Aim: Metabolic dysfunction-associated steatohepatitis (MASH) and steatotic liver disease (MASLD) are progressive liver conditions that can lead to serious long-term outcomes and adverse clinical events. Histologic liver fibrosis is an accepted short-term surrogate end point used in pivotal clinical trials supporting conditionally approved MASH therapies. This study aimed to synthesize up-to-date published associations between histologic liver fibrosis and clinical outcomes, including several novel syntheses. Materials & methods: A systematic literature review identified studies of MASH ± MASLD patients published January 2014 to November 2024 from Ovid MEDLINE®, Embase and grey literature. Studies reporting hazard ratios (HRs) comparing the risk of relevant major adverse liver outcomes (MALO; e.g., cirrhosis, hepatic decompensation, hepatocellular carcinoma) and mortality by histologic liver fibrosis stage were included in meta-analysis. Pooled estimates were reported as HRs and 95% CIs. Results: Of 2810 returned records, there were 32 eligible studies from 39 articles. Higher fibrosis stage was associated with increased risk of clinical outcomes. Risk of progression to cirrhosis was twofold higher in F3 versus F2 (2.05 [1.45, 2.90]). Risk of hepatic decompensation was >ten-times higher in F3-4 versus F0-2 (10.93 [6.31, 18.92]). Risk of MALO and all-cause mortality were also significantly higher in F4 versus F3 and versus F2, and in F3-4 versus F0-2. Results were directionally consistent among studies of MASH-majority (≥80% MASH) populations and individually reported HRs. Conclusion: Increased clinical risk with more advanced fibrosis and/or cirrhosis among patients with significant liver disease supports the value of histologic liver fibrosis as a short-term surrogate for long-term clinical outcomes.
Aim: Lorlatinib and alectinib are next-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) approved for the treatment of ALK-positive (ALK+) advanced/metastatic non-small cell lung cancer (NSCLC) after demonstrating superior efficacy over crizotinib (first-generation ALK TKI) in the CROWN and ALEX trials, respectively. This analysis estimated the US population-level clinical impact of first-line (1L) lorlatinib versus alectinib treatment for ALK+ advanced/metastatic NSCLC. Materials & methods: We developed a decision-analytic model comparing lorlatinib versus alectinib use in 1L. We used a three-state partitioned survival model (pre-progression, post-progression and death) and tracked incidence of brain metastases (BMs). Lorlatinib-eligible population estimates were derived from published literature and market forecasts; treatment effectiveness for lorlatinib was derived from CROWN; alectinib comparative effectiveness was informed using a match-adjusted indirect comparison (CROWN vs ALEX). We assumed lorlatinib uptake of 38% in the base case; selected scenarios included different survival extrapolations, assuming 100% lorlatinib uptake and applying risk of BM post-discontinuation. Results: We estimated that 3096 patients in the US would be eligible for lorlatinib. Compared with 1L alectinib use only, our model projected that 1L lorlatinib treatment results in 1620-5170 and 1590-4880 more life-years and quality-adjusted life-years, respectively, over a 20-year time horizon across scenarios. Per-patient incidence of BM ranged from 0.14-0.18 and 0.21-0.40 for lorlatinib and alectinib, respectively, resulting in 68-256 fewer BMs. Separately, for every 5-15 patients treated with 1L lorlatinib instead of 1L alectinib, one BM would be avoided. Conclusion: This analysis projected that 1L lorlatinib treatment in the US could result in more LYs and quality-adjusted life-years and fewer BMs versus 1L alectinib in ALK+ advanced/metastatic NSCLC.
