PRS11 EVIDENCE SYNTHESIS IN PULMONARY ARTERIAL HYPERTENSION: A CRITICAL APPRAISAL

The clinical landscape of pulmonary arterial hypertension (PAH) has evolved in terms of disease definition and classification, treatment guidelines, available therapies, and trial designs. This study critically appraises published meta-analyses (MAs) and network-meta-analyses (NMAs) to a) better understand their quality, validity and relevance to current clinical practice and b) to provide recommendations on methods, analysis and reporting NMAs in PAH. A systematic literature review to identify MAs/NMAs considering approved and available therapies for treatment of PAH was conducted. Embase, Medline and the Cochrane’s database of systematic reviews (CDSR) were searched from database inception to September 12, 2018, supplemented by searches in the Health Technology Assessment (HTA) websites. The ISPOR checklist covering six domains (relevance, credibility, analysis, reporting quality and transparency, interpretation and conflict of interest) was selected for appraisal of the included MAs/NMAs. Forty-three full publications (31 MAs, 11 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 MAs/NMAs 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 (RCTs), 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.