Ask the Experts: Listing Trial Staff and Others on the Statement of Investigator
The FDA’s Good Clinical Practice Program (GCPP) fields dozens of questions each year related to completing and signing the Form FDA 1572 — Statement of Investigator. The following are some of the questions GCPP has received recently with answers from the program’s senior analysts.
Question: We see inconsistency from industry sponsors on whether clinical research coordinators should be listed in Section 6 of Form 1572. What is the FDA’s current thinking on this?
Answer: Many people do not realize that one of the main purposes of the 1572 is to provide the sponsor with information about the clinical site and investigator qualifications that will enable the sponsor to establish and document that the investigator and site are qualified to conduct the study.
Section 6 asks for the “Names of the sub-investigators (e.g., research fellows, residents, associates) who will be assisting the investigator in the conduct of the investigation(s).” “Sub-investigator” is indirectly defined in the drug and biologics regulations (21 CFR 312.3(b):
“Investigator means an individual(s) who actually conduct(s) a clinical investigation (i.e., under whose immediate direction the drug or biologic is administered or dispensed to a subject). In the event an investigation is conducted by a team of individuals, the investigator is the responsible leader of the team. ‘Sub-investigator’ includes any other individual member of that team.”
Again, the purpose of Section 6 is to capture information about those individuals who will play a key role in the collection and interpretation of data as well as in the conduct of the study itself. Hospital staff, including nurses, residents or fellows, and office staff who provide ancillary or intermittent care but who do not make direct and significant contribution to the data are generally not meant to be listed. A general statement regarding the participation of staff residents on rotation can be included in Section 6.
Whether to list an individual depends on the level of responsibility the individual has in the conduct of the study and in the evaluation of information obtained during the study. If the individual in question has significant study-related duties (e.g., explaining the study to subjects, qualifying the study subjects), then the person should be listed on the 1572. If the individual merely ensures and observes that, for example, a consent form is signed by the subject after the principal investigator has explained the study and qualified the subject, then this person would not have to be listed.
Note: If a research coordinator is performing critical study functions and collecting and evaluating some study data, the coordinator should be listed on the 1572. If the research coordinator is only transcribing data and maintaining study files, the coordinator does not need to be listed.
Question: The sponsor of our phase 1 trial has added to the protocol an assessment performed by a specialist to investigate a specific adverse event that is occurring. The sponsor has contracted with a specialist from one of the trial’s sites to be part of its medical monitor team that evaluates the events reported by the sites and provides guidance to them (e.g., discussion about available treatments and mechanism of action of the study drug that causes the toxicity).
As this specialist has continued to see the active patients at one of the sites, the CRO asked the site to add this specialist to the site team and collect the proper documentation (i.e., financial disclosure form, updated 1572 form and all site logs). However, the site considers the specialist an ancillary physician to the trial (the specialist is not even part of the research institution responsible for the trial) and believes it would not need to add her/him to the site team list and update/collect any documentation. This specialist has a financial interest in the research as the sponsor has paid for his/her services.
Is the site correct or should it add the specialist to the Form 1572?
Answer: From the limited information in your email, it appears the specialist should be listed on the Form 1572, especially if this person is evaluating the toxicity as an adverse event. If this person is listed on the 1572, the other forms should follow.
Please note that a site delegation log is not required by FDA regulations; however, it is recommended by the ICH E6(R2) — Good Clinical Practice guideline, although the guidance does not provide details as to who should be listed. The FDA’s guidance document on the supervisory responsibilities of clinical investigators speaks to the need for delegation of trial tasks only to qualified personnel; the agency therefore considers it important to document what trial task was delegated to whom.
As to who should be included on the delegation log — it would be anyone who has an essential role in the conduct of the trial. For example, if blood draws are essential to either the timing, dosage or follow-up of participants, the identity of the lab tech assigned to the trial may also be important to capture.
Question: We have a protocol that requires audiology and neurological tests. These tests will be performed by external facilities that will be listed in Section 4 of the Form 1572. These tests are related to the safety endpoints of the study, one of which is primary, but they are routine tests for these departments and are not trial-specific.
Should staff of an external facility — such as an audiologist or neurologist — who perform these tests be designated as sub-investigators and listed in Section 6?
Answer: As to whether you have to list the names of the audiologist(s) or neurologist(s) as sub-investigator(s) in Section 6, this is a sponsor decision. In general, if the tests being performed at the audiologist and neurologist offices are standard routine tests and there may be a few different personnel who may perform the tests, you could consider not listing all such names in Section 6 but perhaps choose to list them in the trial records instead. However, the decision about whether to list a specific audiologist(s) and/or neurologist(s) in Section 6 is a matter of judgment that depends on the contribution that the individual makes to the trial. Discussing your question with the appropriate staff at your sponsor company should help you to decide the best path forward.