Journal of comparative effectiveness research最新文献

Aim: Continuous glucose monitoring (CGM) supports glycemic control and reduces diabetes complications. CGM systems include intermittently scanned CGM (is-CGM) and real-time CGM (rt-CGM). While rt-CGM may provide better outcomes than is-CGM, it costs more upfront and its cost-effectiveness in Canada has not been established. We assessed the cost-effectiveness of rt-CGM versus is-CGM in people with insulin-treated Type 2 diabetes mellitus (T2DM) from a Canadian healthcare payer perspective. Materials & methods: We used the ECHO-T2DM microsimulation model to estimate incremental lifetime health outcomes and costs of rt-CGM versus is-CGM. Clinical inputs came from an indirect treatment comparison; cost and utility data were drawn from published sources. Sensitivity analyses tested robustness. Results: Rt-CGM was more effective and less costly than is-CGM, yielding 0.346 additional quality-adjusted life-years and CAD 2237 in savings over 30 years. Benefits stemmed primarily from better glycemic control and fewer complications, reductions in glycemic events, and reduced fear of hypoglycemia. Although rt-CGM incurred CAD 3867 higher acquisition costs, these were more than offset by avoided complications. Deterministic analysis showed dominance in 14 of 18 scenarios, and cost-effectiveness in the remaining four. Uncertainty analysis showed rt-CGM had an ICER below CAD 50,000 in 98% of simulations. Discussion: Rt-CGM is potentially a cost-saving alternative to is-CGM among people with insulin-treated T2DM in Canada. This finding was strengthened by rigorous sensitivity analysis. Study strengths include use of a validated microsimulation model and adoption of conservative assumptions. Limitations include absence of head-to-head trial evidence and indirect use of time in and out of range. Conclusion: Rt-CGM is a potentially cost-saving option for managing insulin-treated T2DM in Canada, with implications for clinical practice and reimbursement policy.

Aim: Bruton's tyrosine kinase inhibitors (BTKis), including ibrutinib and acalabrutinib, transformed the treatment landscape of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) by improving outcomes compared with chemoimmunotherapy. Real-world economic comparisons between BTKis are needed in diverse populations. This study aimed to compare healthcare costs in the Veterans Health Administration (VHA) among patients with CLL/SLL treated with, and remaining persistent on, first-line (1L) ibrutinib versus acalabrutinib monotherapy for 12 months. Materials & methods: This retrospective study used VHA electronic medical record data from January 2006 to July 2024. Eligible patients initiated 1L ibrutinib or acalabrutinib monotherapy on or after November 2019 and remained on continuous treatment for ≥12 months. All-cause and CLL/SLL-related costs were assessed over 12 months of follow-up. Generalized linear models were used to estimate adjusted costs and compare differences between treatment cohorts. Results: A total of 1059 patients were included (ibrutinib: n = 732; acalabrutinib: n = 327). During the 12-month follow-up of continuous 1L treatment, the annual adjusted all-cause total healthcare cost difference between ibrutinib and acalabrutinib was -$2422 (p = 0.46) (adjusted medical cost difference: $5259, p = 0.03; adjusted pharmacy cost difference: -$5886, p = 0.02). The annual adjusted CLL/SLL-related total healthcare cost difference between ibrutinib and acalabrutinib was -$3793 (p = 0.15) (adjusted medical cost difference: $2085, p = 0.05; adjusted pharmacy cost difference: -$5860, p = 0.02). Conclusion: Among VHA patients with CLL/SLL who initiated and remained on treatment with 1L BTKi monotherapy for 12 months, annual all-cause and CLL/SLL-related total healthcare costs were similar between ibrutinib and acalabrutinib. Pharmacy costs were lower for ibrutinib, while medical costs were lower for acalabrutinib, resulting in overall comparable total costs.

Randomized controlled trials (RCTs) are regarded as the highest level of evidence in medical research, but RCTs also have their drawbacks. Over the years, several alternative study designs have been introduced to address these problems. However, many of the alternative designs are often regarded as inferior to RCTs or currently not suitable for widespread implementation due to, for example, ethical or statistical problems. Thus, there is a need for study designs that have the same level of validity as RCTs, but are also suitable for large-scale implementation. The cohort intervention random sampling study (CIRSS) with historical controls meets these requirements, by combining the strengths of abovementioned designs. The CIRSS with historical controls has the potential to optimize implementation of promising new treatments as fluidly and rapidly as possible, representing real-world clinical population. Further research is required to address the range of analyses, implementation, issues, barriers and facilitators and ethical questions related to CIRSS.

