Monitoring is the act of overseeing the progress of a clinical trial, and of ensuring that it is conducted, recorded, and reported in accordance with the protocol, Standard Operating Procedures (SOPs), Good Clinical Practice (GCPs), and the applicable regulatory requirement(s). Typically, academic sites are familiar with monitors assigned by a sponsor or a contract research organization (CRO). However, GCP requires that investigator-initiated trials enrolling human subjects also provide a monitoring plan to assure that the data collected throughout the study are accurate. In addition, the Code of Federal Regulations requires monitoring under 21 CFR 312 subpart D (for INDs) and 21 CFR 812 subpart C (for IDEs). Sponsors (including Sponsor-Investigators) of clinical investigations conducted under an IND or IDE are required to provide oversight to ensure adequate protection of the rights, welfare, and safety of human subjects and the quality and integrity of the resulting data submitted to FDA. This oversight is maintained through the regular review of the source data, case report forms, informed consents, regulatory documents, and any other essential documents by a monitor. During a monitoring visit, a monitor reviews individual subject records and source documents, regulatory binder(s), and other essential documents and compares the information with data recorded on the case report forms (CRF) or entered in the electronic case report form (eCRF). The monitor is obligated to ensure the following:
- Subjects meet eligibility requirements
- The rights and safety of human subjects are protected
- Informed consent has been obtained and documented appropriately
- Conduct of trial is in compliance with protocol, good clinical practice (GCP), and applicable regulatory requirements Subject was followed and treated according to the protocol
- Reported trial data are accurate, complete, and 100% verifiable from source documents; all pertinent information in the subject records must be accurately recorded on the CRF
- The CRF is complete, legible, and consistent throughout visits
Typically, in an industry-sponsored study, the pharmaceutical company will provide the monitor for the study. However, in the case of a study conducted by a Sponsor-Investigator, the Investigator takes on the responsibility of ensuring that the study is being monitored. For industry-sponsored studies a monitoring plan will often be used to guide the frequency of monitoring visits to investigative sites whereas in an Investigator-initiated study the Investigator and/or study staff should develop a monitoring plan. The frequency of visits is affected by the complexity of the study and the rate of enrollment. Monitoring plans can be updated during the course of the study if, for example, enrollment is faster than expected. When a monitor comes to a clinical site to conduct a monitoring visit, he/she will need access to all source documents.