Background: Visible cervical scarring remains a common concern following conventional thyroidectomy and may adversely affect cosmetic satisfaction and quality of life. Although several postoperative wound interventions have been introduced to improve scar healing, their comparative effectiveness remains uncertain because of inconsistent findings across randomized controlled trials (RCTs). Aim: To systematically evaluate the effectiveness of postoperative wound interventions in improving scar outcomes following thyroidectomy and thyroid/parathyroid surgery. Materials & methods: PRISMA 2020-guided systematic review and meta-analysis searched PubMed, Scopus, Web of Science and Cochrane Central Register of Controlled Trials from inception to January 2026 for RCTs of postoperative wound interventions in adults undergoing thyroidectomy or thyroid/parathyroid surgery. Interventions included adhesive/tissue glue techniques, wound-protector devices, and oxygen therapy dressings versus postoperative wound management. Scar outcomes used instruments including the Vancouver Scar Scale and the Patient and Observer Scar Assessment Scale. Random-effects meta-analysis reported standardized mean differences (SMDs) with 95% CIs. Results: Fourteen RCTs met the inclusion criteria for qualitative synthesis, of which seven independent effect sizes were eligible for quantitative meta-analysis. Overall, postoperative wound interventions did not significantly improve scar outcomes compared with conventional wound management when pooled across all intervention types (SMD: -0.21; 95% CI: -0.45 to 0.04; p = 0.10), reflecting substantial heterogeneity between intervention categories (I2 = 74%). Considered separately, wound-protector devices demonstrated a significant improvement in scar outcomes (SMD: -0.84; 95% CI: -1.06 to -0.62; p < 0.001), whereas tissue adhesives produced cosmetic results comparable to conventional subcuticular sutures, with no measurable scar-quality advantage (SMD: 0.14; 95% CI: -0.12 to 0.40; p = 0.29). Continuous diffusion oxygen therapy showed promising early clinical benefits but was evaluated in only one randomized trial and was therefore summarized narratively. Conclusion: Current randomized evidence indicates that the benefit of postoperative wound interventions on scar outcomes is intervention-specific rather than a uniform class effect: wound-protector devices show a consistent, statistically significant benefit, whereas the pooled effect across all intervention types combined does not reach significance. Tissue adhesives provide satisfactory outcomes and efficient wound closure without a measurable scar-quality advantage over standard sutures, and evidence for oxygen therapy remains preliminary. Larger, well-designed trials using standardized scar assessment and longer follow-up are required to establish optimal postoperative scar management.
Aim: To validate ConcertAI's All Source Composite Mortality Endpoint (ASCME), which combines information from electronic health records, obituary, government and administrative claims. To compare overall survival (OS) estimates using ASCME versus a National Death Index (NDI) dataset across clinical cohorts. Materials & methods: Retrospective study of oncology real-world data, reporting sensitivity, specificity, positive predictive value and negative predictive value compared with the NDI standard, plus 5, 7 and 15-day concordance on date of death. Additional comparisons included Kaplan-Meier OS measured by ASCME versus NDI. Data sources included ConcertAI's Patient360™ dataset, and a 2022 annual finalized NDI dataset. The sample included cancer patients prevalent from 1 April 2014 to 31 December 2022 in any of 10 of ConcertAI's solid tumor-specific datasets. Results: Of 32,358 study patients, 14,241 (44.0%) were deceased as defined by an NDI true match. Sensitivity was 95.0% overall (an incremental 5.2% due to claims) and ranged from 92.7% to 97.8% across clinical cohorts. Overall specificity was 96.5%, with positive predictive value and negative predictive value of 95.8% each. ASCME's 5-day concordance was 97.9%, with 7-day and 15-day concordance of 98.2% and 99.1%, respectively. ASCME and NDI-based median OS estimates differed by 12.2 days among non-metastatic cohorts, and 4.5 days among metastatic cohorts. Conclusion: Results show ConcertAI's ASCME death indicator to provide high completeness and accuracy, producing OS estimates largely indistinguishable from NDI-based estimates. Findings show the importance of including claims in composite mortality indicators and demonstrate the value of real-world data in assessing OS outcomes in metastatic and non-metastatic cancer patient populations.
