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. Drug sADR Peer-reviewed Publications (Year) FDA or Manufacturer Warnings (Year) Face-to-face meeting with drug manufacturer Actions by Regulatory Agencies or Stakeholders Ticlopidine Thrombotic Thrombocytopenic purpura Ann Intern Med (1998); Lancet (1998); Arch Intern Med (1999); JAMA (1999) Dear Doctor letter (1998); Boxed Warning (1999) Yes Drug sales diminished to minimal level due to safety concerns (even though generic drug); FDA presentation Clopidogrel Thrombotic thrombocytopenic purpura NEJM (2000); Transplantation (2002); Stroke (2004) Warnings (2000, 2006) Yes Patient message in direct-to-consumer advertisements Epoetin/darbepoetin Venous thromboembolism; mortality JAMA (2008) FDA Alerts (2006, 2007), Black box warning (2007) Yes FDA hearing; CMS policy change; EMEA guidelines change; NCCN guidelines change Epoetin Pure red-cell aplasia NEJM (2004); Blood (2005) Boxed warning (2002); Dear Doctor letter (2005) Yes Manufacturer changes; Canada Health; EMEA statements; FDA presentation Thalidomide/lenalidomide Venous thromboembolism JAMA (2006) Black box warning(2006) Yes Citizen's petition by attorney general of Connecticut (upheld) Gemtuzumab Sinusoidal obstructive syndrome Leukemia Research (2006) Boxed warning (2001) Yes FDA-mandated postmarketing registry Rituximab Progressive multifocal leuko-encephalopathy ASH (2007); ASCO (2008) Black box warning (2006) Yes Under consideration G-CSF/GM-CSF Acute myeloid leukemia; myelodisplatic syndrome JNCI (2007) None Yes Reconsideration of G-CSF administration to pediatric donors in Japan PEG-rHuMGDF Lymphoproliferative disorder British J of Haematology (2006) None No Drug development discontinued because of safety concerns Zoledronate Osteonecrosis of the jaw Lancet Oncology (2008) Dear Doctor letter (2004) Yes Guidelines from radiology, dentistry, hematology, oncology Nevirapine Stevens-Johnson syndrome; hepatotoxicity J Acquir Immune Defic Syndr (2004) Boxed warning (1998); Warning (1999); Dear Doctor letters (2000, 2004) Yes Drug no longer. used for post-needle stick exposure to HIV by healthcare workers