FDA Mailbag: Agency Addresses Monitoring, Study Close Out Concerns

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Clinical trial practitioners seeking direct U.S. Food and Drug Administration (FDA) input for specific questions can leverage an online service from the agency’s Office of Good Clinical Practice. While extensive, it is an often-overlooked and cumbersome data repository. In this occasional series, ACRP wades through the posted questions and answers and provides highlights from some of the most interesting and important interactions between industry and regulators. Answers are generally provided by Doreen M. Kezer, MSN, Senior Health Policy Analyst, Office of Good Clinical Practice, Office of the Commissioner, though she often calls in specific FDA regulatory subject matter experts for additional analysis. 

Q: I wonder if there is a guidance document for PI [principal investigator] participation and oversight in an observational study. I am working on a monitoring plan. We will have a combination of remote visits as well as onsite visits. Would [the] PI be expected to take part in every visit, or only if there is a significant issue to discuss with the investigator? Or perhaps there is a recommended frequency in how often an investigator takes part in the monitoring.

Excerpts from Kezer’s response: Monitoring visits are done periodically, the exact timing and number depend on the specifics of the study in question, and are a check on the sites with regard to compliance with the study protocol, protection of study subjects, and integrity of the data collected.

There is no requirement that the PI be at every monitoring visit. However, the results of the monitoring should be conveyed to the PI and study staff, as they are ultimately responsible for the study data and integrity.

Q: I am searching for some information on when it is acceptable to conduct a close out visit for a clinical investigator once all subject visits are completed. I have read various positions: some say when the data [are] cleaned and the database is frozen, others say once all subjects have completed study activities. I am aware some [institutional review boards (IRBs)] have specific requirements as well, which makes it easy to determine, but when an IRB leaves it up to the sponsor is when we have the question of when is it most appropriate.

Excerpts from Kezer’s response: Some sponsors/contract research organizations (CROs) have standard operating procedures (SOPs) that require a site to maintain IRB oversight throughout the data query process, and do not perform a close out visit until all data queries have been completed and the database is locked.

You may also find that an investigator site, an institution where the site is located, and the IRB itself have an SOP about the timing of close out of IRB oversight, which must be followed by an investigator to be in compliance.

It is important for the investigator to discuss the timing of these activities with the sponsor/CRO, institution, and IRB to ensure an understanding of any responsibilities and requirements. The investigator must ensure that any requirements to maintain IRB oversight per the regulations are met, and that any pertinent SOPs are followed.

Send questions to gcp.questions@fda.hhs.gov

Author: Michael Causey