This blog post serves as an introduction to a series of posts related to maintenance of the reliability and validity of ongoing clinical trial data during the COVID-19 pandemic. Upcoming topics include the following:
- Changes to study visits and assessments during COVID-19: subject safety considerations
- Documenting changes made during COVID-19: protocol amendments and the clinical study report
- Data integrity: handling COVID-19 related missing data
- Site management and monitoring changes during COVID-19
Since the emergence of Coronavirus Disease 2019 (COVID-19) in the US, the FDA has released new guidance and information rapidly and continuously in a comprehensive response to the current pandemic. The Agency is tasked with managing a complex situation, including processing a flood of new requests related to potential products for the treatment of COVID-19, monitoring for drug shortages and manufacturing needs associated with products approved for other indications that have been noted to have potential to treat COVID-19, as well as investigating COVID-19 treatment claims. Importantly, the FDA is also focused on the multitude of clinical trials for other indications ongoing prior to and throughout the pandemic. These clinical trials include products that may result in life saving therapies across a spectrum of indications, and must be carried on in a way that will retain the trial data integrity without adversely impacting subject safety. This is an expectation at any time, but FDA recognizes that the current situation presents some new and unexpected challenges.
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 (with questions and answers), provides support for industry, investigators, and Institutional Review Boards (IRBs) managing these new challenges. These include, but are not limited to, clinical trial site closures, subject and staff infection with COVID-19 impacts on subject participation, and supply chain issues, among others. The guidance covers topics including factors to consider when deciding whether to suspend or continue an ongoing study, how to manage protocol deviations and amendments, and acceptable changes to the informed consent process that may be required due to COVID-19 subject isolation.
In addition to guidance on how to actively respond to COVID-19 related challenges, the guidance also specifies that sponsors, investigators, and IRBs should clearly document changes to study conduct in response to COVID-19 and these changes are expected to be summarized in the clinical study report (or another separate study-specific document). This includes summarizing any changes to the study plan, procedures, or analyses that were made related to COVID-19, including contingency measures taken, a listing of subjects that had COVID-19 related study disruption, and analyses that address the impact of any implemented contingency measures. Information that can be documented within the subject case report forms can be collected in real-time. However, FDA notes that if COVID-19 related issues require a change to study plans, including the statistical analysis plan, sponsors will need to ensure that revisions are submitted to FDA prior to database lock.
Typically, FDA guidance is released in draft form with a period of public comment prior to finalization, but given the current situation, this guidance was released with immediate implementation.
Rho is actively working with sponsors to address many of the challenges noted above. Our core focus, as we work through these challenges, is and always will be subject safety. Rho will continue to update sponsors, study sites, and subjects as more information becomes available.
Monica Frazier, PhD, RAC, Research Scientist, leads and contributes to multiple integrated product development programs at Rho, where she has experience in management of regulatory submissions at multiple stages of product development (INDs, NDAs, etc.) as well as in development of clinical documents to support clinical studies and regulatory submissions. She has over fourteen years of research; scientific and regulatory writing; and project management experience. Her experience includes leading and managing scientific authoring and editing teams, as well as preparing modules of regulatory submissions; briefing packages to support regulatory meetings; clinical study protocols; and clinical study reports.