As a sponsor, you’ve probably had multiple meetings to determine next steps for your clinical trial during the COVID-19 pandemic following the FDA guidance released in March. Do you still feel stumped on how to proceed?
The FDA added an appendix with frequently asked questions and answers on its previously released guidance document on Conduct of Clinical Trials of Medical Products during COVID-19 Pandemic.
The revised FDA guidance document, updated April 2, provides nonbinding recommendations to address these questions.
Here are some key takeaways from the most common questions.
FDA Guidance For Clinical Trials During COVID-19
1. What are some of the key factors that a sponsor should consider when deciding whether to suspend or continue an ongoing study or to initiate a new study during the COVID-19 pandemic?
The sponsor should assess new safety risks, continued principal/co-investigator oversight, availability of trained staff, materials and equipment, where/how assessments can take place, supply of investigational product availability, shelf life, and storage conditions, availability of technology systems, and adequate communication with all necessary staff (i.e. IRB and Data Monitoring Committee) for the clinical trial.
2. What key factors should sponsors consider when deciding whether to continue administering or using an investigational product that appears to be providing benefit to the trial participant during the COVID-19 pandemic?
The sponsor should consider continued investigational product benefits for trial participants and consider alternative treatments and the risks of discontinuation or limitation of the investigational product.
3. How should sponsors manage protocol deviations and amendments to ongoing trials during the COVID-19 pandemic?
The sponsor should document all protocol deviations and the reason for why the deviation occurred. Consideration should be made as to whether the standard documentation process should be followed or an alternative approach. If there are study-wide changes, the sponsor should submit a protocol amendment to the IRB and FDA. Implementing changes immediately will depend on whether the changes were made to assure safety or eliminate immediate hazards of trial participants (see the guidance for additional details regarding Investigational New Drug (IND) and Investigational Device Exemption (IDE) studies).
4. How should a sponsor submit a change in protocol that results from challenges related to the COVID-19 pandemic?
The sponsor should indicate in the FDA cover letter - Subject: “Protocol Amendment – COVID-19” with “Title of Protocol” and provide a summary of COVID-19 related major changes if submitting a formal amendment for their IND study.
The sponsor should indicate in the FDA cover letter - “Subject: Change in Protocol Supplement – COVID-19” or “Notice of IDE Change – COVID 19” with “Title of Protocol,” if submitting for input or a supplement to their existing IDE study.
5. Can a sponsor initiate virtual clinical trial visits for monitoring patients without contacting the FDA if there is an assessment by the sponsor and investigator that these visits are necessary for the safety of the trial participant and it will not impact data integrity?
The sponsor should assure the safety and well-being of trial participants, so such initiation is acceptable. Remember this is still a deviation from the protocol, so IRB review and approval and FDA notification is still needed (see the guidance for additional details for reporting such deviations for IDE studies).
6. With the rapid changes in clinical trial conduct that may occur due to the COVID-19 pandemic, including multiple deviations to address patient safety, what is the best way for sponsors and investigators to capture these data?
The sponsor should create a process for how to report “missing protocol-specified information”, if such information cannot be noted in case report forms. It is important to document the specific details surrounding any missed data and the relationship to the COVID-19 impact. The process should also be systematic across all sites in order to help provide an appropriate data analysis.
7. If patients are currently dispensed investigational product through a pharmacy for self-administration at home, can a sponsor switch that to home delivery without amending the protocol?The sponsor should assess safety. If there are no new safety risks, such delivery is acceptable, if the required accountability and storage of the investigational product remain. A protocol deviation and/or protocol amendment may be required based on distribution changes.
8. If patients are currently receiving an investigational product infusion at the clinical trial site, can a sponsor switch to home infusion?
The sponsor should consider safety risks to trial participants and consult with the “appropriate FDA review divisions”. The sponsor should define the circumstances around continuing the subject in the trial, if it is determined that investigational product cannot be safely administered.
9. Considering that there will be likely delays to on-site monitoring of clinical trials during the COVID-19 pandemic, what are FDA’s expectations in such circumstances?The sponsor should seek alternative approaches in order to ensure the safety of trial participants and data integrity (i.e. remote monitoring). Clinical monitors and sponsors should again document all “unique situations” such as non-compliances and delayed identification of protocol deviations or GCP non-compliance issues that occurred due to COVID-19.
10. How do I obtain a signed informed consent from a patient who is in isolation and the COVID-19 infection control policy would prevent us from removing a document signed by the patient from their hospital room?
The sponsor should recommend that clinical sites consider obtaining informed consent via using electronic methods, three-way call, video conference, witness and investigator attestations, photograph of signed consent with witness attestation, or legally authorized representative (see the guidance for additional details). The investigator should document the consent process thoroughly, ensuring that the clinical trial source records indicate how the trial participant’s signed consent form was obtained and/or why the informed consent could not be retained.
Moving Forward With FDA Guidance In Mind
Now that you know some answers, let’s end with a couple more questions. Do you have your alternative processes outlined for your clinical trial during COVID-19? Can IMARC Research provide you with any remote monitoring or data management support?
Our team has been assisting with remote monitoring, training, Trial Master File audits and more for years. We have secure processes in place to maintain compliance and keep your trial moving forward even while you’re working remotely. You might still have more questions than answers right now, but we can help you determine your next steps.
Contact us today to learn more about how we can help.