MAY 14, 2020 9:00 AM PDT

PANEL: Experimental design and the reproducibility crisis: pitfalls, power, and practical best practice

Speakers
  • Associate Professor of Comparative Medicine and, By Courtesy, of Psychiatry and Behavioral Sciences, Stanford University Medical Center
    Biography
      Joseph Garner, D.Phil., Associate Professor, received his doctoral degree from the Department of Zoology at the University of Oxford, Great Britain, where he studied the developmental neuroethology of stereotypies in captive animals (1995-1999). His postdoctoral research in animal behavior and well-being was undertaken at UC Davis (1999-2004). He served as an Assistant (2004-2010) and an Associate (2010-2011) Professor of animal behavior and well-being in the Department of Animal Sciences at Purdue University, where he also held a courtesy appointment in the Department of Speech, Language and Hearing Sciences (2009-2011). Dr. Garner joined the Department of Comparative Medicine at Stanford in 2011. Here he runs Stanford's Technique Refinement and Innovation Lab, which provides a wide range of support services to assist researchers on campus maximize the efficiency of their work and the well-being of the animals involved. Dr. Garner's research interests include the development of refined methods in behavioral research; abnormal behaviors in animals (including barbering and ulcerative dermatitis) and their relationships with abnormal behaviors in humans; mouse well-being and enrichment; and the scientific impact of well-being problems in lab animals. The goal of this work is to understand why most drugs (and other basic science findings) fail to translate into human outcomes, and how changes in animal research can help resolve this problem. Recognition of Dr. Garner's work includes awards from the National Center for the 3Rs (UK), the American Association for Laboratory Animal Science, the Swiss Laboratory Animal Science Association, and the Universities Federation for Animal Welfare. Dr. Garner serves, or has served, as a council member for the International Society for Applied Ethology, an Editor for Applied Animal Behavior Science, a Special Topics section editor for the Journal of Animal Science, on the AAALAC Board of Trustees, on the SCAW Board of Trustees, on the Scientific Advisory Board of the Trichotillomania Learning Center, the Tourette Association of America, and the Beautiful You MRKH Foundation.
    • Associate Professor of Animal Welfare, Animal Sciences, Purdue University, College of Agriculture
      Biography
        Brianna received her BS from Kansas State University in 2004 and PhD in Animal Behavior and Well-being from Purdue University in 2011. After graduation, she spent 2.5 years as a postdoctoral research scientist at Charles River. She returned to Purdue University in 2014 and was recently awarded tenure. Her research focuses on developing new animal welfare assessment methodologies, rodent well-being, and elucidating the scientific impact of welfare problems in animal based research. Her previous research has covered behavioral and physiological thermoregulation of mice in laboratories and its impact on mouse well-being. Additionally she has been involved in developing new and improved types of cognitive testing for mice that are used in psychiatric and neuroscience research. Brianna has published in the behavior and well-being, laboratory animal, and experimental psychology literatures and has given presentations on her work nationally and internationally. Her research contributions have been acknowledged by receiving the highly commended paper prize from the NC3R's in 2015, the prize for exceptional service in laboratory animal science from the Swiss Laboratory Animal Science Association, and the New Investigator Award from the International Society for Applied Ethology in 2013. Recently she was honored to consult with NASA about mouse welfare on the international space station.

      Abstract

      The justification of sample size is one of the hardest sections of a proposal an IACUC (ethical review board) has to assess, yet is arguably one of the most important (1). This is a key opportunity for the IACUC to assess whether the experiment is well designed, whether animals are being used in the most efficient and productive way possible (2), and even whether the experiment is worth pursuing in its proposed design (3).

      Poor experimental design and poor statistics have two consequences of concern to an IACUC: 1) they increase sample size; and 2) they generate false positives which may then commit animals to further unnecessary experiments. To provide perspective on this issue, consider the fact that only 10% of compounds that ‘work’ in an animal model actually ‘work’ in human trials (4) – that is the false positive rate in terms of human outcomes of animal models is 90%. Poor experimental design plays a huge role in this highly wasteful (and invasive) use of animals (5-7). Similarly, although estimates vary, a very large proportion of published papers contain basic statistical errors (8). For example 38% of papers in a recent review of work published in Nature Medicine contained basic statistical errors (9). Similarly a review of top-tier neuroscience journals revealed basic errors in 50% of behavioral neuroscience papers, and 100% of molecular neuroscience papers surveyed (10).

      Learning Objectives:

      1. This talk will go over in everyday terms, the reasons why good experimental design is so important, what it should look like in an IACUC proposal, how to identify reasonable and unreasonable sample sizes, and how to identify when improved experimental design may allow a PI to perform the same work better with fewer animals.

      2. This talk will be user friendly (it won’t use equations), and the goal is to provide a set of rules of thumb for quick assessment of experimental design and sample size so that IACUC members can triage out protocols where they might want to seek input from a statistician.


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