title: Optimized design and analysis of preclinical intervention studies in vivo.
abstract: Recent reports have called into question the reproducibility, validity and translatability of the preclinical animal studies due to limitations in their experimental design and statistical analysis. To this end, we implemented a matching-based modelling approach for optimal intervention group allocation, randomization and power calculations, which takes full account of the complex animal characteristics at baseline prior to interventions. In prostate cancer xenograft studies, the method effectively normalized the confounding baseline variability, and resulted in animal allocations which were supported by RNA-seq profiling of the individual tumours. The matching information increased the statistical power to detect true treatment effects at smaller sample sizes in two castration-resistant prostate cancer models, thereby leading to saving of both animal lives and research costs. The novel modelling approach and its open-source and web-based software implementations enable the researchers to conduct adequately-powered and fully-blinded preclinical intervention studies, with the aim to accelerate the discovery of new therapeutic interventions.
authors.affiliation: Department of Mathematics and Statistics, University of Turku, Turku, Finland.|Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.|Turku Center for Disease Modeling (TCDM), University of Turku, Turku, Finland.|Drug Research Doctoral Programme (DRDP), University of Turku, Turku, Finland.
authors.forename: Teemu D
authors.initials: TD
authors.lastname: Laajala
authors.affiliation: Turku Center for Disease Modeling (TCDM), University of Turku, Turku, Finland.|Cancer Cell Signaling Group, Turku Centre for Biotechnology, University of Turku, Turku, Finland.
authors.forename: Mikael
authors.initials: M
authors.lastname: Jumppanen
authors.affiliation: Turku Center for Disease Modeling (TCDM), University of Turku, Turku, Finland.|Drug Research Doctoral Programme (DRDP), University of Turku, Turku, Finland.|Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland.|Orion Corporation, Orion Pharma, Department of Oncology and Critical Care Research, Turku, Finland.
authors.forename: Riikka
authors.initials: R
authors.lastname: Huhtaniemi
authors.affiliation: Turku Center for Disease Modeling (TCDM), University of Turku, Turku, Finland.|Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland.|Department of Medical Biochemistry and Genetics, Institute of Biomedicine, University of Turku, Turku, Finland.
authors.forename: Vidal
authors.initials: V
authors.lastname: Fey
authors.affiliation: Cancer Cell Signaling Group, Turku Centre for Biotechnology, University of Turku, Turku, Finland.|Department of Pathology, University of Turku, Turku, Finland.|Turku Doctoral Programme of Molecular Medicine (TuDMM), University of Turku, Turku, Finland.
authors.forename: Amanpreet
authors.initials: A
authors.lastname: Kaur
authors.affiliation: Turku Center for Disease Modeling (TCDM), University of Turku, Turku, Finland.|Drug Research Doctoral Programme (DRDP), University of Turku, Turku, Finland.|Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland.
authors.forename: Matias
authors.initials: M
authors.lastname: Knuuttila
authors.affiliation: Orion Corporation, Orion Pharma, Department of Oncology and Critical Care Research, Turku, Finland.
authors.forename: Eija
authors.initials: E
authors.lastname: Aho
authors.affiliation: Drug Research Doctoral Programme (DRDP), University of Turku, Turku, Finland.|Orion Corporation, Orion Pharma, Department of Oncology and Critical Care Research, Turku, Finland.
authors.forename: Riikka
authors.initials: R
authors.lastname: Oksala
authors.affiliation: Cancer Cell Signaling Group, Turku Centre for Biotechnology, University of Turku, Turku, Finland.|Department of Pathology, University of Turku, Turku, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Westermarck
authors.affiliation: Turku Center for Disease Modeling (TCDM), University of Turku, Turku, Finland.|Functional Foods Forum, University of Turku, Turku, Finland.
authors.forename: Sari
authors.initials: S
authors.lastname: Mäkelä
authors.affiliation: Turku Center for Disease Modeling (TCDM), University of Turku, Turku, Finland.|Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland.|Institute of Medicine, The Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
authors.forename: Matti
authors.initials: M
authors.lastname: Poutanen
authors.affiliation: Department of Mathematics and Statistics, University of Turku, Turku, Finland.|Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.|Turku Center for Disease Modeling (TCDM), University of Turku, Turku, Finland.
authors.forename: Tero
authors.initials: T
authors.lastname: Aittokallio
mesh_terms: D000818:Animals; D006801:Humans; D008297:Male; D051379:Mice; D015233:Models, Statistical; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011897:Random Allocation; D015203:Reproducibility of Results; D012107:Research Design; D018401:Sample Size; D017423:Sequence Analysis, RNA; D012984:Software