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

描述(由申请人提供)：评估传播严重药物不良反应(SADR)信息的障碍对患者安全非常重要。及时传播关于sADRs的信息对肿瘤学药物很重要，因为它们对正常和恶性细胞有毒性，具有较高的sadr率，并且经常得到加速批准和/或优先审查。最近，美国食品和药物管理局(FDA)批准了酪氨酸激酶抑制剂(TKIs)，这是一种重要的新药类别，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。一个令人担忧的问题是，获得加速批准或优先审查的药物与未及时报告的sADR有关。我们的目标是发展南方肿瘤学不良反应网络(SONA)来评估TKIs的sADR，并缩短SADR鉴定和FDA/赞助商行动之间的时间。这项工作的基础是我们确定了50种sADR，我们获得了ERG协助FDA药物评估和研究中心颁发的子奖，我们与康涅狄格州前总检察长理查德·布鲁门塔尔的合作将沙利度胺-SADR鉴定和赞助商/FDA安全行动之间的时间间隔缩短了几年，以及FDA对TKI相关心脏毒性的兴趣。我们之前的工作，在五个R01的支持下，导致了主要出版物、“黑匣子”警告、“亲爱的医生”的信件，以及对阻止药物(例如促红细胞生成素/达贝泊丁)的使用的改变。我们的目标是：识别、评估和报告与TKI相关的心脏毒性和其他sADRs的病例信息；确定与识别/传播sadr信息的时间较短相关的因素；开发一种简化sadr信息传播的新方法(在我们成功的试点工作的基础上)；并参与FDA的一项倡议，该倡议将把分子毒性联系起来 目标研究(基础科学)和器官水平毒性(临床科学)，与TKI相关的心脏毒性是第一个研究领域。我们将向FDA分发25至50份与TKI相关的sADR和“公民请愿书”的简要报告，我们的顾问将这些sADR确定为“黑箱”警告或“亲爱的医生”信函(将研究转化为政策)的候选对象。第二个组成部分将是假设驱动的，确定与延迟的萨德-阿德勒确认/报告有关的因素。这项拟议的创新研究将是第一次系统地试图缩短识别和报告肿瘤学药物相关sADR之间的六到七年的时间间隔，也是第一次合作，为FDA领导的涉及整个药物类别的SADR的生物和临床方面的调查提供信息。

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.