Journal of comparative effectiveness research最新文献

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.

Aim: Surgical site infections pose a significant challenge in postoperative care, traditionally managed by keeping wounds dry. However, recent studies indicate that early postoperative showering may not increase infection risk. This study aimed to assess the impact of permitting tap water showering 24 h after surgery, specifically evaluating its impact on infection rates in level-1 (clean) and level-2 (clean-contaminated) wounds within the field of plastic surgery. Materials & methods: Patients from the Plastic Surgery Department at Taichung Veterans General Hospital, Taiwan were selected. All patients underwent surgery by the same surgeon and were permitted to shower 24 h post operation. The primary outcome was the rate of postoperative wound infections. Data collected included demographics, comorbidities, wound characteristics, anesthesia type and surgical details. Results: A total of 106 patients were included, with a mean age of 48.5 years and a mean BMI of 24.61 kg/m². Males comprised 51.9% of the cohort, with hypertension present in 17.0%, diabetes in 7.5% and smoking in 8.5%. The median albumin level was 4.3 g/dl, and the trunk was the most common injury site (39%). The average operation duration was 40.1 min, with a median wound healing time of 15 days. Remarkably, only one wound infection occurred within 30 days, resulting in an infection rate of 0.9%. Conclusion: Early showering after plastic surgery does not compromise infection outcomes, supporting the safety of this practice for patients with level-1 or level-2 wounds.

Aim: This study compares the efficacy of diroximel fumarate (DRF) with ocrelizumab (OCR) and interferon beta-1a (IFNβ-1a) for treating relapsing multiple sclerosis (MS) through matching-adjusted indirect comparisons (MAICs). Materials & methods: We used individual patient data from the EVOLVE-MS-1 (NCT02634307) study, the phase III trial of DRF (n = 1057), and group-level data from the OPERA I/II studies (NCT01247324 and NCT01412333), the 96-week, randomized, double-blind, phase III trials of OCR (n = 827) and IFNβ-1a (n = 829). EVOLVE-MS-1 data were adjusted to match the inclusion/exclusion criteria and baseline characteristics of OPERA I/II participants. Comparisons were made for annualized relapse rates (ARRs), confirmed disability progression (CDP) and radiological outcomes. Results: Baseline characteristics were balanced post-adjustment. ARR comparisons at 96 weeks showed no significant difference for DRF versus OCR (0.18 vs 0.16, p = 0.347) but favored DRF over IFNβ-1a (0.19 vs 0.29, p = 0.002). At 96 weeks, there were no significant differences in rates of 12-week or 24-week CDP between DRF and OCR (12 week: 6.4 vs 9.1%, p = 0.074; 24 week: 4.8 vs 6.9%, p = 0.14); both CDP outcomes favored DRF over IFNβ-1a (12 week: 6.5 vs 13.6%, p < 0.0001; 24 week: 4.9 vs 10.5%, p < 0.0001). The proportion of patients with gadolinium-enhancing lesions was higher for DRF versus OCR (16.4 vs 9.1%, p < 0.0001) but lower for DRF versus IFNβ-1a (15.7 vs 33.2%, p < 0.0001). The proportion of patients with new/newly enlarging T2 lesions was higher for DRF versus OCR (59.5 vs 38.7%, p < 0.0001), but there was no significant difference for DRF versus IFNβ-1a (58.4 vs 61.7%). Conclusion: While there were no significant differences in clinical outcomes (ARR, 12-week CDP and 24-week CDP) observed for DRF versus OCR, radiological outcomes indicated favorability for OCR. All outcomes favored DRF over IFNβ-1a, except from new/newly enlarging T2 lesions, which showed no significant difference.