In recent decades, clinical trials and their methodologies have evolved significantly. New technologies have led to improved research methods, techniques and strategies in clinical trial management and in site management and monitoring specifically.
Additionally, new regulations and other external factors have resulted in changes to clinical trial approaches. For instance, social distancing restrictions during the COVID-19 pandemic impacted the ability to carry out in-person research and monitoring at investigational sites. Instead, many studies undertook remote or centralised approaches to clinical monitoring.
As a result, the ways that clinical trials are monitored may have changed forever. Now, sponsors and investigators are opting for increasingly adaptive approaches to clinical trial design and monitoring.
In this article we cover the 4 main types of clinical trial monitoring, discussing their appropriateness, benefits and challenges.
What is clinical trial monitoring?
Clinical monitoring is the process of overseeing the progress and conduct of a clinical trial. This is carried out in order to monitor participants’ health, the efficacy of the treatment, and the safety of the trial.
It is a requirement for any clinical trial involving investigational treatments to include clinical monitoring protocols across all 3 main phases of research.
Clinical monitoring oversees several aspects of the trial, including:
- Compliance with the clinical study protocol
- Record keeping and clinical data management
- Reporting of adverse events
- Completion of informed consent forms
- Compliance with regulatory requirements
The purpose of clinical monitoring
The main purpose of clinical monitoring is to ensure that the trial is conforming to the right standards set out in the study protocol and by external regulations. For instance, clinical monitoring checks for compliance with Good Clinical Practice (GCP) and Good Laboratory Practice (GLP) guidelines.
Safety measures are also monitored throughout, protecting the well-being and rights of trial participants. Another key purpose of clinical monitoring is to ensure that all collected trial data is accurate and valid, overseeing data management efforts and recorded data. Clinical monitoring therefore becomes a key consideration in clinical trial project management.
Who is responsible for monitoring clinical trials?
It is the sponsor’s responsibility to oversee monitoring in clinical trials and assess investigator reports. They are also responsible for ensuring that the appropriate submissions are made as required to regulatory authorities, such as the FDA, as well as other investigators.
4 Types of monitoring in clinical trials
1. On-site monitoring
On-site monitoring is the process of evaluating clinical trial procedures at the investigation site. Monitoring is carried out in person by the sponsor or their representatives, overseeing trial processes at sites where the research is taking place.
On-site monitoring is the most traditional form of clinical monitoring, and is used commonly across site-based clinical trials. This is sometimes referred to as clinical site monitoring.
This type of clinical monitoring is most appropriate for trials that take place at a centralised investigation site. However, on-site monitoring is less practical for clinical trials that are spread across multiple investigation sites – especially if sites are not located nearby.
2. Remote monitoring
Remote monitoring oversees clinical trial research, evaluating the study off-site. Monitoring is carried out away from the investigational site where the research is taking place.
This type of clinical monitoring became much more common during the COVID-19 pandemic, when on-site visits were limited due to restrictions and safety measures. On-site monitoring became impossible, and so remote monitoring became the most effective solution.
Even now, after many COVID-19 restrictions have ended, remote monitoring remains an effective way to observe and track clinical trials. As a method that requires no face-to-face interaction with patients or site personnel, remote monitoring comes both with less risk to patients and a lower cost for the study.
Remote monitoring can also improve communication between the site and the sponsor. Most technology systems allow monitoring personnel and sponsors to share notifications, messages and other information – all in one streamlined platform.
3. Centralised monitoring
Centralised monitoring is carried out away from the investigational site at a separate central location.
This centralised approach is similar to remote monitoring, since both involve clinical evaluation away from the study site. The main difference is that centralised monitoring takes place in a central location and can result in an efficient monitoring process that could simultaneously save development budget. The process of reviewing data that has been centrally submitted can also help the study monitors to identify and address data gaps or inconsistencies and take mitigating steps to rectify immediately. For example, it may be that instrumentation at one particular site is incorrectly calibrated. This could potentially be detected when the data from that facility is inconsistent with the other sites participating in the trial. The study monitor would be able to flag this with the on-site team so that the instrumention is correctly calibrated before the next data point is reached.
This type of clinical monitoring is often used to ensure patient safety, trial integrity and data quality throughout the trial, since it limits the role of clinical monitor personnel at the investigation site itself. Centralised monitoring can therefore reduce the risk of interference with human subjects, data collection processes, and other on-site activities.
4. Risk-based monitoring (RBM)
Risk based monitoring (RBM) is used in clinical trials to assess the risks involved with the clinical study. This assesses the risks to investigation quality, human subjects, data integrity, as well as lower-impact risks that are less likely to occur.
RBM is a critical part of clinical monitoring, and is normally used to determine which type of monitoring is the most appropriate for the study.
The risk-based monitoring process works by:
- Identifying any potential risks
- Designing a clinical monitoring plan
- Adjusting the monitoring methodology where necessary
Risks are monitored in a number of ways, often through a combination of the types outlined in this article; on-site, remote and centralised methodologies. This mixed methods approach can help provide a more comprehensive overview of the trial, in turn, helping identify potential risks to data integrity and patient safety.
FDA guidelines on risk-based monitoring
The FDA has issued several guidelines on using risk-based monitoring. They offer general guidelines in their 2019 release “A Risk-Based Approach to Monitoring – Questions and Answers”. More recently, the FDA released risk based monitoring guidelines specifically for clinical trials conducted during the COVID-19 pandemic: “FDA Guidance on Conduct of Clinical Trials of Medical Products During COVID-19 Public Health Emergency”.
These guidelines are designed to advise CROs and sponsors on clinical trial management approaches, and how procedures should be overseen with clinical trial monitoring.
EMA guidelines on risk-based monitoring
The EMA also provides guidelines for risk-based monitoring. These outline how risk based monitoring plans and activities should be carried out in compliance with Good Clinical Practice (GCP) guidelines.
In terms of risk-based monitoring, the EMA provides a step by step overview of risk review and quality management processes. This covers risk assessment, control, review, management and communication processes. The full details can be found in the EMA’s official 2013 release, Reflection Paper on Risk Based Quality Management in Clinical Trials.
Clinical trial management and CRO services
For your clinical development needs, we offer integrated clinical trial management services, including site management and monitoring. We are a full service CRO, supporting you across every stage in the clinical journey. Speak to our team to find out more about how we can help you.