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 MMclinical 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.
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