Development and validation of a disease-relevant patient-reported outcome tool in light chain amyloidosis

轻链淀粉样变性疾病相关患者报告结果工具的开发和验证

基本信息

批准号：
10396983
负责人：
Anita D'Souza
金额：
$ 13.95万
依托单位：
MEDICAL COLLEGE OF WISCONSIN
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：
2019-05-01 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10396983
关键词：
Advocate Amyloid Amyloid Fibrils Amyloidosis Assessment tool Benefits and Risks Biological Biological Markers Blood Bone Marrow Transplantation Bortezomib Cardiac Clinical Clinical Research Clinical Trials Clinical Trials Design Clinical Trials Network Clone Cells Complement Complex Comprehension Conceptual Domain Custom Data Data Coordinating Center Deposition Deterioration Development Diagnosis Disease Fatigue Functional disorder Funding Future Goals Guidelines Health Status Heart Hematology Intervention Interview Kidney Libraries Light Malignant - descriptor Measurement Measures Mentored Patient-Oriented Research Career Development Award Mentors Mentorship Methodology Monitor Morbidity - disease rate Multi-Institutional Clinical Trial Multiple Myeloma National Heart, Lung, and Blood Institute Neurologic Dysfunctions Newly Diagnosed Non-Malignant Observational Study Oncology Organ Outcome Outcome Assessment Outcome Measure Patient Outcomes Assessments Patients Phenotype Physical Function Plasma Cells Positioning Attribute Process Property Proteasome Inhibitor Psychometrics Randomized Randomized Clinical Trials Rare Diseases Reporting Research Research Personnel Review Literature SF-36 Science Source Specialist Staging Symptoms System Techniques Testing Therapeutic Clinical Trial Training Treatment-related toxicity United States National Institutes of Health Validation Work amyloid formation base career career development chemotherapy clinical care clinical outcome assessment cognitive interview cohort expectation experience flexibility international center meetings member mortality multidisciplinary novel novel therapeutics patient oriented patient oriented research primary amyloidosis of light chain type prospective response success symptom management tool

项目摘要

ABSTRACT Light chain amyloidosis (AL) is a plasma cell disorder characterized by organ dysfunction from insoluble fibril deposition derived from clonal light chains. The disease is associated with high early mortality and is treated with chemotherapies similar to multiple myeloma. Decline in health status is predominant in AL and often the signature feature at presentation. Even when chemotherapy produces a successful hematologic response, patients may continue to experience symptoms related to organ (e.g. cardiac, renal, neurologic) dysfunction, due to deposition of fibrils prior to therapy. Therefore, measurement of PROs, such as patient-reported fatigue and physical functioning, is a critical, yet underutilized, aspect of the overall outcomes assessment of trials of AL therapies. The candidate for this mentored patient-oriented research career development (K23) award, Dr. Anita D'Souza, is a hematology/oncology trained amyloid specialist with demonstrated success in conducting investigator-initiated clinical trials. As the Scientific Director of the Plasma Cell Disorders Working Committee in the NIH-funded Center for International Blood and Marrow Transplant Research and member of the Data and Coordinating Center for the NIH-funded Blood and Marrow Transplant Clinical Trials Network, Dr. D'Souza is well positioned for a career in developing and executing clinical trials in plasma cell disorders. Her career goal is to conduct patient-centered amyloid clinical research, where the patient's perspective is a standard and expected component of clinical trials 1) evaluating new treatments for AL amyloidosis and 2) using PROs for symptom monitoring and management . To accomplish this goal, Dr. D'Souza requires didactic training and mentorship in PRO methodology, mentorship in patient-centered research, and mentorship in effective engagement with patients and patient advocates. In this K23 application, and in the context of providing this training and mentorship, we propose to develop and evaluate a PRO tool relevant for AL (the AL-PROfile), utilizing items from the library of NIH PROMIS measures. Specific Aim 1 will determine the most relevant symptom and functioning domains for patient-centered AL research through literature review and qualitative interviews with patients, patient advocates, and clinical and research experts, select items from the PROMIS item libraries to comprise the AL-PROfile, and confirm item comprehension in cognitive interviews with patients; Aim 2 will evaluate the psychometric measurement properties of the AL-PROfile, including convergent and discriminant validity, known groups validity, internal consistency, test-retest reliability, and responsiveness to change; and Aim 3 will track PROs longitudinally in newly diagnosed patients in clinical care. Dr. D'Souza's training plan incorporates didactics, mentoring by a multi-disciplinary team, and research experience that will allow her to augment her expertise in AL clinical trials with a deeper understanding of patient-centered research and PROs. The work will provide preliminary data to support an R01 proposal to conduct a randomized, multicenter clinical trial to test the AL-PROfile as an intervention for symptom management in AL .

