Fisher MJ (Northwestern University, Feinburg School of Medicine), Bennett CL
(VA Center for Management of Complex Chronic Care, Jesse Brown VA, Northwestern University, Feinburg School of Medicine)
Half of serious adverse drug reactions (sADR) are detected and documented seven years after drug approval by the Food and Drug Administration (FDA). The Research on Adverse Drug Reactions and Reports (RADAR) project has reported that lack of a centralized registry for many sADRs results in variable quality and quantity in cases and, ultimately, dissemination efforts. In this study, we compare the number and quality of cases reported in the first published case series with the cases in the manufacturers' and FDA databases. We also compare dissemination efforts between these groups.
Cases and dissemination efforts were compiled from nine sADRs reports made by RADAR. Drug-related toxicities included gadolinium-based contrast media associated nephrogenic systemic fibrosis (NSF), epoetin- and darbepoetin-associated pure red cell aplasia (PRCA), bisphosphonates-associated osteonecrosis of the jaw (ONJ), rituximad-associated progressive multifocal leukoencephalopathy (PML), epoetin- and darbepoetin- associated increased mortality, gemtuzumab associated veno-occlusive disease (VOD), ticlopidine- and clopidogrel- associated thrombotic thrombocytopenic purpura (TTP), thalidomide- and lenalidomide- associated venous thromboembolism (VTE), and G-CSF-associated acute leukemia and myelodysplastic syndrome (MDS).
Number of cases in first report series for sADRs ranged from 2 to 35 (median: 5 cases). Number of cases in the manufacturers' databases ranged from 9 to 2,227 (median: 135 cases). Number of cases in the FDA database ranged from none being reported to 3,607 (median: 467 cases). First case series were reported in seven different peer-reviewed journals. For several of these sADRs, there are conflicting reports and advisories issued by manufacturers, national regulatory agencies, and professional organizations.
An active approach to pharmacovigilance, such as RADAR’s, has yielded better, more comprehensive results and recommendations despite having fewer cases available than regulatory agencies or manufacturers. Case information was more complete and reliable in these fewer cases. Information dissemination was conducted through several peer-reviewed journals for clinicians. Regulatory agencies should release more comprehensive and referenced reports.
The current state of pharmacovigilance causes confusion for patients that have access to disagreeing warnings. Veterans suffer due to untimely and incomplete reporting of sADRs. A switch needs to be made to an active approach to pharmacovigilance.