Aim: While only recently approved for the treatment of metabolic dysfunction-associated steatohepatitis (MASH), many patients with MASH have taken glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for the treatment of comorbid Type 2 diabetes (T2D) or obesity. This real-world study evaluated treatment patterns, weight loss, healthcare resource utilization, and costs among patients with MASH who initiated GLP-1 RAs. Materials & methods: In a linked electronic health records (Veradigm Network EHR) and claims (Komodo Health) dataset, we identified adults (≥18 years old) with a MASH diagnosis who initiated GLP-1 RA treatment (1 July 2018 to 30 April 2023; index date = date of the first GLP-1 RA claim). Patients with other causes of liver disease or severe complications from MASH were excluded. We required ≥12 months of continuous enrollment pre- (baseline) and post-index (follow-up). Patients were stratified into high and low-dose subgroups. We also identified a comparator cohort of patients who initiated a different class of T2D medication (DPP4, SGLT2, or sulfonylurea) during the same time period. We captured patient characteristics, change in BMI, GLP-1 RA treatment patterns, liver-related events, healthcare utilization, and costs. Results: We identified 10,316 patients with MASH who initiated a GLP-1 RA (high dose: 2043 [19.8%]; low dose: 8273 [80.2%]) and 2915 who initiated a non-GLP-1 RA T2D medication. GLP-1 RA users were 52.7 years old and 64.3% female. A 5.8% decrease in the percentage of patients with class III obesity was observed among GLP-1 RA users (10.7% among high-dose users; 0.8% among non-users). Overall, 56.1% of GLP-1 RA users discontinued during the 12-month follow-up. Total costs among GLP-1 RA users and non users were $20,912 and $19,019 in the baseline period and $27,586 and $24,917 in the follow-up period, respectively. Medical costs among GLP-1 RA users were $16,293 (baseline) and $16,886 (follow-up). Results were similar for high and low-dose subgroups. Conclusion: Although some patients with MASH on GLP-1 RAs, particularly those taking higher dosages, may achieve weight loss, outcomes remain suboptimal with frequent discontinuation and high healthcare costs. Real-world GLP-1 RA utilization may be insufficient for resolving chronic metabolic issues, including MASH.

In this update, we examine Spain's comprehensive pharmaceutical legislation reform; France's refined health economic evaluation approach; and the US' proposed Most Favored Nation pricing mechanism.

Aim: Ribociclib + nonsteroidal aromatase inhibitor (NSAI) and abemaciclib + endocrine therapy (ET) are approved for high-risk hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer based on data from the NATALEE and monarchE trials, respectively. No trials have directly compared efficacy and safety of adjuvant ribociclib and abemaciclib. This study compared relative efficacy and safety of adjuvant ribociclib + NSAI versus abemaciclib + ET using matching-adjusted indirect comparison (MAIC). Materials & methods: Individual patient data from NATALEE and aggregate data from monarchE were analyzed, with patients from NATALEE selected to match the key eligibility criteria of monarchE cohort 1. Unanchored MAIC was used to compare invasive disease-free survival, distant relapse-free survival, and grade ≥3 treatment-emergent adverse events between treatment arms in NATALEE versus monarchE. Cox regression was used to estimate hazard ratios pre- and post-MAIC weighting. Logistic regression was used to estimate odds ratios (ORs). Results: After weighting, the effective sample size for the ribociclib + NSAI arm of NATALEE was 448. Cox regression yielded similar invasive disease-free survival with weighted ribociclib + NSAI versus abemaciclib + ET (hazard ratio, 0.901; 95% CI: 0.678-1.197). Unweighted efficacy comparisons were consistent with the weighted approach. Lower odds (OR <1) for diarrhea, leukopenia and lymphopenia and higher odds (OR >1) for increased alanine aminotransferase and neutropenia with ribociclib + NSAI versus abemaciclib + ET were noted before and after weighting. Sensitivity analyses were consistent with the primary analysis. Conclusion: This MAIC suggests similar efficacy between ribociclib + NSAI and abemaciclib + ET but different safety profiles in the HR+/HER2- early breast cancer patient population corresponding to the monarchE cohort 1, which has implications for treatment decisions. This analysis has limitations inherent to unanchored MAIC and should be interpreted in context of the trials and with clinical judgement.

