The development and evaluation of a vancomycin population pharmacokinetic model in children, pre-adolescent, and adolescent patients was performed via non linear mixed effects modeling (NONMEM) in 2 phases. In phase I, a vancomycin population pharmacokinetic model was developed based on data from 200 children (aged 2-17 years) using a two-compartment model. Variables tested for inclusion in the model were serum creatinine (SCR), age (AGE), weight (WT), height (HT), sex (SEX), and body surface area (BSA). Variables were included at the p $ In phase II, the performance of the derived model was evaluated in a naive tested population and then compared to the Schaad, et al. model via prediction error techniques (PE). The predictability of 159 measured concentrations was assessed in 68 new patients. In predicting all concentrations types, the mean prediction error (MPE) with a 95% confidence interval (CI) for both the current study model and Schaad, et al model were: $-$1.42 ($-$3.38, 0.54), and 6.01 (4.46, 7.56) mg/L, respectively. When considering only peaks, a MPE with 95% CI were 1.72 ($-$0.94, 4.38), and 7.61 (5.13, 10.09) mg/L, respectively. Finally, MPE with 95% CI for the troughs were $-$1.45 ($-$3.42, 0.52), and 3.84 (2.98, 4.70) mg/L, respectively. Maintenance dose (MD) tables were designed, based on the relationship of height and serum creatinine to clearance. In addition, a loading dose (LD) was also recommended, which was 5 mg/cm. It is recommended that the current study model be used for dosing the pediatric population while setting an initial target peak of 30 mg/L and a trough of 5-10 mg/L. This should frequently result in optimal serum vancomycin concentrations within the therapeutic window. Individualization of therapy should then be done, once the measured concentrations are available.

Hemophilia is a genetic disorder that is caused by deficiencies in coagulation factor VIII and factor IX. Optimal management of hemophilia requires tailoring the dose of treatment to the individual patient’s need. This tailoring is based on several clinical considerations, for example, bleeding phenotype and desired level of activity, and estimated individual pharmacokinetic (PK) parameters. While a classical PK approach would require several post infusion blood samples taken over multiple days, a population PK approach might enable individual assessment using fewer samples. Health information technologies can support implementation of sophisticated, easily available, point-of care resources to estimate PK values with a population approach. The Web Accessible Population Pharmacokinetic Service-Hemophilia (WAPPS-Hemo) is a proposal for such a solution, developed at McMaster University. Once tested, it will be offered to hemophilia centres worldwide. The objective of the study was to investigate the ease of use (usability) of the WAPPS-Hemo web interface among clinicians and other people who treat hemophilia through two iterative cycles of usability testing. The total number of participants was 13, and they were physicians, nurses and research coordinators. The think aloud technique was selected for testing to gain feedback and comments on the participants’ thought processes while interacting with the system and discover interface design problems. Additionally, the System Usability Scale (SUS) questionnaire was used to obtain data on user satisfaction. The initial assessment of the prototypal WAPPS-Hemo interface with SUS reported a score of 70.5, which is considered an above average score. We received many useful suggestions through two iterations of user testing, ending with a final SUS score of 73 after implementation of the suggested improvements. Verbal feedback from users in the second round showed that users experienced an easier and more intuitive interaction with the system. Usability testing and analyses were conducted in this study to discover user interface issues and to determine the usability and learnability of the WAPPS-Hemo service among various potential users. Through iterative cycles, application of the think aloud technique, and the SUS questionnaire, we optimized the usability of the WAPPS- Hemo program and have moved to implementation (June 2015). / Thesis / Master of Science (MSc)

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