We are now almost a year into the COVID-19 pandemic, and you may be asking whether your clinical trials remained GCP compliant during this public health emergency. With the many site access constraints that have occurred and the elevated concerns for ensuring trial participant safety, sites have had to quickly make changes and put new or modified processes in place to maintain ongoing research.
The FDA published guidance on operating clinical trials during the COVID-19 pandemic which recognized that the COVID-19 public health emergency will impact the conduct of clinical trials which could lead to difficulties in meeting protocol-specified procedures, including adhering to protocol-mandated visits and laboratory/diagnostic testing or permanently revising the protocol to address the new COVID-19 reality. The FDA also cautioned sponsors to expect GCP compliance issues due to COVID-19-related disruptions.
While life is still different, the immediate shift in practices has stabilized a bit and now might be a good time to conduct a self-assessment of your research program. Areas that a site should focus on to detect potential GCP non-compliance include changes related to IRB submissions (amendments and deviations), informed consent process complications, and sponsor monitoring.
Potential GCP Compliance Risk Areas Associated with COVID-19 Disruptions
Your site has probably seen a lot of protocol amendments to account for study changes due to COVID-19. Hopefully, all permanent changes made to the conduct of a study, e.g., changes to study windows, changes to the schedule of events, changes to allow use of telehealth for study visits, were submitted as protocol amendments to the reviewing IRB for review and approval.
Your site may also have been subjected to protocol deviations because of disruptions due to COVID-19. Documentation and reporting requirements vary depending on the type of deviation and the IRB’s policy for reporting deviations. For many IRBs, protocol deviations do not need to be reported to the IRB unless they “impose an increase in the risk of harm to participants or adversely affect the integrity of data”. However, even if not reportable, any change implemented to manage study conduct and interruptions to the study because of COVID-19 must be documented. It is important to document specific information that explains the source of any missing data, including the relationship to COVID-19 (e.g. missed study visits or study discontinuation due to COVID-19).
Most IRBs have published COVID-19 guidance to help study teams determine what needs to be submitted to the IRB and what does not. Make sure that you have appropriately followed the guidance provided by the IRB with oversight over your trial. For Advarra IRB approved clinical trials, refer to the online Coronavirus Guidance resource.
During the pandemic, the informed consent process has been a challenging point for many sites. Many protocols did not allow remote consenting when the pandemic began, but with COVID-19 restrictions and local stay-at-home orders remaining in place for extended periods, study teams needed to find alternative ways to inform prospective participants and satisfy FDA requirements for obtaining and documenting consent. To address the need to pivot to remote consenting during these challenging times, FDA published guidance outlining an alternative, remote consent process; unfortunately, many individuals who adopted the FDA’s remote consent process found the process overly complicated and involved additional steps when remotely consenting a participant. To assess whether your consent process was completed correctly do a check on the documentation. Some items to look for are: correct version of ICF form used, missing signatures, whether the ICF for a participant is missing, was a remote consent process sufficiently documented, and if a witness was used were the proper signatures obtained?
Site study teams may be required to participate in remote monitoring due to on-site visit restrictions caused by COVID-19. On-site monitoring visits could easily be converted to remote visits by sponsors already using electronic data capture (EDC) systems and electronic consent. However, not all sites and monitors are equipped with the technology needed to allow for remote monitoring, leading to less frequent or later than planned monitoring activities. This lack of oversight could result in the delayed identification of non-compliance issues and unreported protocol deviations (Alsumidaie, 2020).
Has your site handled timely data entry into case report forms (CRFs) to ensure your trials can be monitored? During a self-assessment, review study deviation logs and previously identified issues the monitor may have found during earlier visits to look for clues to potential non-compliance. Depending on the depth and breadth of the identified issues you might need to put new policies in place to ensure your sites remain GCP compliant.
Keeping your clinical trials on track during COVID-19 may have felt like a juggling act. If you implemented protocol changes, remote informed consent, telehealth study visits and experienced remote monitoring for the first time during the COVID-19 public health pandemic, consider doing a self-assessment to ensure GCP compliance in these areas and remember if you need assistance Advarra Consulting is here to help.
U.S. Food and Drug Administration (FDA). (2020). Conduct of Clinical Trials of Medical Products During the COVID-19 Public Health Emergence, Guidance for Industry, Investigators, and Institutional Review Boards. https://www.fda.gov/media/136238/download
Alsumidaie, Moe. (2020). New Compliance Issues Emerge Amidst COVID Clinical Operations. Applied Clinical Trials Online. https://www.appliedclinicaltrialsonline.com/view/new-compliance-issues-emerge-amidst-covid-clinical-operations