mild-AD patients living in the community, edoxaban increased lifetime costs by $6603 and increased QALYs by 0.076 compared to warfarin, yielding an incremental cost-effectiveness ratio of $86 882/QALY gained. Even though DOACs increased QALYs compared with warfarin for all patient groups (ranging from 0.019 to 0.085 additional QALYs), no DOAC treatment alternative had an incremental cost-effectiveness ratio <$150 000/QALY gained for patients with moderate to severe AD. For patients living in a long-term care facility with mild AD, the DOAC with the lowest incremental cost-effectiveness ratio (rivaroxaban) costs $150 169 per QALY gained; for patients with more severe AD, the incremental cost-effectiveness ratios were higher. Conclusions- For patients with AF and mild AD living in the community, edoxaban is cost-effective compared with warfarin. Even though patients with moderate and severe AD living in the community and patients with any stage of AD living in a long-term care setting may obtain positive clinical benefits from anticoagulation treatment, DOACs are not cost-effective compared with warfarin for these populations. Compared to aspirin, no oral anticoagulation (warfarin or any DOAC) is cost effective in patients with AF and AD.

Transcatheter aortic valve replacement in nonsurgical candidates with severe, symptomatic aortic stenosis: a cost-effectiveness analysis.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) seems to improve the survival and quality of life of patients with aortic stenosis ineligible for surgical aortic valve replacement. METHODS AND RESULTS: We used a decision analytic Markov model to estimate lifetime costs and benefits in a hypothetical cohort of patients with severe, symptomatic aortic stenosis who were ineligible for surgical aortic valve replacement. The model compared transfemoral TAVR with medical management and was calibrated to the Placement of Aortic Transcatheter Valves (PARTNER) trial. TAVR increased life expectancy from 2.08 to 2.93 years and quality-adjusted life expectancy from 1.19 to 1.93 years. TAVR also reduced subsequent hospitalizations by 1.40 but increased complications, particularly stroke (from 1% to 11% lifetime risk), and also increased lifetime costs from $83,600 to $169,100. The incremental cost-effectiveness of TAVR was $116,500 per quality-adjusted life-year gained ($99,900 per life-year gained). Results were robust to reasonable changes in individual variables but were sensitive to the level of annual healthcare costs caused by noncardiac diseases and to the projected life expectancy of medically treated patients. CONCLUSIONS: TAVR seems to be an effective but somewhat expensive alternative to medical management among patients with symptomatic aortic stenosis ineligible for surgery. TAVR is more cost-effective for patients with a lower burden of noncardiac disease.

Microsimulation model predicts survival benefit of radiofrequency ablation and stereotactic body radiotherapy versus radiotherapy for treating inoperable stage I non-small cell lung cancer.

OBJECTIVE: A subset of patients with stage IA and IB non-small cell lung cancer (NSCLC) is ineligible for surgical resection and undergoes radiation therapy. Radiofrequency ablation (RFA) and stereotactic body radiotherapy are newer potentially attractive alternative therapies. MATERIALS AND METHODS: We added RFA and stereotactic body radiotherapy treatment modules to a microsimulation model that simulates lung cancer's natural history, detection, and treatment. Natural history parameters were previously estimated via calibration against tumor registry data and cohort studies; the model was validated with screening study and cohort data. RFA model parameters were calibrated against 2-year survival from the Radiofrequency Ablation of Pulmonary Tumor Response Evaluation (RAPTURE) study, and stereotactic body radiotherapy model parameters were calibrated against 3-year survival from a phase 2 prospective trial. We simulated lifetime histories of identical patients with early-stage NSCLC who were ineligible for resection, who were treated with radiation therapy, RFA, or stereotactic body radiotherapy under a range of scenarios. From 5,000,000 simulated individuals, we selected a cohort of patients with stage I medically inoperable cancer for analysis (n = 2056 per treatment scenario). Main outcomes were life expectancy gains. RESULTS: RFA or stereotactic body radiotherapy treatment in patients with peripheral stage IA or IB NSCLC who were nonoperative candidates resulted in life expectancy gains of 1.71 and 1.46 life-years, respectively, compared with universal radiation therapy. A strategy where patients with central tumors underwent stereotactic body radiotherapy and those with peripheral tumors underwent RFA resulted in a gain of 2.02 life-years compared with universal radiation therapy. Findings were robust with respect to changes in model parameters. CONCLUSION: Microsimulation modeling results suggest that RFA and stereotactic body radiotherapy could provide life expectancy gains to patients with stage IA or IB NSCLC who are ineligible for resection.

