PMID- 19422096
OWN - NLM
STAT- MEDLINE
DCOM- 20090724
LR  - 20191111
IS  - 1096-0295 (Electronic)
IS  - 0273-2300 (Linking)
VI  - 54
IP  - 1
DP  - 2009 Jun
TI  - Identification of structure-activity relationships for adverse effects of 
      pharmaceuticals in humans. Part A: use of FDA post-market reports to create a 
      database of hepatobiliary and urinary tract toxicities.
PG  - 1-22
AB  - The Informatics and Computational Safety Analysis Staff at the US FDA's Center 
      for Drug Evaluation and Research has created a database of pharmaceutical adverse 
      effects (AEs) linked to pharmaceutical chemical structures and estimated 
      population exposures. The database is being used to develop quantitative 
      structure-activity relationship (QSAR) models for the prediction of drug-induced 
      liver and renal injury, as well as to identify relationships among AEs. The 
      post-market observations contained in the database were obtained from FDA's 
      Spontaneous Reporting System (SRS) and the Adverse Event Reporting System (AERS) 
      accessed through Elsevier PharmaPendium software. The database contains 
      approximately 3100 unique pharmaceutical compounds and 9685 AE endpoints. To 
      account for variations in AE reports due to different patient populations and 
      exposures for each drug, a proportional reporting ratio (PRR) was used. The PRR 
      was applied to all AEs to identify chemicals that could be scored as positive in 
      the training datasets of QSAR models. Additionally, toxicologically similar AEs 
      were grouped into clusters based upon both biological effects and statistical 
      correlation. This clustering created a weight of evidence paradigm for the 
      identification of compounds most likely to cause human harm based upon findings 
      in multiple related AE endpoints.
FAU - Ursem, Carling J
AU  - Ursem CJ
AD  - US Food and Drug Administration, Center for Drug Evaluation and Research, Office 
      of Pharmaceutical Science, Informatics and Computational Safety Analysis Staff 
      (ICSAS), Silver Spring, MD 20993-0002, USA.
FAU - Kruhlak, Naomi L
AU  - Kruhlak NL
FAU - Contrera, Joseph F
AU  - Contrera JF
FAU - MacLaughlin, Philip M
AU  - MacLaughlin PM
FAU - Benz, R Daniel
AU  - Benz RD
FAU - Matthews, Edwin J
AU  - Matthews EJ
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Regul Toxicol Pharmacol
JT  - Regulatory toxicology and pharmacology : RTP
JID - 8214983
RN  - 0 (Pharmaceutical Preparations)
SB  - IM
MH  - *Adverse Drug Reaction Reporting Systems
MH  - Biliary Tract Diseases/*chemically induced
MH  - Chemical and Drug Induced Liver Injury/*etiology
MH  - Cluster Analysis
MH  - *Databases, Factual
MH  - *Drug-Related Side Effects and Adverse Reactions
MH  - Endpoint Determination
MH  - Humans
MH  - Models, Biological
MH  - Pharmaceutical Preparations/administration & dosage/chemistry
MH  - *Product Surveillance, Postmarketing
MH  - Quantitative Structure-Activity Relationship
MH  - United States
MH  - United States Food and Drug Administration
MH  - Urologic Diseases/*chemically induced
EDAT- 2009/05/08 09:00
MHDA- 2009/07/25 09:00
CRDT- 2009/05/08 09:00
PHST- 2009/05/08 09:00 [entrez]
PHST- 2009/05/08 09:00 [pubmed]
PHST- 2009/07/25 09:00 [medline]
AID - S0273-2300(09)00002-6 [pii]
AID - 10.1016/j.yrtph.2008.12.009 [doi]
PST - ppublish
SO  - Regul Toxicol Pharmacol. 2009 Jun;54(1):1-22. doi: 10.1016/j.yrtph.2008.12.009.