Aim: Fludarabine, cyclophosphamide and rituximab (FCR) is a first-line therapy for fit treatment-naive patients with chronic lymphocytic leukemia (CLL); however, its hematotoxicity and related infections necessitate more efficacious, safer treatments. Zanubrutinib is a highly potent and selective next-generation Bruton tyrosine kinase inhibitor approved for treatment-naive patients with CLL and small lymphocytic lymphoma. Given the absence of clinical trials providing head-to-head comparisons, the aim of this analysis was to conduct a matching-adjusted indirect comparison between zanubrutinib and FCR. Materials & methods: Patient-level data from SEQUOIA (zanubrutinib vs bendamustine + rituximab [BR]) was adjusted for interpopulation differences through propensity-score matching with aggregate data from the CLL10 trial (FCR vs BR). Progression-free survival (PFS) was compared among populations matched for immunoglobulin heavy-chain gene mutation, 11q deletion, β2-microglobulin, Binet stage and age. Sensitivity analyses incorporated geographic region, sex, creatinine clearance, the Cumulative Illness Rating Scale, Eastern Cooperative Oncology Group performance status and previous infections. Results: Zanubrutinib improved PFS compared with FCR, with a hazard ratio of 0.41 (95% CI: 0.20-0.81; effective sample size 174). Including geographic region, Eastern Cooperative Oncology Group performance status or previous infections as matching factors one by one in the propensity score model showed similar results. Incorporating Cumulative Illness Rating Scale or creatinine clearance showed numerically favorable PFS with zanubrutinib (hazard ratio [95% CI] 0.45 [0.16-1.24] and 0.52 [0.24-1.13], respectively), owing to the low effective sample size of the expanded model (64 and 123, respectively). Conclusion: Our findings suggest that zanubrutinib offers improved PFS over FCR in fit, treatment-naive patients with CLL, further supporting zanubrutinib as a first-line CLL treatment for multiple patient profiles.
Aim: Progressive familial intrahepatic cholestasis (PFIC) comprises a group of rare, heterogeneous genetic liver disorders characterized by impaired bile formation and cholestasis. Historically, treatment focused on supportive management and symptomatic relief, but disease-specific therapies, including ileal bile acid transporter inhibitors, have recently become available. This systematic review updates previous evidence on the epidemiology, natural history, psychosocial and economic burden of PFIC, and summarizes evidence on the efficacy, safety and cost-effectiveness of therapies used primarily in patients with PFIC type 2 (bile salt export pump [BSEP] deficiency). Materials & m ethods: Twenty-seven databases and supplementary literature sources were searched in February 2021 and updated in January 2025. Studies were selected to address five review questions. Due to substantial heterogeneity in study populations, PFIC subtypes, outcome definitions and study designs, findings were synthesized narratively. Results: A total of 114 publications were included. Findings relating to epidemiology, natural history, psychosocial burden and economic burden were broadly consistent with previous reviews and highlighted the substantial impact of PFIC on children and their caregivers. Many patients treated with maralixibat and odevixibat demonstrated improvements in pruritus, serum bile acid concentrations, quality of life and markers of liver health, particularly those with PFIC2/BSEP deficiency. However, treatment responses varied across studies and genotypes, and long-term data remain limited. Only a small amount of economic evidence was identified. Conclusion: PFIC is associated with significant clinical and psychosocial burden. Ileal bile acid transporter inhibitors provide a novel, targeted, nonsurgical treatment option for many patients: current evidence supports improvements in pruritus and serum bile acid control, particularly in PFIC2/BSEP deficiency; however, treatment responses are heterogeneous and additional long-term clinical and economic evidence is needed.
Aim: Primary biliary cholangitis (PBC) is a rare liver disease associated with high morbidity. This study assessed the burden of fatigue and/or pruritus among patients with PBC in the US. Materials & methods: This retrospective study used IQVIA PharMetrics® Plus data (2016-2022). Patients with PBC and fatigue and/or pruritus were selected as cases. Controls were patients with PBC (no fatigue nor pruritus), matched 1:1 to cases by key characteristics. The index date for cases was a random symptom diagnosis date post-initial PBC diagnosis and for controls, a random medical visit date matching the time distribution from initial PBC diagnosis to index. Cumulative incidence of PBC comorbidities was described using Kaplan-Meier analysis and compared via Cox Proportional hazard models. Generalized estimating equations compared healthcare resource use (HRU) and costs per-patient-per-year. Results: A total of 1839 fatigue cases/controls (mean age [years]: 56.5; 88.7% female) and 760 pruritus cases/controls were included (mean age [years]: 55.8; 90.8% female). Comorbidities at 1, 3 and 5-years post-index were higher for cases than controls (fatigue: 1.7 vs 0.7, 2.2 vs 0.9 and 2.5 vs 1.0; pruritus: 1.9 vs 0.8, 2.3 vs 1.0 and 2.7 vs 1.0; all p < 0.001). Common comorbidities were anxiety, urinary tract infection, depression and sleep disorders (hazard ratios in cases vs controls: fatigue, 1.3-4.0; pruritus, 1.5-2.8; all p < 0.01). One-year post-index, cases had higher rates of healthcare visits (incidence rate ratios: fatigue, 1.8-5.8; pruritus 1.6-6.1) and total healthcare costs (mean cost difference: fatigue, $42,515; pruritus $40,536). Conclusion: Patients with PBC who experience fatigue and/or pruritus faced a greater clinical and economic burden compared with those without these symptoms, highlighting the need for effective treatments to alleviate PBC symptoms.
