Clinical Trial Impact from Coronavirus: New FDA Guidelines for Safety and Integrity

The U.S. Food and Drug Administration (FDA) issued a guidance document today outlining its procedures for conducting clinical trials of investigational products in view of the worldwide COVID-19 outbreak. The guidance does not address how to conduct clinical trials for approval of products to combat the virus, but it does provide important considerations for maintaining good clinical practices and minimizing the risk of compromising the integrity of trials in view of the pandemic.

In addition to the tragic loss of lives and health implications, the outbreak of the COVID-19 virus has upended our everyday lives. It has also provided challenges to safely conducting and completing clinical studies that are necessary for the approval of medical devices. Especially in these difficult times, new and improved medicines and medical devices are important to the ongoing health and well-being of our public. The FDA’s new guidance relates to human drugs and biological products, as well as medical devices, and was issued in response to concerns from the pharmaceutical industry regarding potential challenges to safely conducting clinical studies in view of COVID-19. The guidance provides recommendations for ongoing clinical trials, for trials that do not yet have set policies, and for trials that have been impacted by COVID-19.

Recommendations for Pending Trials

The guidance recognizes that protocol deviations may be necessary in view of quarantine orders, site closures, travel restrictions, or even difficulties in recruitment. The critical aspect is communication regarding deviations, especially communicating changes to trial participants. For ongoing clinical trials, the FDA’s further recommendations include:

• Consider alternative methods for safety assessments besides in-person evaluations (i.e., phone or virtual evaluation, alternative site evaluations, etc.).
• Delay certain assessments under the existing protocol or delaying recruitment of participants.
• Collaborate early with institutional review boards (IRB) for changes to protocol or informed consent.
• Make immediate changes to study protocol without IRB pre-approval where changes seek to “minimize or eliminate immediate hazards or to protect the life and well-being of research participants (e.g., to limit exposure to COVID-19).”  Such changes must be reported afterwards.
• Capture specific information about the cause of any missing safety or efficacy data as a result of schedule changes, missed visits, or patient discontinuation.
• Provide secured delivery methods for products that can be self-administered.
• Use remote or central monitoring programs to maintain oversight of clinical sites.

The FDA encourages that any changes to the protocol or data collection processes are as consistent as possible with the originally approved procedures. Documentation of changes or deviations is the key to maintaining integrity. And, as always, safety of all participants is the FDA’s primary concern.

Recommendations for Trials without Set Procedures and Policies

For studies that have not yet commenced, the FDA is recommending sponsors evaluate, and if necessary revise, procedures so as to protect trial participants and conduct the study with as little disruption as possible. The FDA recommends reviewing policies and procedures relating to informed consent process, study visits and procedures, data collection, study monitoring, adverse event reporting, travel restrictions, quarantine measures, or COVID-19 illness itself. The FDA recommends that any policy changes be consistent with regional or national requirements (i.e., any travel or group size prohibition must be respected), and that the sponsor make any protocol changes that are required by applicable regulations.

Recommendations for Trials Impacted by COVID-19

For any trial that has been impacted by COVID-19, again the key for the FDA is documentation and communication. The FDA recommends that sponsors describe in study reports contingency measures used to manage disruption of the study, a list of all participants who were affected by COVID-19, including a description of how the participating individual was impacted, and analyses and discussions of the impact of contingency measures that were taken on the safety and efficacy results of the study. The FDA encourages documentation of all “robust efforts” that were made by sponsors to maintain the safety and study data integrity, as well as unavoidable protocol deviations.

While studies are underway that look for solutions to the COVID-19 pandemic, the FDA’s recent guidance seeks to maintain the integrity of clinical studies of all medicines and devices in what has become our new normal.

Schiff’s Coronavirus Task Force continues to address the significant business, legal, and economic challenges that accompany the coronavirus pandemic. Stay tuned for additional Insights on ongoing COVID-19 pandemic challenges and issues facing businesses.