Improving the credibility and utility of in vitro research

临床前研究（即在人体测试之前的所有阶段的实验室研究）有助于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的价值，它需要是稳健的。每年都有许多针对人类疾病的新型治疗策略在实验室研究中显示出益处，但很少有在患者中显示出疗效。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稳健，报告的结果往往无法重现。所有经过系统审查的生命科学领域都存在偏倚风险;存在偏倚风险的研究与不可靠的研究结果有关，并导致研究浪费。近年来，已经有大量的活动来解决使用动物的临床前研究的稳健性和再现性的局限性。通过元研究（对研究的研究）研究，强调偏见的存在和影响，资助者，机构，出版商，监管机构和学术团体已经采取措施实施工具和战略，以提高动物研究的严谨性。在人工环境中使用细胞的研究，例如在培养皿或试管中-体外研究-是临床前实验室研究的一个组成部分。不幸的是，体外研究尚未受到与其他生物医学研究领域相同水平的系统审查。动物和临床研究的系统评价框架已经建立，其使用与实验设计和报告质量的改善有关。体外研究没有这样的框架，识别、综合和评价体外研究的工具和基础设施尚未开发。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。我们汇集了多学科的国际合作，包括主要体外研究，元研究（研究研究人员）和实施科学的专家。我们有一个有效和成功的合作记录;我们在实验室动物研究的元研究方面的研究工作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。我们将定义决定其可靠性的体外实验的特征。我们将确定最有效的方法来识别所有相关的体外研究，并开发方法来评估其质量和可靠性。我们将实施自动化方法，以减少识别体外研究的手动工作。最后，我们将进行一个示范性的系统评价，以试点框架，并证明报告和关键研究设计特征对结果的影响。虽然由于我们的专业知识，我们建议，这一范例审查使用神经元损伤研究，这项工作将是相关的跨biomedicine.We建议，通过开发这个基础设施，我们将提供研究社区和相关利益相关者的关键工具，以开发强大的证据，指导在体外研究的设计，实施和报告的改进进行系统的审查。

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.