Clinical Researcher—June 2022 (Volume 36, Issue 3)

PEER REVIEWED

Takoda H. Roland, CCRA, CCRP, CNA

 

I have long been a proponent of the potential of electronic source documentation (eSource) and its advantages in clinical trials. From my experience as a clinical research associate (CRA), I wrote about eSource several times{1,2} in a period when I had come to see that clinical research was only just scratching the surface on leveraging the technology to fundamentally change the way we monitor clinical trials.

At the time, I did not expect to find myself in a position to make a meaningful shift toward remote monitoring. Several years later, while working as a clinical team manager on a global pivotal Phase III study for an Investigational New Drug application, COVID-19 forced contract research organizations (CROs) to rethink their monitoring paradigm. Drawing from both my own and my team’s experience with a leading provider of eSource services, our study was able to successfully implement a remote monitoring process to mitigate the issues of running the trial during the pandemic. Even as someone who had long advocated for remote monitoring using eSource, I found myself astounded at the success our team achieved.

Despite the myriad additional issues caused by COVID-19, our study team’s efficiency dramatically increased with remote monitoring.

As a CRA in 2018, I was fortunate to come across several research sites that were early adopters of eSource and to see how its benefits were immediately evident. Switching to eSource dramatically reduced the workload for sites by streamlining their entire documentation process. The improved efficiencies in data entry vs. handwritten notes, along with a clear step-by-step process for each specific visit, reduced patient visit times.

Leveraging eSource also delivered a significant reduction in errors and missed procedures at sites thanks to real-time data validation. When I did find errors, the audit logs and queries directly on the eSource page were considerably easier to close than the traditional pile of sticky notes monitors are accustomed to utilizing.

One of the inefficiencies I previously noted in earlier publications is the lack of standardization in site sources. Too much time is spent as a CRA familiarizing yourself with each site’s specific source. Due to every site creating a unique source, it is not uncommon for critical datapoints to go uncaptured in the beginning of a study. Standardization of the initial source would reduce the workload of both sites and CRAs, while ensuring critical datapoints are not missed and increasing the chances of noticing trends across sites. With robust eSource tools in play, standardization makes study management and version control in protocol amendment situations much easier, as well. eSource also allows the CRA to spot check the site’s source remotely to ensure it captures all required visits prior to the first patient’s visit.

I have seen firsthand how sites can leverage eSource in several surprising ways. Some sites indicate that using eSource allows them to work with more doctors and in different therapeutic areas that they had previously been unable to find help with. With the ability for principal investigators (PIs) and sub-investigators to review patients charts as eSource from their private practices or homes, the burden on doctors is greatly reduced. For example, investigators’ review times for adverse events are reduced since they no longer need to physically travel to the research office to access charts. One site I encountered even outsourced electronic data capture entry of its source to an offsite facility in a different state.

While eSource offers many advantages to research sites, I believe it benefits sponsors and CROs even more.

To unlock the full potential of eSource by enabling remote monitoring, a study needs the buy-in of both the CRO and sponsor. I had been pushing several years at my CRO to try to implement remote monitoring leveraging eSource to no avail. Then, everything changed when COVID-19 shut down onsite monitoring. Remote monitoring was no longer just an idea or small add-on, it was something we needed immediately and should have started implementing years ago. Flights were getting cancelled, CROs grounded CRAs, and sites decided the last people they wanted to see during a pandemic were CRAs who had travelled through multiple major airports that week.

As soon as the impact of COVID became evident, I started working with our study team and sponsor toward potential solutions. Reaching out to our study sites, we identified several sites that were already using eSource for tasks tied to such areas as their clinical trial management systems (CTMSs), payments, patient recruiting efforts, electronic regulatory needs, and more. Sites that had standardized their eSource practices were able to continue recruiting patients and running trials with minimal to no interruptions. This was not the case for sites that had not made the switch to eSource.

Our team pulled in resources from data management, the sponsor, sites, and our clinical team to amend our study monitoring plan to allow for remote monitoring visits, resulting in improved monitoring metrics across the board.

While other study teams were stuck at the mercy of COVID-19 restrictions, our team achieved some of our highest metrics. Our company’s expectation is around the industry average for days on site (DOS), requiring CRAs to perform in-person onsite monitoring at a research site eight to 10 days per month. However, virtually every study struggled to have CRAs meet their DOS metrics as sites were closed. Even once sites reopened to allow CRAs, the backlog from other studies caused a ton of intra-study competition for space on site for monitors.

Many research sites had additional staffing issues related to cutbacks from COVID-19 that further exacerbated the issue of getting monitoring time onsite. With the implementation of remote monitoring, our CRAs exceeded their traditional DOS metrics, resulting in more pages monitored, improved patient safety due to the reduction of monitoring lag times, and improved CRA efficiency from no longer losing valuable time to travel.

