Journal of comparative effectiveness research最新文献

Aim: Real-world evidence (RWE) - defined here as clinical evidence derived from the analysis of real-world data (RWD) on patient health status and healthcare delivery - has become a cornerstone of regulatory and health technology assessment (HTA) decision making. However, despite broad consensus on its value, policy frameworks governing RWE generation and evaluation remain heterogeneous across jurisdictions. Importantly, this heterogeneity partly reflects the distinct purposes for which RWE is used, including regulatory safety assessment, effectiveness evaluation, health-economic modeling and natural-history research. These functional differences are not inherently problematic; however, fragmented operational requirements can create duplication, inefficiency and delays in patient access. Materials & methods: This study employed a narrative comparative policy review of RWE guidance issued by twelve major regulatory and HTA agencies, including the Medicines and Healthcare products Regulatory Agency (MHRA), the EMA, the US FDA and the Canadian Agency for Drugs and Technologies in Health (CADTH). Frameworks were compared across four domains: data quality, statistical methods, registry governance and transparency. Harmonization is defined as alignment across these domains sufficient to enable consistent planning, analysis and interpretation of RWE across jurisdictions, rather than uniformity of decision making. Results: The analysis identified convergence in high-level principles but persistent divergence in operational expectations. The MHRA emphasizes flexibility and scientific dialogue; the EMA prioritizes consistency and structured governance; and the FDA provides comprehensive but resource-intensive guidance, reflecting detailed documentation requirements, prespecified analytic expectations and extensive methodological review. HTA bodies apply additional evidentiary criteria related to comparative effectiveness and value, sustaining functional fragmentation even within the same healthcare systems. Conclusion: RWE fragmentation reflects both legitimate functional differences and avoidable operational misalignment. Progress toward harmonization therefore requires shared minimum standards and transparency mechanisms rather than additional guidance documents. The UK's post-Brexit autonomy positions it as a test environment for collaborative pilots with the European Medicines Agency, the International Council for Harmonization (ICH) and the International Coalition of Medicines Regulatory Authorities (ICMRA). Six strategic actions are proposed to support pragmatic alignment while preserving contextual flexibility.

Aim: Treatment options for late-onset Pompe disease (LOPD) include enzyme replacement therapy (ERT) with alglucosidase alfa (alg), cipaglucosidase alfa plus miglustat (cipa + mig) and avalglucosidase alfa. However, only one randomized controlled trial (RCT) directly compared cipa + mig and alg and had relatively few ERT-naive patients. A multilevel network meta-regression (ML-NMR) integrated individual patient data and aggregate data into indirect treatment comparisons, with relative effects adjusted to any target population, to compare the efficacy of cipa + mig and alg. Materials & methods: A Bayesian ML-NMR was conducted to compare the efficacy of cipa + mig and alg for 6-minute walk distance (6MWD, meters) and percent predicted forced vital capacity (ppFVC) across any target population, using patient-level and aggregate data from RCTs (PROPEL, COMET, LOTS) and phase I/II and open-label extension (OLE) trials (PROPEL OLE, LOTS OLE, COMET OLE, ATB200-02, NEO-1/NEO-EXT), adjusting for baseline covariates. Relative effect estimates were obtained for 6MWD and ppFVC change from baseline to week 52. Two networks were analyzed: network A (RCTs only) and network B (RCTs and single-arm OLE and phase I/II studies matched to comparator arms). To assess the impact of prior ERT exposure, simulations were conducted by only varying ERT duration among included covariates. Results: For cipa + mig compared with alg, both networks were associated with relative increases in 6MWD (mean difference [95% credible interval], Bayesian probability for network A: 13.48 m [6.79, 19.85], >99.9%; network B: 12.59 m [7.89, 17.45], >99.9%) and ppFVC (network A: 1.63% [0.71, 2.60], >99.9%; network B: 3.17% [2.53, 3.81], >99.9%). Network B suggested cipa + mig was favorable (>99.9%) in all groups for both end points and appeared more favorable with increasing ERT duration. Conclusion: Cipa + mig was associated with an improvement in 6MWD and ppFVC relative to alg independent of prior ERT exposure, which appeared more favorable when all available evidence was used. These data could inform decision-making in treating ERT-naive and ERT-experienced patients with LOPD.

