New methodology papers aim to improve clinical trials monitoring

14 Mar 2023

Experts in clinical trials methodology from the MRC Clinical Trials Unit at UCL have published two papers focusing on issues surrounding the monitoring of clinical trials. Monitoring is needed to ensure patient safety and data integrity, however monitoring activities can be very resource-intensive. 

Monitoring metrics over time 

The first paper, which was published in Research Methods in Medicine & Health Science, explores the need for researchers to collect monitoring metrics in a systematic manner.  

Metrics are numeric measurements used to evaluate how well a study site performs during a trial and highlight any potential risks or problems, such as the number of serious adverse events. If a site reaches a given threshold for a metric, researchers may decide to intervene, for example, by visiting the site or involving the trial management group. However, there is currently no consensus within the clinical trial community about which metrics or thresholds should be used. 

In the paper, the authors present a method for tracking a group of metrics across time to understand how activities within the trial affect different metrics. This can help researchers see which metrics are most useful and what are appropriate thresholds to trigger an intervention. The method uses as a case study the TEMPER ‘study within a trial’ (SWAT), which took place across three clinical trials run by the MRC CTU at UCL.  

The authors encourage other researchers to track metrics using this method or to share their metric data with the MRC CTU trial conduct team for them to do so. 

Monitoring in protocol papers 

The second paper investigates how well monitoring was reported in clinical trial protocol papers. The study was published in Clinical Trials. 

Protocol papers are condensed versions of trial protocols that summarise key aspects of the trial’s study design, conduct and plans for analysis. Unlike full protocols, protocol papers are published in peer-reviewed journals, so they can help other trialists interpret published results. 

Some organisations have published guidelines, such as the 2013 SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) checklist, to ensure monitoring is included in trial protocols. However, this is not translating into published protocol papers. A systematic search of PubMed revealed that of 811 published protocol papers only 48% explicitly reported information on monitoring. Frequency of monitoring was the least reported aspect. 

Not reporting full details about monitoring in publicly available protocol papers means the clinical trial community may not have enough information to judge the validity of a trial, which could jeopardise the trial’s credibility. The paper recommends that the SPIRIT checklist and journal templates for protocol papers should give clearer guidance on the transparent reporting of clinical trial monitoring. 

 Further information: