Anouk Donners

165 General Discussion with LC-MS/MS analysis. Therefore, I recommend early diagnostic screening as a topic on the agendas of patient/clinician organisations (NVHP, WFH), to form a work or focus group at a haemophilia congress (WFH) or to conduct a systematic review on this topic, including expert opinions. The possibilities for LC-MS/MS analysis regarding monitoring haemophilia A are promising due to the method’s multiplex potential, sensitivity and small sampling volume. The studies in this thesis provide the first steps for adopting FVIII concentrations with LC-MS/ MS analysis in haemophilia A care. Although additional research must be conducted before clinical implementation, LC-MS/MS analysis has the potential to optimise the monitoring of FVIII in several ways. Framework for the cost-efficient dosing strategies of biopharmaceuticals Background and rationale Biopharmaceuticals are drug products with an active substance extracted or produced from a biological source through recombinant-DNA technology [49]. Biopharmaceuticals have rapidly emerged as important medical tools that highly specifically target their therapeutic receptors, offering a broad therapeutic window, usually without a ceiling of clinical toxicity [50]. The general challenges of therapy with biopharmaceuticals are immunogenicity (i.e., anti-drug antibodies [ADAs]), immune-mediated adverse effects, and the high costs resulting from drug development and industrial manufacturing [51, 52]. The dose selection for biotherapeutics is frequently set at the upper end of the dose–response curve in the absence of a maximum tolerated dose (MTD), and clinical toxicity is often not dose related [53-55]. Dosing far above a minimal effective target (overdosing) is generally not clinically relevant for biopharmaceuticals but may cause financial toxicity. Due to escalating healthcare costs, global overpopulation and an increasingly older population, a critical approach to drug dosing is vital. This thesis outlines how to establish a cost-efficient dosing strategy for emicizumab (Chapters 4–8). The strategy begins with an idea but could produce actual cost-savings and can be presented as a cycle (Figure 3). Generating this process quickly is crucial from a financial perspective, because manufacturers make drug deals for a specific period with health insurance companies, hospitals and governments. The period opens a window of opportunity for researchers to develop a cost-efficient strategy before the deal ends. The quicker this cycle is generated, the greater the financial benefit, eventually improving patient access to a formerly expensive biopharmaceutical. This strategy can also be beneficial from a medical perspective, as lower injection volumes or less-frequent injections are often part of a cost-efficient strategy. 9