FDA Adds Questions and Answers to Coronavirus Clinical Trial Guidance
The FDA has updated its guidance on conducting clinical trials during the COVID-19 pandemic with an extensive Q&A section, including a long list of factors to consider when deciding the status of ongoing trials and ones soon to be initiated, as well as how to obtain informed consent remotely.
Patient safety is the most important factor to consider when deciding whether to suspend or continue a trial already in progress or to initiate a study during the national health emergency, the FDA said. In the newly added Q&A section, the agency recommends certain assessments sponsors should make in such a decision, including:
- Assessing whether limitations created by the pandemic on protocol implementation pose new safety risks to participants and whether the risk can be practically mitigated by amending study processes and/or procedures;
- Weighing whether the clinical investigator/sub-investigators will be continually available to oversee the trial and assess/handle safety issues that arise;
- Determining if there will be enough trial support staff on hand and adequate equipment and materials available to them;
- Considering whether clinical investigator sites will remain open to participants for required in-person assessments or whether the investigator has the ability to give required in-person assessments at an alternative location(s) or whether the assessments can be done virtually;
- Evaluating the continued availability of trial supplies and continued operations of vendors, especially related to the investigational product and supplies essential to maintaining safety monitoring and other key trial procedures;
- Assessing if IRB, Independent Ethics Committee (IEC) and Data Monitoring Committee staff will continue to operate, and if there will be adequate communication with them to support trial needs;
- Weighing public health measures that may be in place by federal and state authorities for the coronavirus, and if they could impact the trial.
“Given the evolving situation, with likely increasing impacts on investigators, staff and supply chains, sponsors should carefully consider the ability to effectively mitigate risks such that patient safety and trial integrity are assured,” the FDA said.
The agency noted that the risks and benefits of keeping a trial going are likely different than those involved in initiating trials other than ones evaluating COVID-19 treatments and vaccines.
While the agency’s added recommendation to use electronic methods if the technology is available for informed consent is helpful, it doesn’t address all the current difficulties in the consent process, such as obtaining consent from legally authorized representatives (LARs), according to WCG Chief Compliance Officer David Forster.
“One issue that quickly arose is that when a potential COVID-19 research subject lacks the capacity to consent, and the consent of their LAR is required, the LAR is often in quarantine and cannot readily provide a signed consent form,” he said.
The agency advises sponsors to follow certain steps if informed consent cannot be obtained electronically. They should use a healthcare worker to deliver the form to the patient, but if direct communication is unsafe, sponsors can arrange a three-way call or video conference with the patient, an impartial witness and additional participants if requested by the patient, such as next of kin. This should be done using a standard approach that identifies the people on the call, reviews the informed consent with the patient by the investigator, answers any patient questions and confirms various issues, such as the patient’s willingness to participate in the trial.
David Borasky, WCG’s vice president of IRB compliance, said that although IRBs have approved remote consent and data collection for numerous studies, “it’s too soon to tell what the challenges will be when it comes to implementation.”
Right now, it is important to have ongoing dialogue between sponsors, research sites and IRBs, with sponsors considering how they can implement ethically acceptable research that is still scientifically valid and compliant with regulations, he said. Borasky also advised that IRBs be prepared to handle a flood of changes in research spurred by the developing health crisis.
“IRBs should be concerned with managing what is likely an unprecedented influx of changes in research that are necessary to keep research moving forward in a reasonable manner, as well as the review and approval of new research,” he said.
Forster said that the guidance supports increased IRB flexibility during this time — allowing sponsors to bundle amendments and institute changes to deal with apparent immediate hazards or threats to patient safety — but doesn’t explain how sponsors should streamline IRB reporting.
“At this point, I believe most IRBs will be satisfied with receiving notices of protocol deviations or changes in research that are made to eliminate immediate hazards in any format, such as email or letter,” he said. “The IRB’s main concern at this point is to ensure that subject and research staff safety is enhanced as much as possible given the pandemic.”
The Q&A section also expands on how sponsors should manage protocol deviations and amendments made to trials in response to the pandemic. For example, if visits are to be conducted by telephone or video contact rather than at the investigational site as originally specified in a study’s protocol, the agency said it would be acceptable if the sponsor created documentation listing all study visits (study reference number, patient ID and date of visit) that deviated from the protocol.
The agency acknowledged that there will most likely be delays in on-site monitoring of clinical trials during the pandemic and advised sponsors to find alternative ways to maintain trial participant safety and data quality/integrity, such as by enhancing central monitoring, contacting sites by telephone to review study procedures, participant status and study progress, or remotely monitoring individual participants when viable.
In addition, the Q&A section in the guidance touches on home delivery and infusion of investigational products in certain situations, among other topics.
Read the guidance here: https://bit.ly/349rGt9.