抽象的轻链淀粉样变性 (AL) 是一种浆细胞疾病，其特征是不溶性原纤维导致器官功能障碍来自克隆轻链的沉积。该疾病与早期死亡率较高有关，需要接受治疗与多发性骨髓瘤类似的化疗。健康状况的下降是 AL 的主要症状，而且往往是演示时的签名功能。即使化疗产生了成功的血液学反应，患者可能会继续出现与器官（例如心脏、肾脏、神经系统）功能障碍相关的症状，由于治疗前原纤维的沉积。因此，PRO 的测量，例如患者报告的疲劳和身体功能，是试验总体结果评估的一个关键但未得到充分利用的方面 AL疗法。该以患者为导向的研究职业发展（K23）奖的候选人，博士。 Anita D'Souza 是一位接受过血液学/肿瘤学培训的淀粉样蛋白专家，在开展研究者发起的临床试验。作为浆细胞疾病工作委员会的科学主任美国国立卫生研究院 (NIH) 资助的国际血液和骨髓移植研究中心以及数据和骨髓移植研究中心的成员 D'Souza 博士是 NIH 资助的血液和骨髓移植临床试验网络协调中心非常适合开发和执行浆细胞疾病临床试验。她的职业目标是开展以患者为中心的淀粉样蛋白临床研究，以患者的观点为标准，临床试验的预期组成部分 1) 评估 AL 淀粉样变性的新疗法和 2) 使用 PRO 用于症状监测和管理。为了实现这一目标，D'Souza 博士需要进行教学培训并 PRO 方法论的指导、以患者为中心的研究的指导以及有效的指导与患者和患者倡导者的接触。在此 K23 应用程序中，并在提供此内容的上下文中培训和指导，我们建议开发和评估与 AL 相关的 PRO 工具（AL-PROfile），利用 NIH PROMIS 措施库中的项目。具体目标 1 将确定最相关的通过文献回顾和定性研究以患者为中心的 AL 研究的症状和功能领域采访患者、患者倡导者以及临床和研究专家，从 PROMIS 中选择项目项目库组成 AL-PROfile，并在认知访谈中确认项目理解患者;目标 2 将评估 AL-PROfile 的心理测量特性，包括收敛性和判别效度、已知群体效度、内部一致性、重测信度、和反应能力改变； Aim 3 将纵向跟踪临床护理中新诊断患者的 PRO。迪索萨博士的培训计划包含教学法、多学科团队的指导以及研究经验，让她能够更深入地了解以患者为中心的理念，从而增强在 AL 临床试验方面的专业知识研究和 PRO。这项工作将提供初步数据来支持 R01 提案，以开展测试 AL-PROfile 作为 AL 症状管理干预措施的随机、多中心临床试验。

项目成果

期刊论文数量（13）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Development and initial validation of the AL-PROfile patient-reported outcome measure in light chain (AL) amyloidosis.

轻链 (AL) 淀粉样变性患者报告的 AL-PROfile 结果测量的开发和初步验证。

DOI：
发表时间：
2024-06
期刊：
影响因子：
3.1
作者：
D'Souza, Anita;Szabo, Aniko;Akinola, Idayat;Finkel, Muriel;Flynn, Kathryn E
通讯作者：
Flynn, Kathryn E

A cross-sectional study of patient-reported outcomes and symptom burden using PROMIS and PRO-CTCAE measures in light chain amyloidosis.

使用 PROMIS 和 PRO-CTCAE 测量轻链淀粉样变性对患者报告的结果和症状负担进行横断面研究。

DOI：
发表时间：
2023-06
期刊：
影响因子：
0
作者：
D'Souza, Anita;Szabo, Aniko;Akinola, Idayat;Finkel, Muriel;Flynn, Kathryn E
通讯作者：
Flynn, Kathryn E

Adjuvant doxycycline to enhance anti-amyloid effects: Results from the dual phase 2 trial.

辅助强力霉素增强抗淀粉样蛋白作用：双 2 期试验的结果。

DOI：
发表时间：
2020-06
期刊：
影响因子：
15.1
作者：
D'Souza, Anita;Szabo, Aniko;Flynn, Kathryn E;Dhakal, Binod;Chhabra, Saurabh;Pasquini, Marcelo C;Weihrauch, Dorothee;Hari, Parameswaran N
通讯作者：
Hari, Parameswaran N

Prevalence and significance of sarcopenia in multiple myeloma patients undergoing autologous hematopoietic cell transplantation.

接受自体造血细胞移植的多发性骨髓瘤患者肌肉减少症的患病率和意义。

DOI：
发表时间：
2021
期刊：
影响因子：
4.8
作者：
Williams, Alexis;Baruah, Dhiraj;Patel, Jayshil;Szabo, Aniko;Chhabra, Saurabh;Dhakal, Binod;Hari, Parameswaran;Janz, Siegfried;Stolley, Melinda;D'Souza, Anita
通讯作者：
D'Souza, Anita

Development of a conceptual model of patient-reported outcomes in light chain amyloidosis: a qualitative study.

轻链淀粉样变性患者报告结果概念模型的开发：一项定性研究。

DOI：
发表时间：
2022-04
期刊：
影响因子：
0
作者：
D'Souza, Anita;Myers, Judith;Cusatis, Rachel;Dispenzieri, Angela;Finkel, Muriel;Panepinto, Julie;Flynn, Kathryn E
通讯作者：
Flynn, Kathryn E