Journal of comparative effectiveness research最新文献

In this update we cover the US-UK Economic Prosperity Deal announced in December 2025, which includes NICE's first major cost-effectiveness threshold increase in over two decades. We also analyze the latest developments in US pharmaceutical pricing policy, including the second cycle of Inflation Reduction Act drug price negotiations and the implementation of the GENEROUS, GUARD and GLOBE Models for Most-Favored-Nation pricing.

Aim: Proteinuria poses a significant challenge in focal segmental glomerulosclerosis (FSGS), particularly when resistant to standard treatments. Acthar^® Gel, a Food and Drug Administration (FDA)-approved treatment, may be a potential option for proteinuria in nephrotic syndrome (NS) due to FSGS, particularly given the limited alternative therapies. This study assessed the cost-per-response of Acthar Gel versus standard of care (SoC) for the treatment of refractory proteinuria in NS due to FSGS among adults from a US healthcare payer perspective over a 1- to 3-year horizon. Materials & methods: A probabilistic, cohort-based state-transition model tracked adults with nephrotic-range proteinuria due to FSGS through clinically relevant health states in 6-month cycles. All patients entered in relapse and received either Acthar Gel or SoC. At each cycle, individuals could transition to response or remain uncontrolled, progress to renal failure, or continue in relapse; death was permitted from any state. Responders were allowed to either sustain response or experience relapse in subsequent cycles. Model inputs for clinical event rates, healthcare utilization and medical costs were sourced from the published literature, and drug costs were valued using wholesale acquisition cost. Cost-per-response was defined as total healthcare costs (drug and nondrug medical costs) per patient divided by the response rate. Results: Acthar Gel showed a lower cost-per-response ($469,735) versus cyclophosphamide ($2,140,400) and rituximab ($1,272,477) over 1 year. This advantage for Acthar Gel was sustained for 2 and 3 years. Acthar Gel was potentially a dominant treatment option at 2 and 3 years, with a lower overall cost of care and higher response rates than SoC. Conclusion: From a US healthcare payer perspective, Acthar Gel appears to be a cost-effective, value-based treatment option for adults with proteinuria in NS due to FSGS over 1 to 3 years. These findings may aid providers and payers in making informed treatment decisions when conventional therapies are ineffective for these patients.

Stroke prevalence is highest in adults ≥65 years, the majority of whom are Medicare beneficiaries. Fee-for-Service Medicare (FFS) incentivizes utilization by paying for each service. Medicare Advantage (MA) uses capitated payments to reduce overutilization. It is not clear if stroke patients with FFS or MA receive different stroke preventive care and whether those differences are associated with differences in post-acute care utilization, cost and clinical outcomes. We performed an empirical narrative review of published peer-reviewed studies in the PubMed, EMBASE and Web of Science databases comparing stroke preventive care between FFS and MA using the American Heart Association's Life's Essential 8 and American Heart Association/American Stroke Association national guidelines. We added atrial fibrillation (AF), post-acute care utilization and outcomes, including mortality. 7/1356 studies met inclusion criteria. Studies were heterogenous in their design and settings. There was limited availability of clinical data. Within those limitations, published studies suggest that MA appears to allow for guideline-directed stroke preventive care for hyperlipidemia, smoking cessation and AF in specific study populations. Post-acute care utilization was generally lower in MA. Functional outcomes improvements were similar but occurred in fewer days in MA, though the absence of acute stroke treatment data is notable. Mortality data were mixed. Given the importance of stroke in Medicare and the growth in MA enrollment, comparing the effectiveness of MA and FFS warrants further study among appropriately matched MA and FFS beneficiaries with stroke.

External comparator (EC) studies can improve identification of compounds with the most promising performance in pre-pivotal single-arm trials (SAT). As SAT output lacks comparative insights, EC studies allow efficient contextualization of compound performance in early phases of drug development. Improving insights from pre-pivotal SATs allows more informed prioritization of compounds and investment choices and enables faster and more substantiated development of the most promising molecules to the benefit of patients. The extensive digitization of healthcare information routinely generated during patient treatment journeys makes EC studies using real-world data an attractive alternative to other approaches (such as systematic literature review and repurposed trial data). Using oncology as an illustration, this paper presents how real-world data EC studies can address some of the fundamental challenges the pharmaceutical sector faces in developing novel therapies, and especially those pertaining to emerging biopharma companies.