An integrated health-economic analysis of diagnostic and therapeutic strategies in the treatment of moderate-to-severe obstructive sleep apnea.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a common disorder associated with substantially increased cardiovascular risks, reduced quality of life, and increased risk of motor vehicle collisions due to daytime sleepiness. This study evaluates the cost-effectiveness of three commonly used diagnostic strategies (full-night polysomnography, split-night polysomnography, unattended portable home-monitoring) in conjunction with continuous positive airway pressure (CPAP) therapy in patients with moderate-to-severe OSA. DESIGN: A Markov model was created to compare costs and effectiveness of different diagnostic and therapeutic strategies over a 10-year interval and the expected lifetime of the patient. The primary measure of cost-effectiveness was incremental cost per quality-adjusted life year (QALY) gained. PATIENTS OR PARTICIPANTS: Baseline computations were performed for a hypothetical average cohort of 50-year-old males with a 50% pretest probability of having moderate-to-severe OSA (apnea-hypopnea index [AHI] ≥ 15 events per hour). MEASUREMENTS AND RESULTS: For a patient with moderate-to-severe OSA, CPAP therapy has an incremental cost-effectiveness ratio (ICER) of $15,915 per QALY gained for the lifetime horizon. Over the lifetime horizon in a population with 50% prevalence of OSA, full-night polysomnography in conjunction with CPAP therapy is the most economically efficient strategy at any willingness-to-pay greater than $17,131 per-QALY gained because it dominates all other strategies in comparative analysis. CONCLUSIONS: Full-night polysomnography (PSG) is cost-effective and is the preferred diagnostic strategy for adults suspected to have moderate-to-severe OSA when all diagnostic options are available. Split-night PSG and unattended home monitoring can be considered cost-effective alternatives when full-night PSG is not available.

An evaluation of strategies to reduce waiting times for total joint replacement in Ontario.

BACKGROUND: In 2005, the median waiting time for total hip and knee joint replacements in Ontario was greater than 6 months, which is considered longer than clinically appropriate. Demand is expected to increase and exacerbate already long waiting times. Solutions are needed to reduce waiting times and improve waiting list management. METHODS: We developed a discrete event simulation model of the Ontario total joint replacement system to evaluate the effects of 4 management strategies on waiting times: (1) reductions in surgical demand; (2) formal clinical prioritization; (3) waiting time guarantees; and (4) common waiting list management. RESULTS: If the number of surgeries performed increases by less than 10% each year, then demand must be reduced by at least 15% to ensure that, within 10 years, 90% of patients receive surgery within their maximum recommended waiting time. Clinically prioritizing patients reduced waiting times for high-priority patients and increased the number of patients at all priority levels who received surgery each year within recommended maximum waiting times by 9.3%. A waiting time guarantee for all patients provided fewer surgeries within recommended waiting times. Common waiting list management improved efficiency and increased equity in waiting across regions. DISCUSSION: Dramatically increasing the supply of joint replacement surgeries or diverting demand for surgeries to other jurisdictions will reduce waiting times for total joint replacement surgery. Introducing a strictly adhered to patient prioritization scheme will ensure that more patients receive surgery within severity-specific waiting time targets. Implementing a waiting time guarantee for all patients will not reduce waiting times--it will only shuffle waiting times from some patients to others. To reduce waiting times to clinically acceptable levels within 10 years, increases in the number of surgeries provided greater than those observed historically or reductions in demand are needed.