FDA regulations provide that sponsors select principal investigators (PIs) qualified by training and experience. The regulations do not, however, provide answers for every possible contingency sponsors face in PI selection or management.
FDA’s Office of Good Clinical Practice responds to questions from the public interpreting FDA’s position, offering advice on how to proceed and pointing out key documents and resources that provide more guidance.
The following examples of questions and OGCP answers regarding PI eligibility are excerpted from the book GCP Questions: FDA Answers.
Principal Investigator Eligibility
Q: We have a PI, principal investigator who has moved from a Pennsylvania clinical research facility to a Missouri facility. His license in Pennsylvania is current and active and he has applied and is waiting for his Missouri license to be issued. May he be used by a Pharma Sponsor to be PI for a clinical trial in Missouri? My understanding is this is left to the sponsors but I wanted to inquire if the FDA would have any issues with this.
A: The regulations are very broad. The regulations require that sponsors choose investigators qualified by training and experience (see 21 CFR 312.53(a)). The regulations also require that investigators commit themselves to personally conduct or supervise the investigation (see 21 CFR 312.53(c)(1)(vi)(c)).
Please see the guidance document, “Frequently Asked Questions – Statement of Investigator:
[“ICH E6 – Good Clinical Practice Consolidated Guidance” states:]
4. Must the investigator be a physician? The regulations do not require that the investigator be a physician. Sponsors are required to select only investigators qualified by training and experience as appropriate experts to investigate the drug (21 CFR 312.53(a)). In the event the clinical investigator is a non-physician, a qualified physician (or dentist, when appropriate) should be listed as a subinvestigator for the trial and should be responsible for all trial-related medical (or dental) decisions.
Training, education, and experience required for sponsor personnel may necessarily, and appropriately, vary depending on the type of product, the indication, the study being conducted, and its associated risk. FDA’s regulations are not explicit as to what constitutes adequate training, education and experience, nor do they outline specific qualifications, including whether such personnel must hold an active medical license. Moreover, sponsors have discretion in determining what qualifications are needed in certain positions based on the general recognition that this would include education, training and experience pertinent to the particular clinical study and its design and execution, as well as familiarity with human subject protection (HSP) regulations, recordkeeping, data integrity, and good clinical practice (GCP) standards and requirements. Whether or not certain sponsor personnel should hold an active medical license depends on the considerations outlined above.
It might be helpful for you to review FDA’s guidance on Investigator Responsibilities - Protecting the Rights, Safety, and Welfare of Study Subjects.
FDA would expect physicians to follow state and local laws regarding medical licensure and medical practice requirements in addition to sponsor requirements.
Backup Principal Investigator
Q: Is there any guidance or regulatory requirement for a clinical site to have a backup for the PI, with same/similar credentials to take over if needed?
A: Thank you for your question. While not a regulatory requirement most clinical study sites do have subinvestigators. The requirement that the sub-CI have the same credentials as the PI would be up to the sponsor and state and local laws governing licensing. The investigator (also referred to as the principal investigator or PI) is responsible for supervising the conduct of the clinical investigation and to protect the rights, safety, and welfare of participants in drug and medical device clinical trials. PI’s commit themselves to personally conduct or supervise the investigation. It is common practice for investigators to delegate certain study-related tasks to employees (including the sub-CI), colleagues, or other third parties, but the investigator remains responsible for providing adequate supervision of those to whom tasks are delegated. Essentially, the PI may delegate tasks on a given study, but they may not delegate their role or responsibilities as PI.
FDA encourages each study site to have their own CI, who signs a 1572, for the conduct of the study at the specific site. Sub-investigators are intended to assist the CI conduct the study at a specific site and not to substitute for the CI. The intention of FDA regulations are for the CI to conduct and/or supervise all aspects of a clinical study for which he/she agrees to conduct, according the investigational plan and applicable regulations, when he/she signs the 1572.
FDA’s definition of investigator is found at 21 CFR 312.3:
“Investigator means an individual who actually conducts a clinical investigation (i.e., under whose immediate direction the drug 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. “Subinvestigator” includes any other individual member of that team.”
FDA has a guidance document for industry titled, “Investigator Responsibilities - Protecting the Rights, Safety, and Welfare of Study Subjects.” This guidance was developed to clarify for investigators and sponsors FDA’s expectations concerning the investigator’s responsibility (1) to supervise a clinical study in which some study tasks are delegated to employees or colleagues of the investigator or other third parties and (2) to protect the rights, safety, and welfare of study subjects.
Clinical trials professionals can ask OGCP their own questions via email to email@example.com.