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

描述（由申请方提供）：严重药物不良反应（sADR）信息传播障碍的评估对患者安全性非常重要。及时发布关于sADR的信息对于肿瘤药物非常重要，因为它们对正常和恶性细胞具有毒性，sADR发生率高，并且通常会获得加速批准和/或优先审评。最近，美国食品药品监督管理局（FDA）批准了酪氨酸激酶抑制剂（TKI），这是一种重要的新型药物，用于治疗慢性骨髓性白血病、胃肠道间质瘤、肾细胞癌和肝细胞癌。一个问题是，获得加速批准或优先审评的药物与未及时报告的sADR有关。我们的目标是开发南方肿瘤学不良反应网络（SONAR），以评价TKI的sADR，并缩短sADR识别与FDA/申办者采取行动之间的时间。这项工作建立在我们对50种sADR的鉴定、ERG协助FDA药物评价和研究中心的子奖项、我们与前康涅狄格州总检察长Richard布卢门塔尔的合作（将沙利度胺-sADR鉴定与申办者/FDA安全措施之间的时滞缩短了数年）以及FDA对TKI相关心脏毒性的兴趣的基础上。我们之前的工作得到了五个R 01的支持，导致了主要的出版物，“黑匣子”警告，“亲爱的医生”信，以及重磅炸弹药物（例如促红细胞生成素/达贝泊汀）的使用变化。我们的目标是：识别、评价和报告TKI相关心脏毒性和其他sADR的病例信息;识别与sADR信息识别/传播时间较短相关的因素;开发简化sADR信息传播的新方法（基于我们成功的试点工作）;并参与FDA将分子毒性与 目标研究（基础科学）和器官水平毒性（临床科学），TKI相关心脏毒性是第一个研究领域。我们将向FDA分发25至50份TKI相关sADR的简要报告和“公民请愿书”，我们的顾问将其确定为“黑匣子”警告或“亲爱的医生”信函（将研究转化为政策）的候选人。第二个组成部分将是假设驱动的，确定与延迟sADR识别/报告相关的因素。拟议的创新研究将首次系统性地尝试缩短肿瘤药物相关sADR的识别和报告之间的6至7年时滞，并首次合作为FDA领导的涉及整个药物类别的sADR的生物学和临床方面的研究提供信息。

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.