Background & aim: Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease that can lead to increased morbidity and mortality. This study described real-world treatment patterns and clinical outcomes by line of treatment among patients with PBC in the US. Materials & methods: Adults (≥18 years) diagnosed with PBC on or after 1 January 17 were identified in the IQVIA PharMetrics® Plus database and grouped into newly diagnosed, first-line (1L) and second-line or more (2L+) cohorts. Index date was initial PBC diagnosis or initiation of 1L or 2L therapy; follow-up continued until the earliest of end of continuous enrollment, death or data end. Time to treatment initiation, treatment discontinuation and negative clinical outcomes were assessed with Kaplan-Meier analysis. Results: The newly diagnosed, 1L and 2L+ cohorts included 1748, 1659 and 181 patients, respectively (average age at index: 52.7-54.5 years; female: 84.2-89.0%). Of the newly diagnosed cohort, 34.8% did not initiate PBC treatment within 1.5 years post-diagnosis. In the 1L cohort, median time from diagnosis to 1L initiation was 1.2 months; median time from 1L initiation to 1L discontinuation/2L initiation was nearly 5 years. In the 2L+ cohort, median time from 2L initiation to 2L discontinuation was approximately 4 years. In the untreated, 1L, and 2L+ cohorts, 18.9%, 14.4% and 19.3% of patients developed ≥1 negative clinical outcome post-index (usually cirrhosis). Conclusion: Results of this US population-based study demonstrate a potential unmet need for early intervention and effective treatment options for patients with PBC, as one in three patients with PBC remain untreated years after diagnosis.
Aim: Indirect treatment comparisons (ITCs), as outlined in NICE and ISPOR guidance, require careful evaluation of cross-trial heterogeneity to ensure valid comparisons, particularly in rare diseases with limited evidence. C3 glomerulopathy (C3G) is an ultra-rare, complement-mediated kidney disease with high unmet need, making appropriate application of ITC frameworks especially critical. This appraisal evaluates the feasibility of applying ITC principles to compare Phase III trials of iptacopan (APPEAR-C3G) and pegcetacoplan (VALIANT) in the absence of head-to-head evidence. Materials & methods: Feasibility of an ITC in C3G was assessed through critical appraisal of APPEAR-C3G and VALIANT randomized controlled trials, focusing on alignment of eligibility criteria, baseline characteristics and outcome definitions, in line with NICE DSU TSD-18, CHTE2020 and ISPOR guidance. A systematic literature review (SLR) was then conducted to identify published ITCs comparing iptacopan and pegcetacoplan in C3G, which were evaluated for methodological rigor, transparency and credibility according to NICE and ISPOR recommendations. Results: Substantial heterogeneity was observed between APPEAR-C3G and VALIANT. Overlap was limited to small subpopulations, with imbalances in baseline characteristics, differences in end point reporting, and noncomparable placebo responses. These issues indicate that anchored ITCs are not feasible using currently available data without extensive adjustments that conflict with NICE and ISPOR guidance. The SLR identified one ITC poster with limited methodology comparing these trials. However, when the results were subsequently published in a manuscript, crucial methodological details including justification of effect modifiers, modeling diagnostics, analytic procedures, were still unavailable. Other concerns, such as using standard matching-adjusted indirect comparison methodology in the presence of substantial cross-trial heterogeneity, and the resulting limited ESS observed frequently in rare diseases, were confirmed, thus undermining credibility of conclusions. Conclusion: ITCs in C3G face significant methodological challenges due to pronounced trial heterogeneity and small sample sizes inherent to this ultra-rare disease. These limitations complicate the conduct and interpretation of arising ITCs, highlighting the need for transparent and methodologically robust approaches. Consequently, payers, decision makers, and HTA bodies should interpret existing C3G ITCs with caution. These findings inform broader application of ITC methods in rare diseases, identifying areas for future evidence generation and analytical innovation.
