The Usefulness of Systematic Reviews of Animal Experiments for the Design of Preclinical and Clinical Studies

Abstract

The question of how animal studies should be designed, conducted, and analyzed remains underexposed in societal debates on animal experimentation. This is not only a scientific but also a moral question. After all, if animal experiments are not appropriately designed, conducted, and analyzed, the results produced are unlikely to be reliable and the animals have in effect been wasted. In this article, we focus on one particular method to address this moral question, namely systematic reviews of previously performed animal experiments. We discuss how the design, conduct, and analysis of future (animal and human) experiments may be optimized through such systematic reviews. In particular, we illustrate how these reviews can help improve the methodological quality of animal experiments, make the choice of an animal model and the translation of animal data to the clinic more evidence-based, and implement the 3Rs. Moreover, we discuss which measures are being taken and which need to be taken in the future to ensure that systematic reviews will actually contribute to optimizing experimental design and thereby to meeting a necessary condition for making the use of animals in these experiments justified.

Intracerebral microdialysis of adenosine and adenosine monophosphate – a systematic review and meta‐regression analysis of baseline concentrations

“…The search strategies are described in our protocol (Van der Mierden et al 2016). For PubMed and EmBase, we used the previously published filters for animal studies (Hooijmans et al 2010b;de Vries et al 2014a). For Web of Science no animal filter was used, as no validated animal filter is available.…”

“…SRs differ from narrative reviews by using a thorough transparent methodology to retrieve, select and analyse all relevant papers for the review (de Vries et al 2014b). While many interesting narrative reviews on microdialysis are available (refer to the microdialysis handbook by Westerink and Cremers (2007) for an excellent selection), only few SRs of the microdialysis technique have been performed to date.…”

An overview of maternal separation effects on behavioural outcomes in mice: Evidence from a four-stage methodological systematic review

“…Systematic reviews of animal studies, including rodent models, are needed because they provide reliable information on the appropriate methods and procedures to be chosen by researchers according to their goals (de Vries et al, 2014;Hooijmans et al, 2010). Thus, the focus of the present study was to perform a systematic review of mice maternal separation studies, addressing methodological and procedural aspects and describing the results.…”

The great debate: Should Osteoarthritis Research Focus on “Mice” or “Men”?

“…Only with this knowledge will we define the best therapeutic targets of both OA pain/disability and structural disease. Using such data from pre-clinical OA models remains the most common path to develop new therapeutic approaches, and testing in these models optimises treatment use (e.g., timing, disease stage, OA phenotype) to guide design of appropriate clinical trials and ultimately their introduction into clinical practice 6 . The majority of drug development programs in Phase II and III fail because of inadequate clinical efficacy that is attributed to insufficient linkage of the molecular/cellular target with the disease, no validated models, and use in indications not fitting the strongest pre-clinical evidence 7,8 .…”