REMOTE MONITORING IN CLINICAL TRIALS

 

INTRODUCTION

Since 2013, the Food and Drug Administration (FDA) has advocated the use of centralized or remote monitoring on the basis of evidence showing increased data quality, access and monitoring effectiveness. Despite encouragement from regulators, clinical research sites and sponsors have been reluctant to implement remote monitoring practices due to change in management issues, access to technology, lack of clear objectives, concerns regarding patient privacy and safety, budgetary limitations, and administrative work needed to update clinical research site operations and policies. However, at the beginning of 2020, global circumstances disrupted the potential of the industry and have renewed their support for the use of remote monitoring practices to ensure the supervision of clinical trials.

What is Remote-Based Monitoring in Clinical Trials & How Does It Work? 

Remote-based monitoring is a system where, for monitoring purposes, monitors are not expected to visit the research clinic physically; instead, they remotely review data from protected online workspaces. The protocol is executed in the usual manner by the research clinics and additional data is entered in the eCRFs (electronic case report form). All source files, medical documents, lab history and documents including informed consent forms are uploaded to the secure online workstation. The data can be instantly accessed by the Clinical Research Associate (CRA) and is notified to the Research Clinic regarding the same. The CRA compares the source document data with that data provided on the eCRF once the data is uploaded and this becomes his 'monitoring visit', often the majority of time spent on-site is consumed by this task. As source data verification is carried out remotely, this is referred to as remote-based monitoring.

What does the monitor do during site visits?

The monitor performs a range of activities during visits to ensure that the clinical study is executed properly. Monitoring is the activity which ensures that a trial is carefully evaluated and can also be carried out in compliance with guidelines, regulations, Standard Operating Procedures ( SOPs) and Good Clinical Practices (GCPs). The monitor carries out the following tasks:

 Scrutinizing informed consent documentation; 

 Evaluating information on enrollment, including subject recruitment and criteria for eligibility

 Evaluating the familiarity of the site with the protocol and required procedures 

 Reviewing essential regulatory documents and evaluating the familiarity of the site with IRB policies, study agreements and FDA regulations applicable 

 Evaluating the involvement of investigators with the study , in particular, oversight of the principal investigator

 Conducting investigational product accountability

 Reviews Adverse effects 

 Reviews deviations from protocol and 

 Building, working relationships with the Principal Investigator and site employees.

Decision tree for implementation and identification of remote measurements

HOW TO ESTABLISH REMOTE MONITORING AT A SITE

 

o Plan: identify goals, incorporate process tracking tools, and prioritize studies.

o Assess: evaluate resources and approaches for generating source documents.

o Update: promotes best practices for facilitating source document review and revising existing policies and documentation to support remote monitoring.

o Implement: outlines the need for study-specific source plans, promotes effective communication when changes impact study participants and ensures alignment with study sponsors.

WHAT CAN BE DONE USING REMOTE BASED MONITORING?

• Real-time detection of non-compliance or training deficiencies: Sponsors may review in-house screening logs to recognize high screen failure rates and can identify a high number of violations of research eligibility. 

• Perform data checks for completeness and consistency:  For missing fields or out of range data, queries can be generated as the data is entered.

• Review study-wide data for inconsistencies: The sponsor may detect and examine overall processes across sites through clinical review of data. While on-site inspection, certain trends could not be detected as they review one site's data at a time,

• Both CRFs and source data can be accessed remotely.

• Regular inventory of site files can be carried out by using a shadow file of documents submitted by the site to ensure that current and complete records are maintained.  Regulatory review can also include the review of IRB approvals and analysis of informed consent form.

• Determines which sites need on-site review: based on real-time review of incoming data.

On-site monitoring often involves 100% Source data verification (SDV). Remote monitoring strategy coupled with risk-based monitoring, you are moving away from 100% on-site SDV and this process includes remote source data verification (rSDV). rSDV can be conducted using the below options:

o Direct EMR access: providing direct access to the EMRs. It should be carefully incorporated because of data privacy, security concerns as well as technological challenges. Generally, this type of access should be approved by an organization's privacy officer. 

o Non-Purpose-Built Systems such as email, fax, USB flash drives, cloud based file shares, Remote desktop access software and through Video chat (FaceTime, zoom, telehealth software) are commonly used.

o Purpose-Built Systems A purpose-built system is designed to meet specific business needs or requirements. eRegulatory, Clinical Trial Management System (CTMS), and eSource systems are considered ‘purpose-built’. They support and simplify processes, freeing sites to focus on more critical activities.

