AIMS: This study evaluates the cost-effectiveness of surgical revascularization versus conservative management for adult moyamoya disease (MMD) patients with posterior hemorrhage from the perspective of the Japanese public healthcare payer. MATERIALS AND METHODS: We developed a combined decision tree and Markov model for adult posterior hemorrhagic MMD patients (mean age: 41 years; baseline modified Rankin Scale [mRS] 0-2) over a 60-year lifetime horizon with 1-year cycles. We estimated the treatment effect using the composite endpoint hazard ratio (0.07) from the JAM Trial posterior hemorrhage subgroup as a proxy for the effect on recurrent hemorrhage. We informed health utilities with recent EQ-5D-5L data from the Fukuoka Stroke Registry, weighted by the Japan Stroke Data Bank. We estimated direct medical costs based on the national fee schedule. We discounted costs and outcomes at 2% annually. We set the willingness-to-pay threshold at JPY 7,500,000 per quality-adjusted life year (QALY). RESULTS: In the base case, surgical revascularization yielded 21.49 QALYs for JPY 6,323,426 (USD 40,302), compared with 15.59 QALYs and JPY 5,308,637 (USD 33,835) for conservative management. The incremental cost-effectiveness ratio was JPY 172,220 (USD 1,098) per QALY, which falls below the reference value of JPY 7,500,000 per QALY. In scenario analyses with 5- and 10-year horizons, the ICERs were JPY 8,926,784 and JPY 2,031,693 per QALY, respectively. Probabilistic sensitivity analysis also favored surgical revascularization across the modeled parameter distributions. LIMITATIONS: The base-case estimate of surgical efficacy was based on a composite outcome from a small subgroup, and long-term recurrence risks beyond the 5-year trial period remain uncertain. CONCLUSION: Surgical revascularization is likely to be cost-effective for adult MMD patients with posterior hemorrhage within the Japanese healthcare system, although limited evidence leaves uncertainty about long-term rebleeding risks and the durability of surgical benefit.
AIMS: Nusinersen 12 mg was the first regulator-approved disease-modifying therapy (DMT) for spinal muscular atrophy (SMA); intrathecal onasemnogene abeparvovec-brve (OAV101 IT) and nusinersen 50/28 mg have gained recent approval. In absence of head-to-head evidence, this research assessed the comparative efficacy of these treatments in DMT-naïve and DMT-experienced SMA patients using indirect treatment comparisons (ITCs). MATERIALS AND METHODS: An ITC feasibility assessment was conducted. Individual patient data (IPD) from CHERISH (NCT02292537) and DEVOTE Part B (NCT04089566) clinical trials assessing nusinersen in DMT-naïve, later-onset participants were trimmed to align with STEER (NCT05089656). DMT-experienced IPD from DEVOTE Part C (NCT04089566) were trimmed to align with STRENGTH (NCT05386680). Matching adjusted indirect comparisons (MAIC) were conducted to assess motor function improvement using the Hammersmith Functional Motor Scale-Expanded (HFMSE) and Revised Upper Limb Module (RULM). RESULTS: The anchored MAIC in DMT-naïve participants numerically favored nusinersen 12 mg compared with OAV101 IT in change from baseline (CFB) in HFMSE (mean difference [MD]: 1.86; 95% confidence intervals [CIs]: -1.08, 4.80; starting sample [N]/effective sample size [ESS]: 97/58), and RULM (MD: 1.52; CIs: -0.57, 3.61; N/ESS: 97/58) in participants aged 2 to <5 years. The unanchored MAIC in DMT-experienced participants numerically favored nusinersen 50/28 mg compared with OAV101 IT in CFB in HFMSE (MD: 1.02; CIs: -1.31, 3.34; N/ESS: 10/3), and RULM (MD: 1.41; CIs: -3.64, 6.46; N/ESS: 10/5) in participants aged <18 years. Trends were consistent across weighting scenarios. After applying participant weights, the ITC of DEVOTE Part B and STEER was deemed infeasible. LIMITATIONS: As is common in rare diseases, small sample sizes from available trial data may have limited the precision of the estimates despite consistent numerical trends. CONCLUSIONS: Nusinersen resulted in numerical functional gains compared with OAV101 IT in both DMT-naïve and DMT-experienced patients. Further studies should be undertaken to validate any between-treatment difference.
