Anna Christina Hoerster, Ph.D.
One thing is certain: COVID-19 is going to change the way clinical trials are managed long after an approved vaccine becomes available. This crisis has forced sponsors across the globe to rapidly shift the way they treat study participants during a crisis, as well as how they can continue to monitor outcomes – while keeping patients and staff safe on site.
One common solution that is emerging from this experience is the adoption of centralized, or remote, clinical trial monitoring.
Remote monitoring of clinical trials has been possible for years, and is considered a viable option by many regulatory bodies for its utility to support data-driven monitoring. A remote approach enables an adaptive and flexible monitoring environment, allowing monitors to dedicate more of their time to data review and risk mitigation, and less time to traveling and compiling manual documents.
The US Food and Drug Administration (FDA) has openly argued that advances in the use of electronic medical records, and shared monitoring databases, make remote monitoring a viable solution for contemporary trial management. The agency’s Guidance for Risk Based Monitoring expressly encourages greater use of centralized monitoring methods where appropriate.
Since the pandemic began, most global regulatory bodies have published guidance documents for industry on how to adapt clinical trials during COVID-19, though they all offer a different approach. This means sponsors have to be highly adaptive in their application of remote monitoring and virtual trial elements, in order to maintain patient safety while adhering to regulatory requirements.
With nearly all trial sites across the globe closed and CRAs on lockdown due to social distancing, monitors can no longer visit sites to collect and review trial data. If sponsors want to keep their trials moving forward, they have to adopt new ways of engaging with patients and monitoring trial data. In cases where sponsors have trial sites in multiple countries, their strategies have to be customized to each site.
In most cases, these Sponsors are relying on their CROs to help them navigate this transition. And most CROs are positively responding to the challenge.
Remote Monitoring Made Easier through a Formal Risk Mitigation Plan
Prior to the pandemic, Advanced Clinical had a formal risk mitigation plan that we were able to quickly adapt for COVID-19. The plan, which is based on Transcelerate’s Risk-Based Monitoring Initiative, provides a framework for sponsors and sites to identify risk indicators and perform remote oversight throughout the trial lifecycle. It can be adopted for any type or phase of a clinical trial in any country.
Our Clinical Monitoring Team is also leveraging our pre-defined Remote Monitoring SOP, which included processes for implementing secure portals to ensure workflow, and easy document hand-off.
These two documents provided the framework for our response strategy, which we then adapted to the needs and regulations governing each trial site.
A Customized Approach for Sites: US Case Study
Even with a formal response strategy, there is not a singular approach to shift to remote monitoring during this pandemic. Every site’s journey has been different based on how much of their data is already electronic, how accessible that data is to auditors, how willing stakeholders are to make the necessary changes to enable remote monitoring, and what they allowed to do under current regulations.
Advanced Clinical’s CRAs are responding by helping each site customize their strategy to their unique situation. We are successfully transitioning all visit types* to a remote format and that conversion rate across our sites is 86.5% and trending up as the pandemic and social distancing persists.
For example, in early April, we conducted a remote site initiation visit (SIV) with a renowned US academic center in the Midwest. It was the first SIV for this study, however not for the site, and they were eager to move forward without delay. Both the sponsor and site leaders were in attendance. The study coordinator provided us with a virtual tour of the facility via GoToMeeting, and we were able to see the pharmacy, discuss data collection methods, and ensure all trial data could be captured and shared. The entire meeting was completed in a few hours. The site team then coordinated with all clinic nurses, PI, SC, and pharmacy to remotely complete the training in approximately three hours. The entire experience went very smoothly and everyone was pleased with the results.
Successful Ways for Sites to Transition to Remote Monitoring
For sites that are in active enrollment, the transition to remote interim monitoring visits (IMV) is based on data access and regulations. The sites that use electronic regulatory and pharmacy software solutions have been able to transition to full regulatory and IP accountability virtually.
In cases where sites that choose to limit their EMR access due to institutional policies or EMR capabilities, we developed a hybrid approach, in which they use our secure solution for uploading documents ahead of a scheduled IMV so they have time to prepare and redact agreed upon sources based on critical data points effecting subject safety, eligibility, and protocol endpoints
However, in countries with more restrictive regulations and/or at sites with less accessible data systems, the solutions have been more customized.
In Germany and the UK for example, the shift to remote monitoring must align with the EU’s General Data Protection Regulation (GDPR), which sets specific rules around the use of patient data and patient consent forms. In these cases, our CRAs are helping sites using webinars with shared cameras to monitor trial data remotely while adhering to GDPR rules.
In France and in Spain, where regulations limit the use of remote monitoring, and many sites use multiple digital and paper-based documentation strategies, the response has been focused primarily on staying connected with patients. In these cases, our CRAs are working directly with investigators and study coordinators to connect with patients via phone and email so they can monitor their health status remotely, and to implement investigational drug courier services and home health professionals to ensure their continued treatment and safety. We are also helping them document every step in this process to keep regulators informed, and to update trial data as soon as they are able to return to the site.
All of these transitions have required collaboration between sponsors, site staff and our CRAs to embrace whatever strategies best meet the needs of the sites and patients.
Remote Monitoring as the “New Normal”
Regardless of regulatory limitations, sponsors need to keep their current and future trials moving forward. That means finding innovative ways to continuously monitor trial data, and ensuring patient needs are being met, adverse events are being identified, and endpoint data is consistently captured. The only way to do that right now is through a remote approach.
Of equal importance to note is that the longer they wait the longer it will take to catch up, because the backlog of monitoring tasks is growing higher every day.
We know that remote monitoring isn’t an easy transformation particularly in the midst of a crisis. But when sites have the support of strong partners, and clear SOPS and risk mitigation plans to follow, it can ease the disruption and help sites rapidly adapt.
* Visit Types: Pre-Qualification Visit (PQV), Site Initiation Visit (SIV), Interim Monitoring Visit (IMV) and Close-out Visit (COV)