Network connectivity, between-study heterogeneity and timepoint challenges in generalized myasthenia gravis: a feasibility assessment of indirect treatment comparisons.

IF 1.9 4区 医学 Q3 HEALTH CARE SCIENCES & SERVICES
Nils Erik Gilhus, Saiju Jacob, Mahmoud Hashim, Suzy Van Sanden, Christopher Drudge, Anna Nero, Sumeet Singh, Kavita Gandhi, Brian Hutton
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Abstract

Aim: We performed a feasibility assessment to systematically evaluate randomized controlled trials (RCTs) for generalized myasthenia gravis (gMG) treatments. The goal was to identify the advantages and disadvantages of different indirect treatment comparison (ITC) methods. Materials & methods: A systematic literature review was conducted to identify relevant gMG RCTs for ITCs. The feasibility of ITCs was assessed by comparing design (including study duration and dosing schedules), population and outcome characteristics of retrieved trials, investigating network connectivity and considering appropriate ITC methods to address identified challenges. Results: The feasibility assessment considered 15 relevant RCTs for gMG treatments. Several barriers to conducting robust ITCs were identified, including within-trial imbalances in patient characteristics, small trial sizes and cross-trial differences in potential treatment effect modifiers (TEMs; e.g., antibody status, disease duration and prior treatment exposure). Further, heterogeneity in placebo administration characteristics and background therapies, and cross-trial variation in placebo response for key outcomes were noted. Additionally, treatment strategies (i.e., cyclical vs continuous), dosing schedules and outcome assessment timepoints were inconsistent across trials, necessitating careful consideration of methods and timepoints when interpreting outcomes. The findings suggest that ITCs anchored on placebo as a common comparator may be prone to bias, and more than one ITC approach may be necessary. Conclusion: ITC analyses in gMG have inherent challenges related to imbalanced treatment effect modifiers, network connectivity, varying dosing strategies and assessment timepoints. Multiple approaches to ITCs, with careful evaluation of underlying assumptions and limitations, are advised to limit bias and ensure robust comparative efficacy estimates are available to decision makers.

广泛性重症肌无力的网络连通性、研究间异质性和时间点挑战:间接治疗比较的可行性评估
目的:系统评价随机对照试验(rct)治疗广泛性重症肌无力(gMG)的可行性。目的是确定不同的间接处理比较(ITC)方法的优缺点。材料和方法:进行了系统的文献综述,以确定与ITCs相关的gMG随机对照试验。通过比较设计(包括研究持续时间和给药计划)、检索试验的人群和结果特征、调查网络连通性以及考虑适当的ITC方法来应对已确定的挑战,评估了ITC的可行性。结果:可行性评估考虑了15项相关的rct治疗gMG。确定了进行强有力的ITCs的几个障碍,包括患者特征的试验内不平衡、试验规模小和潜在治疗效果调节剂的交叉试验差异(TEMs;例如,抗体状态,疾病持续时间和先前的治疗暴露)。此外,还注意到安慰剂给药特征和背景疗法的异质性,以及关键结果安慰剂反应的交叉试验差异。此外,各试验的治疗策略(即周期性与连续性)、给药方案和结果评估时间点不一致,因此在解释结果时需要仔细考虑方法和时间点。研究结果表明,将安慰剂作为通用比较物的ITC可能容易产生偏差,因此可能需要多种ITC方法。结论:gMG的ITC分析存在与不平衡的治疗效果调节剂、网络连通性、不同的给药策略和评估时间点有关的固有挑战。建议采用多种方法处理国际贸易技术,仔细评估基本假设和局限性,以限制偏见,并确保决策者可以获得可靠的比较功效估计。
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来源期刊
Journal of comparative effectiveness research
Journal of comparative effectiveness research HEALTH CARE SCIENCES & SERVICES-
CiteScore
3.50
自引率
9.50%
发文量
121
期刊介绍: Journal of Comparative Effectiveness Research provides a rapid-publication platform for debate, and for the presentation of new findings and research methodologies. Through rigorous evaluation and comprehensive coverage, the Journal of Comparative Effectiveness Research provides stakeholders (including patients, clinicians, healthcare purchasers, and health policy makers) with the key data and opinions to make informed and specific decisions on clinical practice.
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