Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Sequential genome-wide association studies for monitoring adverse events in clinical evaluation of new drugs.
AU - Whitehead, John
AU - Kelly, Patrick J.
AU - Stallard, Nigel
AU - Zhou, Yinghui
AU - Bowman, Clive
N1 - RAE_import_type : Journal article RAE_uoa_type : Statistics and Operational Research
PY - 2006/9/30
Y1 - 2006/9/30
N2 - 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 idák, that assumes that the tests are independent. Copyright © 2006 John Wiley & Sons, Ltd.
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 idák, that assumes that the tests are independent. Copyright © 2006 John Wiley & Sons, Ltd.
KW - drug development • pharmacogenetics • pharmacovigilance • safety monitoring • sequential methods
U2 - 10.1002/sim.2499
DO - 10.1002/sim.2499
M3 - Journal article
VL - 25
SP - 3081
EP - 3092
JO - Statistics in Medicine
JF - Statistics in Medicine
SN - 1097-0258
IS - 18
ER -