Aim: This nationwide cohort study primarily aimed to descriptively characterize real-world treatment patterns, including treatment initiation, adherence, treatment duration and discontinuation of the first treatment drug, among patients who experienced a recurrent osteoporotic fracture. Materials & methods: This population-based, retrospective cohort study used data from the Health Insurance Review and Assessment Database of South Korea. It included male and female patients aged 55 years and older who experienced a recurrent osteoporotic fracture within 2 years of their index fracture in 2013. Results: The study period was from 1 January 2012 to 31 December 2021, with an outcome assessment period from 1 January 2013 to 31 December 2017. A total of 34,558 patients with recurrent osteoporotic fractures were observed, and just over half (n = 18,462, 53.4%) received osteoporosis medication, with a significant difference in medication rates between males (23.7%) and females (58.8%) (p < 0.001). The estimated median duration of osteoporosis medication was 146 days (interquartile range: 61-365 days). The discontinuation rate of medication within 2 years of follow-up after their recurrent fracture was 80.5%, with the highest discontinuation rate (90.4%) observed among patients taking daily oral bisphosphonate medication. Conclusion: Although patients with recurrent fractures require intensive management, our results showed a significant unmet need in the initiation and persistence of osteoporosis medication. Therefore, it is crucial to establish a strategic treatment approach to address the treatment gap in managing osteoporosis among very high-risk patients. Dataset name: Health Insurance Review and Assessment Database of South Korea.
Aim: Cervical cancer, caused primarily by human papillomavirus infection, affects patients' health-related quality of life (HRQoL). Despite research on quality of life in cancer patients, studies using the HINT-8 instrument, especially for cervical cancer, are scarce. This study evaluates the validity of HINT-8 in measuring HRQoL among Korean cervical cancer patients by comparing it with EQ-5D-5L. Materials & methods: Demographic and clinical characteristics were analyzed. Mean, median and standard deviations for each domain of both instruments were calculated. Spearman and Pearson correlation coefficients assessed relationships between HINT-8 and EQ-5D-5L indices and domains. Results: Increased problem intensity in HINT-8 domains (e.g., stair climbing, pain and vitality) was correlated with decreased EQ-5D-5L index, indicating a higher response level in HINT-8 aligns with lower EQ-5D-5L scores. Significant variables were consistent across tools, showing no substantial functional difference. A strong correlation between HINT-8 and EQ-5D-5L indices (r = 0.771, p < 0.01) supports HINT-8’s effectiveness in evaluating HRQoL for cervical cancer patients. Conclusion: The HINT-8 demonstrated a strong correlation with the EQ-5D-5L index and a substantially lower ceiling effect, suggesting that it can capture subtle differences in HRQoL among cervical cancer patients. Furthermore, the HINT-8 may provide complementary information beyond the EQ-5D-5L by capturing distinct dimensions such as memory, sleep and happiness, which are not explicitly represented in the EQ-5D-5L descriptive system. These findings support the validity of the HINT-8 as a complementary instrument for assessing HRQoL in Korean cervical cancer patients.
Aim: To evaluate the clinical effectiveness of a digitally delivered balance program relative to an attention-control comparison group in older adults at risk for falls. Materials & methods: This nonrandomized controlled trial recruited adults aged 65 years and older with moderate-to-high fall risk. Participants were assigned to a digital balance program (exercise therapy, education and health coaching) or an attention-control group (education materials). Outcomes were assessed via self-report surveys at baseline and 3 months. Analyses including all assigned participants evaluated changes in fall rate, fall severity, physical function and medical care utilization. Results: A total of 687 participants were included in the analysis (intervention: n = 344; attention-control: n = 343). The mean age was 68.8 years, and 74.1% of participants were female. In the primary analysis, adjusting for baseline factors, the intervention group demonstrated a 37% lower fall rate compared with the attention-control group at 3 months (IRR: 0.63, 95% CI: 0.48–0.82, p < 0.001). The intervention group also demonstrated significant improvement in physical functioning (β = 6.86, 95% CI: 3.80–9.92, p < 0.001) and lower odds of emergency department visits (OR: 0.43, 95% CI: 0.24–0.76, p = 0.004). Intervention participants engaged in an average of 25.2 exercise therapy sessions over the 12-week period. Conclusion: Findings suggest that participation in the digital balance program was associated with reductions in self-reported fall rates, improvements in self-reported physical function, and lower odds of emergency department utilization. High engagement levels further indicate that digitally delivered programs offer a viable option for improving health outcomes in this population. Trial Registration: Clinicaltrials.gov NCT06868680 retrospectively registered 6 March 2025.
