In March 2020, the FDA published a guidance entitled “Conduct of Clinical Trials of Medical Products during COVID-19 Public Health Emergency - Guidance for Industry, Investigators, and Institutional Review Boards.” On April 16th, the Agency issued an update that included a question and answer section. With this blog, we hope to provide more clarity into this update and provide a resource for those in the midst of a clinical trial. If you missed part one of this series, you can read it here.
Ongoing clinical research that has the potential for patient benefit should be continued; ongoing observation studies or Phase I studies should be paused. All new studies should be paused until government authorities give a clear signal that patients as well as health care workers are not in harm's way.
The ethical thinking of FDA is comparable to that of the EMA. Their guidance documents are remarkably similar in that both acknowledge the difficulty presented by the current crisis when trying to consider the initiation of new studies or the changes to the conduct of previously approved studies. Both agencies have set the expectations for robust efforts by Sponsors, investigators, and IRBs/IECs to maintain the safety of trial participants and study data integrity. Any efforts to modify ongoing research or to initiate new research should be well documented. FDA and EMA recognize that protocol modifications may be required, including unavoidable protocol deviations due to COVID-19 illness and/or COVID-19 control measures. Efforts to minimize the impacts on trial integrity, and to document the reasons for protocol deviations, will be important. The guidance documents from both EMA and FDA are highly similar with the message that all decisions and changes made to trials should be proportionate and based on benefit-risk considerations and impact on the health and safety of the subject.
However, with that being said, there are also some differences. As with all FDA guidance documents, the Agency states that the document it represents its current thinking on the topic and that it does not establish any rights for any person and is not binding on FDA or the public. Sponsors can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. The document emphasizes the requirements for Sponsors to have established policies and procedures in place that detail and justify the measures taken to react to obstacles encountered or deviations caused by the pandemic. The measures taken may come in the form of clinical study report narratives that outline the contingency measures implemented to respond to any disruption caused by the COVID-19 outbreak, listing of impacted subjects and/or sites, overall analysis of the impact to the study, as well as any protocol modifications or deviations that are necessary to minimize the impact of trial integrity.
Ongoing clinical research that has the potential for patient benefit should be continued, ongoing observation studies or Phase I studies should be paused. All new studies should be paused until government authorities give a clear signal that patients as well as health care workers are not in harm's way. The FDA halted Phase I studies and observational studies.
The FDA addressed COVID-19 screening procedures that may be mandated by the health care system in which a clinical trial is being conducted. Consequent changes do not need to be reported as an amendment to the protocol even if done during clinical study visits unless the Sponsor is incorporating the data collected as part of a new research objective.
Reporting and Permission of Changes
Any change that enhances the safety to the patient or the health care worker can be implemented before IRB approval. This includes changes such as: elimination of study visits, addition of tele-medicine, changes regarding lab visits, and/or imaging visits should be reported within a five-day window. Administrative changes can be reported during the annual review.
To return on our very first question, posed in part one of this blog series:
In this case, the Sponsor felt strongly that they obtain the additional COVID-19 data. They did however, recognize the importance of protecting the staff as well as other patients. With that being said, the Sponsor made a home visit so that the study volunteer could be tested in relative isolation.
Amidst all these considerations for executing clinical studies during a time of uncertainty, ensuring and demonstrating the compliance and quality aspects of your company’s clinical quality management system and ongoing clinical trials remains a regulatory requirement. If you’re unsure how your compliance policies and procedures measure up, our complimentary GCP Auditing Checklist can help.
In the face of new challenges, having Good Clinical Practices (GCPs) in place can lessen the impact these obstacles have on the integrity and overall success of your clinical trials. If you find yourself struggling to keep up with the FDA’s new guidance, ProPharma Group is here to assist.
Our clinical quality consultants have extensive auditing, technical writing, and operational experience to support your organization’s clinical quality needs. Additionally, our wide array of regulatory and compliance services includes vendor qualification audits, mock regulatory inspections, gap analyses, quality management system development and optimization, and interim quality management.
Are you in the midst of a clinical trial? Although the COVID-19 pandemic certainly poses some challenges and there are some changes that must be made in order to adjust to the current regulatory landscape, it is not impossible and can be done as painlessly as possible. We are here to help ensure that this happens. To learn more about how we can help with your ongoing clinical trials, contact us today.
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