Expert opinion on the UK standard of care for haemophilia patients with inhibitors: a modified Delphi consensus study

Abstract

Background and aims: Despite advances in haemophilia care, inhibitor development remains a significant complication. Although viable treatment options exist, there is some divergence of opinion in the appropriate standard approach to care and goals of treatment. The aim of this study was to assess consensus on United Kingdom (UK) standard of care for child and adult haemophilia patients with inhibitors.

Methods: A modified Delphi study was conducted using a two-round online survey. A haemophilia expert steering committee and published literature informed the Round 1 questionnaire. Invited participants included haematologists, haemophilia nurses and physiotherapists who had treated at least one haemophilia patient with inhibitors in the past 5 years. Consensus for 6-point Likert scale questions was pre-defined as ⩾70% participants selecting 1-2 (disagreement) or 5-6 (agreement).

Results: In all, 46.7% and 35.9% questions achieved consensus in Rounds 1 (n = 41) and 2 (n = 34), respectively. Consensus was reached on the importance of improving quality of life (QoL) and reaching clinical goals such as bleed prevention, eradication of inhibitors and pain management. There was agreement on criteria constituting adequate/inadequate responses to immune tolerance induction (ITI) and the appropriate factor VIII dose to address suboptimal ITI response. Opinions varied on treatment aims for adults and children/adolescents, when to offer prophylaxis with bypassing agents and expectations of prophylaxis. Consensus was also lacking on appropriate treatment for mild/moderate patients with inhibitors.

Conclusion: UK healthcare professionals appear to be aligned on the clinical goals and role of ITI when managing haemophilia patients with inhibitors, although novel treatment developments may require reassessment of these goals. Lack of consensus on prophylaxis with bypassing agents and management of mild/moderate cases identifies a need for further research to establish more comprehensive, evidence-based treatment guidance, particularly for those patients who are unable/prefer not to receive non-factor therapies.

Keywords: Delphi panel; adult; children; consensus; haemophilia; inhibitors.

Figure 1.

Delphi study design. (a) SurveyMonkey® questionnaire distributed as a web link via email to haematologists and haemophilia nurses/physiotherapists with experience of treating at least one haemophilia patient with inhibitors in the last 5 years. (b) Consensus: ⩾70% agreement/disagreement. (c) Restated if achieved between ⩾60% and <70% agreement/disagreement or rephrased if <60% agreement/disagreement. (d) Number of questions asked in the Round 2 questionnaire increased due to some Round 1 questions being rephrased as multiple questions. SC, steering committee.

Figure 2.

Single-option questions relating to the number of bleeds per year justifying prophylaxis. Results shown are from the Round 2 questionnaire (questions were informed by numerical questions in Round 1), excluding participants who indicated they had insufficient expertise. The threshold for achieving consensus (⩾70% participants selecting the same option), is marked by the dashed horizontal line. (a) Annual bleed rate. Question worded as ‘What annual bleed rate do you feel justifies prophylaxis?’. (b) Number of major bleeds per year (joint or muscle). Question worded as ‘What number of major bleeds per year (joint or muscle) justifies prophylaxis?’. (c) Number of joint bleeds per year. Question worded as ‘What number of joint bleeds per year (any severity) justifies prophylaxis?’.

Figure 3.

Single-option questions relating to the percentage reduction in bleeds deemed to be a clinically significant improvement. Results shown are from the Round 2 questionnaire (questions informed by numerical questions in Round 1), excluding participants who indicated they had insufficient expertise. The threshold for achieving consensus (⩾70% participants selecting the same option), is marked by the dashed horizontal line. (a) Bleeds per year (any severity). Question worded as ‘Based on your response to the previous questions, what percentage reduction in bleeds per year (any severity) on prophylaxis would you then consider to be a clinically significant improvement?’. (b) Joint bleeds per year (any severity). Question worded as ‘Based on your response to the previous question, what percentage reduction in joint bleeds per year (any severity) on prophylaxis would you then consider to be a clinically significant improvement?’. (c) Major bleeds per year (joint or muscle). Question worded as ‘Based on your response to the previous question, what percentage reduction in major bleeds per year (joint or muscle) on prophylaxis would you then consider to be a clinically significant improvement?’.

Figure 4.

The most important factor when treating mild/moderate patients with inhibitors, when aiming to eradicate their inhibitors. Single-option question; results shown are from the Round 2 questionnaire, excluding participants who indicated they had insufficient expertise; n = 31. The threshold for achieving consensus (⩾70% participants selecting the same option), is marked by the dashed horizontal line. Question worded as ‘Please select the most important factor to consider when treating mild/moderate haemophilia A patients with inhibitors, when the aim is to eradicate their inhibitors’.