After a few successful trial remote monitoring visits using our favored eSource tool, the study team started to reach out to more sites to see if there were any others using potential eSource solutions. We identified two sites that were using a particular CTMS in this manner. While it did seem to have the potential to be used as an eSource that was compliant with the expectations of the Code of Federal Regulations (CFR) Part 11, we met with mixed results using it. One site was successfully using it in a way that met industry standards for source data capture, however our CRA’s page monitoring rates there were a bit lower than at sites using the eSource our company favored. The other site was using that same CTMS in a way that was not CFR Part 11­–compliant, and this continued to be an issue throughout the study.

We had several sites implement eSource mid-study as a COVID-19 mitigation with mixed results. While implementing eSource mid-study did allow us to complete remote monitoring for new study information, it remained a challenge to verify source data for earlier visits. Some coordinators reported that learning a new system mid-study was an additional burden under already-stressful conditions.

Ideally, an eSource solution is implemented prior to study start. While eSource has great potential, it is critical that due diligence is being done when selecting a vendor and that there is a defined plan to ensure successful implementation.

On our study, we also utilized a hybrid model for monitoring support. Our monitors would attempt to achieve their full DOS expectations at their dedicate sites, however logistics challenges related to COVID-19 made this impossible. Last-minute cancellations due to new policies, COVID-19 outbreaks at sites, flight cancellations, and site closures often left our monitors without scheduled DOS.

Sites with eSource can accommodate many monitors with much shorter notice since they do not need to plan for physical space for the monitors. Monitors onsite are more disruptive to a study coordinator who likely has patients to see. With eSource queries, study coordinators were willing and able to accommodate last-minute visits and address study findings without the visit disrupting their schedules.

Beyond the obvious increase in DOS that we were able to achieve with our monitors not losing time to travel, our study team also saw an increase in the number of pages monitored per day with the remote model.

Our monitors gained access to study data more quickly without the restriction of planning onsite visits. Early access to data meant errors were captured more quickly and corrective actions implemented faster. With corrective actions in place, our sites participating in the remote monitoring saw fewer errors overall.

Further, study timelines were much more easily managed for our sites participating in remote monitoring. Last-minute visits were no trouble to schedule for our sites enrolling their first patient, allowing our study team to meet our monitoring plan requirement of monitoring the first patient within two weeks of enrollment. Meeting schedules for data management batch-cleaning and achieving goals for database locks were also easy for our team with remote monitoring, due to reduced friction in timelines. Medical review timelines were met with remote monitoring access to data, cutting out the traditional middleman between the PI and medical monitor.

Our study team members were more efficient when monitoring with multiple screens from the comfort of their home offices as opposed to being crammed in a makeshift monitoring room. This change in the monitoring workflow resulted in improved CRA retention, as many studies had CRAs leaving the clinical trials industry completely. Even from our less tech-savvy monitors, the feedback was unanimous:

Remote monitoring was preferred due to lifestyle comfort, efficiency in monitoring, and ease of scheduling.

Our CRAs were happy to increase their monthly DOS from the expected eight to 10 to as high as 12 to 16 when it meant not having to endure long hours at airports away from their families. Our study was so successful due to our implementation of remote monitoring, that our study alone accounted for more than 25% of the company’s third-quarter revenue.

The study greatly exceeded revenue expectations despite the pandemic, all thanks to our implementation of remote monitoring.

Our study implemented remote monitoring as a COVID-19 mitigation. While I was excited to finally leverage eSource to enable remote monitoring, it is disappointing that is took a global pandemic for the clinical research enterprise to finally wake up to the 21st century. Remote monitoring should be the integral component of every clinical trial. With remote access to source study data, the model of dedicating an entire DOS to one specific site will change.

Specific visits like those for first enrollment and pages like those for adverse events can be prioritized study-wide for monitors to add the most value toward the study and improve patient safety.

Continuous monitoring breaks the traditional monitoring cycle. Trip reports are based on the frequency at which monitors can get onsite and are not always an accurate representation of the amount of work being performed at a given site. Continuous monitoring allows for regular reports for individual sites to be run and written at scheduled intervals to improve their value. Regular reporting across all sites also allows for easy site-to-site comparisons. Performing such comparisons makes it easy for study teams to identify high-risk sites and allows for true risk-based monitoring, which calls for clear action when risks are identified.

When remote monitoring is the standard, onsite monitoring serves as an excellent tool to mitigate risks identified in site risk reviews.

While our study team was able to prove many of the benefits of eSource not just for sites, but also for the CRO and sponsor, I’ll wrap up with the same message I started with:

We have still only scratched the surface of how eSource will change monitoring in clinical trials.

References

1. https://www.socra.org/blog/modern-cra-perspective-on-the-use-of-technology-in-clinical-trials/
2. https://acrpnet.org/2019/01/15/opinion-a-futurist-view-on-the-use-of-technology-in-clinical-trials/

Takoda H. Roland, CCRP, CCRA, CNA, (takodaroland@gmail.com) is the Owner of Philadelphia Pharmaceutical Research, a Clinical Project Manager with Five Eleven Pharma, and a Contract Clinical Trial Manager with ICON.