Journal of comparative effectiveness research最新文献

Aim: To assess patient characteristics, burden of disease, healthcare resource utilization and costs of acute myeloid leukemia (AML) by treatment intensity in German claims data. Materials & methods: In this retrospective cohort study using claims data from the German sickness fund AOK PLUS, we identified incident AML patients between 2012 and 2022. Incident AML patients were stratified into groups receiving intensive chemotherapy (IC) or nonintensive therapy (NIC). We then conducted descriptive analyses of patient characteristics, disease burden, including blood and platelet transfusions, healthcare resource utilization and costs. Results: We identified 1533 incident AML patients who received treatment (male: 53%; mean age: 67.7 years; median Charlson comorbidity index [CCI]: 5.0), corresponding to an incidence rate of 4.4/100,000. A total of 688 patients (44.9%) were categorized as IC, 845 patients (55.1%) as NIC. Notably, 860 additional patients (male: 48%; 78.0 years; median CCI: 5.0) had no relevant treatment code. NIC patients were older than IC patients (78.0 vs 61.0 years) and had a higher comorbidity burden (median CCI: 6.0 vs 4.0). NIC patients were hospitalized to a lesser extent (81.3% vs 87.9%), had shorter lengths of stay (64.0 vs 103.1 days/patient-year [PY]) and lower hospitalization costs/PY (56,063€/PY vs 110,186€/PY) compared with IC patients. Anemia and thrombocytopenia (NIC: 40.5 and 39.5%, IC: 76.9 and 42.6%) as well as blood and platelet transfusions were common, especially among IC patients (NIC: 93.0 and 74.3%, IC: 99.4 and 98.5%). Conclusion: Compared with IC patients, NIC patients were older, had a higher comorbidity burden and fewer hospitalizations. Combined with the high number of older patients not receiving AML treatment, this points to a lack of adequate treatment options for this patient population. The high rates of blood and platelet transfusions, particularly among IC patients, underscore the high disease burden and emphasize the need for better-tolerated therapies.

What is this summary about?: This plain language summary is based on an article about the APHENITY trial that was published in The Lancet journal in October 2024. The APHENITY trial was a phase 3 clinical trial to find out whether sepiapterin helped people living with phenylketonuria (PKU) and to learn more about its safety. PKU is a rare, genetic condition that causes high levels of phenylalanine (Phe) to build up in the body. High levels of Phe in the body can cause symptoms such as seizures, rashes, and problems with movement, and can also affect brain development, thinking skills, and behaviour. These symptoms can have an impact on people's health-related quality of life.

What happened in the aphenity trial?: Previous studies have shown that sepiapterin is able to decrease Phe levels in the blood. In the APHENITY trial, the researchers wanted to learn more about the efficacy and safety of sepiapterin in a large group of people living with PKU over the course of 8 weeks of treatment. The researchers wanted to: Assess the efficacy of sepiapterin by seeing whether sepiapterin decreased Phe levels in the blood compared with a placebo Assess the safety of sepiapterin by seeing how many health complaints the participants who took sepiapterin had compared with those who took the placebo The APHENITY trial was carried out in two parts: During Part 1, the participants took sepiapterin for 2 weeks to find out if it decreased their Phe levels During Part 2, the participants who benefitted from sepiapterin during Part 1 were randomly assigned to either continue taking sepiapterin or start taking a placebo for a further 6 weeks.

What were the results?: During Part 1, the researchers found that 114 out of 156 participants benefitted from sepiapterin. This was 73% or about 7 in 10 participants. During Part 2, the researchers found that the participants who took sepiapterin had reduced blood Phe levels compared with those who took the placebo. The researchers also found that compared with those who took the placebo, more of the participants who took sepiapterin reduced their blood Phe levels to within the ranges recommended by treatment guidelines. For both parts of the trial, the participants did not have any serious health complaints. So, the researchers concluded that no safety concerns were seen with sepiapterin in this trial.

What do the results of the trial mean?: These results showed that sepiapterin helped to reduce blood Phe levels in the participants, and there were no unexpected safety concerns in people living with PKU. ClinicalTrials.gov NCT number: NCT05099640.

Aim: Lorlatinib demonstrated superior efficacy over alectinib as a first-line treatment for ALK-positive (ALK+) advanced/metastatic non-small cell lung cancer in a matching-adjusted indirect comparison (MAIC) using 3-year follow-up data from CROWN (lorlatinib). This study aimed to update these findings using the latest extended 5-year follow-up data from CROWN. Materials & methods: We conducted an anchored MAIC using data from CROWN and ALEX (alectinib). Patients were matched based on prespecified effect modifiers. We compared progression-free survival (PFS) using hazard ratios (HRs), restricted mean survival time and PFS probabilities and adverse events (AEs) using rate ratios and rate differences. PFS was analyzed in subgroups with and without baseline brain/CNS metastases. Results: Lorlatinib demonstrated superior PFS over alectinib, reducing the risk of progression or death by 45% (HR: 0.55, 95% CI: 0.34, 0.88). Lorlatinib extended restricted mean survival time by 8.5 months up to 4 years and 11.2 months up to 5.5 years, with generally higher annual PFS probabilities across years 1-5. While lorlatinib was associated with a higher incidence of grade ≥3 AEs, the rates of AEs leading to treatment discontinuation, dose interruption and dose reduction were similar between the treatments. In patients with baseline brain/CNS metastases, lorlatinib showed a numerical PFS benefit, with significant improvement at year 1. In patients without brain/CNS metastases, lorlatinib significantly improved PFS, with significant increases at years 2-4. Conclusion: This extended analysis reaffirms lorlatinib's superior efficacy over alectinib in prolonging PFS. Despite the higher grade ≥3 AE incidence, similar rates of dose reduction, interruption, or discontinuation suggest these AEs are manageable. Lorlatinib remains a first-line treatment option for ALK+ metastatic non-small cell lung cancer, offering meaningful benefits to appropriate patients.

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: 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.

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.