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Title: | Clinical application of the Web-Accessible Population Pharmacokinetic Service – Hemophilia (WAPPS-Hemo): proposal for a pilot study of a population pharmacokinetic approach to tailored prophylaxis in hemophilia. |
Authors: | Matino, Davide |
Advisor: | Iorio, Alfonso |
Department: | Health Research Methodology |
Publication Date: | 2018 |
Abstract: | Background A possible way to improve the global clinical benefit of hemophilia treatment could be adopting a tailored prophylaxis regimen. To execute a tailored prophylaxis treatment scheme is necessary the evaluation of pharmacokinetic (PK) parameters acquired after the infusion of clotting factor concentrates at the individual patient level. However, an individual, complete, PK study for either FVIII or FIX can be demanding and impractical. An alternative to the traditional PK studies is the population PK (popPK) approach. The Web Accessible Population Pharmacokinetic Service - Hemophilia (WAPPS-Hemo) is an independent population PK calculator developed at McMaster University by Dr. Alfonso Iorio. Sparse data from individual patients are fitted using a Bayesian iterative approach to estimate terminal half-life and times to critical concentrations and to produce an interactive graphical display of the concentration time curve. Objective The aim of this project is to develop a protocol for a pilot study to assess the feasibility of an interventional trial designed to test the efficacy of the PopPK approach to tailored prophylaxis in hemophilia. Methods Design: The proposed study is multi-centre, prospective (pre-post), open label, clinical trial. This study is designed to be primarily a feasibility study. Setting: Canadian Hemophilia Treatment Centers. Study population: In this study, we will enroll severe congenital hemophilia A and B patients (baseline factor level <1%) who have been on factor with any factor concentrate for at least 12 months and have reached a minimum of 150 exposure days. Intervention: The study intervention is the new personalized dosing recommendation based on PopPK, produced through the WAPPS-Hemo application. Feasibility Criteria for success: We’ll consider the pilot study to be feasible and successful if at least 50% of enrolled patients are eligible for a regimen adjustment (switch to personalized dosing regimen); at least 75% of patients who start the new prophylaxis regimen based on the personalized dosing recommendation complete the 12 months’ follow-up. Conclusion The goal of dose individualization for clotting factor concentrates is to improve the outcomes in severe hemophilia patients. The PopPK approach has this potential, but whether the use of PopPK will be will translate into clinically or economically meaningful changes in the practice of hemophilia care remains to be demonstrated. The pilot study described in this proposal will assess the feasibility of a full-scale interventional study designed to this purpose. |
URI: | http://hdl.handle.net/11375/22855 |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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Matino_Davide_2017December_MSc.pdf | 1.11 MB | Adobe PDF | View/Open |
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