Data review
The clinical team’s QC ensured all data entries to the eCRF platform corresponded to the paper source documentation. The data management’s QC subsequently checked the eCRF platform data on MedDRA coding, duplicates, incomplete or non-QC-ed records, etc. Once data had passed the clinical and data management QCs successfully, they were transferred to the pharmacometric team. The integrated database as a result of the pharmacometric processing script was subject to a data review complementary to these QCs. The pharmacometric data review had three objectives, and was performed by running the integrated data through an R-script after which results were reviewed by members of the pharmacometrics team. First, data was reviewed to comprehend the clinical meaning of the data entries, including in the context of new data and information on COVID-19 that arose throughout the trial and the ongoing pandemic. Second, once integrated by the pharmacometric processing script, the consistency between the data entries was reviewed, e.g. to not have conflicting records from different datasets for the same timepoint. Third, a check was done to ensure the eCRF data output of the eCRF platform (Mobenzi), was correctly input into the data handling software used by the pharmacometric team (R). This more technical review considered missing values, leading spaces, spelling, lower or upper cases, and numerical or character values, among others. A dedicated R chunk in the pharmacometric processing script was developed for the data review which was updated frequently. After every data transfer, the updated integrated database was reviewed using this code and queries were directed to the data management team. After all queries were resolved and data review was passed successfully, the integrated database was used for graphical and numerical exploration in the pharmacometric processing script, as well as for the DSMB report.