The buck stops at the PI

by Wendy Tate, PSP, CIP

Just this year, a mere four months since the start of the year, the United States Food and Drug Administration (FDA) has issued seven warning letters to clinical investigators. Four of these letters cite investigators for failure to personally supervise their human subjects research. This is a violation of FDA regulation 21 CFR 312.60, which specifically states that:

“An investigator is responsible for ensuring that an investigation is conducted according to the signed investigator statement, the investigational plan, and applicable regulations; for protecting the rights, safety, and welfare of subjects under the investigator’s care; and for the control of drugs under investigation. An investigator shall, in accordance with the provisions of part 50 of this chapter, obtain the informed consent of each human subject to whom the drug is administered, except as provided in 50.23 or 50.24 of this chapter. Additional specific responsibilities of clinical investigators are set forth in this part and in parts 50 and 56 of this chapter.”

The FDA outlines their expectations in two guidance documents, The Use of Clinical Holds Following Clinical Investigator Misconduct and FDA Inspections of Clinical Investigators, and requires documentation of the responsible party on FDA Form 1572. The Office for Human Research Protections (OHRP) shares the FDA’s perspective and discusses the investigator’s ultimate responsibility in its Frequently Asked Questions.

Delegation of tasks is not investigator negligence; in fact, it is almost always required to complete a clinical trial properly. It is not the intent of the FDA to have a busy medical doctor personally execute all aspects of a study alone. When done properly, delegation can significantly improve subject safety by assigning qualified people to complete complex tasks.

However, the investigator must be aware of what is being delegated, to whom, and how the designee(s) are completing the assigned tasks. The people delegated to execute the tasks must be qualified to do so, with appropriate credentials and experience. Designees must receive appropriate, thorough training, and have expectations set out that must be met. Ongoing oversight by the investigator must be a priority throughout the life of the project through regular communication and meetings.

Resources are available to help investigators. Some institutions have clinical research offices that provide support. Investigators must be cautious when using such a service, though, so that they do not lose sight of their responsibilities. Many institutions have quality assurance/quality improvement (QA/QI) programs designed to give investigators tools to run their research effectively while ensuring compliance. Such programs also perform site visits to evaluate and educate investigators on FDA expectations. Institutions that do not have a QA/QI program may instead offer these services through their IRB office.

Being an investigator is a complex and high-stakes line of work. It is about adequately protecting human subjects by ensuring appropriate conduct of a study. The FDA Form 1572 summarizes the requirements an investigator promises to uphold when leading a clinical trial. The FDA will hold investigators responsible to every one of these requirements. The duties are broad and the penalties can be severe. It is important for compliance programs to reach out to investigators before the FDA comes auditing, and for investigators to seek out help and appropriately delegate duties to ensure compliance with all of the regulations.