Linked Life Data

15814066

Source:http://linkedlifedata.com/resource/pubmed/id/15814066

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-4-7
pubmed:abstractText
The genetic mapping of drug-response traits is often characterised by a poor signal-to-noise ratio that is placebo related and which distinguishes pharmacogenetic association studies from classical case-control studies for disease susceptibility. The goal of this study was to evaluate the statistical power of candidate gene association studies under different pharmacogenetic scenarios, with special emphasis on the placebo effect. Genotype/phenotype data were simulated, mimicking samples from clinical trials, and response to the drug was modelled as a binary trait. Association was evaluated by a logistic regression model. Statistical power was estimated as a function of the number of single nucleotide polymorphisms (SNPs) genotyped, the frequency of the placebo 'response', the genotype relative risk (GRR) of the response polymorphism, the strategy for selecting SNPs for genotyping, the number of individuals in the trial and the ratio of placebo-treated to drug-treated patients. We show that: (i) the placebo 'response' strongly affects the statistical power of association studies--even a highly penetrant drug-response allele requires at least a 500-patient trial in order to reach 80 per cent power, several-fold more than the value estimated by standard tools that are not calibrated to pharmacogenetics; (ii) the power of a pharmacogenetic association study depends primarily on the penetrance of the response genotype and, when this penetrance is fixed, power decreases for larger placebo effects; (iii) power is dramatically increased when adding markers; (iv) an optimal study design includes a similar number of placebo- and drug-treated patients; and (v) in this setting, straightforward haplotype analysis does not seem to have an advantage over single marker analysis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1479-7364
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
2
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
28-38
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Trick or treat: the effect of placebo on the power of pharmacogenetic association studies.
pubmed:affiliation
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't