COVID-19 FDA Response: Site Management and Monitoring
April 17, 2020
This blog post is the next in a series related to maintenance of the reliability and validity of ongoing clinical trial data during the COVID-19 pandemic. Previous topics included changes to study visits and assessments during COVID-19: subject safety considerations and documenting changes made during COVID-19: protocol amendments and the clinical study report. A future post is planned on data integrity: handling COVID-19 related missing data.
In this post, the focus is on site management and monitoring changes during COVID-19.
In the FDA Guidance on conduct of clinical trials of medical products during the COVID-19 pandemic, released initially on March 18th and updated on March 27th and April 2nd (with questions and answers), FDA addresses questions related to delays in on-site monitoring during the COVID-19 pandemic and recognizes access to trial sites may be limited or not available. With a focus on participant safety and trial data quality and integrity, the FDA expectation is that sponsors will identify alternative approaches to on-site monitoring and document these in updates to the Clinical Monitoring Plan. Some alternative approaches include enhanced centralized monitoring and off-site (remote) monitoring: review of subject status, data entry and query resolution, training, regulatory document review and collection, investigational product (IP) compliance, and safety reviews. More frequent off-site (remote) monitoring may need to be considered.
FDA has indicated that delays in monitoring should be carefully documented. Additionally, documentation should track protocol deviations and other GCP non-compliance issues that are a result of delayed monitoring visits due to COVID-19.
Study teams will be expected to conduct targeted risk assessments specifically focused on risks related to COVID-19 impacts on study conduct: new safety risks to trial participants; ability/willingness of trial participants to travel or travel restrictions that limit travel; continued availability of investigators, site staff and facilities; availability of trials supplies, vendors, and IP; gaps resulting from shifts in monitoring strategy due to restricted on-site monitoring. The outcome of this risk assessment should drive the mitigation response, which may include, but is not limited to: protocol amendments, holds on screening and enrollment, and updates to monitoring strategy and Clinical Monitoring Plan.
Study teams will need to determine which altered monitoring strategy best fits the current status of their studies. The study team should collect information on restrictions and the duration of those restrictions both for study participants and for on-site monitoring and confirm whether or not the site allows remote review of their electronic medical records (if applicable) or has some other secure way of reviewing site data remotely.
Study teams should ensure succession planning for themselves in the event of team member absences, limitations, or sickness related to COVID-19.
Vendor limitations or changes in service and reporting should be tracked and communicated to sites if impact is expected.
Sharon Duffy, Associate Director, Clinical Monitoring at Rho, has over 25 years of clinical research experience at both large and small CROs and sponsor companies. Starting as a CRA, she later moved into monitor training, process and compliance support. She received her B.A. in Biology from the University of Virginia.
Marina Acosta-Enslen, Associate Director, Clinical Management is a diversely skilled clinical research professional with 20 years of experience across Phase 1 through 4 studies. Prior to joining Rho, Ms. Acosta-Enslen has held positions in the areas of clinical monitoring, site level study coordination, site start-up, and clinical study management. Ms. Acosta-Enslen has extensive experience working on regional and global HIV, Oncology, Acute Pain and Vaccine clinical trials. Nearly half of her career has been focused in HIV/AIDS research working on NIH and industry funded clinical trials