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 |
| 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 |
Disclosures: No relevant conflicts of interest to declare.
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