Systematic Reviews of Animal Studies; Missing Link in Translational Research?

Luijk, Judith van; Bakker, Brenda; Rovers, Maroeska M.; Ritskes‐Hoitinga, Merel; Vries, Rob B. M. de; Leenaars, Marlies

doi:10.1371/journal.pone.0089981

Cited by 80 publications

(64 citation statements)

References 16 publications

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“…This trend might reflect increasing awareness by both researchers and authorities of the importance of reporting, and it is consistent with recent evidence from a random sample of life sciences publications [28]. However, despite the many systematic reviews revealing flaws in experimental design and conduct since Ioannidis’ seminal opinion paper [38], and the wealth of solutions that have since been proposed [2,5,32,39], little progress has been made. Like Baker et al in 2014 [33], we did not find convincing evidence that reporting had increased from applications authorized before (2008) to those authorized after (2012) publication of the ARRIVE guidelines.…”

Section: Discussionsupporting

confidence: 69%

Authorization of Animal Experiments Is Based on Confidence Rather than Evidence of Scientific Rigor

et al. 2016

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Accumulating evidence indicates high risk of bias in preclinical animal research, questioning the scientific validity and reproducibility of published research findings. Systematic reviews found low rates of reporting of measures against risks of bias in the published literature (e.g., randomization, blinding, sample size calculation) and a correlation between low reporting rates and inflated treatment effects. That most animal research undergoes peer review or ethical review would offer the possibility to detect risks of bias at an earlier stage, before the research has been conducted. For example, in Switzerland, animal experiments are licensed based on a detailed description of the study protocol and a harm–benefit analysis. We therefore screened applications for animal experiments submitted to Swiss authorities (n = 1,277) for the rates at which the use of seven basic measures against bias (allocation concealment, blinding, randomization, sample size calculation, inclusion/exclusion criteria, primary outcome variable, and statistical analysis plan) were described and compared them with the reporting rates of the same measures in a representative sub-sample of publications (n = 50) resulting from studies described in these applications. Measures against bias were described at very low rates, ranging on average from 2.4% for statistical analysis plan to 19% for primary outcome variable in applications for animal experiments, and from 0.0% for sample size calculation to 34% for statistical analysis plan in publications from these experiments. Calculating an internal validity score (IVS) based on the proportion of the seven measures against bias, we found a weak positive correlation between the IVS of applications and that of publications (Spearman’s rho = 0.34, p = 0.014), indicating that the rates of description of these measures in applications partly predict their rates of reporting in publications. These results indicate that the authorities licensing animal experiments are lacking important information about experimental conduct that determines the scientific validity of the findings, which may be critical for the weight attributed to the benefit of the research in the harm–benefit analysis. Similar to manuscripts getting accepted for publication despite poor reporting of measures against bias, applications for animal experiments may often be approved based on implicit confidence rather than explicit evidence of scientific rigor. Our findings shed serious doubt on the current authorization procedure for animal experiments, as well as the peer-review process for scientific publications, which in the long run may undermine the credibility of research. Developing existing authorization procedures that are already in place in many countries towards a preregistration system for animal research is one promising way to reform the system. This would not only benefit the scientific validity of findings from animal experiments but also help to avoid unnecessary harm to animals for inconclusive research.

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Section: Discussionsupporting

confidence: 69%

Authorization of Animal Experiments Is Based on Confidence Rather than Evidence of Scientific Rigor

et al. 2016

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“…One evaluation of such research found that main quality features such as proper randomization and blinding of investigators assessing outcomes are rarely adhered to . Other efforts have addressed biases in animal studies of experimental treatments or toxicology assessments of chemicals . Instead of performing more such animal studies and retrospective meta‐analyses thereof that highlight more of these same biases, research in these fields should be recast with better study methods, and a prospective design of meta‐analyses that includes all the studies launched.…”

Section: Meta‐analyses Of Experimental Animal Studiesmentioning

confidence: 99%

The Mass Production of Redundant, Misleading, and Conflicted Systematic Reviews and Meta‐analyses

2016

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“…This translation is affected by numerous factors, such as biological differences between species, internal validity, differences in experimental design between animal studies and clinical trials, insufficient reporting, and publication bias. 39,40 Therefore, the rationalized use of animal and sample size discrepancy can be reviewed whereas disparity in translation of animal experiment to clinical trial can be resolved by pooling the inconsistencies in the results and poor sample size of different studies through meta-analysis based on specific questions. If it is considered that the effect and biases are potentially the same, then validation of the signal cannot be proven.…”

Section: Discussionmentioning

confidence: 99%

“…39,40 However, the results from these experiments must be accurate. 41,42 Reproducible and consistent results from animal models can provide reliable data of relevance to human medicine.…”

Section: Systematic Review and Meta-analysis Of Literaturementioning

confidence: 99%

Critical evaluation of challenges and future use of animals in experimentation for biomedical research

Singh

Pratap

Sinha

et al. 2016

Int J Immunopathol Pharmacol

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Animal experiments that are conducted worldwide contribute to significant findings and breakthroughs in the understanding of the underlying mechanisms of various diseases, bringing up appropriate clinical interventions. However, their predictive value is often low, leading to translational failure. Problems like translational failure of animal studies and poorly designed animal experiments lead to loss of animal lives and less translatable data which affect research outcomes ethically and economically. Due to increasing complexities in animal usage with changes in public perception and stringent guidelines, it is becoming difficult to use animals for conducting studies. This review deals with challenges like poor experimental design and ethical concerns and discusses key concepts like sample size, statistics in experimental design, humane endpoints, economic assessment, species difference, housing conditions, and systematic reviews and meta-analyses that are often neglected. If practiced, these strategies can refine the procedures effectively and help translate the outcomes efficiently.

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Systematic Reviews of Animal Studies; Missing Link in Translational Research?

Cited by 80 publications

References 16 publications

Authorization of Animal Experiments Is Based on Confidence Rather than Evidence of Scientific Rigor

Authorization of Animal Experiments Is Based on Confidence Rather than Evidence of Scientific Rigor

The Mass Production of Redundant, Misleading, and Conflicted Systematic Reviews and Meta‐analyses

Critical evaluation of challenges and future use of animals in experimentation for biomedical research

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