Journal of comparative effectiveness research最新文献

Aim: The use of amyloid-beta (Aβ) clearance to support regulatory approvals of drugs in Alzheimer's disease (AD) remains controversial. We evaluate Aβ as a potential trial-level surrogate endpoint for clinical function in AD. Materials & methods: Data on the effectiveness of anti-Aβ monoclonal antibodies (MABs) on Aβ and multiple clinical outcomes were identified from randomized controlled trials through a literature review. A Bayesian bivariate meta-analysis was used to evaluate Aβ as a surrogate endpoint for clinical function across all MABs and for each individual anti-Aβ MAB. The analysis for individual therapies was conducted in subgroups of treatments and by applying Bayesian hierarchical models to borrow information across treatments. Results: We identified 23 randomized controlled trials with 39 treatment contrasts for seven MABs. The surrogate relationship between treatment effects on Aβ and Clinical Dementia Rating-Sum of Boxes (CDR-SOB) across all MABs was strong: with a meaningful slope of 1.41 (0.60, 2.21) and small variance of 0.02 (0.00, 0.05). For individual treatments, the surrogate relationships were suboptimal, displaying large uncertainty. Sharing information across treatments considerably reduced the uncertainty, resulting in moderate surrogate relationships for aducanumab and lecanemab. No meaningful association was detected for other clinical outcomes, including Mini Mental State Examination and Alzheimer's Disease Assessment Scale-Cognitive Subscale. Conclusion: Although our results from the analysis of data across all MABs suggested that Aβ was a potential surrogate endpoint for CDR-SOB, individually the surrogacy patterns varied across treatments and showed no evidence of association. Bayesian information-sharing revealed moderate surrogate relationship only for aducanumab and lecanemab.

Background: The impact of race and ethnicity on prognosis and clinical outcomes in patients with significant tricuspid regurgitation (sTR) is not well understood. Aim: Describe healthcare utilization trends preceding the development of sTR and assess clinical outcomes 1-year post-sTR status by race and ethnicity. Materials & methods: We conducted a retrospective, longitudinal descriptive study using data from a large database containing electronic health record and insurance claims information. We employed multivariate modeling to assess the relationship between 1-year clinical outcomes and mutually exclusive race/ethnicity groups and other baseline factors. Results: Black patients were more likely to be identified as having sTR as inpatients when compared with White patients (p < 0.001) and had fewer outpatient visits to cardiac specialists before and after developing sTR (p < 0.01). Black and Hispanic patients with sTR were at increased risk of heart failure hospitalization compared with White patients at 1 year (adjusted HR: 1.21, 95% CI: 1.16-1.26, p < 0.001 and adjusted HR: 1.10, 95% CI: 1.02-1.19, p < 0.05 respectively). However, both Black and Hispanic patients had lower 1-year mortality than White patients in the adjusted model. Conclusion: Black and Hispanic patients are less likely to have received outpatient care by a cardiac specialist prior to the development of sTR, and have higher rates of heart failure hospitalization after diagnosis. In contrast, their mortality rates following sTR identification are lower than White patients. Further investigation into the underlying mechanisms of these observations is needed to improve TR-related outcomes.

Aim: This study assessed the acceptability of external control-arm (ECA) use in nononcology health technology assessment (HTA) submissions in Europe. Materials & methods: We conducted a sequential mixed method study to investigate the study objective. First, we summarized published documentation from three HTA agencies in Europe - the National Institute for Health and Care Excellence (NICE) in England, the French National Authority for Health (HAS) and the German Institute for Quality and Efficiency in Healthcare (IQWiG) - to assess the availability of guidance on ECA methodology and implementation. We then reviewed independent nononcology HTA appraisals common across England, France, Germany and Italy to understand variations in agencies' perceptions of ECA use. Finally, we conducted six double-blinded interviews with HTA experts from England, France, Germany and Italy to validate the findings and obtain illustrative insights on drivers of acceptability. Results: While NICE and HAS provide some level of ECA-related guidance on topics such as data suitability, methods and reporting, guidance from IQWiG remains limited. Overall, ECA use is mainly restricted to oncology, particularly given that only two nononcology appraisals were common across HTA agencies. However, NICE appears more open to accepting ECA use in supplementing clinical trial data, whereas IQWiG has a strong preference for traditional controlled clinical trials. Experts indicate that ECA use is most acceptable when accompanied by valid justification, suitable data sources and a rigorous methodology to minimize the risk of bias. Situations that experts perceive as appropriate for ECA use include missing comparators (i.e., single-arm trials), limited comparator data availability, or rapidly changing standards of care. Conclusion: There is a need to focus awareness on the value of ECA use as a supplement to randomized controlled trials, and to engage with HTA agencies early in clinical development.

