Healthcare Inspection Human Subjects Protections in One Research Protocol VA Medical Center, Washington, DC

This review, on the use of a medication called varenicline (Chantix®) in a particular VA research study, followed an incident in which a veteran alleged that Chantix® caused him to become aggressive and engage in inappropriate activities. The Food and Drug Administration (FDA) had reported the possibility of an association with changes in mood, behavior, or suicidal thoughts and Chantix® on November 20, 2007. The FDA upgraded this warning to a public health advisory on February 1, 2008. Our review focused on the timeliness of patient notification following warnings from FDA, the adequacy of the informed consent process, and the reporting of adverse events. We found that the facility Pharmacy Service responded appropriately to FDA communications in notifying providers of these newly defined risks. However, the Research Service did not ensure that patients with post-traumatic stress disorder (PTSD) who were also enrolled in a smoking cessation study received adequate and timely notice of these risks. We further found that the facility failed to ensure that patients in this study who had taken Chantix® signed an addendum to the consent form disclosing these risks. We made nationwide recommendations regarding notification of all patients currently taking Chantix®, development of a mechanism to notify have Institutional Review Boards of FDA communications regarding medications involved in research protocols, and appropriate administrative action. We also made facility specific recommendations regarding data validation and auditing of active protocols involving human subjects.