Protection of human rights is paramount in clinical trials and clinical research should be designed and implemented ethically and scientifically. Clinical trial monitoring is an essential activity for quality assurance to ensure the protection of human rights, the reliability and transparency of the data collection process.
What is clinical trial monitoring?
Clinical trial monitoring is defined as the act of overseeing the progress of a clinical trial, and ensuring that they are conducted, recorded, and reported in accordance with the protocol, Standard Operating Procedure (SOPs), The Principles of Good Clinical Practice (GCP), and the medicines for human use regulations wherever applicable.
Why do you need to monitor your clinical trials?
- Ensures to protect the rights of participants.
- Helps to checks data accuracy and verify data from source documents.
- Ensures that the clinical trials are in compliance with GCP and other regulatory requirements.
According to the U.S. Food and Drug Administration’s Center of Drug Evaluation and Research, the top five failures caught by clinical monitors are
- Follow investigation protocol (the procedures and treatment subjects must undergo, as well as the schedule of assessments)
- Failure to keep adequate and accurate records
- Problems with the informed consent form
- Failure to report adverse events
- Failure to account for the disposition of study drugs
In clinical monitoring, a clinical monitor observes each trial undertaken whether they follow standardized operation procedure, report and manage any deviations from the investigation plan as they occur.
Also 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 procedure, and advises central monitoring in exceptional circumstances.
Who performs clinical monitoring?
Monitors may be referred to by many different titles, such as
- Clinical Research Associate,
- “on-site” monitor,
- Clinical Research Monitor,
- Study Site Monitor and
- Quality Specialist.
And all the team members with different job titles perform clinical trial monitoring.
General functions performed during monitoring
- Monitors check the Informed Consent Forms (ICFs) completeness, to ensure they have been duly signed by the patients.
- Verify the eligibility criteria and ensures that all subjects are eligible for the trial.
- Makes sure that all the adverse events are being reported by the site by verifying the source systems and the reports.
- Verifies the accuracy and completeness of the case report forms with respect to the source documents.
- Checks whether the dose and treatment modifications done for any specific patients are accurately documented.
After verification, monitors submit a report after each site visit to the sponsors. These reports include the following
- Detailed summary of review during visits
- Significant findings if any
- Actions taken and
What are different types of monitoring
There are a some of ways in which a clinical trial can be monitored
- On-site Monitoring
- Remote Monitoring
- Centralized Monitoring
The traditional site monitoring methods are costly, subject to data quality errors, and manual. Sponsors spend about 20% to 30% of the clinical trial cost going into monitoring. But, during the COVID pandemic, many sponsors have started adopting modern monitoring techniques. One such monitoring is centralized remote monitoring. It resolves many traditional monitoring issues and is cost-effective. So the monitoring selection depends on several aspects of clinical trial.
Factors that affect the selection of monitoring type
The level of scrutiny of monitoring varies across studies based on the risks and nature of the trial. Below are some of the factors that affect monitoring and the type of monitoring necessary for the trials.
- First and foremost, the critical factor that affects the complexity of monitoring is the protocol design. These include duration of treatment, interaction intensity necessary, the requirement of a special population, etc.
- The therapeutic area under evaluation
- The severity of the treatment
- Number of patients involved in the study
- Number of clinical trial sites
- The phase of the clinical trial.
The overall monitoring plan should remain fairly consistent, but the strategy for individual sites may change considerably depending on study conditions and site performance.
Let’s discuss each monitoring method in detail.
On-site monitoring involves in-person evaluation carried out by sponsor personnel or representatives at the investigation site. On-site monitoring is a traditional method of monitoring and provides many advantages.
- The presence of monitors at the site is necessary for some kinds of trials where remote monitoring is inadequate. In some cases where patient information protection is a priority, remote access is not possible, and monitors shall physically review the documents.
- It helps maintain a more effective relationship with both the stakeholders, the investigator, and the sponsor. When there is a good relationship, it help monitors detect and resolve any issues in the early stages.
- In physical presence, clinical monitors may provide immediate solutions for a few problems and can actively involve study teams.
- It helps motivate study teams, which in turn helps attain high-quality data and compliance in the study end.
Remote monitoring in clinical trials means clinical trials monitors do not visit the site to transfer and review the data. Instead, the data monitoring is done virtually using digital platforms and applications. CROs and study sponsors/stakeholders supervise the data from wherever they are located.
The COVID-19 pandemic has made remote monitoring a necessity for ongoing clinical trials. Remote site access and monitoring platforms have become an essential element of the clinical trial process and created a pivotal connection between the research site, sponsor, and clinical research organization (CRO).
The sponsor or CRO needs to ensure that the trial is performed as per the clinical trial protocol, Standard Operating Procedures (SOPs), Good Clinical Practices (GCPs), and other regulatory requirements. Previously sponsored would monitor sites through various communication mediums such as online, fax, email, cloud-based file share systems, and site visits.
FDA has recommended using remote monitoring long back in 2013. However, this was not a necessity for the clinical trial industry, but now COVID-19 has accelerated the whole industry see toward remote monitoring. Here is the guidance for remote access by FDA.
In multi-center clinical trials, centralized moitoring is a good option. It ensures patient safety, trial integrity, and data quality.
The centralized monitoring came into action after the publication of regulatory guidance on risk-based monitoring (RBM). Global regulators recommend centralized monitoring in conjunction with on-site monitoring to oversee clinical trials. Before implementing centralized monitoring, it is critical to understand the concept of risk management.
In the centralized monitoring the central coordinating team identifies and reviews key data at pre-specified time points. The study team can review eligibility criteria, adverse events, and consent forms centrally to assure the trial team the completeness and correctness. The central team can also review the drug accountability logs to ensure that the site has sufficient stock, dosing, and enrolment data.
One factor the central monitoring team needs to consider is the internet connection at the site. Poor internet connection may impact timely data upload and review by the study team.
Other than these mentioned monitoring, there are several adopted monitoring techniques such as Safety monitoring, and Risk-based monitoring, Lets understand them.
Safety monitoring is another important aspect in clinical trials. The monitor reviews adverse events and follows up with timely resolution. Monitoring is performed on regulator basis. An independent physician with relevant expertise monitors safety of a clinical trial.
Who conducts the safety monitoring
The monitoring may be conducted by
- sponsor or
- Contract research organization (CRO) staff or
- contractor, and/or
- by the Principal clinical investigator/project manager
However, the overall monitoring activity is the responsibility of the sponsor.
Risk based monitoring
Risk-based monitoring is an aggressive strategic approach that uses connectivity and data analytics to ensure the safety and quality of the study. It streamlines error detection and replaces all or most of the site visits. Risk-based monitoring (RBM) is a powerful application to efficiently ensure data integrity and patient safety in a clinical trial.
Why is Risk-based monitoring so important?
In recent years the cost and complexity of clinical trials have increased drastically. Efficient monitoring is becoming critical to protect the well-being of trial participants and maintain the integrity of final results. The risk-based approach allows a more targeted, flexible, and less costly approach. The risk-based monitoring uses centralized monitoring techniques.
Which is the best monitoring approach for your clinical trial?
There is no single monitoring system that works best for every clinical trial. The monitoring approach depends on many dynamic factors, and this shall be strategically thought based on the risk to make a successful clinical trial by all means. In most cases, the mixed approach works well.
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