In July 2008, FDA released a draft guidance to answer frequent questions about Form FDA-1572, also called the Statement of Investigator form. A Food and Drug Administration Guidance is non-binding, but it does serve as useful information on how to interpret the agency's regulations. Keep in mind that this is only a draft; with the recent change in administration this draft may never be released as final or it may be significantly modified.
While we wait, there are some interesting points in this draft guidance. Little if any of this is new, but it is the first time this information has appeared in a single place:
- Form 1572 must be signed before an investigator may begin participation in a clinical study conducted under the IND regulations. The investigator should sign this form only AFTER having been given enough information to be informed about the study and to understand the regulatory commitments made via the form. This typically means the investigator must have received, read, and understood the investigator brochure and protocol, and be familiar with the regulations before signing a 1572. For sponsors and sites, this means the FDA-1572 should be signed late in the process of initiating a site rather than as part of the site screening process, i.e., at or right before site initiation visit.
- The investigator has to be qualified by training and experience as an appropriate expert to investigate the drug, but does not necessarily have to be a physician. However, a qualified physician should be listed as a sub-investigator and be responsible for all trial-related medical decisions. FDA has allowed non-physician investigators previously but the more recent ICH E6 regulations (Section 4.3.1) codified the explicit requirement fora qualified physician to be on the site team.
- Sponsors do not need to send the FDA-1572 to the FDA, but the FDA does accept it as an efficient means of submitting required information about the clinical sites so most sponsors will continue to do so.
- The FDA-1572 does not need to be updated and re-signed by the investigator when information changes (adding sub-investigators, changing labs, IRB address change, etc.) but the changes should be documented in the site’s records and the sponsor must be notified. But, again, most sponsors use the FDA-1572 as a means to relay this information to the FDA and will therefore likely request a new version. Likewise, there is no need to sign a new FDA-1572 when the OMB expiration date in the top left corner is reached.
- An FDA-1572 is required for drug or biologic studies conducted under an IND, whether in the U.S. or abroad. Medical device trials require only a signed agreement from each investigator that contains information similar to that requested in the 1572. Sponsors may conduct non-U.S. drug or biologic studies that are not under a U.S. IND (and thus would not require Form-1572), but there are restrictions on the use of such data in a U.S. regulatory application.
- As specified in Form-1572, IRB review and approval is required before a study can be initiated under an IND. Foreign studies will require a specific waiver of this requirement from the FDA, and instead they must be reviewed by an Independent Ethics Committee (IEC) that complies with ICH E6. FDA suggests the waiver should be attached to the FDA Form 1572 and be retained both at the site and in the sponsor’s files.
- It is acceptable to print the FDA-1572 on separate pages (as opposed to a double-sided single page) but, as the signature is only on the second page, the two pages should be stapled together. The printed form may be completed by hand (as opposed to requiring it be typewritten).
- There is no such thing as a co-investigator under FDA regulations; Form FDA-1572 must be signed by an individual. However, it is acceptable to have more than one investigator at a particular site if both wish to fulfill ALL of the regulatory obligations.
- CVs do not need to be updated during a study and they do not need to be signed and dated! If this remains in the final guidance, it will certainly be welcome news to many monitors and coordinators! Of course, it may take a while for sponsors to revise their SOPs and for monitors and coordinators to be re-educated. This is like the black-pen-only myth; too many Clinical Research Associates (CRA) and Study Coordinators (SC) will swear this is an FDA mandate.
- There has been confusion and disagreement for years over who should be listed as a sub-investigator on the 1572. The FDA is finally providing clarification, by stating it should include in general any individual who is directly involved in the treatment or evaluation or research subjects or who make a direct and significant contribution to the data. Thus, nurses, residents, pharmacists, fellows and office staff who provide only ancillary or intermittent care probably don’t need to be listed. In contrast, a specific pharmacist that is compounding the drug or monitoring compliance probably SHOULD be listed. Likewise, a coordinator that is only transcribing data and maintaining regulatory files does not need to be listed, but a coordinator that is collecting and evaluating study data (say, patient questionnaires, BP&P readings, etc.) SHOULD be listed.
- Financial Disclosure is required of everyone listed on the FDA-1572, specifically including the sub-investigators, pharmacists, coordinators, etc. In this draft, the FDA is less specific about CVs for sub-investigators, but it appears that sub-investigators do not need to provide any statement of qualifications.