Aim: To evaluate the performance of four stent types (BMS, bare metal stents; Eluvia, a polymer-based paclitaxel-eluting stent; Viabahn, a covered stent; and Zilver PTX, a polymer-free paclitaxel-coated stent) in femoropopliteal lesions at 12 and 24months using a meta-analysis of proportions. Materials & methods: This systematic review (PROSPERO CRD42024528559) used PubMed to identify relevant single-arm and comparative studies (with ≥50 patients/study) published between 1 January 2009 and 1 July 2024. Data on patient/lesion characteristics and outcomes were extracted. Subgroup analyses were based on lesion length (<150mm vs ≥150mm) and study quality. A random-intercept logistic regression model was used to pool the data. The 95% CI around the pooled effect was calculated using Knapp-Hartung adjustments. Results: Data were extracted from 141 of the 870 screened studies, corresponding to 35,897 patients. The mean patient age was 70.9 (range: 63.3-80.0) years; 69.6% were male. The overall mean lesion length was 153.1 (range: 37-330) mm. Although all stent types performed well in the main analysis, Eluvia exhibited consistently high primary patency and low target lesion revascularization rates at both timepoints and across lesion lengths. Mortality rates for all stent types were stable for short lesions but more variable for long lesions. Conclusion: All stents used in short lesions performed well; however, Eluvia also demonstrated reliable performance in long lesions.

In this update, we review a new bias appraisal tool, explore lessons from a trial emulation study, and describe the development of real-world evidence guidance in the Philippines.

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:Two fixed-dose combination triple therapies, budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) 320/14.4/10 μg and fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 μg, have been shown to reduce all-cause mortality in phase III trials. A recent matching-adjusted indirect comparison showed greater mortality reduction with BGF versus FF/UMEC/VI. However, the comparative cost-effectiveness of these treatments remains unknown. This study aimed to use a cost-effectiveness model to compare BGF with FF/UMEC/VI in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD) who are eligible for triple therapy from a UK third-party payer perspective.Materials & methods:A cohort-based semi-Markov model was used with the natural progression of COPD defined by four lung function levels. Input parameters included participant characteristics and clinical efficacy parameters derived from the ETHOS and KRONOS trials, the UK general population and published literature. Unit costs were obtained from the UK National Health System Schedule of Reference Costs (2021/2022), the Personal Social Services Research Unit (2022) and published literature. Outputs included an incremental cost-effectiveness ratio, costs, quality-adjusted life years and life years at time horizons of 1 and 5 years. Model inputs and assumptions were subject to deterministic and probabilistic sensitivity and scenario analyses.Results:At both 1- and 5-year time horizons, BGF was less costly (-£7.24 and -£23.03 per patient) and more effective (0.002 and 0.21 quality-adjusted life years per patient) versus FF/UMEC/VI, respectively. Due to a reduced mortality rate, more patients remained on BGF treatment than on FF/UMEC/VI, which induced higher treatment-related costs; however, the latter was offset by decreased end-of-life costs, as BGF avoided more deaths.Conclusion:BGF may improve health outcomes and reduce healthcare costs compared with FF/UMEC/VI in patients with moderate-to-very severe COPD in a UK setting.

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.

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: To assess the predictive effect of threshold deviations for multiple liver biomarkers on negative clinical outcomes, including hepatic decompensation, liver transplantation, and death in patients with primary biliary cholangitis (PBC) using longitudinal data from a large administrative claims database. Materials & methods: A time-dependent Cox proportional hazards model with time-dependent covariates assessed time to first occurrence of hospitalization for hepatic decompensation, liver transplantation, or death in patients with PBC in the Optum Clinformatics Data Mart™ database. Separate models analyzed proportion of time outside prespecified biomarker thresholds (defined as multiples of upper limit of normal [ULN] for alkaline phosphatase [ALP], total bilirubin [TB], aspartate aminotransferase [AST], and alanine aminotransferase [ALT]; lower limit of normal for albumin). Another model evaluated both ALP and TB with the lowest relevant threshold applied for each biomarker. Results: Overall, 2402 patients were included; 85.3% were female, mean age was 63.3years, median follow-up was 2.2years (interquartile range: 1.1-3.9years). On average, patients had approximately five reported measurements for each biomarker evaluated. Each 10% increase in time outside thresholds was associated with a 6.5%, 9.2%, 9.9%, 7.3% and 23.3% increase in risk of negative outcomes for ALP, TB, AST, ALT and albumin, respectively. Conclusion: In patients with PBC, values outside predefined thresholds for biomarkers including ALP, TB, AST, ALT and albumin strongly predicted negative clinical outcomes. These findings highlight the importance of managing biomarkers beyond ALP in monitoring and the treatment of patients with PBC.