Aims Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy for patients with hematologic malignancies, but its success is limited by graft-versus-host disease (GVHD), which carries considerable clinical and economic burden. A cost-effectiveness model was developed to evaluate whether the higher upfront costs of allogeneic regulatory T cell-based immunotherapy with HSPC and T cells-vldq (Tregzi [Orca-T; Orca Bio, Menlo Park, CA, USA]) are offset by reductions in GVHD and associated healthcare costs compared with conventional allo-HCT using TAC/MTX or PTCy.Methods A three-state partitioned survival model (relapse-free, relapsed, and dead) with a lifetime horizon and monthly cycles was developed. Overall survival and relapse-free survival data from the Phase 3 Precision-T study (ClinicalTrials.gov Identifier NCT05316701) were incorporated using a cure-mixture modeling approach to estimate long-term survival, relapse status, and cure fraction for patients. Costs included transplant procedure, GVHD management, infection management, and terminal care. Outcomes included life-years, quality-adjusted life-years (QALYs), and direct healthcare costs. Both costs and outcomes were discounted at 3% annually. A scenario analysis was conducted to determine the cost-effectiveness of Orca-T vs allo-HCT with PTCy for GVHD prophylaxis, and sensitivity analyses were conducted to test the uncertainty of the model inputs.Results Orca-T was associated with lower lifetime costs ($1,026,856 vs $2,170,875) and higher QALYs (15.28 vs 13.00) than conventional allo-HCT with TAC/MTX, yielding cost savings of $1,144,019 and a gain of 2.28 QALYs per patient. GVHD-related costs were substantially lower with Orca-T ($495,447 vs $1,998,621). Compared with PTCy, Orca-T remained dominant, with cost savings of $158,144, a gain of 2.85 QALYs, and lower GVHD-related costs ($476,448 vs $999,945).Conclusions Orca-T reduced costs and increased QALYs versus conventional allo-HCT with TAC/MTX or PTCy, driven by lower GVHD and infection burden. These findings support Orca-T as a high-value treatment option.
Aim Multi-target stool DNA (mt-sDNA) and fecal immunochemical testing (FIT) are home-based options for colorectal cancer (CRC) screening. Next-generation mt-sDNA has enhanced sensitivity for CRC and advanced precancerous lesions compared with FIT and is not subject to the same capacity constraints as colonoscopy. This analysis evaluated the economic and clinical implications of increasing the proportional utilization of next-generation mt-sDNA.Methods A budget impact model was developed from the validated CRC-AIM microsimulation model. The model simulated a cohort of 1 M average-risk, screen-eligible adults over a 3-year time horizon from an integrated delivery network perspective. The status quo scenario assumed an initial utilization of 20% next-generation mt-sDNA, 20% FIT, and 60% colonoscopy screening. In a hypothetical increased next-generation mt-sDNA scenario, its utilization expanded to 35% within 3 years, while FIT and colonoscopy utilization decreased to 15% and 50%, respectively. Test performance characteristics, real-world adherence, and cost inputs (i.e. screening test and programs, colonoscopy adverse events, CRC treatment) were derived from published literature. Multiple scenario analyses were conducted.Results Among 1 M members, total costs in the status quo scenario were $1.058B and with increased next-generation mt-sDNA use were $1.046B, generating an estimated savings of $12.5 M (-$0.35 per member per month). Increasing next-generation mt-sDNA improved the CRC screening rate by 1.1%. Overall, 10,467 fewer screening colonoscopies and 1,912 more follow-up colonoscopies after a positive stool-based test were performed. An additional 17 CRCs were screening-detected, 11 fewer were clinically detected, and there was one less CRC-related death. Increased next-generation mt-sDNA utilization remained cost-saving with all scenario analyses.Conclusions In this budget impact model, shifting a small proportion of current FIT and colonoscopy utilization to next-generation mt-sDNA for average-risk CRC screening is estimated to be cost-saving. Increasing the next-generation mt-sDNA utilization also improves the screening rate and clinical outcomes while optimizing availability of capacity-limited colonoscopy resources.
AIMS To evaluate and quantify potential efficiencies associated with introducing a hypothetical combination influenza/COVID-19 vaccine in pharmacy settings in the United States. MATERIALS AND METHODS This noninterventional, cross-sectional study combined qualitative interviews with a quantitative web-based survey. Insights from semistructured interviews of pharmacists who administer vaccines in commercial pharmacy settings were used to develop a quantitative survey, which was administered to a convenience sample of pharmacists. Survey responses were analyzed to understand existing vaccination workflow activities, evaluate benefits and barriers to a combination vaccine, and explore how using a hypothetical combination influenza/COVID-19 vaccine could increase operational efficiency. RESULTS Among the 10 pharmacists interviewed, participants had an average of 22.5 years of pharmacy experience and 16.4 years of experience administering vaccines. Interviewees noted that using a combination vaccine instead of separate influenza and COVID-19 vaccines could improve vaccination workflow efficiency, attributing time savings to reduced preparation, administration, documentation, and insurance processing. The quantitative survey was completed by 267 pharmacists, with an average of 13.4 years' experience in vaccine administration. Whether an appointment or walk-in visit, it was estimated from the survey responses that 11 min could be saved in a single vaccination visit for customers aged ≥ 65 years if administering 1 combination vaccine compared with 2 standalone vaccines during peak vaccination season. Pharmacists reported operational efficiencies and public health benefits of a hypothetical combination influenza/COVID-19 vaccine. LIMITATIONS Pharmacists were recruited via convenience sampling. Interview and survey responses were self-reported, leading to possible recall bias. CONCLUSIONS Pharmacists' workflow efficiencies may be gained due to time savings from adopting a combination influenza/COVID-19 vaccine. These operational improvements could increase vaccine uptake during respiratory virus seasons and contribute to broader public health benefits.
