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（sADRs）每年导致10万名患者死亡。这与癌症治疗药物的标签外使用尤其相关。迄今为止，在多发性骨髓瘤（MM）患者的治疗中，sADR信号的识别已经延迟了很多年。一些MM药物已经从FDA获得了非MM临床适应症的“加速批准”，并且在批准后不久，这些药物“扩散”到标签外MM设置。这种情况通常发生在临床肿瘤学家没有具体指导他们如何监测毒性的情况下。根据我们之前的经验，我们期望改进的药物警惕性将使以前未被识别的与新型MM药物相关的sadr能够比过去更快地在同行评审文献中被识别、评估、合成和描述。该提案的创新之处在于识别12个主要转诊MM中心（超过10,000名MM患者）实时输入的MM信号。这个项目背后的概念框架是，目前FDA的数据挖掘实践——一个被动的报告系统——导致安全信号识别的延迟，需要大量的报告来产生信号。然而，一个积极的药物警戒网络将允许更快速地识别安全信号和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、评估和报告与用于治疗MM患者的新型药物相关的sadr的综合病例系列信息（这些药物中许多是“标签外”使用的，因此它们在这些情况下的安全性不太清楚）；2)比较来自MM临床站点与FDA MedWatch数据库中包含的与这些药物相关的单个sADR报告的完整性；3)比较RADAR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个独特的adr（研究期间约有20个adr）；2)对于我们数据集中的sADR， MedWatch报告的事件与RADAR报告的事件相比，单个sADR病例报告的完整性较差；3)对于sADR报告，与作为RADAR调查人员的简短报告传播相比，作为Dear Doctor信函或FDA批准的包装说明书修订版传播的摘要报告的完整性将较差。

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.