Evidence synthesis in pulmonary arterial hypertension: a systematic review and critical appraisal
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RESEARCH ARTICLE
Open Access
Evidence synthesis in pulmonary arterial hypertension: a systematic review and critical appraisal Max Schlueter1* , Amélie Beaudet2, Evan Davies2, Binu Gurung1 and Andreas Karabis3,4
Abstract Background: 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-metaanalyses (NMA), to better understand their quality, validity and discuss the impact of the findings from these studies on current decision-making in PAH. Methods: 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. Results: 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. Conclusions: 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. Keywords: Pulmonary hypertension, Evidence synthesis, Quality appraisal, Literature reviews, Meta-analysis, Network meta-analysis
Background Pulmonary arterial hypertension (PAH) is a rare and debilitating chronic disease of the pulmonary vasculature [1]. Disease progression is characterized by increasing * Correspondence: [email protected] 1 IQVIA, 210 Pentonville Road, London N1 9JY, UK Full list of author information is available at the end of the article
pulmonary vascular resistance (PVR) and non-specific symptoms (e.g., dyspnoea during exercise, fatigue, chest pain, and light-headedness), that ultimately leads to right heart failure and premature death [1, 2]. Prior to the availability of PAH-specific therapies, median survival time was documented as 2.8 years in the US patients
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