Bringing Evidence to Translational Medicine

CAMARADES (Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies) provides a supporting framework for groups involved in the systematic review and meta-analysis of data from experimental animal studies...




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3rd International Symposium on Systematic Review and Meta-Analysis of Laboratory Animal Studies New

3rd International Symposium on Systematic Review and Meta-Analysis of Laboratory Animal Studies will be held during 13-14th November 2014 in Washington, D.C., United States.

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About CAMARADES
Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies


The CAMARADES collaboration provides a supporting framework for groups involved in the systematic review and meta-analysis of data from experimental animal studies.

Our interests range from identifying potential sources of bias in animal work; developing recommendations for improvements in the design and reporting of animal studies; developing the meta-analysis methodology the better to apply it to animal studies; through to the selection of candidate stroke drugs for clinical trial.

CAMARADES aims to provide a central focus for data sharing; to act as a resource for those wishing to carry out such reviews; to provide a web based stratified meta-analysis bioinformatics engine (under development!); and to act as a repository for completed reviews.

Excess significance in animal studies

We team up with the Ioannidis group to show excess significance across a range of in vivo disease models.

Dopamine Agonists in Parkinson's Disease

Evelien Rooke and Hanna Vesterinen tackle the animal modelling of Parkinson's Disease, and find low levels of reporting of measures to avoid bias.

Call for increased transparency

We were delighted contribute to the Nature Perspective calling for greater transparency in in vivo research.

Animal models of brain cancer

A fantastic project from medical student Theo Hurst looking at the in vivo data for temozolomide, a treatment for brain tumours.

Improving the Translational Hit of MS Research

Hanna Vesterinen's paper shows that problems of internal and external validity are also common in the experimental allergic encephalomyelitis literature.


Why CAMARADES?

Every year around 5 million people are affected by stroke, and the cellular and molecular pathophysiology of ischaemic brain injury is - at least in animal models of the disease - well understood. Where it has been possible to observe pathophysiological processes in human stroke these same pathophysiological processes appear to operate. However, results from preclinical testing of candidate neuroprotective drugs in experimental stroke models have not translated to positive results in human studies. Over 350 interventions have published efficacy in animal stroke models, of which around 100 have been tested, and been found to be ineffective, in human stroke studies. The number of animals used varies considerably from drug to drug, but a highly conservative estimate would be that over the last 20 years at least 250,000 animals have been sacrificed in the pursuit of treatments for acute stroke.

If animal models of cerebral ischaemia faithfully represent human pathophysiology (and what evidence there is suggests that this is, for the most part, the case) there are a number of potential explanations for the systematic failure of animal experiments to identify effective human neuroprotectants:

  • The interpretation of results from the animal experiments may be biased or imprecise.
  • Systematic flaws in experimental design or conduct might exaggerate efficacy (that is to say such flaws may introduce a study quality bias or a study design bias), or a disproportionate publication of positive studies may introduce a publication bias.
  • The animal models used might not faithfully reflect human pathophysiology, and so the results might not be generalisable to patient populations.
  • The population characteristics of the animals used might be different - in terms of age, sex, co-morbidity - from those of the patient population in whom the disease usually occurs.
  • Clinical trials may have failed to detect a treatment effect where one exists.

It is our contention that there is significant scope for improvements in the design, conduct, analysis and reporting of animal experiments. By minimising bias, such improvements would improve the amount of valid information gained from those animals used. By providing (using systematic review and meta-analysis) a precise and robust overview of existing data the need for further experiments, and the precise areas in which those experiments should focus, this approach would ensure that unnecessary replication did not occur. The proposed research is therefore crucial to the development of "reduction"strategies.

This has been reflected in the recent report from the Nuffield Council on Bioethics, "The Ethics of Research Involving Animals", which recommends...

  • "At present, there is a relatively limited number of useful systematic reviews and meta-reviews that address the question of the scientific validity of animal experiments and tests.

    In principle, it would therefore be desirable to undertake further systematic reviews and meta-analyses to evaluate more fully the predictability and transferability of animal models (paragraph 10.39). We recommend that the Home Office in collaboration with major funders of research such as the Wellcome Trust, the MRC, the Biotechnology and Biological Sciences Research Council (BBSRC), animal protection groups and industry associations such as the Association of the British Pharmaceutical Industry (ABPI) should consider ways of funding and carrying out these reviews."


From "Stroke" to "Studies"

CAMARADES began as the "Collaborrative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies", refelecting the interests of the investigators in translational failure in Stroke.

However, through the work of others (Bebarta et al, Bednar et al) it was apparent that some of the issues of internal and external validity which we have identified on the stroke field might also be relevant in animal modelling of other diseases.

We were interested to take our approach to thre modelling of other neurological diseases where we perceived there to be translational failure, partly to ascertain whether the apparent shortcomings in the stroke field were more generally prevalent.

As a result we have now looked systematically across the modelling of a range of conditions including spinal cord injury, multiple sclerosis, cerebral glioma, Parkinson's disease, Huntington's disease and Alzheimers disease; many of these are either published or in press. Broadley speaking, our hypothesis that findings in these domains might similarly be confounded by poor study quality has been confirmed.

It seems likely that similar issues might confound animal modelling of non-neurological disease, or indeed more fundamental research in the life sciences. This is an increasing focus of our current work, and to reflect this we have decided to change the S of CAMARADES from "Stroke" to "Studies". Although we will also be looking at non-animal studies, for the time being we leave the third A as it stands!


Funding

The Edinburgh group acknowledge the support of the MRC Trials Methodology Hub, the MS Society, the Scottish Chief Scientist Office and the NC3Rs