By Todd Johnson and Hannah Yee, Halloran Consulting Group, Inc.
COVID-19 ramifications on clinical trial conduct continue to evolve at an astounding pace, requiring rapid adaptation, mitigation, and innovation. Now that the shock has worn off and we have a better picture of the pandemic’s impact on the life sciences industry, it’s time for us to get creative and find a path forward. I believe the most valuable way to start that journey is by working together to forge ahead. There is no one-size-fits-all solution to addressing the impacts of our trials, but the more knowledge we can share, the faster we can get products to patients who need them most.
On April 3, as part of Halloran’s Virtual Town Hall series, industry colleagues convened to discuss issues and solutions specifically related to accelerating the uptake of remote monitoring (RM) — conducting monitoring activities that were previously conducted on-site (not to be confused with centralized monitoring) — in the wake of COVID-19. From logistics to operations, to systems and processes, the considerations are endless when adapting monitoring to take place off-site. As we begin to chart out our next steps around business continuity, we must leverage our collective knowledge and experience. This article captures the key questions asked and the answers provided by participants during our third Virtual Town Hall. (Links to reports from previous Town Halls can be found at the end of this article.)
I want to implement remote monitoring (RM) at my company. Where do I even begin?
Sponsors indicated they had built site assessment checklists that included questions around geographic RM regulations, study and protocol requirements, and site-level capabilities to help them evaluate site RM readiness. Sponsors already piloting RM were able to condense six months of work into a span of a few days to get their RM processes in flight.
Important elements to consider include external electronic medical record (EMR) access / relevant local regulations to allow it, the technology ecosystem, local lab availability, and protocol/procedure complexity, among others. Fortunately, some sites are allowing access to EMR, and others are working toward temporary solutions to reduce the red tape our industry faced under normal circumstances.
Training is a key success factor for RM implementation. Training sessions should be lean, quick, and delivered to small audiences at multiple timepoints. This makes it easier to address questions, ensure quality instruction, and foster better learning overall.
Following is a high-level, step-by-step process for RM implementation, mapped out for deployment:
- Identify available options by conducting an RM assessment via a site assessment checklist, local regulations, and site-specific policies.
- Update study documents as needed, and set up storage.
- Train the internal team, external sites, and subjects.
- Execute on remote monitoring.
Site coordinators and investigators are short on time and may be working across multiple studies. Therefore, coordinating RM communications across sites is critical. We recommend designating one sponsor contact to ensure a successful collection of updates and a smooth implementation into operations.
What are the considerations for uploading documents to secure shared file areas (SFAs), such as Box or SharePoint?
Secure shared file area (SFA) platforms provide coordinators a secure place to redact and upload documents for monitors to review remotely, assuming sites have scanning ability and Wi-Fi access. (Remote EMR access is a plus.)
Focus on uploading documents related to 1) study safety and 2) study efficacy. Safety is the primary focus at this time (e.g., lab tests, imaging reports, any documents directly linked to primary study endpoints, safety data/reports, etc.).
Informed consent forms (ICFs) may require minor language updates or procedural updates. However, generally speaking, ICFs don’t need procedural updates for RM. Participants should be informed of any procedural changes via letter, memo, or other documents. See WCG’s IRB FAQ page for some practical questions and answers on this topic. If you are considering implementing virtual consenting, discuss the process with sites/institutions and refer to local guidelines to determine if local agencies should be notified. Also, note that the process and implementation plan should be documented in the monitoring plan addendum.
Contract updates are generally minor and easy to achieve, as sites have been willing to collaborate to swiftly make necessary changes. It’s important to maintain central documentation of these changes, especially when sites are used across multiple studies. This ensures control of information distribution, as well as internal sponsor alignment, so sites are not bombarded with contract updates and sponsors are aligned internally on required changes to contracts and budgets.
Should we be making changes to existing monitoring plans? If so, what should we focus on?
RM requires minor edits or an addendum to your monitoring plan. Addendums should spell out what the new plan is, why the new plan is in place, how to react appropriately, where to upload documents, naming conventions, access permissions, and how the remote visit will be documented (e.g., if using something other than the trip report template, etc.)
Another way to document RM process changes is to make an overarching note to file (NTF), citing that COVID-19 may require deviations from the monitoring plan, that deviations will not threaten patient safety, and that the monitoring [lan will be reconciled upon return to normalcy (predetermined date).
Record any deviations as COVID-19-related — including missed visits — ensuring they’re trackable, and ensure they’re easily extractable at the end of the study. Specific deviations associated with COVID-19 will need to be summarized in the clinical study report. Refer to FDA’s guidance on clinical trials during COVID-19 and EMA’s guidance on points to consider on implications of COVID-19 on ongoing clinical trials for further information on maintaining documentation and recording deviations.
