International Society on Thrombosis and Haemostasis Clinical Practice Guideline for Treatment of Congenital Haemophilia—A Critical Appraisal
Manuela Albisetti 1); Jesús Ardila 2); Jan Astermark 3),4); Jan Blatny 5); Manuel Carcao 6); Pratima Chowdary 7); Nathan T. Connell 8); Miguel Crato 9); Yesim Dargaud 10), 11); Roseline d’Oiron 12); Amy L. Dunn 13); Miguel A. Escobar 14); Carmen Escuriola Ettingshausen 15); Kathelijn Fischer 16); Emna Gouider 17); Annie Harroche 18); Cedric Hermans 19): Victor Jimenez-Yuste 20); Radoslaw Kaczmarek 21); Gili Kenet 22); Liane Khoo 23); Robert Klamroth 24); Florian Langer 25); David Lillicrap 26); Johnny Mahlangu 27); Christoph Male 28); Maria Elisa Mancuso 29); Tadashi Matsushita 30); Sandrine Meunier 31); Wolfgang Miesbach 32); Beatrice Nolan 33); Johannes Oldenburg 34); Brian O’Mahony 35); Margareth Ozelo 36); Glenn F. Pierce 37); Gloria Ramos 38); Michael Recht 39), 40); Olivia Romero-Lux 9); Dawn Rotellini 40); Rita C. Santoro 41); Tammuella C. Singleton 42); Mark W. Skinner 43), 44); Alok Srivastava 45); Sophie Susen 46); Kate Talks 47); Huyen Tran 48); Leonard A. Valentino 49); Jerzy Windyga 50); Renchi Yang 51); also on behalf of AICE, AHAD-AP, AHCDC, ATHN, CLAHT,EHC, French CRH & MHEMO, GTH, HTCCNC, NBDF, PEDNET, UKHCDO, WFH
ABSTRACT
Introduction
Evidence-based clinical practice guidelines drive optimal patient care and facilitate access to high-quality treatment. Creating guidelines for rare diseases such as haemophilia, where evidence does not often come from randomized controlled trials but from non-randomized and well-designed observational studies and real-world data, is challenging. The methodology used for assessing available evidence should consider this critical fact. In formulating guidelines, it is essential to include treatment goals and patient preference.
Aim
This paper comprehensively critiques, against this background, the recommendations of the ISTH clinical practice guidelines for the treatment of haemophilia.
Methods
Each recommendation was critically reviewed against available evidence as well as existing guidelines and commented upon for its scientific validity, impact on clinical practice and access to care globally. The validity of the way in which the GRADE methodology was applied to existing evidence was also assessed.
Results
The critique provided shows that these recommendations have major limitations: they did not state treatment goals and contradict existing guidelines; opportunities for providing access to innovation were missed when the therapeutic benefits of the products approved in the last decades were not included. A major reason for this is the inappropriate adoption of the GRADE methodology without adaptations and without considering treatment goals and patient-relevant outcomes.