Aim: Polycythemia vera (PV), a rare, chronic myeloproliferative neoplasm, that negatively impacts patient outcomes, and optimal therapy remains unclear due to a lack of head-to-head trials. A targeted literature review and feasibility assessment for an indirect comparison of ropeginterferon alfa-2b-njft versus peginterferon alfa-2a or ruxolitinib, using standard of care comprising hydroxyurea (HU) as a common comparator was conducted. Materials & methods: A targeted literature review evaluated clinical comparative evidence for PV treatments published between January 2014 and May 2024 in PubMed and relevant conference abstracts. End points of interest included complete hematologic response, molecular response, allele burden, event-free survival and safety. The feasibility of a network meta-analysis (NMA) was evaluated based on homogeneity of patient populations, treatment regimens and end point definitions. Results: Of 193 PubMed records and 460 conference abstracts screened, 40 records were included, representing evidence from 11 randomized controlled trials and 10 observational studies. Among these, 20 studies formed connected evidence networks for the end points of interest. Substantial heterogeneity across studies precluded a robust NMA: patient populations varied (newly diagnosed, high-risk, low-risk, HU-refractory or -intolerant), complete hematologic response definitions differed (e.g., requirement for absence of disease-related symptoms), molecular response thresholds were inconsistent, follow-up durations varied and definitions of standard of care ranged from almost exclusive use of HU to mixed regimens. Conclusion: An NMA for PV treatments was not feasible due to significant clinical and methodological heterogeneity across studies, including differences in patient characteristics, treatments, outcome definitions and follow-up times. These findings highlight the importance of standardized clinical trial designs and outcome definitions to enable robust comparative evidence generation for rare conditions like PV.

Aim: Fractional Polynomial (FP) models are widely used in survival analysis for health technology assessment and network meta-analysis (NMA). However, current implementations rely on a fixed set of pre-specified powers, which may constrain model flexibility, limit predictive performance and increase computational cost in Bayesian settings. This study introduces and evaluates a Bayesian FP modeling approach in which the powers are estimated as continuous parameters rather than fixed, aiming to simplify model selection and improve fit. Materials & methods: Second-order Bayesian FP models were implemented in STAN, allowing the time transformation powers (p1, p2) to be estimated from the data. Model performance was evaluated across three oncology NMA datasets; in advanced non-small-cell lung cancer, metastatic prostate cancer and early breast cancer. The performance was assessed using visual fit, leave-one-out-information-criteria, root mean square error, incremental survival estimates and computational efficiency. Validation steps included posterior predictive checks, sensitivity analyses and long-term extrapolation. Results: Across all datasets, variable power models consistently achieved better statistical fit (lower leave-one-out-information-criteria and root mean square error) than fixed power models. Incremental survival estimates were also more stable and clinically plausible, particularly in datasets with complex hazard dynamics. While variable models required slightly more time per run, the approach greatly reduced the number of required model configurations, leading to lower overall computational burden. Conclusion: Bayesian FP models with variable powers not only improve model fit and simplify model selection but also reduce structural uncertainty by replacing exhaustive grid searches with a unified, data-driven estimation of transformation powers, while retaining interpretability and computational efficiency. By producing robust, well-calibrated survival projections and streamlining model selection, this approach strengthens survival analysis for health technology assessment and supports more reliable decision-making in comparative effectiveness research.

Background: The impact of significant tricuspid regurgitation (sTR) on healthcare costs and utilization in real-world populations remains understudied. Aim: Describe healthcare costs and utilization before and after development of sTR and describe differences by patient demographic characteristics. Materials & methods: We conducted a retrospective, longitudinal descriptive study using a large database containing electronic health record and insurance claims data for US patients. Healthcare costs and utilization are summarized for up to 3 years prior to sTR and for 1 year after sTR. Results: Costs and utilization increased in the 3 years leading up to and the year after sTR. Costs were higher for patients who were: aged 50-79 years, male, and Black or Hispanic (p < 0.01). Cardiovascular hospitalizations were an important driver of costs in all groups. Patients aged 80 years and over, women, and Black nonHispanic patients had fewer outpatient visits to cardiac specialists in the year following sTR (p < 0.01). Conclusion: Healthcare costs and utilization of patients with TR increase as clinical disease progresses, with important differences by age, sex and race. Increasing recognition of signs of TR progression and improved outpatient cardiac specialty access may be important means to reduce heart failure hospitalization duration as well as overall costs.

In this update, we explore a review on transportability methods to enable the use of cross-jurisdictional evidence when local data are limited, a review of clinical trials that use pragmatic elements and finally, we discuss a study highlighting the potential transformative role of large language models in disease progression modeling.