What should we consider for patients who require complex or invasive procedures that are not possible to administer remotely (e.g., transfusions, lumbar punctures, blood draws, etc.)?
RM processes for complex procedures must be executed on a case-by-case basis and should take into consideration geography, procedure frequency, procedure type, out-of-window threshold, patient status/history, etc. When necessary, collaborate with sites to identify local labs/clinics that can perform the procedure. Some sites have been very cooperative in this regard.
Document the occurrence of local lab procedures in a trackable, extractable format and location. Do not worry about normal ranges and other details. In the monitoring plan addendum, spell out how/when you will retrospectively reconcile the data and how this will be captured in EDC.
The general sponsor should also adjust their approach to invoicing for missed procedures to include payment for missed minor/low-cost procedures, and to negotiating invoicing of missed complex/expensive procedures during follow-up visits.
Telemedicine / virtual monitoring visits are becoming more commonplace in pandemic operations. What should we consider when implementing such measures?
Map out all available options for remote data access up front, such as:
- Direct EMR access
- Video visits (WebEx, Zoom, telephone, etc.)
- Documenting uploads to Box or another compliant document sharing tool
- Faxing / scanning / emailing
- eSource solutions
Take a tiered approach to planning RM visits:
- Do you aim to conduct a video/telephone visit?
- If yes, make sure you’re prepared by creating a detailed worksheet that includes steps to guide the clinical research associate (CRA) through the execution and documentation of monitoring visit activities.
- If no, is the EMR externally accessible?
- If no, is it feasible to communicate and share documents using encrypted emails or secure SFAs?
- If yes, leverage these solutions to conduct an RM visit; conduct source data verification (SDV) with a focus on safety data.
It was noted that a new industry term, “offsite interim monitoring visit” (OIMV, or tele-MV), has been coined, describing remote monitoring visits during which digital “over the shoulder” monitoring activities replace in-person interaction.
Remote data access is a notable obstacle. How can we use the demands of remote clinical trials to set our industry’s data access standard going forward?
Sponsors have found success with eSource platforms, as they have made entry, integration, and access seamless, which is important in crises like COVID-19. Data is entered into these platforms in real-time via tablet, and transfers are scheduled daily, rendering data integrated and accessible on the same day it is collected. Data visualization provides standardization and efficiency across teams — 80 percent of the data criteria were the same across studies, and data were more focused on clinical trial endpoints.
One hurdle to eSource implementation is gaining CRO agreement to work in the sponsor’s systems, and change management and training also present challenges. These platforms also assume Wi-Fi access; site adherence to data safety, data security best practices, and daily data entry; and the ability to train all personnel with system touchpoints. However, the results can be dramatic — in one case study, monitoring visits were decreased by 30 to 40 percent.
What COVID-19 innovations could (and should) outlast this pandemic?
The top three answers from Town Hall participants were:
- Increased real-time data access
- Remote access to EMRs
- Telehealth/virtual solutions
For many companies, COVID-19 is becoming the impetus for digital transformation, and that’s not a bad thing. Despite the devastation, disruption, and sadness that has spread across the globe with COVID-19, we’ve seen remarkable camaraderie in our industry. These conditions have compelled us to act as one collaborative industry with one shared goal: to get life-saving therapies to patients in need. We must carry forth this mindset even after COVID-19 has run its course and reference these learnings to propel us forward. As a participant noted at the closing of the Town Hall, together we will make our trials smarter and safer.
Links to additional key guidance document links are listed below. However, I recommend visiting these health authority websites often as they are updated frequently as new information becomes available.
Articles From Previous COVID-19 Virtual Town Halls:
If you would like to be included in future Halloran Virtual Town Halls on COVID-19, please send an email request to email@example.com.
About The Authors:
Todd Johnson, principal consultant at Halloran Consulting Group, has more than 20 years of experience in pharmaceutical development and clinical systems – from beginning his career as a clinical site monitor to developing operational performance dashboards and KPI/data reporting strategies. Having successfully managed clinical programs and assets, Johnson is knowledgeable in ICH/GCP, has clinical operations experience across multiple therapeutic areas, and has assisted in several successful IND and NDA submissions. Before joining Halloran, he led the Clinical Information and Informatics groups at Astellas and PPD, with an emphasis on operational performance metric/KPI assessment, data quality, benchmarking, dashboard development and reporting.
Hannah Yee, MPH, a consultant at Halloran Consulting Group, has more than three years of experience in clinical research, product management, and product design in health technology. Her focuses are in organizational change, process improvement and design, root cause analysis, human-centered design, and user/patient experience. She has recently worked with early- and commercial-stage companies on systems implementations, organizational redesign, and change management in both the pharma and medical device industries. Prior to joining Halloran, Yee worked as a human factors engineering consultant at Emergo by UL, where she supported usability evaluations of medical devices for regulatory compliance and design.