Research on Adverse Drug Events and Reports: Novel Multiple Myeloma Drugs

药物不良事件研究及报告：多发性骨髓瘤新药

基本信息

批准号：
7658446
负责人：
CHARLES L. BENNETT
金额：
$ 2.88万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-06 至 2010-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7658446
关键词：
Accounting Address Area Autologous Stem Cell Transplantation Bone Diseases Bone necrosis Bortezomib Cancer Patient Case Series Case Study Cessation of life Clinical Clinical Data Clinical Investigator Collaborations Condition Data Set Databases Detection Development Diffuse Disease Drug Exposure Drug Interactions Drug usage Etiology Evaluation Event Funding Grant Individual Intravenous Jaw Label Letters Literature Malignant Neoplasms Medical Medical Surveillance Monitor Morbidity - disease rate Multiple Myeloma Neuropathy Numbers Oncologist Output Package Insert Patients Peer Review Persons Pharmaceutical Preparations Pharmacologic Substance Pharmacotherapy Population Publishing Radar Rate Reaction Reporting Research Research Methodology Research Personnel Review Literature Safety Series Signal Transduction Source Summary Reports Supportive care Syncope System Thalidomide Therapeutic Thromboembolism Time Toxic effect United States Food and Drug Administration Work base bisphosphonate clinical research site data mining experience improved innovation lenalidomide mortality novel novel therapeutics post-market prototype

项目摘要

DESCRIPTION (provided by applicant): Serious adverse drug reactions (sADRs) account for 100,000 patient deaths per year. This is particularly relevant for off-label use of cancer therapeutics. To date, there have been delays of many years in recognition of sADR signals associated with therapies administered to multiple myeloma (MM) patients. Some MM agents have received "accelerated approval" from the FDA for non-MM clinical indications and shortly after their approval these agents "diffuse" into the off-label MM setting. This usually occurs with no specific guidance to clinical oncologists as to how they are to monitor for toxicity. Based on our prior experience, we expect that improved pharmacovigilance will allow previously unrecognized sADRs associated with new MM agents to be identified, evaluated, synthesized, and described in the peer-review literature more rapidly than has occurred in the past. The innovation in this proposal is the identification of signals from real-time input from MM at 12 major referral MM centers (accounting for over 10,000 patients with MM). The conceptual framework underlying this project is that the current FDA practice of data-mining a passive reporting system leads to delays in identification of safety signals and requires a large number of reports to generate a signal. However, an active pharmacovigilance network will allow for more rapid identification of safety signals and more complete understanding of potential toxicities. If successful, this project will be applicable to other disease areas. Specific aims of this RADAR-MM study are: 1) to identify, evaluate, and report comprehensive case series information for sADRs associated with novel drugs used to treat persons with MM. (Many of these drugs are used "off-label" and hence their safety profile in these settings is less well understood); 2) to compare the completeness of individual sADR reports associated with these drugs derived from the MM clinical sites versus those that are contained in the FDA's MedWatch database; and 3) to compare the completeness of sADR summary reports disseminated by the RADAR project versus those disseminated by the pharmaceutical supplier or the FDA. We hypothesize that 1) we identify 1 to 5 unique ADRs per year (approximately 20 ADRs during the study period); 2) for the sADRs in our data set, the completeness of individual sADR case reports will be poorer for events reported from the MedWatch versus RADAR; and 3) for the sADR reports, the completeness of the summary report will be poorer when disseminated as Dear Doctor letters or revisions to the FDA approved package insert versus dissemination as brief reports from RADAR investigators.

描述（由申请人提供）：严重的不良药物反应（SADR）每年占100,000例患者死亡。这与标签外癌症治疗剂的使用尤其重要。迄今为止，已经有很多年的延迟，以识别与多发性骨髓瘤（MM）患者施用的疗法相关的SADR信号。一些MM代理商已从FDA获得了非MM临床指示的“加速批准”，并且在批准后不久，这些代理将“扩散”到标签外MM设置中。通常，这是对临床肿瘤学家如何监测毒性的特定指导。根据我们先前的经验，我们预计改善的药物疗法将使以前未识别的与新MM代理相关的SADR可以在同行评审文献中被鉴定，评估，合成和描述，比过去更快。该提案的创新是确定来自12个主要推荐MM中心的MM实时输入的信号（占10,000多名MM患者）。该项目的基础概念框架是，当前的FDA挖掘被动报告系统的FDA实践导致延迟安全信号，并且需要大量报告来生成信号。但是，主动的药物保护网络将使安全信号更快地识别，并对潜在毒性进行更完整的了解。如果成功，该项目将适用于其他疾病领域。这项雷达-MM研究的具体目的是：1）识别，评估和报告与用于治疗MM患者的新型药物相关的SADR的全面病例序列信息。（其中许多药物被使用“标签之外”，因此在这些情况下它们的安全性不太了解）； 2）比较与从MM临床部位得出的这些药物相关的单个SADR报告的完整性与FDA MEDWATCH数据库中包含的药物的完整性； 3）比较雷达项目传播的SADR摘要报告与药品供应商或FDA传播的SADR摘要报告的完整性。我们假设1）我们每年识别1到5个独特的ADR（在研究期间约20个ADR）； 2）对于我们的数据集中的SADR，单个SADR病例报告的完整性对于MedWatch与Radar报告的事件的完整性将较差； 3）对于SADR报告，作为雷达调查人员的简短报告，摘要报告的完整性将作为亲爱的医生的信件或对FDA批准的包裹插入与传播的修订时的完整性较差。