Journal of comparative effectiveness research最新文献

Real-world evidence (RWE) from outside Canada or the UK is sometimes included in submissions to health technology assessments by Canada's Drug Agency/L'Agence des médicaments du Canada (CDA-AMC) and National Institute for Health and Care Excellence when local data are lacking, particularly in rare diseases. However, differences in population demographics, healthcare systems and clinical practice patterns between different jurisdictions can pose challenges for contextualizing nonlocal data for health technology assessments. This primer outlines the challenges of using nonlocal RWE for decision-making, presents assumptions necessary for transportability of RWE, and describes quantitative methods to address these challenges. This primer is written for a broad audience, including industry stakeholders, researchers and clinicians, who are seeking accessible guidance on the use of nonlocal RWE and developments in the field of transportability.

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.

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 ≥5 years, on a stable corticosteroid regimen for ≥12 months, and baseline 6-minute walk distance (6MWD) ≥150 m. Randomization: 1:1, ataluren (40 mg/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 ≤16 years with baseline 6MWD ≥300 m and stand from supine ≥5 s; patients with baseline 6MWD 300-400 m. Results: In the intention-to-treat population (n = 359), over 72 weeks, 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 10 m walk/run time (p = 0.0422) and change in time to climb four stairs (p = 0.0293) versus placebo. In the 6MWD 300-400 m 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 ≥300 m and time to stand from supine ≥5s subgroup (n = 185), there was a 9% slower rate of 6MWD decline for ataluren versus placebo over 72 weeks (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.

Aim: Given the limited availability of real world diffuse large B-cell lymphoma (DLBCL) data in Germany, we assessed the baseline characteristics, treatments, clinical complications, healthcare resource utilization and costs of DLBCL across treatment lines using German claims data. Materials & methods: In a retrospective cohort study using claims data from a German sickness fund (AOK PLUS), we identified patients with an incident DLBCL diagnosis between 2012 and 2022. Using an algorithm based on German treatment guidelines, patients were stratified into first (1L), second (2L) and third line (3L) treatment. We then descriptively analyzed baseline characteristics, treatments, clinical complications, healthcare resource utilization and costs. Results: A total of 2423 patients with DLBCL and 1L treatment were included in the study (49.1% female; mean age: 69.7 years; mean CCI: 7.0; median follow-up: 29.3 months). A total of 1209 (49.7%) and 505 (20.8%) patients progressed to 2L and 3L, respectively. A total of 209 patients received a stem cell transplant (SCT; mean age: 56.1 years); 37 received a chimeric antigen receptor T-cell therapy (CAR-T; mean age: 60.8 years). Most patients had at least one DLBCL related hospitalization during follow-up (1L: 79.2%; 2L: 60.0%; 3L: 71.9%; mean length of stay [days/patient year]: 1L: 15.2; 2L: 6.4; 3L: 14.2), with corresponding hospitalization costs of 12,777€ (1L), 5993€ (2L) and 17,408€ (3L) per patient year. Clinical complications were common, particularly in 3L, including neutropenia (1L: 31.9%; 2L: 27.0%; 3L: 46.9%), pneumonia (1L: 19.6%; 2L: 16.8%; 3L: 30.3%), anemia (1L: 17.8%; 2L: 18.7%; 3L: 35.2%), thrombocytopenia (1L: 17.3%; 2L: 21.8%; 3L: 45.1%) and sepsis (1L: 14.6%; 2L: 13.0%; 3L: 23.2%). Conclusion: The high proportion of patients with second or later-line treatment (indicating a relapse or refractory disease), the low number of SCTs together with many clinical complications and healthcare resource use underscore the need for novel effective and well-tolerated DLBCL treatment options.

Aim: The aim of this study was to describe treatment patterns among patients with acromegaly who are newly treated with acromegaly medical therapy. Materials & methods: Data from IQVIA Pharmetrics Plus^® Database from 1 January 2013 to 30 June 2023 were used to identify patients with acromegaly who started a new acromegaly medical therapy and observe their treatment patterns. Patients were required to have at least 12 months of data without any acromegaly therapy (medication or surgery) prior to the index date and at least 6 months of follow-up. Comorbidities were measured during the baseline period. Adherence, persistence, medication and switching were measured during follow-up. Results: A total of 453 patients with acromegaly who were newly treated with acromegaly medical therapy and had no evidence of acromegaly therapy for at least 12 months were identified. Among these patients, 46.1% (n = 206) were treated with cabergoline as their index treatment, 24.5% (n = 111) with injectable octreotide, 15.0% (n = 68) with lanreotide, 5.5% (n = 25) with bromocriptine, 4.9% (n = 22) with pegvisomant, 2.2% (n = 10) with pasireotide, 1.1% (n = 5) with oral octreotide, 0.4% (n = 2) with cabergoline + octreotide, and 0.2% (n = 1) with cabergoline + lanreotide. By the end of the follow-up period, 54.3% (n = 246) were not on any treatment, 19.6% (n = 89) remained on the index treatment, and the remaining 26.0% (n = 118) switched to another treatment. Conclusion: This study contributed to the growing evidence that patients with acromegaly are not well-served by current therapeutic options, as indicated by high rates of treatment discontinuation, switching and add-on therapy. However, treatment switching and add-on therapy represent ongoing efforts to optimize patient care toward more effective and tolerable treatments. Expanded treatment options may serve an unmet need in this patient population.

