The European Association for Haemophilia and Allied Disorders (EAHAD) commends the International Society’s on Thrombosis and Haemostasis (ISTH) initiative to publish evidence-based guidelines. These guidelines have been subject to considerable discussion, with numerous clinicians and organisations expressing concerns, and we acknowledge the disquiet within the wider community. Nevertheless, it is crucial to remember that guidelines are recommendations only, and their applicability should be carefully considered at both local and national levels.
ISTH’s endeavour to publish evidence-based guidelines has been challenged by the lack of data that meet the stringent criteria for high-quality evidence, in particular the paucity of randomized controlled trials (RCTs). The influence of RCTs on clinical practice is significant, but evidence-based medicine should be grounded in a broader and deep understanding of disease mechanisms, including pathophysiology and the biological plausibility underpinning treatment exposure and outcomes. Indeed, meticulous observations and progressive understanding of disease pathophysiology have resulted in significant treatment advances that would not merit an RCT today. Moreover, there is no disagreement that the absence of RCTs does not equate to the absence of efficacy. It is also important to acknowledge that not all questions require answers through RCTs, many can be effectively addressed through natural history studies, available real-world evidence, and post hoc analyses. As we know, the decision to embark on an RCT is typically based on the demonstration of clinical equipoise, the value of the research question to the community, prevailing beliefs, and the potential risks to participants through participation.
As we advance into an era of precision medicine and shared decision-making, treatment outcomes should move beyond simplistic metrics such as annual bleed rates. It is imperative that organisations develop innovative approaches to guideline writing that prioritise patient-related outcomes in clinical practice and enable improved health outcomes for individuals. The community would greatly benefit from guidelines that not only address the efficacy of treatments but also focus on treatment goals, often requiring a multipronged strategy.
We acknowledge the complexity of assembling a large group of experts for guideline development and the time required to reach a consensus. However, in an era of patient-centred care, a broad representation of haemophilia experts—both clinicians and patients—along with greater stakeholder engagement with a methodological approach suitable to rare disorders is invaluable. As we navigate an era of increasing subspecialisation, advanced statistical methods and data analysis tools should enable complex decision-making. Furthermore, greater emphasis should be placed on supporting research and practice that generate robust evidence through diverse methodologies.
We strongly encourage the haemophilia community to support initiatives that address the unique challenges involved in developing guidelines for rare disorders. We urge ISTH to broaden community representation in guideline development by involving all relevant stakeholders in a transparent and inclusive manner and exploring new methodologies that prioritise meaningful treatment outcomes and rigorous research.
This is a call to action for the broader community to collaborate in refining these processes to ensure optimal outcomes in clinical practice. EAHAD stands ready to play an active role in this critical endeavour.