Barbara Wright, FDA Consumer Safety Officer and Bioresearch Monitoring Specialist, addressed a packed room at the latest Alabama Society of Clinical Research Associates chapter meeting, held at UAB on April 26^th. The talk helped attendees understand the purpose and scope of an FDA inspection of clinical investigators; the obligation principal investigators have to ensure regulations on Good Clinical Practice and Human Subject Protections are met; how to avoid the most common deficiencies cited by FDA inspections; and how to prepare for possible enforcement actions.

Concerns about data integrity and human subject protection are the leading reasons why FDA inspects a research project. Wright underscored the link between poor recordkeeping, failure to follow an investigational plan, and even fraud and the inability to conduct statistical analyses of safety and effectiveness profiles. “We trust but verify,” she said. 

During an investigation of a clinical investigator, the FDA looks at facilities and equipment; subject case histories; communications with sponsors and the IRB; test article accountability; and delegation of authority/staff qualifications. Alabama, for instance, requires licenses for staff to administer certain tests, and this falls within the scope of an FDA review. The FDA also checks clinical investigators are following IRB requirements regarding number of subjects enrolled and submission of progress reports.

Among the reasons Wright cited for why a particular clinical investigator’s site was selected for an FDA inspection, she listed the following:

• The site’s application has been filed and an approval decision is pending
• The site is producing pivotal data, outliers, or has high enrollment
• A complaint has been filed against the site
• There is a prior inspection history for the site
• The site comes up via an FDA sampling survey 

Wright urged the audience “not to panic if the FDA calls” and “be forthright in communicating” about the impending inspection. “Identify commitments that can’t easily be changed, work with the agent to find a date, mark your calendar, gather your records, and allocate a work space for the agent,” she advised. She then walked the audience through the steps of an investigation, from the initial showing of the FDA badge to the closing meeting, a process that takes 3-5 days on average. 

“Agents need access to all data,” Wright emphasized, including the subjects’ clinical files for six months prior to enrolling in the study. Other needed records include the protocol with any amendments, the investigator’s recruiting materials and cv, test article accountability, informed consent forms, a statement from the investigator (FDA-1572), financial disclosure forms, and case reports. Clinical investigators can request daily interviews, if they wish, to discuss any issues the agent found in checking data points against source documents. She advised investigators to “retain records for at least two years after approval or termination of the study.”

The last half of the talk examined more closely the commitments of a clinical investigator, including the appropriate delegation of study related tasks. Wright noted that every site in a multisite study must have a clinical investigator to take responsibility for each site. “Supervision of a site cannot be delegated to a sub-investigator,” she said. 

Investigators must also ensure the adequate training of all staff participating in the conduct of the study. Adequate training included formal training in Good Clinical Practice as well as ensuring staff are familiar with the purpose and protocol of the study; are aware of regulatory requirements; are competent to perform delegated tasks; and receive clear communication of any pertinent changes during the trial. Wright also reviewed the investigator’s reporting responsibilities, which are “defined in plain language.” 

Wright reviewed the most common deficiencies: failure to follow the investigational plan (“lack of compliance with protocol”); failure to prepare or maintain adequate case histories; inadequate disposition records; improper or poorly documented informed consent; and failure to report unanticipated problems that pose a risk to subjects to the IRB. The enforcement actions ranged from a warning letter to criminal prosecution.

“We expect a lot from our clinical investigators,” she said in closing. “These are human lives, and the responsibilities are defined in plain language—the ultimate purpose of an FDA inspection is to ensure a clinical investigator is doing everything required to protect the rights, safety and welfare of study subjects.”

The FDA guidance document for clinical investigators can be found here. CCTS offers numerous regulatory supports to clinical investigators, including GCP training, reporting, and assistance with IND and other FDA forms, via our Clinical Research Support Program.