A Critical Appraisal of Clinical Practice Guidelines for Pharmacological Treatments of Paroxysmal Nocturnal Hemoglobinuria

Aims: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare chronic disease characterized by complement-mediated hemolysis, thrombosis, and bone marrow failure. This study aims to identify methodological limitations in Clinical Practice Guidelines (CPG) for the treatment of PNH. Thus, we critically evaluate the guidelines, highlighting relevant recommendations supported by high-quality evidence to improve healthcare strategies.

Methodology: A systematic search was carried out in PubMed/MEDLINE, Scopus, Embase, COCHRANE, and TRIP databases. From 1995 initially identified references, 1649 articles underwent title and abstract screening. Twenty-three references were selected for full-text screening. Ultimately, 12 CPGs were included. Four independent reviewers assessed the CPGs’ methodological quality using the instruments “Appraisal of Guidelines for Research and Evaluation II” (AGREE II) and “Recommendation Excellence” (AGREE-REX). Their characteristics, as well as any differences in recommendations, were summarized and compared.

Results: Twelve guidelines published from 2011 to 2022 by Spain, Brazil, Mexico, Israel, Canada, Turkey, Scotland, and the United Kingdom were included. The UK’s and Brazil’s CPGs received the highest scores. Overall, the CPGs scored strongly in the domains of “Scope and Purpose” and “Clarity of Presentation” since they addressed fundamental aspects, such as aim, specific health questions, target population, and language. All guidelines presented deficiencies in the “Editorial Independence” in AGREE II, and “Values and Preferences” in AGREE-REX, demonstrating the need for a careful revision and improvement of future versions.

Conclusion: We found disparities in the methodological quality of the available CPGs. Despite being extremely important, recommendations on adapting treatment to local policies and further updates that include newly approved medications were absent. Approaches that prioritize the engagement of methodologists and multidisciplinary collaborators may also lead to higher quality CPGs for treating PNH.