PMID- 25670520
OWN - NLM
STAT- MEDLINE
DCOM- 20150408
LR  - 20181113
IS  - 1532-6535 (Electronic)
IS  - 0009-9236 (Print)
IS  - 0009-9236 (Linking)
VI  - 97
IP  - 2
DP  - 2015 Feb
TI  - Systems pharmacology augments drug safety surveillance.
PG  - 151-8
LID - 10.1002/cpt.2 [doi]
AB  - Small molecule drugs are the foundation of modern medical practice, yet their use 
      is limited by the onset of unexpected and severe adverse events (AEs). Regulatory 
      agencies rely on postmarketing surveillance to monitor safety once drugs are 
      approved for clinical use. Despite advances in pharmacovigilance methods that 
      address issues of confounding bias, clinical data of AEs are inherently noisy. 
      Systems pharmacology-the integration of systems biology and chemical genomics-can 
      illuminate drug mechanisms of action. We hypothesize that these data can improve 
      drug safety surveillance by highlighting drugs with a mechanistic connection to 
      the target phenotype (enriching true positives) and filtering those that do not 
      (depleting false positives). We present an algorithm, the modular assembly of 
      drug safety subnetworks (MADSS), to combine systems pharmacology and 
      pharmacovigilance data and significantly improve drug safety monitoring for four 
      clinically relevant adverse drug reactions.
CI  - (c) 2014 American Society for Clinical Pharmacology and Therapeutics.
FAU - Lorberbaum, T
AU  - Lorberbaum T
AD  - Department of Physiology and Cellular Biophysics, Columbia University, New York, 
      New York, USA; Department of Biomedical Informatics, Columbia University, New 
      York, New York, USA; Departments of Systems Biology and Medicine, Columbia 
      University, New York, New York, USA.
FAU - Nasir, M
AU  - Nasir M
FAU - Keiser, M J
AU  - Keiser MJ
FAU - Vilar, S
AU  - Vilar S
FAU - Hripcsak, G
AU  - Hripcsak G
FAU - Tatonetti, N P
AU  - Tatonetti NP
LA  - eng
GR  - T32 GM082797/GM/NIGMS NIH HHS/United States
GR  - R43 GM093456/GM/NIGMS NIH HHS/United States
GR  - T32 HL120826/HL/NHLBI NIH HHS/United States
GR  - R01GM107145/GM/NIGMS NIH HHS/United States
GR  - R01 LM006910/LM/NLM NIH HHS/United States
GR  - R44 GM093456/GM/NIGMS NIH HHS/United States
GR  - MH099712/MH/NIMH NIH HHS/United States
GR  - R01 GM107145/GM/NIGMS NIH HHS/United States
GR  - R43 MH099712/MH/NIMH NIH HHS/United States
GR  - GM93456/GM/NIGMS NIH HHS/United States
GR  - T32HL120826/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20141220
PL  - United States
TA  - Clin Pharmacol Ther
JT  - Clinical pharmacology and therapeutics
JID - 0372741
SB  - IM
MH  - Algorithms
MH  - Drug-Related Side Effects and Adverse Reactions/*prevention & control
MH  - Genomics
MH  - Humans
MH  - Models, Biological
MH  - *Patient Safety
MH  - *Pharmacology
MH  - *Pharmacovigilance
MH  - *Systems Biology
PMC - PMC4325423
MID - NIHMS631704
COIS- The authors declare that they have no conflict of interest.
EDAT- 2015/02/12 06:00
MHDA- 2015/04/09 06:00
PMCR- 2016/02/01
CRDT- 2015/02/12 06:00
PHST- 2014/03/27 00:00 [received]
PHST- 2014/09/12 00:00 [accepted]
PHST- 2015/02/12 06:00 [entrez]
PHST- 2015/02/12 06:00 [pubmed]
PHST- 2015/04/09 06:00 [medline]
PHST- 2016/02/01 00:00 [pmc-release]
AID - 10.1002/cpt.2 [doi]
PST - ppublish
SO  - Clin Pharmacol Ther. 2015 Feb;97(2):151-8. doi: 10.1002/cpt.2. Epub 2014 Dec 20.