Aim: Stroke is a clinically defined syndrome characterized by an acute, focal neurological deficit due to vascular injury. Strokes can result in various disabilities, including sensory and motor abnormalities, leading to difficulties with motor control, balance and posture. Physical therapists use various neurorehabilitation approaches to enhance the functional abilities and independence of stroke patients. The motor relearning program (MRP) is a task-oriented, self-monitored, structured program based on motor control theories and neuroplasticity used in the rehabilitation of stroke patients. Therefore, this study aimed to evaluate the effectiveness of MRP in improving sit-to-stand transfer and activities of daily living in individuals with chronic stroke. Materials & methods: A prospective, single-blinded, multi-centered randomized controlled trial was conducted in Saudi Arabia involving 32 chronic stroke patients randomly assigned to experimental (n = 16) and control (n = 16) groups. The experimental group received 45 minutes of MRP combined with conventional physical therapy, while the control group received conventional physical therapy alone. Interventions were delivered thrice weekly over 6 weeks (18 sessions). Outcome measures included the Barthel Index (BI) and the sit-to-stand component of the motor assessment scale (MAS), assessed pre- and post-intervention. Results: The experimental group demonstrated statistically significant improvements in both MAS and BI scores (p < 0.001), with large effect sizes (r = -0.865; for MAS, Cohen's d = 1.46 for BI). ANCOVA analyses revealed that baseline MAS scores (MAS_pre) significantly influenced post-intervention outcomes (F[1, 29] = 65.33, p < 0.001), and the group effect remained significant after adjusting for MAS_pre (F[1, 29] = 41.89, p < 0.001). The model explained 72.6% of the variance in MAS_post scores (adjusted R² = 0.707), confirming the predictive strength of MRP. Similarly, BI_post scores were significantly predicted by BI_pre and group assignment (F[1, 29] = 21.15, p < 0.001), with the model accounting for 85.8% of the variance (Adjusted R² = 0.849). Conclusion: The motor relearning program significantly improves sit-to-stand transfer and activities of daily living performance in chronic stroke patients. Despite the small sample size and baseline MAS imbalance, these improvements remained robust after statistical adjustment, underscoring MRP's clinical utility in neurorehabilitation. Clinical trial registration was done prospectively at https://clinicaltrials.gov/ with the registration no: NCT06690073.

Patient and public involvement in health technology assessment (HTA) has progressed from best practice to policy requirement, yet communication barriers persist. This perspective explores how plain language summaries (PLSs) and summaries of information for patients (SIPs) can enhance equity and transparency in HTA. Building on recent European regulatory developments and emerging research, it discusses the balance between accessibility, quality and feasibility. Generative artificial intelligence offers the potential to scale PLS and SIP production, but its responsible integration requires oversight, collaboration and a continued focus on equity and patient-centeredness within evolving HTA frameworks.

Aim: We compared the effects of nefecon, an oral targeted-release budesonide formulation, and sparsentan, an oral, dual endothelin-angiotensin receptor antagonist, on estimated glomerular filtration rate (eGFR) in patients with immunoglobulin A nephropathy, a leading cause of chronic kidney disease. Materials & methods: We conducted an anchored matching-adjusted indirect comparison (MAIC) using patient-level data from NefIgArd (NCT03643965; n = 364), a randomized (1:1) trial of nefecon plus optimized renin-angiotensin system inhibitor (RASi) therapy versus placebo plus RASi; and aggregate data from PROTECT (NCT03762850; n = 404), a randomized (1:1) trial of sparsentan versus irbesartan, an angiotensin receptor blocker. Mean absolute eGFR change and mean relative urine protein-to-creatinine and urine albumin-to-creatinine ratio changes from baseline at 9, 12 and 24 months (NefIgArd) or 36, 48 and 106 weeks (PROTECT) were analyzed using a mixed-effects model for repeated measures. A composite outcome (time to confirmed 40% eGFR reduction, end-stage kidney disease or all-cause mortality) was also included. An unanchored MAIC and network meta-analysis were used as sensitivity analyses. Results: The matching process reduced the effective sample for the NefIgArd trial from 364 to 208. Absolute eGFR change significantly favored nefecon over sparsentan at 9 months (mean difference, ml/min/1.73 m² [95% credible interval]: 5.7 [3.1-8.2]), 12 months (3.5 [1.0-6.0]) and 24 months (3.3 [0.0-6.5]). Differences in other outcomes were generally not statistically significant. Sensitivity analysis results were consistent with the main findings. Conclusion: In patients with immunoglobulin A nephropathy, nefecon plus optimized RASi may preserve kidney function to a greater extent than sparsentan.