Assessment of the current state of the consideration of specific features of time-to-event analyses in meta-analyses: re-analysis of systematic reviews and implementation of guidance

在临床研究中，事件时间的测量和比较是通过事件发生时间分析进行的，例如，在总体生存评估中也是如此。这些分析具有挑战性，并包含具体的方法特征。因此，他们的结果并不总是直截了当地进行解释和评估。虽然在研究水平和个别患者数据存在的情况下，对事件发生时间分析的广泛指导是可用的，但缺乏对基于聚集数据的荟萃分析的指导，这些数据越来越多地被用于系统审查和指南。此外，现有的指导主要侧重于恢复结果数据，以汇集影响估计，而纳入的估计数中的确定性基本不受影响。然而，由于逐次事件分析的特殊困难和特点，当现有的不确定性没有得到充分考虑或报告时，缺乏指导对审查的质量构成了相当大的威胁。该项目的主要目标是可持续地改进事件间隔时间荟萃分析的应用和报告。因此，本项目包括对系统评价及其纳入的研究的评估，以引出综述作者在进行时间到事件的荟萃分析和得出结论时，目前如何处理初级研究中存在的问题。这将为今后的改进工作奠定基础。为此，将审查包括在合格系统评价的时间-事件元分析中的初步研究的时间-事件分析的效果估计和特点。这样就可以评估评审作者是否以及如何在其系统评审中考虑方法特点和存在的问题。除其他外，评估将包括对所包括的事件间隔时间荟萃分析进行重新分析。为了积极提高系统审查的质量，避免今后的错误，系统评估的结果将被用来为制定有针对性的指导材料提供信息。为了加强指南的用户友好设计，开发过程将包括与审查作者和指南制定者进行多次磋商。该项目的调查结果旨在为今后旨在改进和加强系统审查和准则质量的举措提供基础，其中包括对事件的时间汇总分析。

The measurement and comparison of event times in clinical research is done by means of time-to-event analysis, so for example in the assessment of overall survival. These analyses are challenging and contain specific methodical features. Their results are therefore not always straight forward to interpret and evaluate. While extensive guidance on time-to-event analysis at the study level and in presence of individual patient data is available, guidance for meta-analyses based on aggregated data, which are increasingly used in systematic reviews and guidelines, is lacking. Moreover, existing guidance is primarily focused on recovering result data to pool effect estimates while leaving the certainty in the included estimators largely untouched. Due to the particular difficulties and features of time-to-event analyses, however, the absence of guidance introduces a considerable threat to the quality of reviews when existing uncertainties are not taken into account or reported adequately. The main objective of this project is to improve the application and reporting of time-to-event meta-analyses sustainably. Therefore, this project includes an assessment of systematic reviews and their included studies to elicit how review authors currently deal with existing problems in primary studies when conducting time-to-event meta-analyses and deriving conclusions. This will then form a basis for future improvement efforts. For this purpose, the effect estimates and characteristics of time-to-event analyses from primary studies included in time-to-event meta-analyses of eligible systematic reviews will be examined. This then allows to evaluate whether and how the review authors consider methodological features and existing problems in their systematic reviews. The assessment will include, amongst other things, a re-analysis of the included time-to-event meta-analyses. In order to actively improve the quality of systematic reviews and to avoid future mistakes, the results of the systematic assessment will then be used to inform the development of targeted guidance materials. To enhance the user friendly design of the guidance, the development process will include multiple consultation rounds with review authors and guideline developers. The findings of this project are intended to provide a foundation for future initiatives that aim to improve and strengthen the quality of systematic reviews and guidelines which include time-to-event meta-analyses.