January 16, 2015 - Memorial Sloan-Kettering Cancer Center

Dear Dr. Sabbatini:

Thank you for your October 27, 2014 report in response to our September 30, 2014 letter regarding questions about allegations of noncompliance by Memorial Sloan-Kettering Cancer Center (MSKCC) with Department of Health and Human Services (HHS) regulations for the protection of human research subjects (45 CFR part 46).  Based on review of your response, we make the following determination:

Determination

The complainant alleges that research on subjects with retinoblastoma involving intra-vitreal injections of digoxin and other chemotherapy into the eye has been conducted without institutional review board (IRB) review and approval.  We note the following regarding this matter:

a) A single patient with bilateral retinoblastoma was treated at New York Presbyterian Hospital and MSKCC.  

b) Given the clinical state of the patient’s open second degree burn, history of pneumonia and bacteremia, and the extensive cost of intra-arterial treatment, it was felt that different treatment options should be offered for each eye.  One eye (left) was treated with intra-vitreal melphalan.  For treatment of the second (right) eye, it was felt that an option with less potential for immunosuppression was needed. Dr. Abramson proposed intra-vitreal use of digoxin.  Digoxin given intra-arterially had been successful in patients with retinoblastoma, but had not been tried by intra-vitreal administration. It was explained that this approach would hopefully have a reasonable benefit to risk ratio by avoiding the potential for immunosuppression (particularly with two doses of melphalan) and offered a reasonable chance at preserving vision. In addition, MSKCC stated “in the event of adverse events, it is not our practice to use the same agent in each eye simultaneously.”

c) Dr. Abramson confirms that the patient in question is the only one to receive such treatment. MSKCC performed a search of pharmacy records from January 1, 2011 through October 10, 2014; the Pharmacy results show that only one patient (referenced above) received digoxin via intra-vitreal route.

Based on the documentation provided in your October 27, 2014 correspondence, we have determined that the allegations of noncompliance are unproven.  No evidence was presented to us indicating that research on subjects with retinoblastoma involving intra-vitreal injections of digoxin and other chemotherapy into the eye has been conducted without IRB review and approval.

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,
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. Roger S. Wilson, Chairman, IRB, Memorial Sloan-Kettering Cancer Center
Dr. David Abramson, Memorial Sloan-Kettering Cancer Center
Dr. Jasmine Francis, Memorial Sloan-Kettering Cancer Center
Dr. Brian Marr, Memorial Sloan-Kettering Cancer 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