FDA officials responsible for the agency's good clinical practices (GCP) program emphasize that few, if any, GCP-related areas
generate as much industry uncertainty as the Form FDA 1572—Statement of Investigator. Through this seemingly mundane form,
a clinical investigator must provide a study sponsor with information on the education, training, and experience that qualifies
him/her to conduct a particular study as well as his/her commitment to conduct the proposed study in accordance with the protocol
and federal regulations.
Over the years, several factors have contributed to industry uncertainty regarding the 1572 and its use, among them the fact
that, today, the 1572 has both mandatory and practical, nonmandatory uses. Complicating matters has been lingering uncertainty
regarding the 1572's use at non-U.S. study sites, and questions about what U.S. sponsors can and should require of foreign-based
investigators who may be reluctant to sign the 1572, which is often viewed as a formal contract.
In developing the May 2004 second edition of our new text, Good Clinical Practice: A Question & Answer Reference Guide we invested considerable time and effort to explore and resolve many of the long-standing and troublesome questions regarding
the 1572. The series of questions below, which is excerpted directly from the text, addresses several of these questions.
Q: Because it is used for a few different purposes, there is uncertainty in some cases about the Form FDA 1572—Statement of Investigator,
in particular when its use and submission is mandatory. What is the 1572's regulatory purpose, and in what ways is the form
used in practice?
A: The 1572 itself declares that, "No investigator may participate in an investigation until he/she provides the sponsor with
a completed, signed Statement of Investigator, Form FDA 1572." And FDA regulations at 21 CFR 312.53(c)(1) add that, "Before
permitting an investigator to begin participation in an investigation, the sponsor shall obtain the following: (1) A signed
investigator statement (Form FDA—1572)...." Therefore, the Form 1572 is a document that an investigator must submit to the study sponsor.
Through the 1572 Form and the attachments typically sent with it, an investigator provides a sponsor with, among other things,
information on his or her education, training, and experience (CV or other statement of qualifications) that qualifies him
or her to undertake the clinical investigation, information on the relevant facility, IRB, and subinvestigators, protocol
information, and the investigator's commitment to conduct the study in accordance with the protocol and FDA regulations.
So where is there uncertainty about the 1572's use? In many cases, companies submit the completed and signed 1572s to the
FDA in the original IND and subsequently when new investigators are added to a study. IND applicants and holders do this as
a convenient way of fulfilling an FDA requirement at 21 CFR 312.23(a) (6)(b), which calls for a clinical trial protocol submitted
in an IND to provide "the name and address and a statement of the qualifications (CV or other statement of qualifications)
of each investigator."
Because this has become such a common practice, some incorrectly assume that this is an FDA requirement. In fact, the IND
form (Form FDA 1571) explicitly gives sponsors the option of fulfilling 312.23(a)(6)(iii)(b) by submitting either "Investigator
data [21 CFR 312.23(a) (6)(iii)(b)] or completed Form(s) FDA 1572."
In informal correspondence on this issue, the FDA stated that, "People seem to obsess over the 1572. We wonder how many people
realize that the 1572 is not even required to be submitted to the FDA. In theory, we could never even see it. In practice,
however, the 1572 is typically submitted to the IND by the sponsor as an efficient means to provide information required under
21 CFR 312.23(a)(6) (iii)(b)."
Q: Since it is such common practice for companies to provide the 1572 and accompanying CV and other information to the FDA in
the original IND and subsequently when a new investigator is added to the study, has that become an agency expectation or
even a de facto requirement?
A: None of several Center for Drug Evaluation and Research review divisions contacted recently claimed that the submission of
the 1572 was a divisional expectation. And most did not express even a preference in terms of the format (i.e., a 1572 or
alternative format) in which IND applicants should provide investigator qualification-related information.
It is important to note, however, that there are differences between some CDER review divisions, and that applicants should
ask about a division's policy in this area. Under a 1992 policy, for example, the Division of Oncology Drug Products asks
that sponsors of commercial INDs (i.e., those submitted by industry) not submit either the 1572 or the investigator's CV for
new investigators because such submissions are "inefficient and cumbersome." Rather, in its "no CV letter," the division asks
all IND holders to submit summary information, including "the minimum qualifications of investigators selected for the protocol...and
a statement that each investigator meets or exceeds those qualifications" (see sidebar, "Division of Oncology Drug Products'
'No CV Letter'").
Division of Oncology Drug Products' "No CV Letter"
In the letter, the Division of Oncology Drug Products emphasizes to applicants that, "You are, of course, also required to
maintain the information provided to you by the investigator on the form FDA 1572, which is to be retained by you. In addition,
you must maintain in your files a current C.V. of each investigator which must be updated as investigators are added. Only
upon request of the Agency, will you be required to submit the current C.V. for a specific investigator."