Discussion
SECONDARY
A reproducible pharmacometric workflow was developed here to review data iteratively during a clinical trial, report the trial data frequently to the DSMB, and prepare for the pharmacometric analyses of the primary and secondary endpoints upon trial completion to answer time-sensitive questions. Early collaboration between clinical, data management, and pharmacometric teams was established in this COVID-19 vaccination trial to ensure preparedness for the short analysis timelines. Investing in the development of this workflow paid off, as the primary endpoint analysis was completed within three days, and the secondary endpoint analyses were completed within two weeks after the data lock and unblinding. The automatically compiled open and closed reports ensured consistent and real-time presentation of the latest data when reporting to the DSMB, with on average three days between cut-off and sending the report. The DSMB repeatedly expressed their appreciation for the latest data and extensive analyses given the short timelines. The data review did not only result in confidence in handling the data, but also progressive insight with each iteration. Every single query from the data review improved the understanding of the data, their structure, and the data handling by the processing script. Additionally, through frequent interactions between the clinical, data management and pharmacometric teams, the appreciation for each other’s expertise and requirements grew which led to a very constructive environment. Drug development would benefit by moving from a conventional linear and sequential paradigm, to a more integrative approach as shown hereThe pharmacometric reproducible workflow developed here falls within a larger context of increasing awareness in reproducibility in both data and modelling. This is especially important because of the increasing size and complexity of data acquisition and data types in drug development. The FAIR principles of findability, accessibility, interoperability and reusability of data are becoming the standard