Anouk Donners

106 Chapter 6 Summary statistics and graphics were performed using GraphPad Prism (GraphPad Software LLC, Version 8.3.0), and modelling was performed using R (R Core Team, version 4.0.2). RESULTS A total of 368 records were identified with the computerized search. After duplicate removal (n = 83), 285 titles and abstracts and 77 full-text articles were assessed for eligibility. The search update in November 2020 yielded 15 studies meeting the inclusion criteria (Supplemental Figure SF1). Study characteristics The 15 included studies were published between 2016 and 2020 in Table 1. During the drugs’ development, phase I (n = 4), simultaneous phase I/II (n = 1) and phase III (n = 6) clinical studies were conducted in combination with two pharmacometric analyses reporting on the dose−response relationship with data from the previously published studies. Two studies were conducted after market approval. The majority of the studies included were global multi-center (n = 8), open-label (n = 12), non-randomized (n = 8), non-controlled (n = 9), industry-funded (n = 13) clinical studies with a follow-up period of at least 16 weeks (n = 11). Eight studies had a parallel comparative design, including six reporting on an intra-individual comparison of emicizumab with previous treatment. The multiple-dose injection studies most often included the weekly dosing interval (QW; 75%), followed by the once per four weeks regimen (Q4W; 14%) and once per two weeks regimen (Q2W; 11%).