Contrasting Approaches in the Implementation of GRADE Methodology in Guidelines for Haemophilia and Von Willebrand Disease

Authors	SKINNER Mark W ALBISETTI Manuela ARDILA Jesus ASTERMARK Jan BLATNÝ Jan CARCAO Manuel CHOWDARY Pratima CONNELL Nathan T CRATO Miguel DARGAUD Yesim D'OIRON Roseline DUNN Amy L ESCOBAR Miguel A ESCURIOLA-ETTINGSHAUSEN Carmen GOUIDER Emna HARROCHE Annie HERMANS Cedric JIMENEZ-YUSTE Victor KACZMAREK Radoslaw KENET Gili KHOO Liane KLAMROTH Robert LANGER Florian LILLICRAP David MAHLANGU Johnny MALE Christoph MATSUSHITA Tadashi MEUNIER Sandrine MIESBACH Wolfgang NOLAN Beatrice OLDENBURG Johannes O'MAHONY Brian OZELO Margareth PIERCE Glenn F RAMOS Gloria RECHT Michael ROMERO-LUX Olivia ROTELLINI Dawn SANTORO Rita C SINGLETON Tammuella C SRIVASTAVA Alok SUSEN Sophie TALKS Kate TRAN Huyen VALENTINO Leonard A WINDYGA Jerzy YANG Renchi MANCUSO Maria Elisa
Year of publication	2025
Type	Article in Periodical
Magazine / Source	Haemophilia
MU Faculty or unit	Faculty of Medicine
Citation
web	https://onlinelibrary.wiley.com/doi/10.1111/hae.15136
Doi	http://dx.doi.org/10.1111/hae.15136
Keywords	GRADE; guideline; haemophilia; ISTH; rare disease; von Willebrand disease
Description	IntroductionThe 2024 ISTH clinical practice guideline (CPG) for treatment of congenital haemophilia, the NBDF-McMaster Guideline on Care Models for Haemophilia Management, and ASH ISTH NBDF WFH guidelines on the diagnosis and management of VWD all utilised GRADE methodology.AimDiscuss missed opportunities and the methodological approach of the ISTH Guideline in contrast to how GRADE was previously applied in rare diseases.MethodsCritically analyse the methodology of each guideline along with best practices in the use of GRADE. Where applicable, the WFH Guidelines for the Management of Haemophilia were analysed.ResultsImportant differentiating features in applying GRADE were identified. Where a strong evidence base is lacking, data other than those from randomized controlled trials, which may not always be justified, need to be considered, including incorporation of outcomes important to people living with the disease. Justification and stakeholder input to prioritize questions requiring a new guideline, panel composition with necessary patient participation and content expertise were also found to be significant differentiating features.ConclusionThe puristic approach taken in the ISTH Guideline development process, without consideration of accepted adaptations to GRADE implementation, created a missed opportunity for progressing haemophilia care, leading to guideline recommendations that have been widely deemed invalid and obsolete by expert healthcare professionals and by those living with the condition, the very people who are expected to implement or bear the impact of the recommendations. Lessons learnt from this comparative analysis should guide future guideline development and encourage collaboration to further advance haemophilia.