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 alert
PEG-rHuMGDF(unapproved) ITP (13) Healthy volunteers (2001) Phase I trials Preclinical detection NA 
PEG-rHuMGDF(unapproved) Lymphomas (3) Healthy volunteers (2003) Case reports Preclinical detection NA 
Ticlopidine (1991) TTP (13) CVA pts (1998) Case reports <1 DHP letter; boxed warning 
Gemtuzumab (2000) VOD (50) Leukemia or AML (2000) Phase II trials <1 Boxed warning 
Lenalidomide (2005) VTE (75) Multiple myeloma (2005) Phase III trial <1 Boxed warning 
Enoxaparin (1993) Hemorrhage (5) PTCA (2003) Case reports NA 
Clopidogrel (1997) TTP (39) CAD pts (1998) Case reports Company warning 
Thalidomide (1998) VTE (91) Multiple myeloma (2002) Phase II trials Black box warning 
Nevirapine (1996) Stevens-Johnson syndrome (3) Healthcare workers (2002) Case series Boxed warning 
Nevirapine (1996) Hepatotoxicity (5) Healthcare workers (2002) Case series Boxed warning; DHP letter 
EPO (1993) PRCA (9) ESRD (2000) Referral hematologist Boxed warning; DHP letter 
EPO (1993) Loss of efficacy (2) Counterfeit drug (2000) Case reports NA 
EPO(1993)/ Darb (2001) VTE (52) Cancer (2004) Phase III trial 10(EPO)/3 (Darb) FDA alert; DHP letter; boxed warning 
EPO (1993)/ Darb(2001) Death (NA) Cancer (2006) Clinical trials 10(EPO)/3 (Darb) FDA alert; DHP letter; boxed warning 
G-CSF (1991) AML/MDS (16) Breast Ca (2007) SEER-Medicare 12 NA 
Piperacillin (1981) Neutropenia (1) Infection (2006) Case reports 25 Precaution 
Drug (FDA approval)sADR (# of reports)Clinical Setting (yr)Data SourceTime to detection (yrs)FDA/Company alert
PEG-rHuMGDF(unapproved) ITP (13) Healthy volunteers (2001) Phase I trials Preclinical detection NA 
PEG-rHuMGDF(unapproved) Lymphomas (3) Healthy volunteers (2003) Case reports Preclinical detection NA 
Ticlopidine (1991) TTP (13) CVA pts (1998) Case reports <1 DHP letter; boxed warning 
Gemtuzumab (2000) VOD (50) Leukemia or AML (2000) Phase II trials <1 Boxed warning 
Lenalidomide (2005) VTE (75) Multiple myeloma (2005) Phase III trial <1 Boxed warning 
Enoxaparin (1993) Hemorrhage (5) PTCA (2003) Case reports NA 
Clopidogrel (1997) TTP (39) CAD pts (1998) Case reports Company warning 
Thalidomide (1998) VTE (91) Multiple myeloma (2002) Phase II trials Black box warning 
Nevirapine (1996) Stevens-Johnson syndrome (3) Healthcare workers (2002) Case series Boxed warning 
Nevirapine (1996) Hepatotoxicity (5) Healthcare workers (2002) Case series Boxed warning; DHP letter 
EPO (1993) PRCA (9) ESRD (2000) Referral hematologist Boxed warning; DHP letter 
EPO (1993) Loss of efficacy (2) Counterfeit drug (2000) Case reports NA 
EPO(1993)/ Darb (2001) VTE (52) Cancer (2004) Phase III trial 10(EPO)/3 (Darb) FDA alert; DHP letter; boxed warning 
EPO (1993)/ Darb(2001) Death (NA) Cancer (2006) Clinical trials 10(EPO)/3 (Darb) FDA alert; DHP letter; boxed warning 
G-CSF (1991) AML/MDS (16) Breast Ca (2007) SEER-Medicare 12 NA 
Piperacillin (1981) Neutropenia (1) Infection (2006) Case reports 25 Precaution 

Author notes

Disclosure: No relevant conflicts of interest to declare.