Methodological changes made to NIHR-funded randomised controlled trials: review of 100 trials

Previous studies have reviewed protocol amendments to trial methods in commercial studies and single centres. These studies identified that many were avoidable changes. This study aimed to assess the types of changes and rationale for changes in publicly funded randomised controlled trials undertaken in the UK.

The most recent 100 published randomised controlled trials, on 23rd June 2024, in two NIHR Journals (Health Technology Assessment and Efficacy and Mechanism Evaluation), were selected for review. Data was collected on trial characteristics and the changes reported in the protocol, published reports, and trial registry entry.

Of the 100 included trials, 90 reported changes to the methods. A total of 846 methodological changes were recorded; 45.49% of the recorded changes occurred within the first year of study conduct. A rationale was provided for 204 of the changes with 39 unique reasons given. Frequent reasons for the changes were oversight committee recommendations, site feedback, COVID, and alignment with clinical guidance. The changes were not universally reported across the report, protocol, and registry entry and less than half were reported on the trial registry.

The majority of NIHR-funded trials make methodological changes throughout the duration of the trial, with a large proportion being made within the first year. Consideration should be given to whether a change in the way trials are designed and planned could reduce the need for changes early on. The reporting of methodological changes also needs improvement to ensure trial documentation is consistent and up to date.

This project was registered on the OSF registry, the details of the registration are available here: https://doi.org/10.17605/OSF.IO/WV2GX . Registered on July 22 2024.