Evaluation of excess significance bias in animal studies of neurological diseases.

Animal studies generate valuable hypotheses that lead to the conduct of preventive or therapeutic clinical trials. We assessed whether there is evidence for excess statistical significance in results of animal studies on neurological disorders, suggesting biases. We used data from meta-analyses of i...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/bca865a5a5cf43c1bf8387fb018d8c16
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spelling	oai:doaj.org-article:bca865a5a5cf43c1bf8387fb018d8c162021-11-18T05:37:00ZEvaluation of excess significance bias in animal studies of neurological diseases.1544-91731545-788510.1371/journal.pbio.1001609https://doaj.org/article/bca865a5a5cf43c1bf8387fb018d8c162013-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23874156/pdf/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885Animal studies generate valuable hypotheses that lead to the conduct of preventive or therapeutic clinical trials. We assessed whether there is evidence for excess statistical significance in results of animal studies on neurological disorders, suggesting biases. We used data from meta-analyses of interventions deposited in Collaborative Approach to Meta-Analysis and Review of Animal Data in Experimental Studies (CAMARADES). The number of observed studies with statistically significant results (O) was compared with the expected number (E), based on the statistical power of each study under different assumptions for the plausible effect size. We assessed 4,445 datasets synthesized in 160 meta-analyses on Alzheimer disease (n = 2), experimental autoimmune encephalomyelitis (n = 34), focal ischemia (n = 16), intracerebral hemorrhage (n = 61), Parkinson disease (n = 45), and spinal cord injury (n = 2). 112 meta-analyses (70%) found nominally (p≤0.05) statistically significant summary fixed effects. Assuming the effect size in the most precise study to be a plausible effect, 919 out of 4,445 nominally significant results were expected versus 1,719 observed (p<10⁻⁹). Excess significance was present across all neurological disorders, in all subgroups defined by methodological characteristics, and also according to alternative plausible effects. Asymmetry tests also showed evidence of small-study effects in 74 (46%) meta-analyses. Significantly effective interventions with more than 500 animals, and no hints of bias were seen in eight (5%) meta-analyses. Overall, there are too many animal studies with statistically significant results in the literature of neurological disorders. This observation suggests strong biases, with selective analysis and outcome reporting biases being plausible explanations, and provides novel evidence on how these biases might influence the whole research domain of neurological animal literature.Konstantinos K TsilidisOrestis A PanagiotouEmily S SenaEleni AretouliEvangelos EvangelouDavid W HowellsRustam Al-Shahi SalmanMalcolm R MacleodJohn P A IoannidisPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 11, Iss 7, p e1001609 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 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 Evaluation of excess significance bias in animal studies of neurological diseases.
description	Animal studies generate valuable hypotheses that lead to the conduct of preventive or therapeutic clinical trials. We assessed whether there is evidence for excess statistical significance in results of animal studies on neurological disorders, suggesting biases. We used data from meta-analyses of interventions deposited in Collaborative Approach to Meta-Analysis and Review of Animal Data in Experimental Studies (CAMARADES). The number of observed studies with statistically significant results (O) was compared with the expected number (E), based on the statistical power of each study under different assumptions for the plausible effect size. We assessed 4,445 datasets synthesized in 160 meta-analyses on Alzheimer disease (n = 2), experimental autoimmune encephalomyelitis (n = 34), focal ischemia (n = 16), intracerebral hemorrhage (n = 61), Parkinson disease (n = 45), and spinal cord injury (n = 2). 112 meta-analyses (70%) found nominally (p≤0.05) statistically significant summary fixed effects. Assuming the effect size in the most precise study to be a plausible effect, 919 out of 4,445 nominally significant results were expected versus 1,719 observed (p<10⁻⁹). Excess significance was present across all neurological disorders, in all subgroups defined by methodological characteristics, and also according to alternative plausible effects. Asymmetry tests also showed evidence of small-study effects in 74 (46%) meta-analyses. Significantly effective interventions with more than 500 animals, and no hints of bias were seen in eight (5%) meta-analyses. Overall, there are too many animal studies with statistically significant results in the literature of neurological disorders. This observation suggests strong biases, with selective analysis and outcome reporting biases being plausible explanations, and provides novel evidence on how these biases might influence the whole research domain of neurological animal literature.
format	article
author	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
author_facet	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
author_sort	Konstantinos K Tsilidis
title	Evaluation of excess significance bias in animal studies of neurological diseases.
title_short	Evaluation of excess significance bias in animal studies of neurological diseases.
title_full	Evaluation of excess significance bias in animal studies of neurological diseases.
title_fullStr	Evaluation of excess significance bias in animal studies of neurological diseases.
title_full_unstemmed	Evaluation of excess significance bias in animal studies of neurological diseases.
title_sort	evaluation of excess significance bias in animal studies of neurological diseases.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/bca865a5a5cf43c1bf8387fb018d8c16
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Evaluation of excess significance bias in animal studies of neurological diseases.

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