Personalized Medicine for Canadians With Hemophilia: a Pragmatic Evaluation of the Web-Accessible Population Pharmacokinetics Service- Hemophilia (WAPPS-Hemo) Tailored Dosing.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 600
- 试验地点
- 7
- 主要终点
- Change in patient quality of life
研究概览
简要总结
Performing an individual pharmacokinetic (PK) estimate is only the first step in implementing tailored prophylaxis, which requires using the PK profile information to design a personalized treatment regimen matching the treatment needs of individual patients. The overarching goal of WAPPS-Hemo is to provide an easy-to-use web application supporting all the steps needed to accomplish tailoring care of individual patients by matching their unique characteristics to the most appropriate treatment regimen, realizing the promise of personalized medicine.
This study will assess the impact of adopting population PK (popPK) based tailored prophylaxis in clinical practice, including proportion of patients eligible for tailoring, and encountered barriers. The impact on patient important outcomes and on societal outcomes, particularly financial impact, vs. current standardized regimens will be measured. It is hypothesized that WAPPS-Hemo, via estimation of precise individual PK profiles and by supporting the simulation of treatment regimens will:
- improve or maintain patient important outcomes, while reducing wastage of factor concentrates; and
- establish best practices and effective knowledge translation strategies for the implementation of personalized medicine.
Additionally, a solid base of data will be generated to model the bleeding risk of severe hemophilia A/B patients undergoing tailored prophylaxis which will enable evaluation of a combination of patient and treatment characteristics predictive of individual bleeding risk.
详细描述
The PMCH study is a Canadian multicentre, open-label, historically-controlled clinical trial to evaluate the effects of implementing WAPPS-Hemo PopPK-based tailoring of hemophilia prophylaxis regimens using the tailoring dosing function of the WAPPS-Hemo system (WAPPS-Hemo clinical calculator).
The study start date at each centre are staggered by 1-3 months in a modified wedge-shaped design, to allow better differentiation of the effect of the intervention from unrelated but concomitant changes in other aspects of care in the Canadian landscape. Outcomes of interest will be measured for one year prior and for one year after the implementation of the WAPPS-Hemo regimen tailoring procedure.
The two main objectives of this study are:
- Evaluate the applicability and effectiveness of WAPPS-Hemo PopPK-based tailoring of factor concentrate regimens.
- Generate a solid base of data to model the bleeding risk of severe hemophilia A/B patients on prophylaxis, evaluating the contribution of patient and treatment characteristics to individual bleeding risk to be reduced by the tailored prophylaxis approach.
PMCH will objectively measure the impact of adopting a PopPK based tailoring of hemophilia treatment. The first goal will be minimizing the occurrence of bleeding events in the hemophilia population. The bleeding rate of Canadian hemophilia patients is still measurable at 2-4 spontaneous joint bleeds per year, which in turn reduce quality of life and consume health resources. It is expected that optimizing treatment goal and modalities will reduce this burden, or at least will not increase it, allowing the pursuit the second goal: minimize the use of resources and prompt a more equitable distribution of factor concentrates. For some patients, standard prophylaxis dosing leads to excessive use of concentrates. It is expected that a small but sizeable proportion of the patient population will be able to successfully reduce their factor concentrate consumption. The third goal will be to generate an evidence-based approach to identify the appropriate target goal(s) for individual patients by modelling the components of their risk of bleeding. Adopting a variable target threshold may enhance objective one and two, maximizing benefits with appropriate allocation of resources.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 6 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •individuals with severe congenital hemophilia A and B;
- •on continuous factor prophylaxis;
- •must be registered on CBDR (iCHIP in BC)
排除标准
- •a history of explicit and documented previous treatment tailoring based on pharmacokinetic profiling;
- •another congenital or acquired bleeding disorders other than Hemophilia A or B;
- •active inhibitors (> 5 Bethesda units) or currently undergoing immune tolerance induction.
结局指标
主要结局
Change in patient quality of life
时间窗: Completed every 3-6 months for duration of the study, from enrollment to study completion.
Patient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire. Scores range from 0-1, with a higher value indicating better health status.
Annualized Bleeding Rate (ABR) pre and post-tailoring implementation
时间窗: Recorded throughout the 2 year duration of the study as they occur.
ABR from the one year prior to WAPPS-Hemo tailoring to the one-year post-tailoring (absolute number of bleeds per year).
次要结局
- Change in physical activity(Completed every 3-6 months for duration of the study, from enrollment to study completion.)
- Adherence to prescribed regimen(Recorded throughout the 2 year duration of the study - frequency is as input by patient.)
- Consumption of factor concentrates(Recorded throughout the 2 year duration of the study - frequency as input by patient.)
- Feasibility and acceptability of the WAPPS-Hemo based prophylaxis tailoring(Recorded after 1 year at the time of tailoring implementation.)
- Characteristics of reported bleeds(Recorded throughout the 2 year duration of the study- frequency as input by patient.)
- Assessment of the predictive performance of the WAPPS-Hemo clinical calculator(Measured within routine clinical practice for 12 months post-tailoring implementation.)
- Change in joint function(Measured at study enrollment and at 2 years at study completion.)