PMID- 16397864
OWN - NLM
STAT- MEDLINE
DCOM- 20070111
LR  - 20131121
IS  - 0277-6715 (Print)
IS  - 0277-6715 (Linking)
VI  - 25
IP  - 18
DP  - 2006 Sep 30
TI  - Sequential genome-wide association studies for monitoring adverse events in the 
      clinical evaluation of new drugs.
PG  - 3081-92
AB  - Pharmacovigilance, the monitoring of adverse events (AEs), is an integral part in 
      the clinical evaluation of a new drug. Until recently, attempts to relate the 
      incidence of AEs to putative causes have been restricted to the evaluation of 
      simple demographic and environmental factors. The advent of large-scale 
      genotyping, however, provides an opportunity to look for associations between AEs 
      and genetic markers, such as single nucleotides polymorphisms (SNPs). It is 
      envisaged that a very large number of SNPs, possibly over 500,000, will be used 
      in pharmacovigilance in an attempt to identify any genetic difference between 
      patients who have experienced an AE and those who have not. We propose a 
      sequential genome-wide association test for analysing AEs as they arise, allowing 
      evidence-based decision-making at the earliest opportunity. This gives us the 
      capability of quickly establishing whether there is a group of patients at 
      high-risk of an AE based upon their DNA. Our method provides a valid test which 
      takes account of linkage disequilibrium and allows for the sequential nature of 
      the procedure. The method is more powerful than using a correction, such as 
      Sidak, that assumes that the tests are independent.
FAU - Kelly, Patrick
AU  - Kelly P
AD  - Medical and Pharmaceutical Statistics Research Unit, The University of Reading, 
      U.K. patrick.kelly@reading.ac.uk
FAU - Stallard, Nigel
AU  - Stallard N
FAU - Zhou, Yinghui
AU  - Zhou Y
FAU - Whitehead, John
AU  - Whitehead J
FAU - Bowman, Clive
AU  - Bowman C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Stat Med
JT  - Statistics in medicine
JID - 8215016
SB  - IM
MH  - Adverse Drug Reaction Reporting Systems
MH  - Clinical Trials as Topic
MH  - *Data Interpretation, Statistical
MH  - *Drug-Related Side Effects and Adverse Reactions
MH  - Genetic Predisposition to Disease
MH  - *Genome, Human
MH  - Humans
MH  - Pharmacogenetics/*methods
MH  - Polymorphism, Single Nucleotide
EDAT- 2006/01/07 09:00
MHDA- 2007/01/12 09:00
CRDT- 2006/01/07 09:00
PHST- 2006/01/07 09:00 [pubmed]
PHST- 2007/01/12 09:00 [medline]
PHST- 2006/01/07 09:00 [entrez]
AID - 10.1002/sim.2499 [doi]
PST - ppublish
SO  - Stat Med. 2006 Sep 30;25(18):3081-92. doi: 10.1002/sim.2499.