Clinical Trials Trends: Remote Monitoring
The COVID-19 pandemic caused an urgent need to transition clinical trials from on-site to remote monitoring. Though the concept of remote monitoring existed before the pandemic, with some sponsors choosing to implement it in their clinical trials, the sudden and global nature of the pandemic has required sponsors, CROs, and clinical sites to prioritize remote monitoring as an essential aspect of clinical trials. Moving forward, remote monitoring will continue to play an important role in clinical research in the post-pandemic setting.
Remote Monitoring Before Coronavirus
Before 2000, nearly every aspect of clinical trials involved hard copies of all trial-related documentation. Clinical Research Associates (CRAs), also referred to as monitors, were required to work on-site to ensure trials were conducted and documented properly. Then, in the early 2000s, electronic data capture (EDC) systems emerged. The industry embraced less paper documentation with the decreased use of paper Case Report Forms (CRF) and welcomed the beginning of remote monitoring due to the ability to review electronic data in real-time from anywhere. The concept of source verifying data remotely was also born, but it was met with opposition by site staff due to the need to spend time deidentifying source documents and then send them to a CRA via fax, email, or even mail. This laborious process revealed to site staff that it was obviously more efficient to have their CRA come to them and to be onsite to review patient charts and source binders, which were popular at that time. Many sites had not yet transitioned to an EMR system. Though paper CRFs had begun to be phased out, medical charts, other source documents, and regulatory documents were all still being maintained as paper files often contained in binders that were readily and easily available for review by a CRA coming to the site.
In the late 2000s, with continued evolutions in technology and a focus on efficiencies, there was a second push for remote monitoring. An increasing number of people at both sponsor organizations and CROs had the ability to review data in real-time, including data management and pharmacovigilance teams. The FDA released draft guidance on a Risk-Based Approach to Monitoring in October of 2011 that seemed to reignite the discussion around trial set-up to include more remote monitoring. Many webinars and training programs devoted to the topic became available to educate clinical trial professionals. The industry, including study site staff, embraced remote monitoring again for a short period of time due to the draft guidance that was released, and remote monitoring seemed to be the new direction of the industry. However, site staff quickly realized that even with the new guidelines, remote monitoring required a lot of work for them, and site staff often felt that they were not adequately compensated for the additional work. There were new challenges, including the fact that not all source documents were part of each site’s EMR system. Additionally, informed consent forms could only be reviewed on-site. Therefore, the need for CRAs to be on-site for data review activities still existed. There was a slight increase in the amount of remote monitoring that went on during this period, but the excitement around remote monitoring seemed to quickly fade away again as site staff pushed back.
In the last ten years, site staff have remained reluctant to allow CRAs to monitor trials remotely. Although specific teams at a sponsor or CRO may be tasked with remote review of data, the industry continues to set up studies with monitoring plans that primarily involve periodic, yet frequent, on-site visits by CRAs who perform the majority of source data verification in-person.
During the Pandemic
When COVID-19 hit the United States in early 2020, there was an immediate impact on the monitoring of clinical trials. CRAs were generally no longer allowed on-site because site visitor policies changed, and CRAs were deemed non-essential. Organizations such as Barnett International and the Association for Clinical Research Professionals (ACRP) started offering more training and support for CRAs who needed to switch to remote monitoring. Emails offering attendance to free webinars on how best to continue monitoring during the COVID-19 pandemic flooded CRAs’ inboxes.
Clinical sites needed to quickly and creatively find ways to continue sponsor/CRO oversight. In the years prior to the pandemic, many hospitals/clinical trial sites had started to add systems that theoretically could handle remote monitoring, including electronic medical record (EMR) and electronic Investigator Site File (ISF) systems, but site policies rarely allowed remote access to CRAs. Sites already set up to provide remote access to their EMR and ISF systems were in the best position to continue clinical trial enrollment, as internal policies for access to technology already in use could be changed relatively quickly to include CRAs. Other hospitals/clinical trial sites instituted procedures to securely provide redacted source documents to CRAs remotely.
With cooperation from many hospitals/clinical trials sites, CRAs have been able to continue study monitoring. CRAs perform source data verification with remote access to EMR or redacted source data, review informed consent forms, and ensure consenting is done appropriately and consistent with site procedures. CRAs are also able to confirm that each site maintains required regulatory documents, including Institutional Review Board (IRB) approvals. Instead of going to the pharmacy for study drug accountability, CRAs compare accountability logs shared by the site staff to dosing information captured in the EDC system. Video calls with the pharmacist provide additional oversight of pharmacy storage and procedures. Lastly, Principal Investigators are available for phone calls to review monitoring findings and ensure proper oversight.
Many hospitals/clinical trials sites are facing unprecedented limitations right now yet are continuing to provide access to clinical trials. Historically, site staff may have resisted remote monitoring, believing it created additional work for them. Over the past two months, many site staff have realized that remote monitoring provides some efficiencies for them, too. While site budgets may be adjusted slightly upward in the future to account for remote monitoring and technology infrastructure changes, that increase will likely be offset by the fact that sponsors and CROs will see significantly reduced travel expenses with the reduction in onsite monitoring activities.
The COVID-19 pandemic required site staff, sponsors, and CROs to think creatively and embrace remote monitoring of ongoing clinical trials in a way not previously seen in the industry. Existing providers of EDC and EMR systems are focusing on their capabilities for remote access, while new companies are providing additional resources for remote data review and implementation of new technologies. Given this experience, there will be continued interest in remote approaches after the crisis passes, and lessons learned from monitoring during COVID-19 will be carried into future clinical trials. Whether monitoring on-site or remotely, the goal remains the same: to provide adequate oversight to ensure patient safety and trial integrity.
—Amy Thorndike is a Lead CRA at Alira Health. Throughout her 15-year career in clinical trials, she has practiced both traditional and remote monitoring approaches to ensure each clinical trial is monitored correctly, within the required time frame, and that each sponsor company receives the data it needs.
For more information on Alira Health Clinical, please contact Chris Rao.