July 8, 2013 - University of Minnesota

Dear Drs. Herman and Sanberg:

Thank you for your reports in response to our November 28, 2012 letter to the University of Minnesota (UM) and the University of South Florida (USF) regarding determinations of noncompliance with Department of Health and Human Services (HHS) regulations for the protection of human research subjects (45 CFR part 46).

In our November 28, 2012 letter, we made the following determination, among others:

A. Determinations Regarding the Above-Referenced Research

(1) We determined that the consent documents for this study (model consent forms dated September 28, 2010) failed to include or adequately address the following basic elements required by HHS regulations at 45 CFR 46.116(a)(2): A description of any reasonably foreseeable risks and discomforts.  Specifically, we determined that the UM IRB-approved consent documents for this study failed to include the risk of gastrointestinal disorders as required by HHS regulations at 45 CFR 46.116(a)(2).

UM Corrective Action:  We acknowledge that to address this finding, a corrective action plan was implemented to revise the consent form to include the statement, "Increased occurrence of stomach or intestinal complaints have been noted in some but not all studies of canakinumab. "  

B. Additional Determination Regarding the Above-Referenced Research

We note from your response that the UM IRB-approved consent forms and the model interventional consent form described the secondary aim of the study. Nevertheless, we determine that the UM-IRB approved interventional consent documents for this study (version September 30, 2010) and the model interventional consent form (dated September 28, 2010 do not adequately explain the potential risk that certain immunizations could be less effective in people who are treated with the study drug, as required by HHS regulations at 45 CFR 46.116(a)(2).  

UM Corrective Action:  We acknowledge that to address OHRP's concern, the consent form was revised to include the statement, "There is a potential risk that certain immunizations could be less effective in people treated with the study drug."

We determine that the corrective actions adequately address the determinations.  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 note that other institutions in this multicenter study may be still enrolling subjects in this trial and may wish to consider whether or not the informed consent documents used for this study at these other sites adequately address a description of the risks referenced above.  Accordingly, we are sending copies of this determination letter to the other institutions in this multicenter study to alert them to this issue.

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.

Sincerely,

Kristina C. Borror, Ph.D.
Director, Division of Compliance Oversight
1101 Wootton Parkway, Suite 200
Rockville, Maryland 20852
Telephone: 240-453-8132
FAX: 240-453-6909
E-mail: Kristina.Borror@hhs.gov

cc:
Dr. Jay S. Skyler, University of Miami
Ms. Debra A. Dykhuis, Executive Director of Human Research Protection Program, U of Minnesota
Dr. Susan Berry, IRB Chairperson, U of Minnesota
Dr. Antoinette Moran, U of Minnesota
Ms. Cheryl L. Byers, Director, Division of Research Integrity & Compliance, U of South Florida
Dr. E. Verena Jorgensen, Chair, Institutional Review Board, U of South Florida
Dr. Janelle Perkins, Chair, Institutional Review Board, U of South Florida
Dr. John L Bixby, U of Miami
Dr. Elizabeth A Boyd, U of California, San Francisco (UCSF)
Dr. Ann M Arvin, Leland Stanford Junior U
Dr. Andrew  Rudczynski, Yale University
Dr. David P Norton, U of Florida
Dr. Eric S Williams, Indiana University Health
Dr. Barbara E Barnes, U Pittsburgh Med Ctr
Ms. Angela  Wishon, University of Texas Southwestern Med Ctr
Mr. Homer  Lane, Benaroya Rsch Inst at Virginia Mason
Dr. Peter N Lewis, U of Toronto

Dr. Margaret Hamburg, Commissioner, Food and Drug Administration (FDA)
Dr. Joanne Less, FDA
Dr. Sherry Mills, National Institutes of Health (NIH)
Mr. Joseph Ellis, NIH
Dr. Griffin P. Rodgers, Director, National Institute of Diabetes and Digestive and Kidney Diseases, NIH