Aim: Oral mucositis (OM) is a common, burdensome complication of chemotherapy (CT), associated with pain, weight loss and increased infection risk. OM can result in CT dose reductions or delay subsequent cycles, compromising treatment efficacy. Current guidelines recommend oral cryotherapy with basic multiagent oral care for prevention of CT-induced OM. Chemo Mouthpiece^® (CMP) is a cryotherapy medical device with FDA 510(k) marketing clearance. A randomized controlled trial demonstrated that CMP effectively reduced the incidence and severity of OM caused by long or short half-life CT regimens in adults, compared with basic supportive oral care (BSOC) alone. The objective of this study was to estimate OM-related clinical and cost impacts associated with reductions in CT-induced OM from use of CMP. Materials & methods: A model was developed to simulate 1000 adult patients undergoing stomatotoxic CT from a US healthcare payer perspective under two scenarios: optimal practice: 100% using CMP plus best supportive oral care (BSOC); and current practice: 100% using BSOC. Clinical outcomes and costs were modeled to estimate the incremental difference between the two scenarios. Two different time horizons were tested in the model: conservative base case (single CT cycle) and real-world base case (six CT cycles). Additional sensitivity analyses were also conducted. Results: The cost of CMP in optimal practice was offset by cost savings from other sources, for a net total cost savings. In the conservative base case, optimal practice with CMP use for a single CT cycle was associated with over one million dollars in cost savings compared with current practice ($20,094,565 vs $21,260,470), largely attributed to reduced hospitalization length of stay. Use of CMP in optimal practice was associated with $1166 total cost savings per patient. Of note, substantially greater cost savings were estimated in the real-world base case with a time horizon of six CT cycles (additional savings of $2846 per patient each subsequent CT cycle). Three of the four sensitivity analyses were also found to result in net cost savings. Conclusion: Adoption of CMP was projected to be associated with reduced OM-associated clinical events and healthcare resource use. For 1000 adults using CMP for one CT cycle, cost savings accumulated to over one million dollars, amounting to $1166 per patient. Results of the real-world base case indicated that the value of CMP is likely underestimated, with cost savings over 15 million dollars, amounting to $15,395 per patient.

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: To study the effect of infertility support education on treatment outcomes in women with unexplained infertility. Materials & methods: This quasi-experimental study with a pretest-posttest comparison group was conducted on women aged 19-45 years who were admitted to EO University Health, Practice and Research Hospital Department of Reproductive Endocrinology and Private D Health Hospital IVF Clinic with the diagnosis of unexplained infertility and decided to undergo in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) and were included in the treatment plan. A study group and a control group were formed by randomization method with at least 25 infertile women for each group. Data were collected using the Introductory questionnaire, Fertility Readiness Scale for women receiving fertility support, Healthy Lifestyle Behaviors Scale II and post-IVF/ICSI success evaluation form. The pretest scales were administered to the education and control groups at the first interview. Infertility support training was given to the education group in three sessions at 15-day intervals. Post-test data were obtained at the interview on the day of ovum pickup. Embryo transfer was performed in 25 infertile women in both groups, and human chorionic gonadotropic hormone evaluation was performed on day 12. Approximately 4 weeks later the presence of a fetal heartbeat was analyzed by reviewing the medical records, and the post-IVF/ICSI success evaluation form was completed. Results: Fetal heartbeat was detected in 15 women in the training group and only in 10 women in the control group, although the pregnancy rate increased after training and this difference was not statistically significant. Conclusion: Infertility support education has been found to have positive effects on fertility as well as general health.

