Oral Chemotherapy Adherence Trajectories in Chronic Myeloid Leukemia

慢性粒细胞白血病的口服化疗依从轨迹

基本信息

批准号：
9904592
负责人：
Katherine Aylward Yeager
金额：
$ 49.09万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9904592
关键词：
Achievement Adherence Age Cancer Survivor Chronic Chronic Disease Chronic Myeloid Leukemia Clinical Cluster Analysis Common Terminology Criteria for Adverse Events Cost Measures Cytogenetics Data Demographic Factors Disease Disease Outcome Distress Dose Drug Costs Drug Targeting Effectiveness Event Exanthema Face Fatigue Female Fluorescent in Situ Hybridization Generations Home environment Imatinib In complete remission Individual Infusion procedures Insurance Insurance Coverage Intervention Interview Life Life Style Malignant Neoplasms Masks Measures Medicare Methods Modeling Molecular Monitor Nature Oral Outcome Pain Participant Patient Noncompliance Patient Self-Report Patients Pattern Pharmaceutical Preparations Regimen Reporting Reverse Transcriptase Polymerase Chain Reaction Savings Structure Subgroup Sum Survival Rate Survivors Swelling System Time Toxic effect Translating Tyrosine Kinase Inhibitor Woman Work base cancer care cancer therapy chemotherapy cohort cost design diaries experience financial toxicity gastrointestinal high risk improved interpatient variability male medical appointment medication compliance new therapeutic target prognostic response sex side effect social time use

项目摘要

The paradigm of cancer treatment is changing as more treatments are administered in oral form. This shift is well illustrated by the current recommended treatment of chronic myeloid leukemia (CML). The 5-year survival rate for CML has doubled over the past two decade (31% to 66%) in large part due to the discovery of targeted drugs, specifically tyrosine kinase inhibitors (TKIs). In contrast to most cancer treatments that are administered by an infusion in a controlled setting, TKIs are oral agents that require daily doses, most likely for life. The individual with CML is responsible for administration of every dose of this life saving drug every day. Although essential, adherence to TKIs is difficult; about a third of CML patients are reported to be nonadherent. Effectiveness of TKI therapy is measured by cytogenetic and molecular response and achievement of complete response is prognostic for long term-survival. Adherence is associate with achievement of a complete molecular response and results in improved overall survival. So why are a third of individuals with CML nonadherent? Specific to CML, patients may miss TKIs due to distress from side effects and financial toxicity. Distressing side effects from TKIs that reduce adherence include fatigue, pain, gastrointestinal upset, swelling and skin rashes. Financial toxicity occurs due to the expense of the TKIs ($30,000- $138,000/year) in combination with increasing insurance co-pays and out of pocket (OOP) costs. For instance, Medicare Part D enrollees paid a mean OOP cost for TKI therapy of $8,503 in 2016. These high drug costs plus other OOP costs related to cancer care result in changes in lifestyle, missed medical appointments and missed doses of medication. To more fully understand adherence and the effects on clinical outcomes, we need to consider the intrapatient and interpatient variability of medication adherence. This study will follow a group of 120 individuals taking TKIs for 12 months, measuring adherence with an objective measure (Medication Event Monitoring System) along with monthly assessments of toxicity (side effects and financial). To understand the variability of long term adherence, we will use these data to determine subgroups of adherence patterns (or trajectories) over time using model-based cluster analysis. Then, using both quantitative and qualitative data, we will examine how different toxicities are associated with the different adherence patterns. Next we will examine the influence of TKI adherence patterns on cytogenetic and molecular response. Identifying differential patterns of adherence in individuals taking TKIs is important for identifying subgroups at the highest risk of nonadherence and will support the design of targeted interventions.

随着越来越多的口服治疗方法的出现，癌症治疗的模式正在发生变化形式。目前推荐的慢性粒细胞治疗方法很好地说明了这种转变白血病（CML）。过去二十年里，CML 的 5 年生存率翻了一番（31%）至 66%）很大程度上是由于靶向药物的发现，特别是酪氨酸激酶抑制剂（TKI）。与大多数由医生进行的癌症治疗相反 TKI 是在受控环境下输注的口服药物，需要每日服用，很可能终生服用。慢性粒细胞白血病 (CML) 患者有责任服用这种救命药物的每一剂每天。尽管很重要，但坚持 TKI 很困难；大约三分之一的 CML 患者据报道不遵守规定。 TKI 治疗的有效性通过细胞遗传学和分子反应和完全反应的实现是长期生存的预后。依从性与实现完整的分子反应有关，并导致提高总体生存率。那么为什么三分之一的 CML 患者不依从治疗呢？具体到 CML 患者可能会因副作用和经济毒性而错过 TKI。令人苦恼 TKI 降低依从性的副作用包括疲劳、疼痛、肠胃不适、肿胀和皮疹。由于 TKI 的费用（$30,000- 138,000 美元/年）加上不断增加的保险自付费用和自付费用 (OOP) 成本。例如，Medicare D 部分参与者为 TKI 治疗支付的平均 OOP 费用为 8,503 美元 2016 年。这些高昂的药品成本加上与癌症护理相关的其他 OOP 成本导致了生活方式、错过医疗预约和错过药物剂量。为了更充分了解依从性及其对临床结果的影响，我们需要考虑患者体内的情况以及患者间用药依从性的差异。这项研究将跟踪 120 人服用 TKI 12 个月的个体，用客观指标衡量依从性（药物事件监测系统）以及每月毒性评估（副作用和财务）。为了了解长期依从性的可变性，我们将使用这些数据来使用基于模型的方法确定一段时间内的依从模式（或轨迹）子组聚类分析。然后，使用定量和定性数据，我们将研究如何不同的毒性与不同的依从模式相关。接下来我们将检查 TKI 依从模式对细胞遗传学和分子反应的影响。识别服用 TKI 的个体的不同依从模式对于识别亚组很重要不依从的风险最高，并将支持有针对性的干预措施的设计。