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dc.contributor.authorAtabaki-Pasdar, Naeimehen_US
dc.contributor.authorOhlsson, Mattiasen_US
dc.contributor.authorShungin, Dmitryen_US
dc.contributor.authorKurbasic, Azraen_US
dc.contributor.authorIngelsson, Eriken_US
dc.contributor.authorPearson, Ewan R.en_US
dc.contributor.authorAli, Ashfaqen_US
dc.contributor.authorFranks, Paul W.en_US
dc.date.accessioned2016-12-02T15:25:33Z
dc.date.issued2016en_US
dc.identifier.citationAtabaki-Pasdar, Naeimeh, Mattias Ohlsson, Dmitry Shungin, Azra Kurbasic, Erik Ingelsson, Ewan R. Pearson, Ashfaq Ali, and Paul W. Franks. 2016. “Statistical power considerations in genotype-based recall randomized controlled trials.” Scientific Reports 6 (1): 37307. doi:10.1038/srep37307. http://dx.doi.org/10.1038/srep37307.en
dc.identifier.issn2045-2322en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:29626156
dc.description.abstractRandomized controlled trials (RCT) are often underpowered for validating gene-treatment interactions. Using published data from the Diabetes Prevention Program (DPP), we examined power in conventional and genotype-based recall (GBR) trials. We calculated sample size and statistical power for gene-metformin interactions (vs. placebo) using incidence rates, gene-drug interaction effect estimates and allele frequencies reported in the DPP for the rs8065082 SLC47A1 variant, a metformin transported encoding locus. We then calculated statistical power for interactions between genetic risk scores (GRS), metformin treatment and intensive lifestyle intervention (ILI) given a range of sampling frames, clinical trial sample sizes, interaction effect estimates, and allele frequencies; outcomes were type 2 diabetes incidence (time-to-event) and change in small LDL particles (continuous outcome). Thereafter, we compared two recruitment frameworks: GBR (participants recruited from the extremes of a GRS distribution) and conventional sampling (participants recruited without explicit emphasis on genetic characteristics). We further examined the influence of outcome measurement error on statistical power. Under most simulated scenarios, GBR trials have substantially higher power to observe gene-drug and gene-lifestyle interactions than same-sized conventional RCTs. GBR trials are becoming popular for validation of gene-treatment interactions; our analyses illustrate the strengths and weaknesses of this design.en
dc.language.isoen_USen
dc.publisherNature Publishing Groupen
dc.relation.isversionofdoi:10.1038/srep37307en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5122840/pdf/en
dash.licenseLAAen_US
dc.titleStatistical power considerations in genotype-based recall randomized controlled trialsen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalScientific Reportsen
dash.depositing.authorFranks, Paul W.en_US
dc.date.available2016-12-02T15:25:33Z
dc.identifier.doi10.1038/srep37307*
dash.contributor.affiliatedFranks, Paul


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