Aim: Pulsed field ablation (PFA) is a minimally thermal alternative to traditional thermal catheter ablation for atrial fibrillation (AF), with comparable efficacy and minimal risk of collateral tissue injury. Three-dimensional (3D) electroanatomical mapping systems have been adopted with nonintegrated PFA catheters to improve precision and procedural efficiency. This study compared arrhythmia-related hospital readmissions and procedure-related complications among patients with AF treated with PFA, using either the CARTO™ 3 or EnSite™ electroanatomical mapping system. Materials & methods: Patients who underwent PFA for AF using nonintegrated pulsed field catheters with either CARTO 3 or EnSite were identified from the 2023-2024 Premier Healthcare Database (PHD). The primary outcome was 30-day inpatient readmission and emergency room (ER) visit for AF/atrial flutter (AFL)/atrial tachycardia following the index PFA procedure. Secondary outcomes included 30-day cardiovascular-related readmissions and procedure-related complications. Cohorts were balanced using inverse probability of treatment weighting. Descriptive analyses and a weighted Generalized Estimating Equation (GEE) model were used to assess differences in outcomes between groups. Results: A total of 2894 patients were treated using CARTO 3 and 2015 using EnSite. After weighting, patient and hospital characteristics were well balanced across cohorts. The CARTO 3 group was significantly less likely to experience AF/AFL/atrial tachycardia-related readmissions (0.3% vs 0.9%, chi-square p = 0.023; odds ratio [OR], 0.39; 95% CI, 0.17-0.90, GEE p = 0.028) and a composite outcome of AF/AFL/atrial tachycardia-related inpatient readmission or ER visits (0.5% vs 1.1%, chi-square p = 0.020; OR: 0.44, 95% CI: 0.21-0.89, GEE p = 0.023) within 30 days of PFA procedure than the EnSite group. No differences were observed in cardiovascular-related readmission or complications. Conclusion: In this retrospective, real-world study, patients with AF who underwent PFA using CARTO 3 had lower 30-day AF/AFL/atrial tachycardia-related readmissions rates than those treated with EnSite suggesting that choice of mapping system may influence early AF outcomes and could translate into reduced downstream hospitalizations and resource use.

Aim: There is limited real-world evidence about prostate-specific antigen (PSA) response to androgen receptor pathway inhibitor treatment in Black patients with metastatic castration-sensitive prostate cancer (mCSPC). This study compared PSA90 (≥90% reduction from baseline PSA level) between apalutamide and enzalutamide among Black patients with mCSPC. Materials & methods: Electronic medical record data (Precision Point Specialty Analytics) were linked to claims data (Komodo Research Database) and used to select cohorts of Black patients with mCSPC treated with either apalutamide or enzalutamide. Inverse probability of treatment weighting was used to balance treatment cohorts. PSA90 response was assessed using weighted Kaplan-Meier curves and hazard ratios with 95% CIs. Results: The study included 451 patients (apalutamide: 230, enzalutamide: 221) with balanced baseline characteristics after inverse probability of treatment weighting. Patients treated with apalutamide had a 42% higher rate of PSA90 response within 6 months post-index compared with those treated with enzalutamide (hazard ratio: 1.42, 95% CI: 1.06, 1.91; p = 0.020). Median time to first PSA90 response was shorter among patients treated with apalutamide (3.3 months) compared with enzalutamide (5.5 months). Conclusion: In Black patients with mCSPC, apalutamide led to faster and significantly deeper PSA responses than enzalutamide, suggesting potential clinical advantages in optimizing early treatment response in this population. Future research should assess PSA90 as a prognostic indicator of overall survival among Black patients.