Aim: Despite evidence of racial/ethnicity health inequities in oral anticoagulant initiation and clinical outcomes for nonvalvular atrial fibrillation, little is known about disparities in treatment patterns, particularly discontinuation and switching. Materials & methods: This retrospective study utilized Komodo Healthcare Map data (1 July 2018 to 30 June 2023) to examine treatment patterns in patients with nonvalvular atrial fibrillation initiating direct oral anticoagulants (DOACs: apixaban, rivaroxaban, dabigatran) versus warfarin, stratified by self-reported race/ethnicity (White, Black and Hispanic) in the USA. Inverse probability of treatment weighting balanced baseline covariates and Cox model computed adjusted hazard ratio (aHR) and 95% confidence interval (CI) for apixaban-warfarin and DOAC-warfarin comparisons in the overall cohort and by race/ethnicity. Results: In the apixaban-warfarin cohort, apixaban patients were 24% less likely to discontinue treatment (aHR: 0.76, 95% CI: 0.75-0.77) and 79% less likely to switch to another oral anticoagulant (aHR: 0.21, 95% CI: 0.20-0.22) versus warfarin. By race/ethnicity, a higher proportion of Black patients discontinued than White and Hispanic (68, 60 and 63%, respectively). Almost 5% of apixaban patients switched to another oral anticoagulant versus 31% on warfarin. Among warfarin switchers, 77% initiated apixaban (80% in White; 76% Black; 76% in Hispanic patients). The DOAC-warfarin cohort followed similar trends. Conclusion: Overall, apixaban/DOACs were associated with more favorable treatment patterns than warfarin. However, racial/ethnicity differences were observed. Given the potential impact of oral anticoagulant discontinuation on clinical outcomes, further research is needed to better understand factors contributing to higher discontinuation and switch rates, particularly among Black and Hispanic patients.

Aim: This systematic review aimed to evaluate the comparative efficacy, safety and cost-effectiveness of safinamide (50/100 mg) versus rasagiline (1 mg) in managing Parkinson's disease (PD). Materials & methods: Randomized clinical trials were identified through systematic searches of PubMed, Embase and Cochrane databases (last searched September 2023). Eligibility criteria included studies assessing Unified Parkinson's Disease Rating Scale (UPDRS) scores, On/Off time and adverse events. Risk of bias was evaluated using funnel plots, and data synthesis employed odds ratios, number needed to treat (NNT) and incremental cost-effectiveness ratios, calculated using the current costs of safinamide and rasagiline in Spain. Results: Thirteen trials (n = 4157 participants) were included. Safinamide demonstrated greater efficacy (NNT-UPDRS: 6 vs 8) and safety (number needed to harm-serious adverse events: 135 vs 83) compared with rasagiline. The benefit-risk balance of safinamide was superior, as evidenced by higher likelihood of being helped over harmed ratios. Cost-effectiveness analysis revealed lower costs per NNT for On/Off time with safinamide. While rasagiline treated more patients within a fixed budget, safinamide achieved better responder-to-nonresponder ratios. Conclusion: Safinamide showed superior efficacy, safety and cost-efficiency compared with rasagiline, supporting its use as a preferred adjunct therapy for PD. Limitations include reliance on clinical trial data and Spanish cost models. Future research incorporating real-world evidence is warranted.

Aim: In the US, lanreotide and injectable octreotide are commonly used to treat acromegaly. For most patients, the recommended injection administration regimen is every 4 weeks, or 13-times over the course of 1 year. The study aimed to quantify the proportion of patients who used a number of injections that is beyond the standard recommended regimen and to assess whether high frequency (HF) use is associated with higher healthcare resource utilization and costs. Materials & methods: IQVIA Pharmetrics Plus data between 1 January 2013 and 30 June 2023 was used to conduct a retrospective, observational study of acromegaly patients who used injectable octreotide or lanreotide for at least 2 years. The primary study outcomes were the number of injections and HF use. HF use is defined as having observed more than 13 injections over a 1-year observation period. Results: There were 420 patients with acromegaly who used injectable octreotide (n = 250) or lanreotide (n = 170) for a median of 4 years. HF use was observed in 32.4% of injectable octreotide users and 30.6% of lanreotide users. Over the course of 1 year, mean total healthcare costs were significantly higher among HF users compared with non-HF users among patients treated with injectable octreotide ($130,238 vs $85,964, p < 0.001) or lanreotide ($143,975 vs $96,518, p < 0.001). Additionally, 10% of HF users incurred $238,070-$281,167 or more. Based on the average cost per injection, patients with HF use had an additional $12,803-$13,480 in injection costs each year. Conclusion: Among those who are consistently treated, nearly a third of patients with acromegaly are HF users of lanreotide or injectable octreotide. The economic burden of HF use is high. Given the high proportion of patients who require administration beyond what is indicated on approved drug labels, further evaluation of new therapies is warranted.

Glucagon-like peptide 1 receptor agonists and glucagon-like peptide 1/gastric inhibitory polypeptide receptor agonists offer weight reduction and associated health benefits that, if sustained over time, have the potential to markedly improve population health. However, over 40% of US adults have obesity, translating into more than 100 million potential new users of obesity medications. Standing in the way of the major opportunity to improve health for these individuals is the massive and likely ongoing cost of treating such a large segment of the population, even though use of the treatments is estimated to be cost-effective over a lifetime. This paper analyzes the range of emerging market approaches and policy reforms that have the potential to help the broader US health system achieve affordable and equitable access to these medications, and the relative advantages, barriers and possible unintended consequences of each approach. We seek to present policymakers and industry leaders with insights and lessons learned from experts while offering a menu of options for the future that will help all stakeholders play an active part in an innovative future of pricing, coverage and payment for new obesity medications.