WASHINGTON, D.C.—The principal investigator (PI) of a clinical trial needs to be heavily involved with every facet of a trial in order to ensure the proper quality control, according to a Feb. 25 presentation at the Cardiovascular Research Technologies (CRT) annual meeting.
“Good research results come only from quality work,” said Christopher D. Metzger, MD, of Wellmont CVA Heart Institute in Kingsport, Tenn. “It’s easy for quality at your site to be less than you assume without quality checks—both internal and external. Your site’s reputation in a small research environment and potential future invitations for additional trials depend on quality work.”
Also, FDA audits may come with little warning. “Our last audit came with two days of advanced warning. You can’t fix everything in two days,” he said.
As a result, PIs need to “sit up and take notice, because it’s your behind that’s on the line,” said Metzger, who advised PIs to read what they sign in their contracts. The PI is ultimately responsible for the conduct of all aspects of the study, regardless of who makes the mistake, he added. “You can’t blame the coordinator for doing crummy work, as it’s ultimately you who will be blamed.”
Therefore, it is essential for PIs to take personal responsibility for the conduct of the study. To accomplish this goal, Metzger recommended that PIs educate, train and monitor the performance of the sub-investigators, coordinators and regulatory staff. Also, meet with the study monitor each and every visit.
He listed ways to avoid mistakes:
- Make sure all investigators and research coordinators know protocol AND follow it.
- Create enrollment inclusion/exclusion lists and worksheets for all studies, along with the information, that will be needed for data entry.
- Have two team members confirm inclusion/exclusion criteria for each participant and do the same for informed consent.
- Reconfirm consent (especially in urgent situations, like acute MI, where things happen quickly).
- Follow research patients each day in the hospital until discharge, when an appointment card is given with the date, time and directions.
- Have protocol available and a coordinator present for all cath lab procedures.
In order to avoid and discover deviations as they happen, the PI, research manager and lead research coordinator for a study should meet with the study monitor often. In addition, hold regular research meetings (monthly) with investigators and the entire research team, and have a representative from the internal review board at these meetings. “This keeps the IRB [institutional review board] engaged and aware of the progress,” Metzger said. “Treat every study as if it will undergo an FDA audit.”
Also, “treat the study monitors like they are friends; they are your allies. They provide quality and help prepare for FDA, so do not be defensive with them.” Therefore, have the lead research coordinator prepare for each of the study monitor’s visits ahead of time. The PI should also meet personally with him or her. After the visit, review the letter and respond in writing. Also, the internal team should generate a to-do list based on the visit and letter.
“That letter is specifically detailing any problems with your site, and it will ultimately be in your regulatory document,” he said. “We take it so far as to check off and initial each item to make sure some improvements occur.”
Finally, Metzger recommended that all research members undergo good clinical practice training, including physicians. “The more training and interaction the better, which includes research meetings, good clinical practice meetings and investigator/research coordinator meetings," he said. "Quality research depends on quality work and some form of quality control at your site, and in order for this to occur PIs need to be hands-on leaders.”