The FDA Guidance on Conduct of Clinical Trials of Medical Products During COVID-19 Pandemic, released Wednesday, are “a really good first step in ensuring that clinical trials continue with minimum disruption,” according to Jim Kremidas, executive director of the Association of Clinical Research Professionals (ACRP).
As the guidance says, the Food and Drug Administration (FDA) recognizes that the COVID-19 pandemic may affect the conduct of clinical trials. Challenges may be caused by quarantines, site closures, travel limitations, supply chain interruptions, or other issues, including infections of site personnel or trial participants.
Those challenges may make it difficult to meet protocol-specified procedures, including administering or using the investigational product or adhering to protocol-mandated visits and laboratory or diagnostic testing. Consequently, there may be unavoidable protocol deviations because of COVID-19 illness or control measures.
Already, ACRP members have reported challenges enrolling patients in new trials and reluctance among existing patients to keep their appointments. Clinicians put patient safety first, but “there’s confusion about how to do that,” Kremidas says.
“The FDA released this guidance to emphasize that at all times, patients’ safety should continue to be at the forefront of considerations. We want to support the continuance of these clinical trials in compliance with good clinical practice and minimizing risks to trial integrity, while also safeguarding the health and well-being of study participants,” Anand Shah, M.D., FDA Deputy Commissioner for Medical and Scientific Affairs, said in a statement.
During the COVID-19 pandemic, the new FDA guidelines allow clinicians to alter the ways in which they see patients who have, or are at risk of contracting, COVID-19. They let certain changes be made without Institutional Review Board (IRB) approval. For example, virtual visits, phone contact, or alternate assessment locations – such as local labs or imaging centers – may be arranged, and “may be sufficient to assure the safety of trial participants,” according to the guidance.
In that regard, the ACRP reminds in a blog series, “Care should be taken that any remote monitoring activities implemented are proportionate to the risks identified, and that they should not place any extra burden on clinical trial sites.” Using centralized monitoring tools that already are in place, and that don’t require addition, sophisticated analytical tools, is one example.
If trial participants no longer have access to the investigational product or site, they may need additional safety monitoring to assess any effects related to the withdrawal of the investigational treatment.
If changes to the protocol or in informed consent are needed, the FDA encourages sponsors and clinical investigators to engage with the IRBs/Independent Ethics Committees (IECs) as early as possible. Changes to minimize or eliminate immediate hazards or to protect the life and well-being of participants may be implemented immediately, but the IRB must be alerted and any amendments to the IND or IDE reported promptly.
While adhering to the original protocols as closely as possible, any changes caused by the COVID-19 pandemic should be documented. Note how restrictions related to the pandemic led to changes in the study, the duration of those changes, whether or how study participants were affected and which individual patients were affected. This includes changes in study visit schedules, missed visits, or patient discontinuations that lead to missing data.
Regarding efficacy assessments, the FDA recommends consulting with the appropriate review division regarding protocol modifications for the collection of efficacy endpoints. If such endpoints cannot be collected, document the reasons why.
“Prior to locking the database sponsors should address in the statistical analysis plan how protocol deviations related to COVID-19 will be handled for the pre-specified analyses,” the guidance advises.
During this pandemic, clear communications and documentation are vital. They help ensure that study sites and trial participants are aware of any changes that may affect them, and they enable the study sponsor to have information on the study as planned and the changes related to COVID-19, for detailed analysis. That combination could become invaluable.
The COVID-19 situation will continue changing for weeks or months to come, creating uncertainty among medical professionals as well as among patients. There is an urgency, as these guidelines show, to ensure that this pandemic does not slow the development of therapeutics and diagnostics and, therefore, clinical trials for other conditions.
These new FDA guidelines help new and existing clinical trials continue with minimal disruption. But, as with any guidelines, Kremidas concluded, “The challenge is always in interpretation.”