A multifaceted intervention improves antibiotic stewardship for skin and soft tissues infections.

OBJECTIVE: Assess the effectiveness of a multifaceted stewardship intervention to reduce frequency and duration of inappropriate antibiotic use for emergency department (ED) patients with skin and soft tissue infections (SSTI). We hypothesized the antibiotic stewardship program would reduce antibiotic duration and improve guideline adherence in discharged SSTI patients. DESIGN: Nonrandomized controlled trial. SETTING: Academic EDs (intervention site and control site). PATIENTS OR PARTICIPANTS: Attending physicians and nurse practitioners at participating EDs. INTERVENTION(S): Education regarding guideline-based treatment of SSTI, tests of antimicrobial treatment of SSTI, implementation of a clinical treatment algorithm and order set in the electronic health record, and ED clinicians' audit and feedback. RESULTS: We examined 583 SSTIs. At the intervention site, clinician adherence to guidelines improved from 41% to 51% (aOR = 2.13 [95% CI: 1.20-3.79]). At the control site, there were no changes in adherence during the "intervention" period (aOR = 1.17 [0.65-2.12]). The between-site comparison of these during vs. pre-intervention odds ratios was not different (aOR = 1.82 [0.79-4.21]). Antibiotic duration decreased by 26% at the intervention site during the intervention compared to pre-intervention (Adjusted Geometric Mean Ratio [95% CI] = 0.74 [0.66-0.84]). Adherence was inversely associated with SSTI severity (severe vs mild; adjusted OR 0.42 [0.20-0.89]) and purulence (0.32 [0.21-0.47]). Mean antibiotic prescription duration was 1.95 days shorter (95% CI: 1.54-2.33) in the time period following the intervention than pre-intervention period. CONCLUSIONS: A multifaceted intervention resulted in modest improvement in adherence to guidelines compared to a control site, driven by treatment duration reductions.

How Much Value Would a Treatment for Alzheimer's Disease Offer? Cost-Effectiveness Thresholds for Pricing a Disease-Modifying Therapy.

BACKGROUND: Recent trials suggest that disease-modifying therapy (DMT) for Alzheimer's disease may become available soon. With the expected high price and a large patient pool, the budget impact will be substantial. OBJECTIVE: We explore combinations of effectiveness and price under which a DMT is cost-effective. METHODS: We used an open-source model to conduct two-way scenario analyses for both payer and societal perspectives, varying price, and treatment effect size simultaneously. The analysis generates costeffectiveness threshold prices over a potential range of DMT effectiveness in patients aged 65+ with mild cognitive impairment due to Alzheimer's disease in the US. RESULTS: Under the willingness-to-pay a threshold of $150,000 per quality-adjusted life year and assuming 30% risk reduction relative to the standard of care, the maximum cost-effective price of a DMT per patient per year is ~$22,000 and ~$15,000 from societal and payer perspectives, respectively. CONCLUSION: Joint variation of price and treatment effect size can help assess the cost-effectiveness of a potential Alzheimer's disease treatment.

Alternative payment models and innovation: a case study of US health system adoption of a sacubitril/valsartan to treat acute decompensated heart failure.

AIM: To understand the financial impact of health system adoption of novel heart failure medications under US alternative payment models (APMs). MATERIALS AND METHODS: This study used a decision tree model to assess the financial impact of health system adoption of sacubitril/valsartan to treat acute decompensated heart failure (ADHF). A comparator scenario modeled current health care utilization and cost for treating hospitalized ADHF patients with angiotensin-converting-enzyme inhibitors (ACEi) or angiotensin-receptor blockers (ARB). The study then measured the impact of adopting sacubitril/valsartan to treat ADHF on health system economic outcomes. Differences in treatment efficacy were based on the PIONEER-HF clinical trial. The financial impact of changes in patient outcomes under the sacubitril/valsartan and ACEi/ARB arms was assessed across three APMs: the Medicare Shared Savings Program, Bundled Payments for Care Improvement, and fee-for-service payments adjusted according to the Hospital Readmission Reduction Program. RESULTS: Sacubitril/valsartan reduced re-hospitalizations after an initial ADHF admission by 46.3% for individuals aged 18-64 years and 23.4% for individuals aged ≥65 years. Health systems' financial benefit of adopting sacubitril/valsartan was $740 per ADHF case per year (PCPY). Savings were larger for patients aged ≥65 years ($803 PCPY) compared to those <65 years ($653 PCPY). The majority of the health system financial benefit came from changes in APM bonus and penalty reimbursements. Value-based payments from the Hospital Readmission Reduction Program ($1,190 financial gain PCPY) and the Bundled Care Payment Improvement Initiative ($645 financial gain PCPY) produced larger financial benefits than participation in the Medicare Shared Savings Program ($253 financial gain PCPY). LIMITATIONS: The model uses clinical trial data, which may not reflect real-world outcomes. Further, the financial implications were modeled based only on three widely used APMs. CONCLUSION: Sacubitril/valsartan adoption decreased hospitalizations and led to a positive net financial impact on health systems after accounting for APM bonus payments.

Cost-Effectiveness Comparison of Ustekinumab, Infliximab, or Adalimumab for the Treatment of Moderate-Severe Crohn's Disease in Biologic-Naïve Patients.

STUDY OBJECTIVE: Ustekinumab was recently approved by the United States U.S. Food and Drug Administration for the treatment of Crohn's disease. In this analysis, we aimed to compare the cost-effectiveness of ustekinumab, infliximab, or adalimumab for the treatment of moderate-severe Crohn's disease in patients who failed conventional therapy (i.e., corticosteroids and immunomodulators) but were naïve to tumor necrosis factor antagonists (i.e., biologic drugs). DESIGN: Cost-effectiveness analysis using a hybrid model structure (decision tree and Markov model). MEASUREMENTS AND MAIN RESULTS: A decision tree simulated biologic induction, and a Markov model simulated biologic and conventional therapy maintenance. Cycle length was 2 weeks with a discounted 5-year time horizon and a limited U.S. societal perspective in the base case; results from a payer perspective are also reported. Transition probabilities, direct costs, indirect costs, and utilities were obtained from the literature. To measure relative treatment value (i.e., order of treatment cost-effectiveness), net monetary benefits were reported for a $150,000 willingness-to-pay threshold per quality-adjusted life-year in the base case. Infliximab dominated both adalimumab and ustekinumab, with a net monetary benefit (NMB) of $9943 and $29,798, respectively, in the base case. Adalimumab dominated ustekinumab, with an NMB of $19,855. All biologics yielded similar quality-adjusted life-years (~3.5), whereas costs varied substantially ($50,510, $54,985, and $72,921 for infliximab, adalimumab, and ustekinumab, respectively). The payer perspective, alternate time horizons, and scenario analyses consistently showed infliximab dominance. One-way, threshold, and probabilistic sensitivity analyses confirmed the robustness of these results with respect to all parameters. Although biosimilars were not explicitly modeled as comparators, one-way sensitivity analysis showed that drug acquisition costs could alter relative treatment value but would have to be varied by at least 50%. CONCLUSION: For moderate-severe Crohn's disease, infliximab yields significantly more NMBs compared with both adalimumab and ustekinumab. Additional clinical (e.g., empiric dosing, biologic cycling) and quality-of-life (e.g., lost productivity, disutility of home injections) research is needed to allow for model frameworks and parameters that more accurately reflect the nuances of Crohn's disease treatment.