ADVANTAGES OF REMOTE MONITORING (RM)

• Effective Collaboration: Remote monitoring enables effective collaboration between sponsors and clinical research associates with respect to the finalization of documents.

• Time Saving: Remote monitoring substantially decreases the time taken  to start screening the study participants by research clinics. Clinical trials deal with a continuous influx of data. This can, of course, create complications. As a result, remote monitoring helps researchers to save time when monitoring patients’ reactions to drugs, maintaining records, filing data, and so on.

• Cost Effective: With remote monitoring the amount of time required to be spent by the clinical research associate at the clinical site is significantly lowered, thus decreasing the budget allocation for the same. 

• Remote Documentation Practices: Another advantage is that RM allows CROs to remotely send and receive vital trial documents via email.

• Patient Centric: Particularly useful in tracking patients with chronic conditions such as diabetes because they do not need to be contained to the hospital setting all the time. 

• Focus on Core Study: Clinical research staff and associates find more time to focus on the core study than to limit themselves to operational checks.

• Patient availability: Remote-based monitoring maximizes the availability of patients and enrolments in clinical trials and decreases the rate of patient drop-outs. 

• Data quality: Data access is immediate and data transfer is most secure, this improving data integrity and quality assurance in clinical trials.

REMOTE MONITORING IS BETTER THAN ON-SITE MONITORING

In recent years, researchers tend to be more digitally driven and technologically more dependent. In an attempt to implement more time and cost-effective methods of observing the trials, experts in the field proposed that the use of remote monitoring (RM) would offer more advantages. Sponsors and investigators are spending a great deal of time and money in the conducting of the trial. Unfortunately, despite routine check-ups and various risk-based precautions, there are still a significant number of problems and unexpected difficulties that obstruct the smoothness of projects. One of the most convenient and purposeful strategy is remote monitoring. Frequent data collection at home is also expected to improve patient safety, and if there is a side effect, researchers would know more about it faster.

DO WE STILL NEED ON-SITE MONITORING VISITS?

While it is true that much of the study oversight and review can be done remotely, considering the following scenarios the value of being on-site cannot be denied.

 On-site monitors can perform in-depth review of the informed consent documentation by verify the patients signatures against other documents to ensure the patients signed the consent themselves and by viewing any additional consenting source documentation that may be present on-site.

 when source documents are provided to the sponsor by the sites, he cannot be sure that all the sources were provided for the monitoring to review enrollment, subject recruitment and eligibility criteria information. 

 Misplaced or lost documentation can be addressed and a full inventory of paperwork can be performed.

 The site’s reaction to monitor queries during site visits can give insight into the comfort the site has with the study. The monitor may provide immediate training while on-site, to the staff in deficient areas to improve compliance for the site’s familiarity with the protocol. 

 On-site visits ensure investigational products are stored in a secured, locked location. 

 Additionally, the monitor can often get a glimpse of principle investigator's (PIs) involvement by reviewing the documentation and in observing the relationship between the PI and study staff and monitor can also work on Building working relationships with the Principal Investigator and site staff.

CONCLUSION

Remote monitoring has made a significant positive contribution to clinical trials. Remote monitoring not only facilitates achieving study goals, but also provide immediate and ongoing value to the personnel by all the technology available to adopt and implement and allows flexibility the teams need to adapt to a constantly changing world.

While, theoretically, remote monitoring method may minimize short-term costs, the complete exclusion of on-site monitoring may prove to have long-term consequences. Rather, combining on-site monitoring with an overall centralized review process and excellent coordination throughout, results in a high-quality approach to detect and maintain compliance. This balanced approach, will provide the sponsors with trust that their investigational product can cross the finishing line.

-By

Bhargavi Neela (Pharm.D) & Aneesha Chatla (BPT, MHM)

Students at Clinosol Research Pvt. LTD.