A user-friendly tool for analysis of complex in vitro experimental data in drug discovery and development

体外体内外推法（IVIVE）是药物开发中的一个迅速兴起的领域，通过对组织匀浆或细胞中产生的体外实验药代动力学/药效学（PK-PD）数据进行分析，并将结果纳入计算机模型，以预测药物在整个体内的作用。全细胞系统的PK-PD数据分析是复杂和耗时的，然而准确的数据分析和知情的数据解释在早期药物开发中至关重要，因为这些信息用于选择在人体试验中进行评估的药物。虽然有许多软件工具可用于体外数据分析，但这些工具是为广泛应用而开发的，并非专门用于药物开发。这些工具不支持更复杂的体外实验系统的分析，这些系统越来越多地用于克服药物开发中的新挑战，缺乏适当的统计严谨性，并且不允许IVIVE。该项目将提供一个用户友好的软件工具来分析体外数据，这些数据首先描述了药物的代谢、转运和受体结合。由数据分析产生的实验不确定性也将被确定。从体外数据分析得出的结果和任何相关的不确定性将被外推，以描述药物在整个体内的行为。该工具将使非专业用户能够确定生成的体外数据的质量，以及在决策过程中使用估计参数的适当性。该工具的开发和利用将使整个制药行业的数据分析保持一致性。该工具的使用将最终导致效率的提高，并增加IVIVE和药物动力学/药效学在药物开发中的应用。反过来，增加IVIVE的使用将有助于减少和取代早期药物开发中的动物实验。

In vitro-in vivo extrapolation (IVIVE) is a rapidly emerging area in drug developmentwhereby in vitro experimental pharmacokinetic / pharmacodynamic (PK-PD) data, generatedin tissue homogenates or cells, are analysed and the results incorporated into computer modelsto predict the effects of drugs in the whole body.PK-PD data analysis in whole cell systems is complex and time consuming, yet accurate dataanalysis and informed data interpretation are crucial in early drug development as thisinformation is used to select drugs to be assessed in human trials. Whilst there are manysoftware tools available for in vitro data analysis, these tools were developed for broadapplication and are not specialised for drug development use. The tools do not supportanalysis of more complex in vitro experimental systems which are increasingly being used inan attempt to overcome newer challenges in drug development, lack appropriate statisticalrigour and do not allow IVIVE.The project will provide a user-friendly software tool to analyse in vitro data describing themetabolism, transport and receptor binding of drugs in the first instance. The experimentaluncertainty arising from the data analysis will also be determined. The results derived fromthe in vitro data analysis and any associated uncertainty will be extrapolated to describe thebehaviour of the drug within the whole body. The tool will enable non-expert users todetermine the quality of the generated in vitro data, and the appropriateness of using theestimated parameters in the decision making process.The development and utilisation of this tool will allow consistency in data analysis across thepharmaceutical industry. Use of the tool will ultimately lead to improved efficiency andincrease the utility of IVIVE and pharmacokinetic / pharmacodynamic understanding in drugdevelopment. In turn, increased use of IVIVE will contribute to reducing and replacing animalexperiments within early drug development.