A phase 3 trial must be carried out exactly as specified in the approved clinical trial protocol. Each clinical trial site will collect data and samples according to standard operating procedures (SOPs).
Ongoing monitoring of trial sites is carried out according to a pre-specified quality assurance audit plan. A wide variety of metrics are monitored to ensure that trial activities are being carried out and data are being collected as specified. If monitoring identifies any potential concerns, site visits may be undertaken to check on adherence to specified trial procedures and data collection guidelines. These activities are designed to ensure that issues that could potentially affect the quality of final trial data are identified and addressed at early stages.
Monitoring of recruitment is important for tracking whether the required sample size will be achieved in the time allocated for the trial. If recruitment is below target, it might be possible to set up additional trial sites or a trial may need to be extended, both of which can have major cost implications. Failure to recruit sufficient numbers of participants will affect statistical analyses and the power to detect a treatment effect.
As phase 3 trials are typically blinded, data analysis does not begin until the end of study. However, an independent data safety and monitoring board (DSMB) or data monitoring committee (DMC) typically undertakes an interim analysis of data (e.g. when 50% of participants have been recruited) and can identify safety issues or lack of efficacy that might require or a trial to be paused or terminated early.
Key activities during phase 3 trials include:
- Microbiological studies to understand the causes of infection.
- Data analyses to identify breakpoints.
- Surveillance activities.
Collaboration with manufacturers of antibiotic susceptibility test (AST) systems.