Rapid Identification of Hematology-Associated Serious Adverse Drug Reactions (sADRS) with Small Datasets: Findings from the Research on Adverse Drug Events and Reports (RADAR) Project.

Abstract

Current FDA and pharmaceutical industry drug safety efforts rely on statistical review of large databases populated with voluntary reports of sADRs. These data are limited by low rates of complete reporting and high rates of underreporting. Improved post-marketing drug surveillance efforts are needed to improve patient safety. The RADAR project is an academic pharmacovigilance program that focuses on small numbers of thoroughly researched cases of sADRs. In the last decade, RADAR has utilized the resources of a comprehensive cancer center and a global network of collaborators to evaluate and disseminate information on sADRs, many of which are related to hematology. Between 1998 and 2007, RADAR investigated and reported 16 hematology-associated sADRs. RADAR disseminated information on over half of the sADRs within 2 years of FDA approval, compared to half of all new sADRs documented in the Physician's Desk Reference within 7 years of FDA approval. RADAR's novel pharmacovigilance methods identified previously undetected sADRs based on small numbers of completely described reports. The RADAR project's experience shows that private sector programs that utilize small yet comprehensive datasets can significantly contribute to pharmacovigilance networks in hematology. As the FDA develops public-private networks to evaluate safety concerns associated with new drugs, focused independent efforts can assume increasing importance to address unmet needs.Summary of 16 hematology-associated sADRs reported by RADAR since 1998.Drug (FDA approval)sADR (# of reports)Clinical Setting (yr)Data SourceTime to detection (yrs)FDA/Company alertPEG-rHuMGDF(unapproved)ITP (13)Healthy volunteers (2001)Phase I trialsPreclinical detectionNAPEG-rHuMGDF(unapproved)Lymphomas (3)Healthy volunteers (2003)Case reportsPreclinical detectionNATiclopidine (1991)TTP (13)CVA pts (1998)Case reports<1DHP letter; boxed warningGemtuzumab (2000)VOD (50)Leukemia or AML (2000)Phase II trials<1Boxed warningLenalidomide (2005)VTE (75)Multiple myeloma (2005)Phase III trial<1Boxed warningEnoxaparin (1993)Hemorrhage (5)PTCA (2003)Case reports1NAClopidogrel (1997)TTP (39)CAD pts (1998)Case reports1Company warningThalidomide (1998)VTE (91)Multiple myeloma (2002)Phase II trials1Black box warningNevirapine (1996)Stevens-Johnson syndrome (3)Healthcare workers (2002)Case series2Boxed warningNevirapine (1996)Hepatotoxicity (5)Healthcare workers (2002)Case series2Boxed warning; DHP letterEPO (1993)PRCA (9)ESRD (2000)Referral hematologist5Boxed warning; DHP letterEPO (1993)Loss of efficacy (2)Counterfeit drug (2000)Case reports7NAEPO(1993)/ Darb (2001)VTE (52)Cancer (2004)Phase III trial10(EPO)/3 (Darb)FDA alert; DHP letter; boxed warningEPO (1993)/ Darb(2001)Death (NA)Cancer (2006)Clinical trials10(EPO)/3 (Darb)FDA alert; DHP letter; boxed warningG-CSF (1991)AML/MDS (16)Breast Ca (2007)SEER-Medicare12NAPiperacillin (1981)Neutropenia (1)Infection (2006)Case reports25Precaution