Novel Dissemination Efforts for Hematology-Related Serious Adverse Drug Reactions (sADRs): Findings from the Research on Adverse Drug Events and Reports Project (RADAR)

Abstract

The Research on Adverse Drug Events and Reports project (RADAR) is one of only a few independent pharmacovigilance programs funded entirely by peer-reviewed grants. It is the only such program that focuses on serious adverse drug reactions (sADRs) related to hematology and oncology. RADAR leverages the resources of a comprehensive cancer center, an academic hematology/oncology program, and a global network of physicians. Since its inception in 1998, RADAR has identified 33 unique sADRs. Information about these sADRs are traditionally disseminated in peer-reviewed manuscripts (21 sADRs), warnings or black box warnings in FDA-approved package inserts or manufacturer warnings (12 sADRs), or Dear Doctor letters (8 sADRs). In the absence of formal collaborations between the FDA, drug manufacturers, and independent pharmacovigilance programs, RADAR has expanded its dissemination efforts to non-traditional strategies, such as face-to-face meetings with drug manufacturers (22 sADRs), which lead to further actions by regulatory agencies and stakeholders (Table). These actions have included revised clinical guidelines from NCCN, ASCO, ASH, and the American College of Radiology, FDA advisory hearings focusing on safety, the first ever drug safety focused citizen's petition filed by a state attorney general, and safety statements from the Centers for Disease Control and Prevention. Moving forward, RADAR is developing novel strategies for dissemination by partnering with Consumer Reports, the internet-based Medpedia Project, and monthly safety columns published in Community Oncology and Oncology News International.Table. Hematology-related sADRs identified by RADAR and novel dissemination efforts.DrugsADRPeer-reviewed Publications (Year)FDA or Manufacturer Warnings (Year)Face-to-face meeting with drug manufacturerActions by Regulatory Agencies or StakeholdersTiclopidineThrombotic Thrombocytopenic purpuraAnn Intern Med (1998); Lancet (1998); Arch Intern Med (1999); JAMA (1999)Dear Doctor letter (1998); Boxed Warning (1999)YesDrug sales diminished to minimal level due to safety concerns (even though generic drug); FDA presentationClopidogrelThrombotic thrombocytopenic purpuraNEJM (2000); Transplantation (2002); Stroke (2004)Warnings (2000, 2006)YesPatient message in direct-to-consumer advertisementsEpoetin/darbepoetinVenous thromboembolism; mortalityJAMA (2008)FDA Alerts (2006, 2007), Black box warning (2007)YesFDA hearing; CMS policy change; EMEA guidelines change; NCCN guidelines changeEpoetinPure red-cell aplasiaNEJM (2004); Blood (2005)Boxed warning (2002); Dear Doctor letter (2005)YesManufacturer changes; Canada Health; EMEA statements; FDA presentationThalidomide/lenalidomideVenous thromboembolismJAMA (2006)Black box warning(2006)YesCitizen's petition by attorney general of Connecticut (upheld)GemtuzumabSinusoidal obstructive syndromeLeukemia Research (2006)Boxed warning (2001)YesFDA-mandated postmarketing registryRituximabProgressive multifocal leuko-encephalopathyASH (2007); ASCO (2008)Black box warning (2006)YesUnder considerationG-CSF/GM-CSFAcute myeloid leukemia; myelodisplatic syndromeJNCI (2007)NoneYesReconsideration of G-CSF administration to pediatric donors in JapanPEG-rHuMGDFLymphoproliferative disorderBritish J of Haematology (2006)NoneNoDrug development discontinued because of safety concernsZoledronateOsteonecrosis of the jawLancet Oncology (2008)Dear Doctor letter (2004)YesGuidelines from radiology, dentistry, hematology, oncologyNevirapineStevens-Johnson syndrome; hepatotoxicityJ Acquir Immune Defic Syndr (2004)Boxed warning (1998); Warning (1999); Dear Doctor letters (2000, 2004)YesDrug no longer. used for post-needle stick exposure to HIV by healthcare workers