Ask the Experts: Rescreening and Monitoring in Medical Device Trials
The FDA’s Office of Good Clinical Practice responds to inquiries on a variety of trial-related subjects, providing answers on the agency’s official regulations as well as best practices. The following is a selection of questions and answers excerpted from the CenterWatch publication, GCP Questions, FDA Answers.
Question: We are intending to broaden the inclusion criteria in one of our medical device trials. Could those participants who previously did not meet the inclusion criteria and therefore were deemed ineligible for the study be rescreened to see whether they would now be eligible for participation? Due to the modified inclusion/exclusion criteria, a new informed consent form (ICF) will be used, for which approval will be sought from the IRB together with the modified protocol. Only once the modified ICF and protocol have been approved will the new inclusion/exclusion criteria be applied.
Answer: Rescreening is influenced by specifics of the protocol, the conditions which are being ruled in/out, etc. Therefore, this response needs to be understood as a qualified response that is subject to modification based upon the facts of the case at hand.
Quite often, protocols do not address screening of potential subjects and even more often do not address rescreening of potential subjects. Depending on many diverse factors, including the conditions that are being evaluated, the tests that are being used for this evaluation, the reasons why initial screening failed and the nature of the study, rescreening may or may not be medically/scientifically appropriate.
It is conceivable, however, that rescreening may make good sense if, for example, the reason for original exclusion from the trial was based upon a self-limited predictably resolving condition or based upon a laboratory test with a high false-positive rate that upon appropriate follow-up proved to be in error.
As you state, you will involve your IRB with new ICF and modified protocol. This information should be put to the IRB that reviewed the study and approved before implementation. The IRB should have approved any and all consents used during the study, including those used for the subject screening process.
Question: In a trial of an implantable device in which field engineers go out and assist the surgical team and activation team on how to operate the device and have the site follow the protocol, can those engineers perform some monitoring duties, such as regulatory document reconciliation, device accountability, etc., without being trained as monitors? They are GCP-trained but are not listed in the monitoring plan as of now, given they are field clinical engineers.
Answer: You would want to avoid the appearance of a conflict of interest. A conflict of interest in a clinical trial related to a clinical investigator may be considered a conflict between the private interests and official responsibilities of the clinical investigator and the objective design, conduct and reporting of the clinical trial. A risk of such interests is that they may lead to intentional or unintentional bias or errors in the clinical trial and may compromise the well-being of the human research subjects.
HHS’ guidance document on financial conflicts of interest raises points to consider in determining whether specific financial interests in research affect the rights and welfare of human subjects and, if so, what actions could be considered to protect those subjects.
You should check your local and national laws and policies to see if there are any requirements related to conflict of interest and clinical trials. The U.S. has regulations related to federally funded studies and ensuring objectivity at 42 CFR Part 50 and 45 CFR Part 94.
To address monitors directly, sponsors are required by FDA regulation (21 CFR 312.50) to ensure proper monitoring of the investigation. It would follow then that monitors will generally be in the employ, either directly or indirectly (e.g., under contract), of the sponsor. This arrangement is anticipated and fully consistent with FDA regulations. FDA inspects sponsors and monitors to ensure that they are meeting regulatory requirements with respect to human subject protection and data quality/integrity.
In any operation, it is prudent to look at sources of real or potential conflict of interest, approach these with transparency and manage them in a way to minimize negative impacts.
Read the HHS guidance here: https://bit.ly/3BKspmO.
For more information on GCP Questions, FDA Answers, click here: https://bit.ly/3QNBOhF.