Pharmacogenomics to Catalyze Decision Support in Oncology Care

药物基因组学促进肿瘤护理决策支持

• 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
• 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

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.

项目总结/摘要 癌症患者是我们医疗体系中最脆弱的人群之一。不仅 这些人是否面临威胁生命的诊断，但治疗方案的毒性使癌症 患者有额外的不良结局风险。此外，大多数癌症患者的经验不足， 治疗疼痛，尽管临床医生采取药物干预措施来解决疼痛。 生殖系药物基因组学信息的使用提供了一种潜在的解决方案，以更好地为治疗提供信息。 决策的许多人认为这是一个理想的学科，通过它来推进和检查临床应用 基因组医学尽管如此，目前还没有预先进行生殖系药物基因组学检测， 在使用大多数抗癌疗法之前，也不适用于疼痛处方。之一 最常提到的原因是缺乏证明其效用的前瞻性随机数据。 我们认为，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。我们假设提供生殖系药物基因组学信息 沿着临床决策支持将指导个性化化疗和止痛药 选择和剂量决定，减少毒性，并导致改善的患者结果。 我们建议利用现有的体制基础设施和大学的两个优势， 芝加哥（药物基因组学，肿瘤学）通过进行第一个已知的广泛的前瞻性随机研究 生殖细胞药物基因组学的最新进展我们将招募准备开始癌症化疗的患者 或疼痛治疗，患有三种主要癌症类型之一（胃肠癌、头颈癌或乳腺癌 恶性肿瘤），并随机分配至前期药物基因组学检测组与非前期药物基因组学检测组 常规护理（Usual Care） 化疗剂量和严重毒性的发生率，以及疼痛治疗的阿片类药物选择 将比较两组之间的疼痛药物反应。此外，我们将评估是否共享 以知情的方式与患者分享药物基因组学结果， 对治疗选择的看法以及与治疗目标的一致性。 总之，该建议将检查和推进广泛有效的临床 基因组发现的转化将通过系统/技术变革以及 在关键临床环境和利益相关者中对基因组知识应用进行战略评估 人口。未来对公共卫生的有效性和影响将不仅仅来自我们的发现 而是通过更好地理解促进和采用风险的决策过程， 减少量身定制的治疗方法。