160 Chapter 9 The key lessons and recommendations from this thesis are as follows: • Bioanalysis with LC-MS/MS is advantageous for measuring plasma proteins (e.g., FVIII and emicizumab) in a clinical setting. In this thesis, the LC-MS/MS method development for measuring FVIII plasma concentration proved challenging and required an additional purification step to dissociate FVIII from the Von Willebrand factor. However, the LC-MS/MS method development measuring emicizumab was straightforward and could be multiplexed with other biopharmaceuticals. Crossvalidation against a standard method is highly recommended for the external validity of the method. • The relationship between the FVIII concentrations measured using LC-MS/MS analysis and the FVIII activity measured using a clotting assay revealed an unexpectedly large variability. Consequently, the role of monitoring FVIII with LC-MS/MS analysis remains unclear, and the added value must still be determined before the method is introduced to the clinic. However, monitoring emicizumab with LC-MS/MS analysis can be implemented in a clinical setting for clinical support, cost efficiency and research. • A cost-efficient dosing strategy for biopharmaceuticals can be developed based on the four studies on emicizumab in this thesis. This strategy involves (i) developing a measurement method to quantify a biopharmaceutical in human plasma; (ii) critically evaluating the literature to identify a minimum effective target of the drug; (iii) evaluating real-world evidence in the target population; and eventually (iv) designing a clinical study comparing cost-efficient dosing with conventional dosing. This general discussion chapter provides a broad perspective on the following two themes: 1. Potential future applications of LC-MS/MS monitoring of FVIII concentrations in haemophilia A 2. Framework for the cost-efficient dosing strategies of biopharmaceuticals This perspective includes clinical implications, future perspectives and recommendations. As outlined below, both themes begin with background and rationale and end with critical notes and conclusion. This general discussion ends with concluding remarks on the thesis.