Principal Investigator (PI)

Key facts

FDA term

Investigator, defined in 21 CFR 312.3

Duties in regulation

21 CFR 312.60 to 312.69

Commitment form

Form FDA 1572, Statement of Investigator

Financial disclosure

21 CFR Part 54

What is a principal investigator?

FDA regulations define an investigator as an individual under whose immediate direction the drug is administered or dispensed to a subject, and, when a team conducts the study, as the responsible leader of that team. In practice that leader is called the principal investigator. Other team members who perform study tasks are sub-investigators.

The term is used at two levels. A site PI runs the study at one location, while a lead or overall PI, often a senior academic specialist, may guide the design and publication of a multisite trial. A sponsor-investigator both initiates and conducts a study and carries the obligations of both roles.

What a principal investigator is responsible for

Under FDA regulations and the commitments signed on Form FDA 1572, the investigator must:

• Conduct the study according to the signed investigator statement, the protocol and applicable regulations.
• Personally conduct or supervise the investigation and make sure staff understand their obligations.
• Obtain informed consent and ensure Institutional Review Board (IRB) review and approval.
• Keep accurate case histories and drug accountability records, and retain them for the required period.
• Report adverse events to the sponsor and provide financial disclosure information required under 21 CFR Part 54.

Why principal investigators matter

Choosing the PI is often the most important decision in site selection. An experienced investigator with access to the right patients drives enrollment speed and data quality, while sites that enroll few or no patients add cost without adding data.

For commercial teams, PIs are often influential specialists whose trial experience signals early familiarity with new therapies. Their names appear in ClinicalTrials.gov records, in publications and in research payment records under the CMS Open Payments program, and can often be matched to National Provider Identifier (NPI) records.

FDA also publishes information on clinical investigators who have been disqualified or restricted, which diligence teams check before engaging a site.