Tony Hagen is senior managing editor for The Center for Biosimilars®.
In guidance issued specifically in response to the COVID-19 pandemic, the FDA has advised that clinical trial protocol modifications may be made but must be documented and reported as promptly as possible. The FDA notes that trial participants may be sickened by COVID-19, supplies of investigational drugs may be interrupted, and quarantines and closings may make on-site patient visits impossible.
Numerous aspects of the COVID-19 pandemic could be disruptive to the success of clinical trials, and in fresh guidance, the FDA has acknowledged that deviations from trial protocol may be necessary. It said these updated guidelines would help to ensure the safety of participants, maintain good clinical practices, and minimize risks to trial integrity.
The challenges that may arise during the current coronavirus outbreak include quarantines, site closures, travel limitations, and interruptions to the supply chain for the investigational product, the FDA noted. There is also the risk that clinical personnel or patients may become infected with COVID-19.
“These challenges may lead to difficulties in meeting protocol-specified procedures, including administering or using the investigational product or adhering to protocol-mandated visits and laboratory and diagnostic testing,” the FDA said.
The FDA added that patient safety should remain a top concern of investigators. Further, they should make assessments and decisions that are in accord with the specific circumstances in each instance that may require a modification of study conduct.
Those decisions may involve whether to continue use of the investigational product in patients who have been participating in the trial, continue trial recruitment, or change patient monitoring. “In all cases it is critical that trial participants are kept informed of changes to the study and monitoring plans that could impact them,” the FDA said.
Following consultation with the clinical investigators, institutional review boards, and independent ethics committees, trial sponsors may decide that for an individual patient, the best course of action may be to continue the trial regimen and thereby protect the patient’s safety, welfare, and rights.
“Such decisions will depend on specific circumstances, including the nature of the investigational product, the ability to conduct appropriate safety monitoring, the potential impact on the investigational product supply chain, and the nature of the disease under study in the trial,” the FDA said.
In the event that trial participants are unable to come to the investigational site for scheduled visits, phone contact and virtual visits are acceptable alternatives when feasible and necessary, and patient safety will not be compromised. Alternative locations for treatment may also be considered, the FDA said, adding that if it becomes impossible to continue to supply a patient with investigational product, the patient may require additional safety monitoring.
“The need to put new processes in place or to modify existing processes will vary by the protocol and local situation. For example, this assessment could include consideration of whether it is appropriate to delay some assessments for ongoing trials, or, if the study cannot be properly conducted under the existing protocol, whether to stop ongoing recruitment, or even withdraw trial participants,” the FDA wrote.
The agency noted that under normal conditions, changes to trial protocol are typically not implemented before review and approval by institutional review boards and independent ethics committees, and in some cases by the FDA. If adhering to this standard is not possible, investigators should engage with these authorities as soon as possible when trial protocol changes are anticipated as a result of COVID-19, the guideline states. Changes should be documented and amendments to trial protocols reported.
The guidance states that for all trials affected by the COVID-19 epidemic, full documentation of trial changes or disruptions should be recorded, along with analyses and discussions “that address the impact of implemented contingency measures on the safety and efficacy results reported for the study.”