Improving the credibility and utility of in vitro research

临床前研究(即人体试验前实验室研究的所有阶段)帮助我们了解疾病，并为新疗法的开发提供信息。为了使这项研究具有最大价值，它需要有说服力。许多针对人类疾病的新治疗策略每年都在实验室研究中显示出益处，但很少有策略继续在患者身上显示效果。这种翻译失败的部分原因可能是大量证据表明，临床前研究不够有力，所报告的结果往往不可重现。所有受到系统审查的生命科学领域都显示出存在偏见的风险；存在偏差风险的研究与不可靠的研究结果有关，并造成研究浪费。近年来，已经有大量的活动来解决使用动物进行的临床前研究的稳健性和重复性方面的局限性。在元研究(研究研究)强调偏见风险的存在和影响的研究的推动下，资助者、机构、出版商、监管机构和学术团体已采取步骤，实施工具和战略，以提高动物研究的严谨性。在人工环境中，例如在培养皿或试管中使用细胞的研究--体外研究--是临床前实验室研究的一个组成部分。不幸的是，体外研究还没有受到与其他生物医学研究领域相同水平的系统审查。对动物和临床研究进行系统审查的框架已经建立，它们的使用与实验设计和报告质量的提高有关。目前还没有这样的体外研究框架，识别、合成和评估体外研究的工具和基础设施也尚未开发出来。研究是渐进的，如果体外研究的结果有缺陷，这是基础生物医学研究中浪费的一个重要来源，也可能导致后期研究阶段的浪费。我们汇集了一个多学科的国际合作，其中包括初级体外研究、元研究(研究人员)和实施科学方面的专家。我们有有效和成功合作的记录；我们在实验动物研究的元研究方面的研究努力对广泛的利益相关者的政策和行动产生了重大和直接的影响。我们将定义体外实验的特征，以确定其可靠性。我们将确定最有效的方法来确定所有相关的体外研究，并开发评估其质量和可靠性的方法。我们将实施自动化方法，以减少人工识别体外研究的努力。最后，我们将进行示范系统审查，以试行该框架，并演示关键研究设计特征对结果的报告和影响。尽管由于我们的专业知识，我们建议这项范例审查使用神经元损伤研究，这项工作将与跨生物医学的体外研究进行系统审查相关。我们建议，通过发展这一基础设施，我们将为研究社区和相关利益相关者提供关键工具，以发展强有力的证据，以指导体外研究的设计、进行和报告的改进。

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.