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Statistical power considerations in genotype-based recall randomized controlled trials
Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, SE-20502 Malmo, Sweden..
Lund Univ, Dept Astron & Theoret Phys, Computat Biol & Biol Phys Unit, Lund, Sweden..
Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, SE-20502 Malmo, Sweden..
Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, SE-20502 Malmo, Sweden..
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2016 (engelsk)Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, artikkel-id 37307Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Randomized 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 genemetformin 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.

sted, utgiver, år, opplag, sider
2016. Vol. 6, artikkel-id 37307
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Identifikatorer
URN: urn:nbn:se:uu:diva-311186DOI: 10.1038/srep37307ISI: 000388480300001PubMedID: 27886175OAI: oai:DiVA.org:uu-311186DiVA, id: diva2:1059260
Forskningsfinansiär
EU, European Research Council, CoG-2015_681742_NASCENT IMI_JU_2010_DIRECTSwedish Research CouncilSwedish Heart Lung FoundationSwedish Diabetes AssociationNovo NordiskTilgjengelig fra: 2016-12-22 Laget: 2016-12-22 Sist oppdatert: 2017-11-29bibliografisk kontrollert

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