This monthly feature presents a variety of questions from clinical trial professionals with answers from WCG’s expert staff. This month features Yvonne Higgins, quality assurance adviser, compliance, and Kelly Fitzgerald, executive IRB chair and vice president of IRB affairs.

Question: Is it possible that a postmarket patient registry that collects patient experience with the use of a medical device would not need informed consent? The study does not involve collection of specimens. Does the FDA require informed consent for this kind of registry study? If an informed consent is needed, can it be administered online?

Answer: If you are contacting the subjects and asking them questions about their experience, you could do online consent with a waiver of the signature requirement. On the other hand, if you are obtaining the information without actual subject contact, e.g., doing a medical chart review, a waiver of consent may be granted by the IRB.

Under current FDA regulations, a waiver of the requirement for informed consent is narrowly limited to emergency research or certain life-threatening situations. The authority of the IRB to waive informed consent for certain kinds of FDA-regulated minimal-risk research is based on a 2017 guidance from the agency.

In this guidance, the FDA noted that allowing a waiver of informed consent for certain FDA-regulated minimal-risk research would facilitate investigators’ ability to conduct studies “that are important to addressing significant public health needs without compromising the rights, safety or welfare of human subjects.” The FDA subsequently published a proposed rule to align its requirements on informed consent waivers with those of the Common Rule. Under the Common Rule, informed consent may be waived for minimal-risk research that meets certain criteria.

The guidance goes on to say that until the FDA promulgates these regulations and that the agency does not intend to object to an IRB waiving the requirement to obtain informed consent when the IRB finds and documents that the following Common Rule criteria are met:

• The research involves no more than minimal risk;
• The waiver or alteration will not adversely affect the rights and welfare of the subjects;
• The research could not practicably be carried out without the waiver or alteration; and
• Whenever appropriate, the subjects will be provided with additional pertinent information after participation.

This is the FDA’s way of allowing enforcement discretion until the regulations are changed. So, it is possible that an IRB will allow a waiver if your research meets these criteria.

Question: My company is developing a medical device that includes software intended to be used by a clinician to program the therapy for each patient. Before we conduct a clinical trial with patients, we plan to conduct human-factors testing with clinicians to ensure that the software is usable. Does this testing require IRB review and approval?

Answer: Human-factors or usability testing plays an important role in the development of medical devices. The application of human-factors testing to new medical devices helps the developer minimize the risks and improve the usability of the device by testing its use in a real-world setting.

Most human-factors testing for medical devices requires IRB review because the testing is considered by the FDA to be a clinical investigation involving human research subjects. In this case, the clinicians participating in the testing are human subjects as defined by the FDA regulations.

Additionally, these investigations require IRB review for the FDA to consider the data as part of a marketing permit. FDA regulations in 21 CFR 56.103(B) state:

“Except as provided in §§56.104 and 56.105, the Food and Drug Administration may decide not to consider in support of an application for a research or marketing permit any data or information that has been derived from a clinical investigation that has not been approved by, and that was not subject to initial and continuing review by, an IRB meeting the requirements of this part.”

Question: Can a physician submit a single humanitarian use device (HUD) submission to the IRB or does a site need to submit an IRB application for each physician at the site authorized to use the device? If a single IRB application can be used, would changes to the list of authorized physicians at the site require review by the convened IRB?

Answer: Like many IRBs, WCG IRB approves HUDs for clinical use for the facility, not the individual. A single application may be submitted to the IRB. You will need to designate a principal investigator (PI) who is responsible for use of the HUD at that facility. The PI must be a licensed medical doctor. The submission does not need to include a list of all the investigators authorized by the site to use the HUD.

A change in the PI responsible for use at that facility requires review and approval by the IRB. That change would likely be eligible for expedited review. However, some changes in research may require review by the convened IRB; for example, if the PI had a conflict of interest with the device manufacturer or an administrative action related to medical licensure.