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

描述(由申请人提供)：严重药物不良反应(SADR)每年导致100,000名患者死亡。这与癌症治疗药物的非标签使用特别相关。到目前为止，对多发性骨髓瘤(MM)患者的治疗相关的SADR信号的认识已经推迟了很多年。一些MM药物已经获得了FDA对非MM临床适应症的“加速批准”，在他们获得批准后不久，这些药物就“扩散”到了标签外的MM设置中。这通常是在没有对临床肿瘤学家如何监测毒性进行具体指导的情况下发生的。根据我们以前的经验，我们预计，改进的药物警戒将允许比过去更快地识别、评估、合成和描述与新MM药物相关的以前未识别的sADR。该方案的创新之处在于在12个主要的转诊MM中心(占10,000多名MM患者)识别来自MM的实时输入的信号。该项目的概念框架是，FDA目前的数据挖掘做法是一种被动报告系统，导致安全信号识别的延误，需要大量报告才能产生信号。然而，积极的药物警戒网络将允许更快地识别安全信号，并更全面地了解潜在的毒性。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、评估和报告与治疗MM的新药相关的sADR综合病例系列信息(许多这些药物是在标签外使用的，因此它们在这些环境中的安全性状况不太清楚)；2)比较从MM临床站点获得的与这些药物相关的单个SADR报告的完整性与FDA的MedWatch数据库中包含的那些报告；以及3)比较雷达项目传播的SADR总结报告与药品供应商或FDA传播的SADR总结报告的完整性。我们假设：1)我们每年确定1至5个唯一的ADR(在研究期间约有20个ADR)；2)对于我们数据集中的sADR，MedWatch与雷达报告的事件相比，单个SADR病例报告的完整性较差；以及3)对于SADR报告，当作为尊敬的医生信函或FDA批准的包裹插入的修订版传播时，摘要报告的完整性将较差，而不是作为雷达调查人员的简短报告传播。

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.