Aim: To compare characteristics of patients with anticitrullinated protein antibody-positive (ACPA+) and rheumatoid factor-positive (RF+) rheumatoid arthritis (RA) who initiated abatacept or a tumor necrosis factor inhibitor (TNFi) as a first-line biologic disease-modifying antirheumatic drug (bDMARD), and to identify factors associated with first-line bDMARD selection. Materials & methods: This retrospective cohort study abstracted data for patients with ACPA+/RF+ RA initiating abatacept or a TNFi as a first-line bDMARD between 1 January 2015 and 19 February 2020. Patient characteristics were compared using chi-square/Fisher exact tests (categorical variables) and Wilcoxon tests (continuous variables). Adjusted odds ratios (OR; 95% confidence interval [CI]) of initiating abatacept versus TNFi were estimated using 2-level logistic regression. Results: The analysis cohort included 301 patients who initiated abatacept and 203 patients who initiated a TNFi. Time from RA diagnosis to first-line initiation (>2 years vs <1 year; OR [95% CI] 2.9 [1.4-6.1]), high and moderate disease activity (versus low; 5.0 [1.8-13.9] and 4.2 [1.5-11.6], respectively), and conventional synthetic (cs) DMARD use within 12 months prior to initiation (versus no csDMARD use; 2.0 [1.1-3.6]) were associated with higher odds of initiating abatacept versus a TNFi (all p < 0.05). Patients with Medicare/other insurance had increased odds of initiating abatacept (versus TNFi) as age increased. Baseline ACPA >250 AU/ml was associated with lower odds of initiating abatacept over a TNFi (versus ACPA 20-250 AU/ml; 0.4 [0.2-0.8]; p < 0.01). Conclusion: In this real-world study, patients with ACPA+/RF+ RA were more likely to initiate abatacept over TNFi as a first-line bDMARD if they had delayed first-line bDMARD initiation, high/moderate disease activity, prior csDMARD use, or were of an older age. There is a need for better understanding of treatment selection and to account for these variables in future studies.

Aim: Opioid use disorder (OUD) leads to significant morbidity and mortality. While opioid agonist therapies like transmucosal buprenorphine and methadone are effective, they face challenges such as poor adherence, diversion risk and suboptimal abstinence rates, prompting the development of long-acting injectable (LAI) buprenorphine. However, comparative evidence among LAIs and versus standard treatments remains limited. The aim of this study is to provide comparative evidence among buprenorphine LAIs and versus oral opioid agonist treatments. Materials & methods: We conducted a systematic literature review and network meta-analysis (NMA) evaluating the effectiveness and safety of LAI buprenorphine treatments (extended-release buprenorphine [BUP-XR; monthly injection] and other BUP-LAI [weekly and monthly injection]) versus transmucosal buprenorphine, methadone and buprenorphine implants in adults with OUD. The review included randomized controlled trials (RCTs) and non-RCTs for LAIs (January 2012 and March 2025). Primary outcomes were treatment discontinuation and illicit opioid use. Secondary outcomes were safety and health-related quality of life. Data were synthesized using univariate NMAs, bivariate NMA with surrogate end point modelling. Studies with limited data and single-arm designs were incorporated by using study-level matching techniques. Results: Ninety-eight studies met the inclusion criteria. BUP-XR demonstrated the highest probability of achieving treatment retention and opioid abstinence across analyses. In combined evidence (RCTs and non-RCTs), BUP-XR showed significantly lower risk of illicit opioid use versus transmucosal buprenorphine (rate ratio [RR] 1.99; 95% credible interval [CrI]: 1.29-3.11) and methadone (RR: 2.66; 95% CrI: 1.40-3.56). BUP-XR showed borderline significantly lower risk of illicit opioid use versus other BUP-LAI (RR: 1.81; 95% CrI: 0.97-3.55) and buprenorphine implant (RR: 2.28; 95% CrI: 0.98-5.38). Treatment discontinuation rates were similar between OUD treatments. Safety outcomes were generally comparable across treatments. Health-related quality of life indicated better recovery among patients treated with BUP-XR. Conclusion: BUP-XR may enhance treatment retention and abstinence over other OUD therapies, supporting its integration into clinical pathways. The results may help guide future updates to OUD treatment guidelines and policies aimed at optimizing the use of long-acting formulations. Additional research is needed to better define the comparative effectiveness of LAIs.