Aim: This study aimed to assess the cost-effectiveness of the annual volumetric-enabled low-dose computed tomography (LDCT) lung cancer screening (LCS), based on the NELSON screening outcomes, versus no screening for the asymptomatic high-risk population in Lithuania. Materials & methods: The previously established model with a decision tree with an integrated state-transition Markov trace was adapted to assess the health benefits and the financial consequences of LCS from the Lithuanian healthcare system perspective. Individuals aged 50-74 years and with a smoking history underwent LCS with LDCT in the screening arm, and it was compared with the absence of screening across a lifetime horizon. The primary outcomes included the clinical benefits (lung cancer cases detected per stage and premature lung cancer deaths averted), direct costs (recruitment, diagnostic and treatment costs) of LCS implementation, quality-adjusted life years, life-years and the incremental cost-effectiveness ratio. One-way sensitivity analysis and probabilistic sensitivity analysis were conducted to ascertain the result's robustness. Results: Annual LCS with volumetric-enabled LDCT for 170,808 eligible individuals in Lithuania resulted in 6117 additional early-stage (I and II) lung cancers detected and 1874 averted late-stage (III and IV) lung cancers, leading to 2606 premature lung cancer deaths averted and 21,639 life-years gained at an uptake rate of 46.5%. The incremental cost-effectiveness ratio was €1372 per quality-adjusted life year with incremental costs of €21.1 million and 15,391 quality-adjusted life years gained. The results were robust based on sensitivity and scenario analyses. Conclusion: This study demonstrated that annual LCS with volumetric-enabled LDCT for a high-risk population could be cost-effective compared with no screening in Lithuania.
Aim: In high income settings, insulin analogues were associated with improved glycemic control among adults with diabetes, mainly measured through HbA1c and hypoglycemic episodes. In low- and middle-income countries, especially those affected by humanitarian crises, analogue insulins may be helpful as proper diabetes care for this population remains challenging; yet, supporting evidence is lacking. Materials & methods: Routinely collected continuous glucose sensor data from patients with Type 1 diabetes, aged 4 to 18 years old, between April 2019 and December 2022 was retrospectively extracted. Changes in glycemic metrics while using analogue insulins were compared with human insulin using multiple linear regression with random effects. Results: Forty-five patients included in the study used continuous glucose monitor devices for an average duration of 73 days (±53) while using human insulin and 170 days (±83) while using analogue insulins. Compared with human insulin, analogue insulins were associated with an additional 26 min (95% CI; 15, 37, p < 0.001) per day spent within the normal target range and a reduction of 11 min (95% CI; -16, -5) and 10 min (95% CI; -13, -7) in overall and nocturnal hypoglycemia, respectively. Analogue insulin was also associated with a reduction of 6 mg/dl in 24 h mean glucose. Conclusion: Insulin analogues were associated with slight improvements in time within and below range compared with human insulin, yet within patient glycemic variability remains high. Further research is needed to explore its acceptability among patients, impact on quality of life and its cost-effectiveness and sustainability in low resource contexts.
Aim: Late-onset Pompe disease (LOPD) is a rare lysosomal disease primarily impacting muscle strength and respiratory function. LOPD has a substantial burden despite the availability of alglucosidase alfa (alg). Patients often require mobility and respiratory support over time. Cipaglucosidase alfa in combination with miglustat (cipa + mig) is one of two more recently approved treatments for adults with LOPD. Given limited data on the lifetime trajectory to mobility and respiratory support in LOPD, a patient-level simulation model was developed to compare the long-term impact of cipa + mig with alg on these outcomes. Materials & methods: The patient-level simulation predicts lifetime mobility and respiratory disease progression outcomes based on the 6-min walk distance and %predicted forced vital capacity for alg and cipa + mig for the overall LOPD population using available data and assumptions from experienced clinicians. PROPEL/PROPEL open-label extension ( NCT03729362 ) and ATB200-02 ( NCT02675465 ) studies informed outcomes for four years with cipa + mig and one year with alg. French Pompe disease registry data were used thereafter. Results: Based on the available data and clinical assumptions, the model predicts cipa + mig slows the overall progression of LOPD, allowing patients an additional 2.72 years without mobility or respiratory support compared with alg. People receiving alg may be wheelchair dependent and require invasive respiratory support for an additional 2.57 and 1.55 years, respectively. Conclusion: Cipa + mig may delay disease progression compared with alg over the lifetime of a patient with LOPD, which would increase the amount of time spent without mobility and respiratory support dependency.
