IVD Clinical Trials in the Era of COVID-19: Time to go Virtual?

Key Elements to Achieving Optimal Virtual Trial Outcomes

With the number of COVID-19 cases on the rise, and no definite end date to nationwide travel restrictions, various Contract Research Organizations (CROs) and Biotech/Pharma companies are hard at work trying to discover how to efficiently conduct ongoing clinical trials while employees work remotely and subjects are restricted to their homes. Faced with site closures, quarantines and limited access to study documents, clinical study teams are now relying heavily on remote monitoring and a more secure means of document sharing/transfering to meet clinical study milestones.

On March 18, the U.S. Food and Drug Administration (FDA) released “Guidance to Conducting Clinical Trials during the COVID 19 Pandemic” to encourage virtual engagement when conducting clinical trials and in an effort to protect patient health. With the exception of certain IVD studies, such as companion diagnostic trials that require interval sample collection to monitor tumor markers, biomarkers, therapeutic responses or toxicities, most IVD trials are limited to non-invasive sample collection. Visits aren’t typically necessary for safety surveillance for most IVD studies, and in fact,  IVD trials have the most potential for virtual efficiencies if electronic records can provide endpoint data and banked samples meet bio-specimen requirements.

To prioritize the safety and wellbeing of both study subjects and site personnel due to the risk of the COVID-19 Pandemic, research activities at most global sites are currently suspended. However, in spite of these challenges, IVD Sponsors must look at the benefits of conducting clinical trials virtually:

• Time and Cost Efficiencies: Time and cost efficiencies have resulted due to the elimination of air travel, hotel, food and commutes.
• Scheduling Flexibility: Scheduling flexibility has been observed as specific times/ dates for visits and meetings with site personnel are fluid.
• Work/Life Balance: Improved work/life balance has been reported for clinical study personnel.
• Increased Patient Availability: Patients have become more available, increasing study participation as a result of  telehealth and the elimination of inconvenient travel and commutes to sites for follow-up visits for studies that do not require routine physical procedures.
• Ease of Investigator Oversight: Through Electronic Data Capture (EDC) and Clinical Trial Management System (CTMS) platforms, investigators are able to securely access study data and other information at all times. 

Pioneers in Virtual Trials
In 2011, Pfizer introduced a virtual clinical trial model; this study was coincidentally titled the “REMOTE” Trial (Research on Electronic Monitoring of Overactive Bladder Treatment Experience). All subject recruitment, enrollment, randomization and study data collection techniques were performed utilizing web-based and smart device-based platforms without physical visits to study sites. The study was conducted to serve as a comparison to conventional trials to determine whether virtual trials would be a more feasible option in the future. Though innovative, the study revealed the older target population faced challenges with the use of technological devices, among other roadblocks. 

Since this time, newly developed technologies and trial platforms, such as secure File Transfer Protocol (FTP) have created new opportunities, and the COVID-19 stay-at-home restrictions have forced even more creative solutions.

Challenging questions that arise when considering virtual IVD clinical trials today, include:

1. Can all phases and processes of IVD clinical trials be conducted virtually?
2. What are the potential barriers to conducting full clinical trials virtually?

Site/Investigator Management in Virtual Clinical Trials
EDC technology has virtually replaced paper Case Report Forms (CRFs) as a means to record, secure, query, scrub, lock, save and export clinical trial data. Multiple systems are commercially available and configured to comply with the the International Council for Harmonisation of Technical Requirements (ICH) E6 (R2) guidelines for data management. The addendum to this guideline emphasizes the ALCOA-C criteria for source data in clinical trials and emphasizes access control and permissions for compliance with 21 CFR part 11 electronic records and signatures regulations.

Clinical and sample data management, through utilization of EDC platforms, is already virtual and in some cases, is designed to manage IVD instrument data. However, it is important to note that four additional key regulatory obligations are slower to evolve as they relate to virtual clinical trials conditions, discussed below.

1. Site Selection and Investigator Qualification
The U.S. Food & Drug Administration (FDA) regulation on Investigator Management requires a Sponsor to select and train qualified investigators. Sites and investigators must have adequate resources and capabilities to conduct a study, as well as documentation of investigator qualifications through resumes/CVs. In addition:

• IVD studies that require on-site sample processing require personnel to accommodate on-site qualification visits.
• If samples are processed by a central laboratory, virtual assessment of site personnel resources requires diligent follow up on feasibility questionnaires. Being alert to potential exaggerations that could manifest in low subject/sample enrollment, more data errors, deviations and improper study oversight is critical.
• In lieu of on-site visits, remote feasibility assessments can include questionnaires followed by virtual tours to assess encounter rooms, secure investigational product storage, labs/specimen processing and testing areas.

2. Personnel Training
Training sessions are typically conducted during site initiation visits with most personnel present; those not in attendance are trained by delegated, trained site personnel. Using web-based platforms like WebEx, Skype for Business and Zoom, Sponsor representatives can productively interact and train investigators and site personnel. Recorded training sessions can be utilized to instruct users on device handling, and video calling can serve to observe user demonstrations of proficiency.

3. Monitoring the Investigation
Per FDA regulations, Sponsors must ensure investigator/site compliance (IRB review, Informed Consent, study conduct in compliance with protocol, device accountability, reporting UADE, etc.).

Remote monitoring as an alternative to on-site monitoring visits has been utilized for years in numerous IVD studies. Monitoring requires detailed review of regulatory binders, study binders and all other essential documents. Currently, sites have resorted to secure drives and compliant cloud-based storage as a favorable storage location for binders. Access to site documents can be allowed by file transfer through secure platforms, or by uploading documents to a secure platform such as Veeva Vault, cloud systems or BOX (with restrictive access for site personnel and Sponsor representatives).

4. Source Data Verification (SDV)
SDV carries the load of monitoring visits, however, virtual SDV can contribute to significant time savings and other benefits.

• Automated redaction has eliminated the risk of exposing protected health information (PHI) which is usually the biggest concerns of remote SDV.
• Virtual monitoring and SDV have proven resourceful for ongoing trials during the COVID-19 Pandemic, bringing to light its numerous advantages.
  • Two major advantages are: 1) continuous workflow to help avoid backlogs of data; and 2) workflow flexibility, which is usually unavailable with restricted work hours during on-site monitoring visits.

Conclusion
While patient safety and health is always of the highest priority, Donald Deieso, PhD, Chairman and CEO of WIRB Copernicus Group (WCG) says it best, “Consider how much CRA time is spent on the road traveling to sites as opposed to actually doing their job.”

Telehealth has come into vogue and technology is keeping people connected while physically distanced. Virtual options for clinical trials are gaining more clinical industry leader and regulator attention at this unique time in history. With the current technological resources available, Sponsors are able to conduct certain IVD clinical trials virtually with full regulatory compliance to FDA guidelines, and with several advantages.

How Can NAMSA Help?
NAMSA’s dedicated team of IVD specialists and scientists not only understand how to guide IVD manufacturers through clinical and regulatory requirements, but we also help Sponsors simplify the development and implementation of effective development strategies. Whether supporting IVD regulatory assessments and submissions, developing IVDR compliant technical files, designing and managing clinical trials or building ISO 13485:2016 and 21 CFR part 820 compliant quality systems… we’ve got you covered. Learn more about NAMSA’s IVD solutions by clicking here.