Ask the Experts: Monitoring
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 GCP Questions, FDA Answers, a book from CenterWatch, a WCG company.
Question: In order to meet our ICH GCP responsibilities, our strategy is to use virtual monitoring to supplement on-site visits. We are working with sites who have strong remote access capabilities and options for virtual assessment of facilities and equipment who would like to use virtual monitoring solely with no on-site visits available. Is it acceptable for sites to determine that there should be no on-site visits for their clinical trials?
Answer: FDA regulations and guidance documents regarding monitoring of clinical trials are general to provide sponsors and clinical investigators the flexibility needed to develop appropriate procedures and practices for specific studies. However, the regulations and guidance documents make clear that it is the sponsor’s responsibility to ensure proper monitoring.
For example, 21 CFR 312.50 states that:
Sponsors are responsible for selecting qualified investigators, providing them with the information they need to conduct an investigation properly, ensuring proper monitoring of the investigation(s), ensuring that the investigation(s) is conducted in accordance with the general investigational plan and protocols contained in the IND, maintaining an effective IND with respect to the investigations, and ensuring that FDA and all participating investigators are promptly informed of significant new adverse effects or risks with respect to the drug.
Additionally, the ICH E6(R2) GCP guidance states in section 5.18.3 (“Extent and Nature of Monitoring”) that monitoring is the sponsor’s responsibility:
The sponsor should ensure that the trials are adequately monitored. The sponsor should determine the appropriate extent and nature of monitoring. The determination of the extent and nature of monitoring should be based on considerations such as the objective, purpose, design, complexity, blinding, size, and endpoints of the trial. In general, there is a need for on-site monitoring before, during and after the trial; however, in exceptional circumstances, the sponsor may determine that central monitoring, in conjunction with procedures such as investigators’ training and meetings and extensive written guidance, can assure appropriate conduct of the trial in accordance with GCP. Statistically controlled sampling may be an acceptable method for selecting the data to be verified.
Question: Do you have any recommendations regarding oversight of payments to subjects? [We have] reviewed the regulations, guidance documents, compliance programs and GCP email replies but did not find any reference regarding oversight of actual payments.
Answer: The FDA regulations don’t mention subject payment specifically. As noted in the ICH GCP E6(R2) guidance, the monitor, in accordance with the sponsor’s requirements, should ensure that the trial is conducted and documented properly by verifying that the investigator and the investigator’s trial staff are performing the specified trial functions in accordance with the protocol and any other written agreement between the sponsor and the investigator/institution, and have not delegated these functions to unauthorized individuals. The monitor is also responsible for determining whether the investigator is maintaining the essential documents for the conduct of a clinical trial, which includes information about subject compensation (see section 8 of the ICH GCP E6(R2) guidance).
Section 5.19 of the ICH GCP E6(R2) guidance addresses sponsor audits as part of implementing quality assurance. The sponsor should ensure that the auditing of clinical trials/systems is conducted in accordance with the sponsor’s written procedures on what to audit, how to audit, the frequency of audits, and the form and content of audit reports.
Different institutions have varying mechanisms for tracking and documenting information on payment to subjects for trial participation, and there are various ways to confirm that payments are occurring in accordance with the payment plan agreed to by the sponsor, investigator and IRB. I’m not sure what type of specific records you were requesting of the institution. Depending on the records requested and how they are stored at the institution, perhaps the institution was unaccustomed to, or hesitant to share, financial records if such records included other types of financial information that is institution-specific.
Given the variation in how subject payment information may be tracked and managed across institutions, you should discuss expectations of access to information to confirm that subjects are being paid in accordance with the IRB-approved payment schedule with the sponsor(s) you are working with and the institution(s) you are auditing. It doesn’t sound like the institution denied you access to the information you were seeking but may need more information to understand why you are asking for such information.
As noted in section 5.9 of the ICH GCP E6(R2) guidance, the financial aspects of the trial should be documented in an agreement between the sponsor and the investigator/institution. If our Office of Clinical Policy receives questions about subject payment, these are usually handled by referring a subject to the IRB to assist them or referring an IRB to the sponsor to discuss and resolve together.