Southern Oncology Network on Adverse Reactions (SONAR) - Focus on Tyrosine Kinase

南方肿瘤学不良反应网络 (SONAR) - 关注酪氨酸激酶

• 批准号: 8680186
• 负责人: CHARLES L. BENNETT
• 金额: $ 42.7万
• 依托单位: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8680186
• 关键词: Accounting; Address; Adverse event; Adverse reactions; Antineoplastic Agents; Area; Australia; Award; Basic Science; Boxing; Canada; Cardiotoxicity; Case Study; Cessation of life; Characteristics; Chronic; Clinical; Clinical Sciences; Collaborations; Communities; Connecticut; Data Set; Drug Evaluation; Erythropoietin; Etiology; Europe; Evaluation; Evaluation Research; Gastrointestinal Stromal Tumors; Grant; Information Dissemination; Investigation; Journals; Laboratories; Lawyers; Length; Letters; Link; Malignant Neoplasms; Medical; Molecular; Normal Cell; Organ; Package Insert; Patients; Peer Review; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phase III Clinical Trials; Policies; Primary carcinoma of the liver cells; Process; Protein Tyrosine Kinase; Publications; Publishing; Reaction; Recommendation; Renal Cell Carcinoma; Reporting; Research; Research Personnel; Research Project Grants; Review Literature; Safety; Severities; System; Testing; Thalidomide; Time; TimeLine; Toxic effect; Translating; Tyrosine Kinase Inhibitor; United States Food and Drug Administration; Work; base; cancer cell; experience; high risk; innovation; interest; leukemia; novel; novel strategies; oncology; patient safety; post-market; public health relevance; reaction rate; success

DESCRIPTION (provided by applicant): Assessments of barriers to dissemination of serious adverse drug reaction (sADR) information are important for patient safety. Timely information dissemination on sADRs is important for oncology drugs, as they are toxic to normal and malignant cells, have high sADR rates, and often receive accelerated approval and/or priority review. Recently, the Food and Drug Administration (FDA) has approved tyrosine kinase inhibitors (TKIs), an important novel drug class administered for chronic mylogenous leukemia, gastrointestinal stromal tumors, renal cell cancers, and hepatocellular carcinoma. One concern is that drugs that receive accelerated approval or priority review are associated with sADRs not reported in a timely manner. Our objective is to develop the Southern Oncology Network on Adverse Reactions (SONAR) to evaluate sADRs for TKIs and DECREASE the duration of time between sADR identification and FDA/sponsor actions. The work builds on our identification of 50 sADRs, our sub-award from ERG assisting FDA's Center for Drug Evaluation and Research, our collaboration with former Connecticut Attorney General Richard Blumenthal that decreased the time-lag between thalidomide-sADR identification and sponsor/FDA safety-actions by several years, and FDA interest in TKI-associated cardiotoxicity. Our prior work, supported by five R01s, led to major publications, "Black Box" warnings, "Dear Doctor" letters, and changes in use of block-buster pharmaceuticals (e.g. erythropoietin/darbepoetin). Our aims are to: identify, evaluate, and report case information for TKI-associated cardiotoxicity and other sADRs; identify factors associated with shorter time periods for identification/dissemination of sADR information; develop a novel approach to streamlining sADR information dissemination (building on our successful pilot effort); and participate in a FDA initiative that will link molecular toxic target studies (basic science) and organ-level toxicity (clinical science), with TKI-associated cardiotoxicity being the first area of study. We will disseminate brief reports for 25 to 50 TKI-associated sADRs and "Citizen's Petitions" to the FDA for sADRS for which our consultants identify as candidates for "Black Box" warnings or "Dear Doctor" letters (translating research into policy). The second component will be hypothesis driven, identifying factors associated with delayed sADR identification/reporting. The proposed innovative study will be the first to systematically attempt to shorten the six to seven year time lag between identification and reporting of oncology drug- associated sADRs and the first collaboration that provides information for FDA-led investigation of biologic and clinical aspects of a sADR involving an entire drug class.

描述（由申请人提供）：对严重不良药物反应（SADR）信息传播障碍的评估对于患者安全很重要。及时的有关SADRS的信息传播对于肿瘤学药物对正常和恶性细胞有毒，具有较高的SADR率，并且经常获得加速的认可和/或优先级审查。最近，食品药物管理局（FDA）批准了酪氨酸激酶抑制剂（TKIS），这是一种重要的新型药物类别，用于慢性神经元性白血病，胃肠道基质肿瘤，肾细胞癌和肝细胞癌癌。一个问题是，获得加速批准或优先审查的药物与未及时报告的SADR有关。我们的目标是开发南部肿瘤网络对不良反应（声纳），以评估TKIS的SADR，并减少SADR识别与FDA/赞助商行动之间的时间。这项工作是基于我们对50个萨德尔的识别，这是我们与ERG协助FDA药物评估和研究中心的子奖，我们与前康涅狄格州检察长理查德·布卢门塔尔（Richard Blumenthal）的合作，将Thalidomide-SADR识别和赞助商/FDA安全性降低了几年，并降低了Thalidomide-SADR识别与FDA的兴趣，并在Tki-i-Assciotiped中降低了时间差。我们的先前工作得到了五个R01的支持，导致了主要出版物，“黑匣子”警告，“亲爱的医生”字母以及块状药品使用的变化（例如erythropoietin/darbepoetin）。我们的目的是：确定，评估和报告有关TKI相关性心脏毒性和其他SADR的案例信息；确定与较短时间段相关的因素，以识别/传播SADR信息；开发一种新颖的方法来简化SADR信息传播（以我们成功的飞行员努力为基础）；并参与FDA计划，该计划将连接分子有毒 目标研究（基础科学）和器官水平的毒性（临床科学），TKI相关的心脏毒性是第一个研究领域。我们将对25至50个TKI相关的萨德尔人的简短报告和向FDA的“公民请愿书”传播给萨德尔人的“公民请愿书”，我们的顾问将其视为“黑匣子”警告或“亲爱的医生”信件的候选人（将研究转化为政策）。第二个组件将是由假设驱动的，可以识别与延迟的SADR识别/报告相关的因素。拟议的创新研究将是第一个系统地试图缩短肿瘤药物相关的SADR的识别和报告之间的六到七年时间的滞后和第一次合作，该合作提供了涉及整个药物类的SADR的生物学和临床方面的信息。