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Where Have All the Rodents Gone? The Effects of Attrition in Experimental Research on Cancer and Stroke

Author

Listed:
  • Constance Holman
  • Sophie K Piper
  • Ulrike Grittner
  • Andreas Antonios Diamantaras
  • Jonathan Kimmelman
  • Bob Siegerink
  • Ulrich Dirnagl

Abstract

Given small sample sizes, loss of animals in preclinical experiments can dramatically alter results. However, effects of attrition on distortion of results are unknown. We used a simulation study to analyze the effects of random and biased attrition. As expected, random loss of samples decreased statistical power, but biased removal, including that of outliers, dramatically increased probability of false positive results. Next, we performed a meta-analysis of animal reporting and attrition in stroke and cancer. Most papers did not adequately report attrition, and extrapolating from the results of the simulation data, we suggest that their effect sizes were likely overestimated.Using a combination of simulation and meta-analysis of stroke and cancer studies, this article highlights the potentially seriously misleading consequences of failing to report the loss of animals in preclinical studies.

Suggested Citation

  • Constance Holman & Sophie K Piper & Ulrike Grittner & Andreas Antonios Diamantaras & Jonathan Kimmelman & Bob Siegerink & Ulrich Dirnagl, 2016. "Where Have All the Rodents Gone? The Effects of Attrition in Experimental Research on Cancer and Stroke," PLOS Biology, Public Library of Science, vol. 14(1), pages 1-12, January.
  • Handle: RePEc:plo:pbio00:1002331
    DOI: 10.1371/journal.pbio.1002331
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    1. Beverly S Muhlhausler & Frank H Bloomfield & Matthew W Gillman, 2013. "Whole Animal Experiments Should Be More Like Human Randomized Controlled Trials," PLOS Biology, Public Library of Science, vol. 11(2), pages 1-6, February.
    2. John P A Ioannidis, 2005. "Why Most Published Research Findings Are False," PLOS Medicine, Public Library of Science, vol. 2(8), pages 1-1, August.
    3. Emily S Sena & H Bart van der Worp & Philip M W Bath & David W Howells & Malcolm R Macleod, 2010. "Publication Bias in Reports of Animal Stroke Studies Leads to Major Overstatement of Efficacy," PLOS Biology, Public Library of Science, vol. 8(3), pages 1-8, March.
    4. Konstantinos K Tsilidis & Orestis A Panagiotou & Emily S Sena & Eleni Aretouli & Evangelos Evangelou & David W Howells & Rustam Al-Shahi Salman & Malcolm R Macleod & John P A Ioannidis, 2013. "Evaluation of Excess Significance Bias in Animal Studies of Neurological Diseases," PLOS Biology, Public Library of Science, vol. 11(7), pages 1-10, July.
    5. Matthew James Shun-Shin & Darrel P Francis, 2013. "Why Even More Clinical Research Studies May Be False: Effect of Asymmetrical Handling of Clinically Unexpected Values," PLOS ONE, Public Library of Science, vol. 8(6), pages 1-6, June.
    6. H Bart van der Worp & David W Howells & Emily S Sena & Michelle J Porritt & Sarah Rewell & Victoria O'Collins & Malcolm R Macleod, 2010. "Can Animal Models of Disease Reliably Inform Human Studies?," PLOS Medicine, Public Library of Science, vol. 7(3), pages 1-8, March.
    7. Carol Kilkenny & William J Browne & Innes C Cuthill & Michael Emerson & Douglas G Altman, 2010. "Improving Bioscience Research Reporting: The ARRIVE Guidelines for Reporting Animal Research," PLOS Biology, Public Library of Science, vol. 8(6), pages 1-5, June.
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    2. Goeschl, Timo & Heyen, Daniel, 2016. "Precision requirements in pesticide risk assessments: Contrasting value-of-information recommendations with the regulatory practice in the EU," Working Papers 0607, University of Heidelberg, Department of Economics.
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    5. Matthias Steinfath & Silvia Vogl & Norman Violet & Franziska Schwarz & Hans Mielke & Thomas Selhorst & Matthias Greiner & Gilbert Schönfelder, 2018. "Simple changes of individual studies can improve the reproducibility of the biomedical scientific process as a whole," PLOS ONE, Public Library of Science, vol. 13(9), pages 1-20, September.
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    7. Neves, Kleber & Amaral, Olavo Bohrer, 2019. "Addressing selective reporting of experiments – the case for predefined exclusion criteria," MetaArXiv a8gu5, Center for Open Science.
    8. Tracey L Weissgerber & Vesna D Garovic & Marko Savic & Stacey J Winham & Natasa M Milic, 2016. "From Static to Interactive: Transforming Data Visualization to Improve Transparency," PLOS Biology, Public Library of Science, vol. 14(6), pages 1-8, June.
    9. Tracey L Weissgerber & Vesna D Garovic & Jelena S Milin-Lazovic & Stacey J Winham & Zoran Obradovic & Jerome P Trzeciakowski & Natasa M Milic, 2016. "Reinventing Biostatistics Education for Basic Scientists," PLOS Biology, Public Library of Science, vol. 14(4), pages 1-12, April.

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