PB0657 - Is implementation of pharmacokinetic-guided dosing of factor replacement therapy in bleeding disorders on TARGET? A scoping review to map barriers and facilitators

Background: Clinical guidelines and expert groups recommend the use of pharmacokinetic (PK)-guided dosing of factor replacement therapy for the treatment of bleeding disorders, especially for patients with hemophilia. Although PK-guided dosing is increasingly applied, it is not considered standard clinical practice. This suggests a disparity between recommendations in clinical guidelines to perform PK-guided dosing and its actual implementation in daily practice.

Aims: The aim of this scoping review is to map barriers and facilitators for the implementation of PK-guided dosing in clinical practice and to identify knowledge gaps in order to bring its application to the next level.

Methods: We followed the methodology to conduct a scoping review including the five stages as described by Arksey and O’Malley. We performed a literature search and two authors independently screened articles that describe PK-guided dosing in patients with bleeding disorders.

Results: We included 110 articles (Figure 1), mostly describing hemophilia A patients. We defined two overarching themes e.g. efficacy and feasibility, and discuss five topics within each theme. For each topic: barriers, facilitators and knowledge gaps were described. For efficacy the following topics were addressed: 1) knowledge on endpoint to target; 2) accuracy of PK-guided dosing; 3) impact on bleeding frequency; 4) effect on infusion frequency; and 5) cost effectiveness. Feasibility was evaluated according to: 6) applicability in clinical practice; 7) useful software tools; 8) patient involvement; 9) burdening of patients and treatment teams; 10) attainment of personalization of treatment. An overview of all barriers and facilitators grouped per topic is provided in Figure 2.

Conclusion(s): Although consensus was found with regard to some topics, contradicting reports were found for others, especially with respect to the efficacy of PK-guided dosing. These contradictions highlight the need for future research to resolve current ambiguities.