April 8, 2016 - University of Virginia

[This letter has been revised to include the dates of correspondence from OHRP and the institution’s report and replaces the previously issued determination letter dated March 21, 2016.]
David J. Hudson, Ph.D.
Associate Vice President for Research
University of Virginia
P.O. Box 400391
Charlottesville, VA 22904-4301

Human Research Protections under Federalwide Assurance FWA-6183

Research Project: Lab Trials to Develop Medications for Cocaine Dependence –Study 1 (BAJ002)
Principal Investigator: Dr. Bankole Johnson
HHS Protocol Number: R01DA012191 (Topiramate to Reduce Cocaine Dependence)

Dear Dr. Hudson:
Thank you for your report dated December 19, 2013 submitted in response to our November 5, 2013 request that the University of Virginia (UVA) respond to allegations of noncompliance with Department of Health and Human Services (HHS) regulations for the protection of human research subjects (45 CFR part 46) in the conduct of the study referenced above.  
Based on the institutional review board’s (IRB) records, the purpose of this study is to evaluate whether topiramate can reduce cravings and euphoria (feeling “high”) associated with cocaine use and to assess the effects of topiramate on memory and reasoning. The study does not provide a treatment for cocaine dependence.

A. Determinations regarding the above-referenced research:

1) A complainant alleged that when he experienced adverse events that he believed to be caused by the study drugs, he went to the University of Virginia clinic as directed by the consent form, informed the doctors that he was in the topiramate study, and the doctors treated him with valium and discharged him.  According to the allegation, the complainant continued to experience side effects but could not reach the research team on the number provided on the consent document. HHS regulations at 45 CFR 46.116(a)(7) require, in part, that informed consent include an explanation of whom to contact in the event of a research-related injury to the subject.  OHRP expects that such information will enable subjects to contact appropriate research team members for assistance. 
Based on the documentation provided by UVA, the informed consent included the appropriate information for subjects to contact the research team in the event of injury.  In addition to the information provided in the consent form, study documents indicated that subjects were given an emergency contact card.  Further, UVA provided copies of emails and telephone logs documenting communications between the complainant and study staff that occurred about his event.  No information was provided by the complainant to support this allegation and we determine that it is unproven.

B. Resolved concerns:

1) OHRP expressed concern that it and the IRB had no record of receiving a report of the event described by the complainant, in possible violation of HHS regulations at 45 CFR 46.103(a), 46.103(b)(5), and 46.108(a) which together require institutions to have and comply with written procedures for ensuring prompt reporting of unanticipated problems involving risks to subjects or others (among other things) to appropriate institutional officials, the IRB, OHRP, and the head of the sponsoring Federal department or agency.
Based on our review of the documentation provided by UVA, the complainant came to the UVA emergency room complaining of “numbness, ‘pressure’ surrounding left eye.”  The consent form, on pages 8-9, indicates that risks associated with cocaine included lightheadedness, shakiness, and feeling stimulated.  On page 9, the form includes “tingling of the skin” as a potential discomfort of topiramate.  According to UVA’s report, it was the assessment of the investigator and the IRB that his event was within the scope of expected events listed in the consent form, and they determined it to be neither serious nor unexpected. OHRP finds the investigator’s assessment of the complainant’s event to be appropriate. 
At this time, there should be no need for further involvement by our office in this matter. Please notify us if you identify new information which might alter this determination.
We appreciate the continued commitment of your institution to the protection of human research subjects.  Please do not hesitate to contact me should you have any questions. 
Lisa Buchanan, MAOM
Division of Compliance Oversight
1101 Wootton Parkway, Suite 200
Rockville, Maryland 20852
Telephone: 240-453-8298
FAX: 240-453-6909
Dr. Richard Stevenson, IRB Chairperson, IRB #1, University of Virginia
Dr. Tonya Moon, IRB Chairperson, IRB #2, University of Virginia
Dr. Bankole A. Johnson, University of Virginia 
Dr. Joanne Less, Food and Drug Administration
Dr. Sherry Rodgers, National Institutes of Health (NIH)
Dr. Michelle Bulls, Director of OPERA, Office of Extramural Research, NIH
Ms. Sarah Carr, Office of Science Policy, NIH
Dr. Nora D. Volkow, Director, National Institute on Drug Abuse, NIH
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