Aim: Recent network meta-analyses (NMAs) in metastatic castration-sensitive prostate cancer have not adequately addressed potential treatment effect modifiers and population imbalances, which introduces bias. Although, individual-patient data (IPD) are seldom available across all trials, recent methodological advances allow adjustments using a combination of IPD and aggregate data. Materials & methods: IPD from the ARASENS trial (darolutamide + docetaxel + androgen-deprivation-therapy [ADT]) and aggregate data from a systematic review were analyzed. Two methods were used to adjust for population imbalances: multilevel network meta-regression (ML-NMR) using baseline characteristics, and network meta-interpolation (NMI) using subgroup data. Relative effects were estimated for an ARASENS-like population, with sensitivity analysis in an average trial population. Results: Twelve studies, including ARASENS, were included. All studies reported baseline characteristics for ML-NMR. Sufficient subgroup data for NMI were available in 8/12 studies for overall survival (OS) and 5/12 studies for progression-free survival (PFS). Darolutamide + docetaxel + ADT showed significant benefit over docetaxel + ADT, ADT and standard-nonsteroidal-antiandrogen + ADT in all analyses. ML-NMR showed improved OS for darolutamide + docetaxel + ADT compared with abiraterone + docetaxel + ADT, apalutamide + ADT, enzalutamide + ADT and abiraterone + ADT. ML-NMR also showed improved PFS for darolutamide + docetaxel + ADT compared with apalutamide + ADT and enzalutamide + ADT. Using NMI, darolutamide + docetaxel + ADT demonstrated OS benefit over abiraterone + ADT and PFS benefit relative to abiraterone + ADT and apalutamide + ADT. Findings were consistent in an average population, although ML-NMR did not show significant OS benefit of darolutamide + docetaxel + ADT over apalutamide + ADT. Conclusion: Improved outcomes were observed with darolutamide + docetaxel + ADT compared with other therapies. By incorporating effect modifiers and addressing population imbalances, we provide clinicians with a more accurate understanding of treatment efficacy for better-informed decision-making.

Aim: In the single-arm MOUNTAINEER trial (NCT03043313) tucatinib in combination with trastuzumab showed an objective response rate (ORR) of 39.3% in patients with previously treated, HER2+ unresectable or metastatic colorectal cancer (mCRC). This study compared the efficacy of tucatinib in combination with trastuzumab with other treatment options in this population. Materials & methods: An unanchored, matching-adjusted indirect comparison was conducted following a systematic literature review that identified the CORRECT trial (NCT01103323), which investigated regorafenib, and the RECOURSE trial (NCT01607957), which investigated trifluridine-tipiracil, as comparators for tucatinib in combination with trastuzumab. Patient and study characteristics, overall survival (OS), progression-free survival (PFS) and ORR data were extracted and compared assuming HER2 status was not prognostic. Differences in adjusted covariates across analyses included patient age, performance status, time since metastatic diagnosis and prior lines of therapy. OS and PFS were compared using Cox proportional hazard models to generate match-adjusted hazard ratios (HRs) and 95% CI. ORR was compared via match-adjusted odds ratios and 95% CIs. As MOUNTAINEER only included patients from Europe and North America, sensitivity analyses used non-Japanese patients from CORRECT and European and US patients from RECOURSE. Results: In the main analysis, the estimated adjusted HR (95% CI) for tucatinib in combination with trastuzumab versus regorafenib was 0.26 (0.14-0.46) for OS and 0.32 (0.23-0.46) for PFS; versus trifluridine-tipiracil, this was 0.34 (0.22-0.51) for OS and 0.38 (0.20-0.58) for PFS. Similar results were seen for OS and PFS in sensitivity analyses. ORR also favored tucatinib in combination with trastuzumab across analyses. Conclusion: These data support that tucatinib in combination with trastuzumab is an effective therapy option in patients with previously treated mCRC.