125The SAEC is not the only federal initiative aimed at improving drug safety. The
Critical Path is also linking the Association of Clinical Research Organizations
with the Clinical Data Interchange Standards Consortium to form the Clinical Data
Acquisition Standards Harmonization project. This group was charged with devel-
oping sample case report forms for reporting adverse events according to a NIH
summary of a Roadmap steering committee meeting that took place in 2006.
According to the summary, the offi ce does cross-cutting coordination and harmoni-
zation of all the centers within the FDA. These include the Oncology Biomarker
Qualifi cation Initiative, which pairs the FDA with the National Cancer Institute and
the Centers for Medicaid and Medicare Services; the Biomarker Consortium, which
brings together the FDA, the NIH, and the Pharmaceutical Research & Manufacturers
of America. Areas of focus in this effort are bioinformatics and data standards,
biomarkers, establishing public-private partnerships, and developing guidance and
regulations.
SAEC has released its fi ndings on the genetics of Stevens-Johnson syndrome and
has participated in studies identifying variants linked to drug-induced liver injury
from the use of the antibiotic fl ucloxacillin. SAEC collaborates with the HMO
(Health Maintenance Organization) Research Network to explore the possibility of
using HMO’s clinical data to study drug-related serious adverse drug reactions. It is
also partnering with researchers at Duke University to look for rare variants corre-
sponding to adverse reactions to the antipsychotic drug clozapine. All of the infor-
mation SAEC gains from these studies is openly accessible so it may be developed
into tests.
SAEC’s work is based on the hypothesis the differences in response to drugs by
side effects have (in part) a genetic basis, and its research studies examine the
impact genetic variation on how individuals respond to a large variety of medicines.
Majority of the SAEC’s genetic fi ndings have been specifi c to a given drug versus
across multiple drugs. However, a number of cross drug genetic alleles are starting
to emerge that may provide important insights into the underlying biology/mecha-
nism of drug induced SAEs (e.g. HLA5701 or UGT1A128). These fi ndings
clearly demonstrate an important role for the MHC genomic region (Chromosome
6), in the pathology of immunologically mediated SAEs. They also emphasize the
importance of immune regulation genes, in addition to a number of well character-
ized drug metabolism genes. SAEC’s second phase (2010–2015) will develop
novel, international clinical networks to deepen an understanding of the genetics of
the following SAEs across a diverse range of ethnic populations:
- Acute hypersensitivity syndrome
- Excessive weight gain (associated with class 2 antipsychotic medications)
- Hepatotoxicity
- IBD therapy related SAES (four different phenotypes)
- Nephrotoxicity
- Osteonecrosis of jaw
- Serious skin rash
Role of Pharmacogenetics in Pharmaceutical Industry