IQVIA, 210 Pentonville Road, London, N1 9JY, UK.
Actelion Pharmaceuticals Ltd, Gewerbestrasse 16, CH-4123, Allschwil, Switzerland.
BMC Pulm Med. 2020 Jul 28;20(1):202. doi: 10.1186/s12890-020-01241-4.
The clinical landscape of pulmonary arterial hypertension (PAH) has evolved in terms of disease definition and classification, trial designs, available therapies and treatment strategies as well as clinical guidelines. This study critically appraises published evidence synthesis studies, i.e. meta-analyses (MA) and network-meta-analyses (NMA), to better understand their quality, validity and discuss the impact of the findings from these studies on current decision-making in PAH.
A systematic literature review to identify MA/NMA studies considering approved and available therapies for treatment of PAH was conducted. Embase, Medline and the Cochrane's Database of Systematic Reviews were searched from database inception to April 22, 2020, supplemented by searches in health technology assessment websites. The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) checklist covering six domains (relevance, credibility, analysis, reporting quality and transparency, interpretation and conflict of interest) was selected for appraisal of the included MA/NMA studies.
Fifty-two full publications (36 MAs, 15 NMAs, and 1 MA/NMA) in PAH met the inclusion criteria. The majority of studies were of low quality, with none of the studies being scored as 'strong' across all checklist domains. Key limitations included the lack of a clearly defined, relevant decision problem, shortcomings in assessing and addressing between-study heterogeneity, and an incomplete or misleading interpretation of results.
This is the first critical appraisal of published MA/NMA studies in PAH, suggesting low quality and validity of published evidence synthesis studies in this therapeutic area. Besides the need for direct treatment comparisons assessed in long-term randomized controlled trials, future efforts in evidence synthesis in PAH should improve analysis quality and scrutiny in order to meaningfully address challenges arising from an evolving therapeutic landscape.
肺动脉高压（PAH）的临床领域在疾病定义和分类、试验设计、可用疗法和治疗策略以及临床指南方面都发生了演变。本研究批判性地评估了已发表的证据综合研究，即荟萃分析（MA）和网络荟萃分析（NMA），以更好地了解它们的质量、有效性，并讨论这些研究的结果对当前 PAH 决策的影响。
系统检索了评估已批准和可用于治疗 PAH 的疗法的 MA/NMA 研究，检索了 Embase、Medline 和 Cochrane 系统评价数据库，检索时间截至 2020 年 4 月 22 日，并在卫生技术评估网站上进行了补充搜索。选择涵盖六个领域（相关性、可信度、分析、报告质量和透明度、解释和利益冲突）的国际药物经济学和结果研究学会（ISPOR）清单来评估纳入的 MA/NMA 研究。
52 项关于 PAH 的完整出版物（36 项 MA、15 项 NMA 和 1 项 MA/NMA）符合纳入标准。大多数研究质量较低，没有一项研究在所有清单领域都被评为“强”。关键限制包括缺乏明确的、相关的决策问题、评估和解决研究间异质性的不足，以及对结果的不完整或误导性解释。
这是对已发表的 PAH MA/NMA 研究的首次批判性评估，表明该治疗领域发表的证据综合研究质量和有效性较低。除了需要在长期随机对照试验中评估直接治疗比较外，PAH 中的证据综合未来工作应提高分析质量和审查，以便从不断发展的治疗领域中出现的挑战。
