Pharmacogenomics to Catalyze Decision Support in Oncology Care

药物基因组学促进肿瘤护理决策支持

基本信息

批准号：
10675381
负责人：
Peter Hugh O'Donnell
金额：
$ 88.42万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-06-01 至 2028-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10675381
关键词：
Address Adopted Adoption Adverse event Analgesics Cancer Patient Caring Cessation of life Chemotherapy-Oncologic Procedure Chicago Childhood Leukemia Clinical Codeine Data Decision Making Diagnosis Discipline Dose Education Effectiveness Emergency department visit Evolution Face Fostering Future Genomic medicine Genomics Genotype Germ-Line Mutation Goals Head and neck structure Healthcare Systems Hospitalization Hydrocodone Incidence Individual Infrastructure Institution Intervention Knowledge Life Malignant Neoplasms Medical Mission Nature Oncologist Oncology Opioid Outcome Pain Pain management Patient Recruitments Patient-Focused Outcomes Patients Pattern Perception Pharmaceutical Preparations Pharmacogenomics Population Pragmatic clinical trial Process Public Health Quality of life Randomized Recommendation Reporting Research Risk Safety Supportive care System Technology Testing Therapeutic Toxic effect Tramadol Treatment Protocols Treatment-related toxicity UGT1A1 gene Universities Variant Vulnerable Populations adverse outcome arm breast malignancies cancer care cancer initiation cancer pain cancer risk cancer therapy cancer type chemotherapy clinical application clinical decision support clinical translation expectation experience fluoropyrimidine gastrointestinal high risk improved individualized medicine irinotecan pain relief personalized chemotherapy pharmacologic point of care prescription opioid prevent primary endpoint prospective response shared decision making side effect standard of care tool translational genomics treatment as usual treatment choice

项目摘要

PROJECT SUMMARY/ABSTRACT Patients with cancer represent one of the most vulnerable populations in our healthcare system. Not only do such individuals face a life-threatening diagnosis, but the toxicities of treatment regimens place cancer patients at additional risk for adverse outcomes. Additionally, most cancer patients experience inadequately treated pain, despite pharmacologic interventions by clinicians to address pain. The use of germline pharmacogenomic information offers a potential solution to better inform therapeutic decision-making. Many consider it an ideal discipline by which to advance and examine the clinical application of genomic medicine. Nevertheless, preemptive germline pharmacogenomic testing does not currently constitute the standard of care before utilization of most anti-cancer therapies, nor for pain prescribing. One of the most frequently cited reasons is the lack of prospective randomized data demonstrating its utility. We posit that preemptive genotyping and the upfront use of pharmacogenomic information offers the potential to improve cancer care. We hypothesize that providing germline pharmacogenomic information along with clinical decision support will guide personalized chemotherapy and pain medication choices and dosing decisions, reduce toxicity, and result in improved patient outcomes. We propose to leverage our existing institutional infrastructure and two strengths of the University of Chicago (pharmacogenomics, oncology) by performing the first known broad prospective randomized studies of germline pharmacogenomics in oncology. We will recruit patients preparing to initiate cancer chemotherapy or pain treatment who have one of three major cancer types (gastrointestinal, head and neck, or breast malignancies), and randomize to upfront pharmacogenomic testing versus no upfront pharmacogenomic information (usual care). Chemotherapy dosing and the incidence of severe toxicities, as well as opioid selection for pain treatment and pain medication response will be compared between arms. Additionally, we will evaluate whether sharing of pharmacogenomic results with patients in an informed manner improves patients’ knowledge about and perceptions of treatment choices and alignment with treatment goals. In summary, this proposal will examine and advance the idea that widespread efficacious clinical translation of genomic discoveries will be actualized both by systems/technology changes as well as the strategic assessment of genomic knowledge applications within key clinical settings and stakeholder populations. Future effectiveness and impact on public health will result not just from the findings we generate but from an improved understanding of decision-making processes involved in promoting and adopting risk- reductive, customized treatment practices.

项目摘要/摘要癌症患者是我们医疗保健系统中最脆弱的人群之一。不仅这样的人是否面临威胁生命的诊断，但是治疗方案的毒性将癌症置于癌症患者面临不良后果的风险。此外，大多数癌症患者的经历不足临床医生治疗的疼痛，dospite药学干预措施以解决疼痛。种系药物基因组学信息的使用提供了一种潜在的解决方案，以更好地告知治疗决策。许多人认为这是一个理想的学科，可以通过该学科进行进步和检查临床应用然而，先发制性种系药物基因组学测试目前尚未在利用大多数抗癌疗法之前，也构成了护理标准，也构成疼痛处方。之一最常见的原因是缺乏证明其效用的前瞻性随机数据。我们指出，先发制人的基因分型和药物基因组学信息的前期使用提供了改善癌症护理的潜力。我们假设提供种系药物基因组学信息除临床决策支持外，还将指导个性化的化学疗法和止痛药选择和剂量决策，降低毒性并改善患者预后。我们建议利用我们现有的机构基础设施和大学的两个优势芝加哥（药物基因组学，肿瘤学）通过进行首次已知的广泛前瞻性随机研究肿瘤学中种系药物基因组学。我们将招募准备开始癌症化学疗法的患者或具有三种主要癌症类型之一（胃肠道，头颈或乳房）中的一种或疼痛治疗恶性），并随机到前期药物基因组学测试与无前药基因组学信息（通常护理）。化学疗法剂量和严重毒性的事件以及疼痛治疗的阿片类药物选择臂之间将比较止痛药物的反应。此外，我们将评估是否共享患者以知情方式与患者的药物基因组成果的结果改善了患者对和对治疗选择的看法和与治疗目标的一致性。总而言之，该提案将研究并推进宽度有效临床的想法基因组发现的翻译将通过系统/技术的变化以及在关键临床环境和利益相关者中对基因组知识应用的战略评估人群。未来的有效性和对公共卫生的影响不仅会源于我们产生的发现但是，从对促进和采用风险涉及的决策过程的深入了解中 - 还原，定制的治疗实践。