Improving the credibility and utility of in vitro research

Preclinical research (i.e. all stages of laboratory research prior to testing in humans) helps us understand diseases and informs the development of novel therapies. For this research to be of maximal value it needs to be robust. Many novel treatment strategies for human diseases show benefit in laboratory studies every year, but very few go on to show efficacy in patients.

This failure in translation may be, in part, explained by substantial evidence showing that preclinical research is not sufficiently robust and that reported findings are often not reproducible.

All areas of the life sciences subjected to systematic scrutiny have shown to be at risk of bias; research at risk of bias is associated with unreliable research findings and contributes to research waste. There has been substantial activity in recent years to address the limitations in the robustness and reproducibility of preclinical research using animals.

Informed by meta-research (research on research) studies highlighting the presence and impact of risks of bias, funders, institutions, publishers, regulators and learned societies have taken steps to implement tools and strategies to improve the rigour of animal studies.

Research using cells in an artificial environment, such as in a petri dish or test tube - in vitro research - is an integral component of preclinical laboratory research. Unfortunately, in vitro research has not yet been subjected to the same levels of systematic scrutiny as other biomedical research domains. Frameworks for the systematic review of animal and clinical research are well-established, and their use is associated with improvements in the quality of experimental design and reporting.

No such framework exists for in vitro research and the tools and infrastructure to identify, synthesise and appraise in vitro research are not yet developed. Research is incremental, and if findings from in vitro studies are flawed this represents an important source of waste in basic biomedical research that can also lead to waste in later research stages.

We bring together a multi-disciplinary international collaboration that includes experts in primary in vitro research, meta-research (researchers that research research) and implementation science. We have a track record of effective and successful collaboration; and our research efforts in the meta-research of laboratory animal research have had substantial and direct impact on the policies and actions of a wide range of stakeholders.

We will define the characteristics of an in vitro experiment that determine its reliability. We will determine the most effective approach to identify all relevant in vitro studies and develop methods to assess their quality and reliability. We will implement automated methods to reduce the manual efforts to identify in vitro research.

Finally, we will conduct an exemplar systematic review to pilot the framework and demonstrate the reporting and impact of key study design characteristics on outcomes. Although due to our expertise, we propose that this exemplar review uses neuronal injury research, this work will be relevant to conduct systematic reviews of in vitro studies across biomedicine.

We propose that by developing this infrastructure, we will provide the research community and associated stakeholders with the key tools to develop robust evidence to guide improvements in the design, conduct and reporting of in vitro research.