In this update, we review the US FDA’s updated compendium of real-world evidence (RWE) use in medical device regulatory decisions, a comprehensive scan of RWE utilization in Canadian drug reimbursement submissions, and Institute for Clinical and Economic Review’s use of RWE to inform US Medicare drug price negotiations under the Inflation Reduction Act.
In this update we examine the inaugural report of the Health Economics Methods Advisory group on defining appropriate benefits for economic evaluation and the responses it has generated. We also review recent research on the timeliness of commercial health plan coverage policy updates following US FDA label revisions, which reveals substantial delays and wide variation across plans that may limit patient access to specialty therapies.
Background: Ciltacabtagene autoleucel (cilta-cel) was approved for patients with relapsed or refractory multiple myeloma who received 1–3 prior lines of therapy in April 2024. Although traditionally administered inpatient (IP), there is an increasing trend in outpatient (OP) cilta-cel administration. However, few studies have quantified the healthcare resource utilization (HCRU) and cost implications of OP versus IP administration in clinical practice. Aim: To compare HCRU and costs following OP versus IP administration of cilta-cel among patients with relapsed or refractory multiple myeloma after 1–3 prior lines of therapy. Materials & methods: This retrospective observational study used the Loopback Analytics electronic medical records database (28 February 2017 to 30 June 2025). We classified patients into OP or IP cohorts. All-cause and multiple myeloma-related HCRU and per-patient-per-month imputed costs were compared over 30 and 90 days post-infusion. Results: There were 99 patients included (OP: 37; IP: 62). In the first 30 days post-infusion, 40.5% of the OP cohort did not require IP admission. Compared with the IP cohort, the OP cohort had significantly lower all-cause IP days (adjusted incidence rate ratio: 0.31; p < 0.001) and significantly lower all-cause IP-related imputed costs (adjusted mean difference: -$39,786; p < 0.001). Results were consistent over the first 90 days post-infusion and for multiple myeloma related HCRU and costs. Overall, OP administration was associated with an estimated cost savings of approximately $40,000 and $53,000 per patient in the first 30 and 90 days post-infusion, respectively. Conclusion: OP administration of cilta-cel was associated with significantly lower IP resource utilization and imputed costs over the first 3 months post-infusion relative to IP administration, supporting the potential economic value and adoption of OP cilta-cel delivery.
Aim: Network meta-analyses (NMAs) of seasonal vaccines face distinct challenges that can compromise the validity and relevance of findings. While established frameworks offer guidance for evaluating the feasibility of NMAs, they do not address factors specific to seasonal vaccines. This study aims to highlight unique methodological challenges related to conducting NMA feasibility assessments of seasonal vaccines. The considerations are framed to be compatible with existing guidance and recommendations for the conduct and reporting of NMAs. Materials & methods: We developed a set of key considerations that should be applied when assessing the feasibility and/or validity of NMAs comparing seasonal vaccines. The considerations were based on systematic reviews and critical appraisals of published NMAs of seasonal vaccines, hands-on experience performing feasibility assessments of seasonal vaccines, and input from consultations with vaccine experts. Results: Unique considerations for evaluating comparability across seasonal vaccine studies include: whether vaccines should be compared by platform, formulation, dose, and/or valence; the impact of seasonality, strain evolution and definitions of placebo/unvaccinated controls on network connectivity; target population characteristics including history and recency of prior vaccination and/or infection(s), and baseline infection/severe disease risk; antigenic match (i.e., the degree of concordance between vaccine composition and circulating viral strains), which directly influences effectiveness and outcome measurement approaches that consider time varying epidemiology and assay and measure discrepancy. Comprehensively integrating these elements into existing guidance frameworks ensures transparent assessment of the key assumptions underlying NMA (i.e., transitivity and homogeneity) within the context of unique study design and methodological features of seasonal vaccine studies. Conclusion: The concepts highlighted in this paper address important gaps in the feasibility assessment process for NMAs of seasonal vaccines, which are crucial for informing public health decisions and guiding vaccine policy and implementation.