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 24h 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 24h 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 48.5years and a mean BMI of 24.61kg/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 40.1min, with a median wound healing time of 15days. Remarkably, only one wound infection occurred within 30days, 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: To report the efficacy and safety of ataluren in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD) from the phase III, 72-week, placebo-controlled period of Study 041. Materials & methods: Inclusion criteria: boys with nmDMD aged ≥5years, on a stable corticosteroid regimen for ≥12months, and baseline 6-minute walk distance (6MWD) ≥150m. Randomization: 1:1, ataluren (40mg/kg/day):placebo. Primary end point: slope of 6MWD change (average rate of change). Secondary end points: changes in 6MWD, time to 10% persistent worsening in 6MWD, North Star Ambulatory Assessment score, timed function tests and safety. Study populations: intention-to-treat; patients aged ≥7 to ≤16years with baseline 6MWD ≥300m and stand from supine ≥5s; patients with baseline 6MWD 300-400m. Results: In the intention-to-treat population (n=359), over 72weeks, ataluren reduced the rate of 6MWD decline by 21% (p = 0.0248), reduced the average 6MWD change (p = 0.0248), delayed time to 10% persistent worsening in 6MWD (p = 0.0078), and reduced North Star Ambulatory Assessment total score decline (p = 0.0235), change in 10m walk/run time (p=0.0422) and change in time to climb four stairs (p = 0.0293) versus placebo. In the 6MWD 300-400m subgroup (n=169), ataluren reduced the rate of 6MWD decline by 30% (p = 0.0310) versus placebo. Ataluren treatment benefits were seen in secondary end points in this subgroup, except for change in time to descend four stairs. In the 6MWD ≥300m and time to stand from supine ≥5s subgroup (n=185), there was a 9% slower rate of 6MWD decline for ataluren versus placebo over 72weeks (p = 0.3626). Ataluren reduced change in time to climb four stairs (p = 0.0179) versus placebo in this subgroup; no treatment benefits were seen for other secondary end points. Ataluren was well tolerated (serious adverse events: ataluren, 7.1%; placebo, 6.8%); no deaths occurred. Conclusion: Long-term ataluren treatment has a favorable benefit-risk profile, slowing motor function decline in the largest phase III nmDMD study to date.

The first paper of this two-part series critically examined the role of composite endpoints in health technology assessments (HTAs) and outlined strategies for determining whether to employ the composite estimate of treatment effect or disaggregate into the component endpoints of the composite and apply separate treatment effects within a modeling framework. In this second paper, we expand the discussion beyond a pivotal trial and consider the way in which additional evidence from the same indication for different drugs in the same class, or the same drug for different indications, could be employed within HTAs. We offer a continuation of the case study of dapagliflozin for the treatment of heart failure with preserved or mildly reduced ejection fraction, where the evidence base was expanded to consider empagliflozin for the same indication, as well as both dapagliflozin and empagliflozin for heart failure with reduced ejection fraction. We conclude that, where there are multiple drugs in the same class and/or multiple indications for a class of drugs, HTAs should consider the exchangeability of the information that comes from additional evidence beyond the pivotal registration study. Further, we show how consideration of this additional evidence can support the decision concerning whether to disaggregate the components of a composite endpoint or employ the treatment effect from the composite for each endpoint.