Indirect Estimation of the Comparative Treatment Effect in Pharmacogenomic Subgroups

dc.contributor.author Sorich, Michael J
dc.contributor.author Coory, M
dc.contributor.author Pekarsky, B
dc.date.accessioned 2014-04-09T02:16:28Z
dc.date.available 2014-04-09T02:16:28Z
dc.date.issued 2013-08
dc.description 2013 Sorich et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. en
dc.description.abstract Evidence of clinical utility is a key issue in translating pharmacogenomics into clinical practice. Appropriately designed randomized controlled trials generally provide the most robust evidence of the clinical utility, but often only data from a pharmacogenomic association study are available. This paper details a method for reframing the results of pharmacogenomic association studies in terms of the comparative treatment effect for a pharmacogenomic subgroup to provide greater insight into the likely clinical utility of a pharmacogenomic marker, its’ likely cost effectiveness, and the value of undertaking the further (often expensive) research required for translation into clinical practice. The method is based on the law of total probability, which relates marginal and conditional probability. It takes as inputs: the prevalence of the pharmacogenomic marker in the patient group of interest, prognostic effect of the pharmacogenomic marker based on observational association studies, and the unstratified comparative treatment effect based on one or more conventional randomized controlled trials. The critical assumption is that of exchangeability across the included studies. The method is demonstrated using a case study of cytochrome P450 (CYP) 2C19 genotype and the anti-platelet agent clopidogrel. Indirect subgroup analysis provided insight into relationship between the clinical utility of genotyping CYP2C19 and the risk ratio of cardiovascular outcomes between CYP2C19 genotypes for individuals using clopidogrel. In this case study the indirect and direct estimates of the treatment effect for the cytochrome P450 2C19 subgroups were similar. In general, however, indirect estimates are likely to have substantially greater risk of bias than an equivalent direct estimate. en
dc.identifier.citation Sorich MJ, Coory M, Pekarsky BAK (2013) Indirect Estimation of the Comparative Treatment Effect in Pharmacogenomic Subgroups. PLoS ONE 8(8): e72256. en
dc.identifier.doi https://doi.org/10.1371/journal.pone.0072256 en
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/2328/27532
dc.language.iso en
dc.publisher PLOS en
dc.relation http://purl.org/au-research/grants/nhmrc/1028492 en
dc.relation.grantnumber NHMRC/1028492 en
dc.rights Copyright © 2013 Sorich et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. en
dc.rights.holder Sorich et al. en
dc.rights.license CC-BY
dc.subject Pharmacogenomics en
dc.subject Drug therapy en
dc.subject Meta-analysis en
dc.title Indirect Estimation of the Comparative Treatment Effect in Pharmacogenomic Subgroups en
dc.type Article en
local.contributor.authorOrcidLookup Sorich, Michael J: https://orcid.org/0000-0003-1999-866X en_US
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