Evidence synthesis in pulmonary arterial hypertension: a systematic review and critical appraisal

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.

Risk Factors for Pulmonary Arterial Hypertension in Patients With Systemic Lupus Erythematosus: A Systematic Review and Expert Consensus

“…Pulmonary arterial hypertension (PAH) is a rare, progressive, and severe cardiopulmonary disorder ( 1 ). In patients with PAH, the small pulmonary arteries are obstructed because of cellular proliferation, fibrosis, and vascular remodeling, leading to premature death from right‐sided heart failure ( 2 , 3 , 4 ). PAH differs from other forms of pulmonary hypertension (PH) in that it is characterized by the presence of precapillary PH and it excludes PH induced by lung diseases, left‐sided heart failure, chronic thromboembolism, and other diseases ( 5 ).…”

Medications for the treatment of pulmonary arterial hypertension: a systematic review and network meta-analysis

“…These analyses remain an important part of clinical practice guideline development in order to inform best clinical practice. However, there have been significant disparities in the quality of evidence synthesis in past NMAs and conventional meta-analysis [6], as well as older methodology with lack of assessment of clinically significant benefits. We investigated the comparative effectiveness of both approved and investigational drug treatment for PAH using NMA, applying current Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methods [7].…”