Clinical trial monitoring refers to the supervision of a clinical trial’s progress, ensuring that it is carried out, documented, and reported according to the protocol, Standard Operating Procedures (SOPs), The Principles of Good Clinical Practice (GCP), and relevant regulatory requirements. It is important to monitor clinical trials to safeguard the rights of participants, ensure the accuracy of data, and comply with GCP and regulatory requirements. Clinical monitors identify and manage any deviations from the investigation plan as they occur, such as following standardized operating procedures and recording and reporting adverse events. The International Conference on Harmonization of Technical Requirements for registration of Pharmaceuticals for human use (ICH-GCP) recommends on-site monitoring before, during, and after the trial, but also acknowledges the need for central monitoring in exceptional circumstances. The top five shortcomings identified by clinical monitors include failure to follow the investigation protocol, maintaining adequate and accurate records, problems with informed consent forms, failure to report adverse events, and accounting for the disposition of study drugs.
Clinical trial monitoring can be carried out in different ways, including on-site, remote, and centralized monitoring. The conventional on-site monitoring methods are expensive, prone to errors in data quality, and involve manual work. Typically, 20% to 30% of the clinical trial budget is spent on monitoring. However, due to the COVID-19 pandemic, many sponsors have turned to modern monitoring techniques such as centralized remote monitoring, which is more cost-effective and can address many of the challenges of traditional monitoring methods. Therefore, the choice of monitoring method depends on various factors related to the clinical trial.
The process of on-site monitoring involves conducting evaluations in person at the location where the clinical trial is taking place. This type of monitoring is useful for identifying mistakes in data entry, such as inconsistencies between source records and case report forms (CRFs), as well as detecting missing information in source records or CRFs. Additionally, it can confirm the presence of study documentation and assess the familiarity of the site’s study staff with the protocol and necessary procedures. On-site monitoring can also evaluate compliance with the protocol and investigational product accountability, providing an indication of the quality of the trial’s overall conduct at a particular site. This type of monitoring can be especially useful early in a study, particularly if the protocol involves novel procedures that the principal investigator (PI) may not be familiar with. In such cases, findings from the site may lead to training efforts not only at the visited site but also elsewhere.
In clinical trials, remote monitoring refers to the process of monitoring data without physically visiting the site. Instead, digital platforms and applications are used to virtually monitor the data. This approach has become particularly important during the COVID-19 pandemic, as it allows for continued monitoring while minimizing the risk of infection. Remote monitoring has become an essential aspect of the clinical trial process, providing a crucial connection between the research site, sponsor, and CRO. To ensure compliance with the clinical trial protocol, SOPs, GCPs, and regulatory requirements, sponsors and CROs use various communication channels such as online, fax, email, cloud-based file share systems, and site visits.
Centralized Statistical monitoring
The trial database can be examined using statistical algorithms to identify unusual data patterns at the participant or site level, which can help identify systemic errors or falsified data. Central statistical monitoring includes checks for missing or invalid data, unusual data patterns, and pharmacovigilance signal surveillance for adverse event data. Statistical monitoring can be especially useful for trials where on-site visits are not possible. By minimizing errors from the beginning through careful training and real-time centralized monitoring, the amount of on-site monitoring visits required can be reduced. Regular training updates may also be beneficial.