146 Chapter 8 applicable due to the type of intervention, self-treatment, and the crossover design of the study. Patient and public involvement A representative from the Dutch Haemophilia Patients Organisation (NVHP) has been involved in grant applications, study design and protocol drafting. As a member of the multidisciplinary study steering committee, he will be a full author on any publications originating from this project. This study is supported by the Dutch federation of academic hospitals. Intervention The following will be compared within each participant: - Comparator: 6 months of conventional dosing of emicizumab (i.e., 6mg/kg per 4 weeks at individualized 1‒4-weekly intervals); - Intervention: 12 months of individualized PK-guided dosing of emicizumab to achieve a target Ctrough of 30 µg/mL (range 25‒35 µg/mL). The research pharmacists of the SYMPHONY consortium will provide a PK-guided dose advice based on a maximum a posteriori (MAP) Bayesian analysis of the individual observed concentration using an online platform https://opticlot.nl [21, 22]. MAP Bayesian will be performed using NONMEM software (v 7.4.1, Icon Development Solutions, Gaithersburg, Maryland, United States). Population PK parameters will used as reported by Retout . The patient variables (i.e., body weight, height, age, and serum albumin) will be included in the PK simulations. A dose advice consists of: a lag-time period providing a restart date for new dosing, a dose in entire vials and a dosing interval. The research pharmacists will also provide a window for the next Ctrough measurement, to check if the target Ctrough is reached following the intervention. In general, this will be done after one or two half-lives (30–60 days) based on the Ctrough. Both a target Ctrough between 25–35 µg/mL, as well as a varying dosing interval between 7 to 42 days, are allowed to enable use of entire vials only. The maximum dose-reduction at each step will be 50%, and doses will be increased if the new Ctroughs is less than 25 µg/mL. The target Ctrough between 25–35 µg/mL reflects the target for the PK model; while during the dose intervention, Ctrough between 25–39 µg/mL in individual participants will be accepted. The dose advice also takes individual preference in dosing interval and maximum injection volume of 2mL/dose into account. Outcomes Primary outcome The proportion of patients without treated bleeds during 6 months on conventional dosing (comparator) compared to 6 months on individual PK-guided dosing (intervention).