5/6/2016

An FDA warning letter issued by Director David Burrow, Pharm.D., J.D. of the U.S. Food and Drug Administration to Benedict S. Liao, M.D. informs Dr. Benedict of the “objectionable conditions observed during” the course of an FDA inspection conducted at his clinical site between August 11 and September 29, 2015. This letter is a great example of the importance of having proper investigator training on research and the study protocol. Many of the findings outlined in the Form FDA 483 can be traced back to the investigator’s brazen disregard for the protocol and lack of understanding of the difference between standard of care and clinical research, as seen in his written response:

“In your October 6, 2015, written response to the Form FDA 483, you indicated that because (b)(4) is nontoxic, you did not see the need to follow the protocol strictly. In addition, you stated that some subjects were noncompliant with the protocol instructions to have laboratory tests and CT scans performed. You also indicated that for subjects who did not have thyroid carcinoma, TSH assessment was unnecessary; and that for all subjects, appropriate cancer markers were used instead [e.g., prostate-specific antigen (PSA) for subjects with prostate cancer]. You also stated that some subjects had CT scans every 4 months instead of every 3 months, and some subjects were followed by vaginal colposcopy in addition to pelvic and rectal ultrasound examinations, rather than by CT scan, PET scan, or both.”

This investigator’s oversights clearly jeopardize subject safety and data integrity. He enrolled participants in the study who did not meet inclusion criteria, did not keep appropriate records, did not maintain proper drug accountability records or followed study procedures and timelines. The investigator not only failed to comply with the protocol but he failed to address the FDA’s findings and put in place appropriate corrective and preventive actions.

This letter provides some good examples of how important it is to train an investigator in research, not only on the protocol but the difference between research and clinical practice. Additionally, it is critical to verify that the investigator comprehends the difference between their autonomy as a patient’s physician and the role of the investigator.

What would have been an adequate investigator response?

Thanks, SAM, Chuck & Laidy (Clinical Pathways, LLC)