Raising the standards of preclinical pain studies
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Vesa Kontinen
A consensus report on the design and reporting of pre-clinical pain studies compiled by a major international pain research consortium is published in this issue of Scandinavian Journal of Pain [1]. This proposed new guideline is more detailed in pain-specific issues than the present gold standard, the ARRIVE-guideline [2,3,4], which is generic for all kinds of preclinical research. The IMI-Europain guideline has been initially developed for internal use of the research group, which has decided to follow it in their own work. I was delighted to find a detailed description of the steps taken in the consensus process in the paper [1].
Now the authors are submitting the guideline for open discussion within the pain research community in general. We can foolishly ignore this initiative, adopt it as it is, or start a discussion that could lead to an even more refined set of rules of practice. The Scandinavian Journal of Pain is proud to provide a forum for such discourse. I hope that in the next journal strategy meeting there will be a discussion on embracing this guideline as the journal policy. Admittedly the Scandinavian Journal of Pain is at present not big on experimental pain research, but I’m convinced that as a journal we would be in good company as an early adopter of the guideline.
Naturally, like in any recommendation or rule, it may be that some details or even bigger issues in the guideline may need adjustment. One of the peer-reviewers of this paper, a highly regarded pain researcher and scientist, criticized strongly the brevity of discussion on the construct validity of the experimental research models. It is indeed true that measuring wrong things with perfect methodology and diligence is misleading and useless. The authors of the guideline agree: “we recognize that process quality does not guarantee outcome quality” [1]. Validity of preclinical models used for pain research has been discussed in detail elsewhere [5,6,7,8,9]. If the validity of the model is acceptable, it should be executed in proper manner, minimizing risk of bias. Additionally, good documentation may help us to find out if right things have been measured.
Trial registers for preclinical trials are proposed to diminish publication bias from negative experiments that remain unpublished. As Knopp and co-workers admit in the paper, implementation and oversight of such a database would be challenging [1]. Indeed, very challenging, and perhaps less crucial than registering clinical trials.
At best, a negative experiment shows that the treatment did not work in the conditions tested. It is not possible to know if the reason for this is that the target (mechanism, receptor, etc.) cannot be influenced by drugs, or is it just that the some details of the experiment (dose, timing, administration route, animal species or strain, pain model, etc.) were not quite right? It is common to perform pilot experiments with small numbers of animals to find the right conditions for an appropriate experiment, where the protocols outlined in the guideline would be followed. In rational development, negative pilot would not lead to a full-scale experiment. It is likely that most academic research groups would report also negative full-scale experiments as a part of publication where a whole development project would be described, and thus there would not be significant publication bias. In industry, however, issues related to commercial competitiveness and especially patent issues dictate what is published, and when.
Congratulations to the IMI-Europain group for an important step in the excellence of the pre-clinical pain research! In the Scandinavian Journal of Pain, we are looking forward to a lively discussion on how the guideline could be still improved. Thereafter, the higher standards need to be adopted by both researchers and journals publishing the results and findings.
DOI of refers to article: http://dx.doi.org/10.1016/j.sjpain.2015.01.006.
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Conflict of interest: The author declares no conflict of interest.
References
[1] Knopp KL, Stenfors C, Baastrup C, Bannon AW, Calvo M, Caspani O, Currie G, Finnerup NB, Huang W, Kennedy JD, Lefevre I, Machin I, Macleod M, Rees H, Rice ASC, Rutten K, Segerdahl M, Serra J, Wodarski R, Berge O-G, Treede R-D. Experimental design and reporting standards for improving the internal validity of pre-clinical studies in the field of pa consensus of the IMI-Europai consortium. Scand J Pain 2015;7:58–70.Search in Google Scholar
[2] Kilkenny C, Browne W, Cuthill IC, Emerson M, Altman DG. NC3Rs reporting guidelines working group animal research: reporting in vivo experiments: the ARRIVE guidelines. Br J Pharmacol 2010;160:1577–9.Search in Google Scholar
[3] Rice ASC, Morland R, Huang W, Currie GL, Sena ES, Macleod MR. Transparency in the reporting of in vivo pre-clinical pain research: the relevance and implications of the ARRIVE (animal research:reporting in vivo experiments) guidelines.Scand J Pain 2013;4:58–62.Search in Google Scholar
[4] Kontinen VK. From clear reporting to better research models. Scand J Pain 2013;4:57.Search in Google Scholar
[5] Kauppila T. Correlation between autotomy-behavior and current theories of neuropathic pain. Neurosci Biobehav Rev 1998;23:111–29.Search in Google Scholar
[6] Kontinen VK, Meert TF. Predictive validity of neuropathic pain models in pharmacological studies with behavioural outcome in the rat: a systematic review. In: Proceedings of the 10th World Congress on Pain. Seattle: IASP-Press; 2003. p. 489–98.Search in Google Scholar
[7] Mogil JS. Animal models of pain: progress and challenges. Nat Rev Neurosci 2009;10:283–94.Search in Google Scholar
[8] Le Bars D, Hansson PT, Plaghki L. Current animal tests and models of pain. In: Beaulieu P, Lussier D, Porreca F, Dickenson AH, editors. Pharmacology of Pain. Seattle: IASP-Press; 2009. p. 475–504.Search in Google Scholar
[9] Berge O-G. Predictive validity of behavioural animal models for chronic pain. Br J Pharmacol 2011;164:1195–206.Search in Google Scholar
© 2015 Scandinavian Association for the Study of Pain
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