Composite endpoints amalgamate multiple clinical outcomes into a single measure, offering efficiency gains in clinical trials through increased event rates and reduced sample sizes, thus accelerating clinical development and regulatory approval. However, employing composite endpoints introduces complexities into health technology assessments (HTAs), particularly in economic modeling, due to the varying clinical significance and cost implications of the components. In this paper, we explore best modeling practice for HTAs that are based on clinical trials that employ composite endpoints. We examine regulatory guidance and discuss statistical solutions for differential component impacts, before presenting a case study based on a recent dapagliflozin submission for reimbursement in heart failure. Our investigation reveals that while composite endpoints can streamline trial analyses and hasten regulatory approval, they also pose a risk of bias in HTA if treatment effects for the components are inappropriately pooled. The paper discusses HTA principles in the context of composite endpoint trials and proposes strategies to develop modeling scenarios and interpret results, especially concerning whether to combine or split out estimates of component treatment effects. A particular focus is the accurate capture of uncertainty, both in terms of the parameter inputs to the model and over the ultimate decision to reimburse. This paper serves as a potential resource for researchers, practitioners and decision-makers, offering insights into best modeling practices that can unlock the full potential of composite endpoints in the pursuit of evidence-based healthcare decision-making.

Aim: Persistently active noninfectious keratitis can lead to permanent corneal damage and loss of vision. Given the limited treatment options, Acthar Gel, a US FDA-approved treatment for ocular inflammatory conditions, can be a potential therapy. This study evaluated the cost-per-response of Acthar^® Gel compared with standard of care ([SoC]; adalimumab or infliximab) for noninfectious keratitis from a US healthcare payer perspective over 1-3 years. Materials & methods: A probabilistic, cohort-level state-transition decision-analytic model was developed to assess the economic value of Acthar Gel. The model simulated the treatment pathway over 3 years, divided into 3-month cycles. Patients started with active keratitis and received Acthar Gel or SoC. Based on treatment success, patients transitioned between relapse, response and no-response states, with no response potentially leading to complications. Clinical parameters for Acthar Gel were derived from a phase IV open-label study and for SoC from observational studies. Healthcare resource utilization and costs were derived from administrative claims data or published literature. Results: Over 1 year, Acthar Gel demonstrated a lower cost per response ($167,928) than SoC, adalimumab ($228,450) and infliximab ($195,083). This benefit for Acthar Gel over SoC was sustained for 2 and 3 years. Acthar Gel, despite having a higher acquisition cost than SoC, had lower disease management costs and incurred no treatment-related (administration, monitoring or adverse event) costs over 1 year. Acthar Gel also demonstrated a lower overall cost of care than SoC at 2 and 3 years. Further, Acthar Gel had higher response rates versus SoC over 1-3 years. Acthar Gel was a dominant treatment option versus SoC at 2 and 3 years. Conclusion: From a US healthcare payer perspective, Acthar Gel may be a cost-effective, value-based treatment option for appropriate patients with noninfectious keratitis.

Aim: Stent-assisted endovascular coiling is a safe and effective treatment for unruptured intracranial aneurysms (UIAs). This study compared 180-day inpatient readmission and cost among patients with UIA who underwent stent-assisted coiling (SAC) using the ENTERPRISE^® 2 or Neuroform^® Atlas stent. Materials & methods: In this retrospective cohort study, adults with UIA undergoing SAC were identified in the Premier Healthcare Database (2016-2022) and grouped based on the stent used: ENTERPRISE 2 or Neuroform Atlas. Outcomes included all-cause and UIA-related inpatient readmission in the 180 days following treatment, index admission and supply cost. Inverse probability of treatment weighting of propensity score method balanced the two cohorts on study covariates. A weighted generalized estimating equation model assessed study outcomes. Results: A total of 1017 patients were included (ENTERPRISE 2, n = 126; Neuroform Atlas, n = 891). Hospital and patient characteristics except race were well-balanced after weighting. Patients treated with ENTERPRISE 2 versus Neuroform Atlas were 55% less likely to have an all-cause inpatient readmission in the 180-day follow-up period (odds ratio 0.45, 95% CI: 0.20-0.98, p = 0.04). Further, the ENTERPRISE 2 cohort had significantly lower index supply cost ($20,442 vs $27,561, exponentiated ratio 0.74, 95% CI: 0.61-0.90, p = 0.002) compared with the Neuroform Atlas cohort. No significant differences were observed in UIA-related inpatient readmission or total index admission cost between cohorts. Conclusion: Among patients with UIA undergoing SAC, the use of ENTERPRISE 2 stent was associated with a significantly reduced risk of all-cause inpatient hospital readmission and significantly lower index supply cost compared with the Neuroform Atlas stent.