Advancing Disease Modeling in Animal-Based Research in Support of Precision Medicine Proceedings of a Workshop (2018) / Chapter Skim
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4 Reproducibility and Predictivity
4 Reproducibility and Predictivity
Pages 51-60
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From page 51... ...
T he fourth chapter recapitulates the discussions around essential elements of reproducibility that have been studied in translational fields, such as stroke research, or that arise through the use of communal and large datasets, and how reproducibility can be sustained in the context of precision modeling.
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From page 52... ...
Second, many of these studies also suffer from a lack of external and construct validities. Dirnagl compared a group of mouse subjects, all of whom are young inbred twins who have been raised in isolation and fed on a strict diet of granola, to the diversity of the human population, who vary widely by age, sex, comorbidities, medications, and exposure to pathogens and antigens throughout life.
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SYSTEMATIC REVIEWS Merel Ritskes Hoitinga, professor in evidence-based laboratory animal science at Radboud University Medical Center in the Netherlands, said that in order to move forward with animal-based research for precision
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From page 54... ...
SYRCLE holds workshops, provides coaching and supervision, develops guidelines and tools, and has started an international network of ambassadors who promote systematic reviews of animal studies in their local areas. In addition, SYRCLE executes systematic reviews and attempts to identify success factors for translation of animal studies.
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From page 55... ...
Hoitinga concluded with a simple statement: "Transparency provided by systematic reviews leads to subsequent improvements in quality of reporting," and high-quality reporting leads to a more reliable assessment of the translation potential of data. Moving forward in precision medicine will require the use of animal models that are chosen based on high-quality evidence from well-reported and replicable studies.
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From page 56... ...
The crisis of reproducibility in science has been particularly prominent in drug development, but he noted several efforts to monitor it, including Retraction Watch, a blog that tracks retractions as a window into the scientific process (retractionwatch.com) , and multiple studies that have identified numerous instances of irreproducible data (e.g., Begley and Ellis, 2012)
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From page 57... ...
In a recent publication documenting the importance of reproducible precision medicine, Manrai examined classifications of patient records at a leading testing laboratory, and he found that genetic variants were misclassified and that these misclassifications disproportionately affected African Americans as compared to other populations (Manrai et al., 2016)
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THE PARADOXES OF PRECISION MEDICINE Jonathan Kimmelman, associate professor in the Biomedical Studies Unit/Social Studies of Medicine at McGill University, Canada, introduced workshop participants to the five paradoxes of precision medicine. These paradoxes, he said, are creating a very heavy demand for and an expectation about the quality of preclinical evidence, while concomitantly reducing the ability to produce high-quality, reproducible evidence.
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From page 59... ...
The need for high-quality evidence to inform patient classification algorithms compounds the demands on the quality of preclinical evidence. The fourth paradox concerns the rapid evolution of knowledge and diagnostic techniques in the area of precision medicine.
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From page 60... ...
As other speakers discussed, there is a tendency to publish only positive studies, which Kimmelman said is a real problem in the context of precision medicine. As an example, he said that a meta-analysis of sorafenib research found that the mean effect size dropped by about 37% when statistically corrected for non-published preclinical studies (Mattina et al., 2016)
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