Aim: This study examined the clinical outcomes of patients in the US with low/intermediate-risk localized prostate cancer (LIR-LPC) and high-risk localized prostate cancer (HR-LPC) who received radical prostatectomy (RP) as initial treatment. Materials & methods: This is a retrospective analysis of the SEER-Medicare database. Patients newly diagnosed with LPC at age of ≥65 years during 2012-2019 who underwent RP as initial definitive treatment and had continuous Medicare Fee-For-Service for ≥12 months prior to RP were included. Eligible patients were stratified into LIR-LPC and HR-LPC cohorts. Overall survival, metastatic free survival and time to advanced prostate cancer treatment (TTAT) were described and compared using the Kaplan-Meier method and Cox proportional-hazards model. Results: The LIR-LPC cohort (n = 4120) and the HR-LPC cohort (n = 5359) had comparable socio-demographic characteristics, with a mean age of approximately 70 years. Survival analysis showed that HR-LPC was associated with significantly shorter overall survival, metastatic free survival and TTAT than LIR-LPC (log rank p < 0.001). After adjusting for comprehensive socio-demographic and baseline clinical characteristics, patients with HR-LPC had an approximately 70% increased risk for all-cause death (hazard ratio [HR]: 1.72; confidence interval [CI]:1.39-2.12), 2.5-fold increased risk for metastasis or death (HR: 2.57; CI: 2.14-3.09), and ninefold increased risk for initiating advanced treatments (HR: 9.06; CI: 6.22-13.18) compared with patients with LIR-LPC. Conclusion: In patients with LPC who received RP as initial definitive treatment, high risk is strongly associated with suboptimal clinical outcomes. Novel therapeutic approaches are needed to enhance the management and improve the outcomes for this patient population.

Aim: Complications of primary biliary cholangitis (PBC) are proposed to confer substantial economic burden to patients and healthcare systems. This retrospective observational study evaluated the cost of PBC-related hepatic decompensation and liver transplantation using a large administrative claims database. Materials & methods: Patients aged ≥18 years at the time of first claim with a diagnosis of PBC were identified using Optum's de-identified Clinformatics^® Data Mart Database. Two cohorts were established based on the type of event (hepatic decompensation or liver transplantation) that patients experienced on or after the date of their first claim with the PBC diagnosis. Costs for the hepatic decompensation hospitalization and 30-day post-discharge period were examined at the event level. Hospitalizations occurring within the 30-day post-discharge period after a hepatic decompensation event were considered readmissions, and costs from the initial event were combined with those from the ensuing readmissions. In the liver transplantation cohort, costs for the pretransplant evaluation, hospitalization for transplantation, and post-transplant care and complications were assessed per patient. Results: A total of 2118 and 163 patients met study inclusion criteria in the hepatic decompensation and liver transplantation cohorts, respectively. The overall mean cost per hepatic decompensation event (n = 3581) was $63,612.09. The mean cost per event with readmission within 30 days (n = 991, 27.7%) was $116,424.25; for events without readmission, the mean cost was $43,404.81. The mean total cost of liver transplantation per patient was $328,336.60. The mean cost per patient was highest for the hospitalization for transplantation ($226,908.70). Conclusion: This comprehensive cost analysis demonstrates the high-cost burden of PBC disease progression. Appropriate patient management may help to mitigate the economic burden of PBC-related hepatic decompensation and liver transplantation.

Aim: To compare oral corticosteroid (OCS) burden and healthcare resource utilization (HCRU) in patients with chronic rhinosinusitis with nasal polyps undergoing functional endoscopic sinus surgery (FESS; intervention) versus not undergoing FESS. Materials & methods: Retrospective cohort study using US claims data (Optum's de-identified Clinformatics^® Data Mart Database; 2011-2021). Groups were propensity score (PS) matched to adjust for confounding. OCS burden (cumulative dose in mg prednisone equivalents) and HCRU were assessed during baseline (365 days pre-index), intervention (days 0-44), and follow-up (days 45-365); costs during intervention and follow-up. Results: Before PS-matching, both groups had substantial comorbidity burden (>50% allergic rhinitis; >25% asthma) and over half of patients had used OCS (65% [FESS] vs 52% [non-FESS]; p < 0.01). After PS-matching (n = 8909 per group), OCS cumulative dose during follow-up was 18% lower among FESS versus non-FESS patients (mean difference: -40 mg per patient [95% CI: -57, -23; p < 0.01]). Similar proportions of patients filled OCS prescriptions during follow-up (35% [FESS], 36% [non-FESS]) and in these patients, OCS burden remained high (mean [SD] cumulative dose 521 [786] vs 612 [906] mg, respectively). Mean total healthcare costs per patient during the intervention period were $28,832 (FESS) and $2537 (non-FESS), but similar during follow-up ($15,659 and $15,926, respectively). HCRU was similar in follow-up, except more FESS patients visited an otolaryngologist (57% vs 32%, p < 0.01). Conclusion: In US clinical practice, OCS burden in patients with chronic rhinosinusitis with nasal polyps was significantly lower but remained substantial following FESS, and HCRU and costs during follow-up were similar to matched patients without FESS.

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.

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.