Pharmacometric analysis preparation
RTI, SECONDARY
The pharmacometric processing script was also developed to include the pharmacometric analysis dataset creation. This resulted in a transparent, traceable, and version-controlled workflow from the raw eCRF input data to the analysis dataset in NONMEM format. Moreover, because the same script and integrated database was utilized to that aim, the datasets were consistent with the figures and tables in the DSMB reports.The reproducible workflow and subsequent confidence in handling of the data allowed for preparation of the pharmacometric analysis of the primary and secondary endpoints while the trial was still ongoing. Based on interim graphical exploration of the data, modelling strategies were developed per endpoint including which functions to test. Model scripts were written, tested, and code reviewed before the data lock. Analysis of the primary endpoint had the highest priority. Because of the reproducible workflow and preparations for the pharmacometric analysis before the data lock, the primary endpoint analysis was completed and reviewed within three days after data lock and unblinding, and shared with the DSMB and the clinical team. Analysis of the secondary endpoints, including a total of 7 time-to-event analyses for COVID-19, RTI, and hospitalization due to all causes in both intention-to-treat and per-protocol datasets, as well as an exploratory time-to-SARS-CoV2 specific vaccination analysis, was completed and reviewed within two weeks after data lock and unblinding, and presented to the DSMB and the clinical team. As we focus here on the reproducible pharmacometrics workflow, the results of these analyses are out of scope and reported separately.