September 30, 2015 - Detroit Medical Center

Dear Dr. White:

Thank you for your reports submitted in response to our September 20, 2012 request that Detroit Medical Center 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 track the build-up of tryptophan in the brain using positron emission tomography (PET) scanning. Tryptophan, in its natural state, is an amino acid (one of the building blocks of protein) that is normally present in the brain, and is used by the brain cells to create various other compounds. This process is altered in the presence of a brain tumor.  By using a form of tryptophan marked with a radioactive tracer (alpha[C-11]methyl-tryptophan, or  AMT), researchers hope to track this process during the course of the PET scan and determine whether AMT PET is a useful method to recognize and differentiate between various types of brain tumors.  

Based on the information you provided, this protocol has been open at Detroit Medical Center under Dr. Juhasz’s (principal investigator) direction since 2002and had enrolled approximately 300 subjects. Approximately 55 of those 300 were newly diagnosed or recurrent subjects with glioblastoma multiforme tumors (GBM). Of those 55 subjects, 23 were Dr. Sandeep Mittal’s (co-investigator and surgeon) patients.  Dr. Mittal had been a co-investigator on this protocol since 2007.

A. Determinations regarding the above-referenced research:

1) A complainant alleged that because the AMT tracer was not readily available and because Dr. Mittal wanted to stage PETs immediately before surgery to collect data for his research study, he would delay surgeries until the PET tracer was available, or until he could schedule the PET scan, an MRI scan, and surgery on the same day. Allegedly, such delays represented an increase in risks to subjects.

According to your audit report, all maintenance records for the research PET scanner and the cyclotron, precursor materials for the AMT accountability forms, and the Research PET scanner appointment log from 2007 to present were compared to the dates of Dr. Mittal’s participants. Those comparisons demonstrated that the AMT tracer and PET scanner were always available.

The audit report noted that there were no surgery delays in Dr. Mittal’s patients enrolled in this research because of non-availability of the AMT-PET tracer, and scheduling surgery was never done to accommodate an AMT-PET scan.  Further, no subject in the study underwent AMT-PET scan, MRI brain scan, and surgery on the same day.  

The materials we reviewed revealed no evidence indicating that the AMT tracer was not readily available or that Dr. Mittal staged PETs immediately before surgery to collect data for this study.  Further, no evidence was presented to suggest that he delayed surgeries until the PET tracer was available, or until he could schedule the PET scan, an MRI scan, and surgery for the same day. We have determined that this allegation is unproven.

2) A complainant alleged that Dr. Mittal would delay surgery for three to five weeks from the preoperative MRI or the first consult or the first referral. The complainant alleged that such deliberate delays are highly unethical because glioblastoma multiforme tumors (GBM) are very aggressive, and the longer one delays surgery the worse the prognosis.  

Based on the information provided in your report, the average time between initial patient contact and surgery was 15.3 days in the AMT-PET group and 10.4 days in the eligible control group.  The audit revealed that the average time between initial contact with Dr. Mittal and surgery for patients with newly diagnosed GBM was not significantly different in patients enrolled in the AMT-PET study compared to those who did not enroll in the study.

The materials we reviewed revealed no evidence indicating that Dr. Mittal sometimes delayed surgery for three to five weeks from the preoperative MRI or the first consult or the first referral.  We have determined that this allegation is unproven.

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.

Sincerely,

Lisa Buchanan, MAOM
Division of Compliance Oversight
1101 Wootton Parkway, Suite 200
Rockville, Maryland 20852
Telephone: 240-453-8298
FAX: 240-453-6909
E-mail: Lisa.Buchanan@HHS.gov

cc:
Dr. Dorothy A. Nelson, Associate Vice President for Research, Wayne State University, Detroit Medical Center
Dr. Lawrence Crane, Chair, Wayne State University IRB #1
Ms. Gayle A. Kusch, Sr. Director, Compliance, Wayne State University - Division of Research
Dr. Sandeep Mittal, Investigator, Detroit Medical Center

Dr. Joanne Less, Food and Drug Administration
Dr. Sherry Mills, National Institutes of Health (NIH)
Dr. Michelle Bulls, Director of OPERA, Office of Extramural Research, NIH
Ms. Sarah Carr, Office of Science Policy, NIH