Recommended Set

18. Generalisability/ translation

An important purpose of publishing research findings is to inform future research. In the context of animal studies, this might take the form of further in vivo research or another research domain (e.g. human clinical trial). Thoughtful consideration is warranted, as additional unnecessary animal studies are wasteful and unethical. Similarly, human clinical trials initiated based on insufficient or misleading animal research evidence increase research waste and negatively influence the risk-benefit balance for research participants [1,2].

Consider the type of study conducted to assess the implication of the findings. Well-designed hypothesis-testing studies provide more robust evidence than exploratory studies (see item 13 – Objectives). Findings from a novel, exploratory study may be used to inform future research in a broadly similar context. Alternatively, enough evidence may have accumulated in the literature to justify further research in another species or in humans. Discuss what (if any) further research may be required to allow generalisation or translation. Discuss and interpret the results in relation to current evidence, and in particular whether similar [3] or otherwise supportive [4] findings have been reported by other groups. Discuss the range of circumstances in which the effect is observed, and factors which may moderate that effect. Such factors could include for example the population (e.g. age, sex, strain, species), the intervention (e.g. different drugs of the same class), and the outcome measured (e.g. different approaches to assessing memory). 

 

References

  1. Chalmers I, Bracken MB, Djulbegovic B, Garattini S, Grant J, Gülmezoglu AM, Howells DW, Ioannidis JPA and Oliver S (2014). How to increase value and reduce waste when research priorities are set. The Lancet. doi: 10.1016/S0140-6736(13)62229-1
  2. Wieschowski S, Chin WWL, Federico C, Sievers S, Kimmelman J and Strech D (2018). Preclinical efficacy studies in investigator brochures: Do they enable risk–benefit assessment? PLOS Biology. doi: 10.1371/journal.pbio.2004879
  3. Voelkl B, Vogt L, Sena ES and Würbel H (2018). Reproducibility of preclinical animal research improves with heterogeneity of study samples. PLOS Biology. doi: 10.1371/journal.pbio.2003693
  4. Munafò MR and Davey Smith G (2018). Robust research needs many lines of evidence. Nature. doi: 10.1038/d41586-018-01023-3

 

Example 1

“Our results demonstrate that hDBS robustly modulates the mesolimbic network. This finding may hold clinical relevance for hippocampal DBS therapy in epilepsy cases, as connectivity in this network has previously been shown to be suppressed in mTLE. Further research is necessary to investigate potential DBS-induced restoration of MTLE-induced loss of functional connectivity in mesolimbic brain structures.” [1]

Example 2

“The tumor suppressor effects of GAS1 had been previously reported in cell cultures or in xenograft models, this is the first work in which the suppressor activity of murine Gas1 is reported for primary tumors in vivo. Recent advances in the design of safe vectors for transgene delivery may result in extrapolating our results to humans and so a promising field of research emerges in the area of hepatic, neoplastic diseases.” [2]

 

References

  1. Van Den Berge N, Vanhove C, Descamps B, Dauwe I, van Mierlo P, Vonck K, Keereman V, Raedt R, Boon P and Van Holen R (2015). Functional MRI during Hippocampal Deep Brain Stimulation in the Healthy Rat Brain. PLOS ONE. doi: 10.1371/journal.pone.0133245
  2. Sacilotto N, Castillo J, Riffo-Campos ÁL, Flores JM, Hibbitt O, Wade-Martins R, López C, Rodrigo MI, Franco L and López-Rodas G (2015). Growth Arrest Specific 1 (Gas1) Gene Overexpression in Liver Reduces the In Vivo Progression of Murine Hepatocellular Carcinoma and Partially Restores Gene Expression Levels. PLOS ONE. doi: 10.1371/journal.pone.0132477