January 17, 2013 - Tata Memorial Hospital

Dear Dr. D'cruz:

Thank you for your November 19, 2012 report in response to our October 15, 2012 letter to Tata Memorial Hospital (TMH) 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 July 5, 2012 letter, we made the following determinations, among others:

A. Determinations regarding the above-referenced research

(1) We determined that subjects were not adequately informed of the alternative procedures or courses of treatment regarding screening for breast cancer or cervical cancer, namely, mammography and Pap testing.  This was in violation of HHS regulations at 45 CFR 46.116(a)(4) which require the disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject, as part of informed consent.

(2) We determined that the subjects were not provided, in writing, with information about the possible alternative of seeking breast or cervical cancer screening outside of the research, as required by HHS regulations at 45 CFR 46.116(a)(4) and 46.117(b)(1).    

Corrective Action:  We acknowledge that, in addition to the corrective actions you have already taken and outlined in our October 15, 2012 letter, the IRB unanimously decided that the study subjects should be informed about modalities like mammography and Pap smear, and the differences from the study related procedures. The IRB unanimously agreed that this information could be provided verbally, and waived the requirement for written informed consent in this regard. We also acknowledge that the IRB unanimously decided that the PI should offer screening for cervical cancer by Visual Inspection with Acetic Acid (VIA) to subjects in the control group.  We determine that the corrective actions adequately address the determination.  

(3) We determined that minutes of IRB meetings do not exist (or were not provided to our office upon request) for numerous meetings; and that minutes of IRB meetings that were provided to us are not in sufficient detail to show the vote on actions taken by the IRB including the number of members voting for, against, and abstaining, as required by HHS regulations at 45 CFR 46.115(a)(2).  

(4) We determined that the IRB failed to meet the quorum requirement for the IRB meeting of April 11, 2007.  This was in violation of HHS regulations at 45 CFR 46.108(b) which require that research be reviewed at convened meetings at which a majority of the members of the IRB are present, except when an expedited review procedure is used.

Corrective Action:  We have reviewed the TMH written IRB standard operating procedures (SOPs) developed this year.  We note that the SOPs adequately address the quorum issue and provide for recording of minutes of IRB meetings.  We note that the SOPs and minutes of the most recent IRB meeting do not include recorded votes as required by HHS regulations at 45 CFR 46.115(a)(2).  The date of that meeting took place after we had already made a determination that voting was not being recorded.  We also note that the SOPs do not include the procedures for ensuring prompt reporting to appropriate institutional officials, any U.S. Federal Department or Agency head, and OHRP of (a) any unanticipated problems involving risks to subjects or others; (b) any serious or continuing noncompliance with 45 CFR Part 46 or the requirements or determinations of the IRB; and (c) any suspension or termination of IRB approval, as required by 45 CFR 46.103(a) and (b)(5).

Required Action:  Please provide OHRP revised SOPs that ensure that when the IRBs review research involving HHS support, votes on the actions taken by the IRB are recorded as required by  HHS regulations at 45 CFR 46.115(a)(2).  Please also provide minutes of the most recent IRB meeting at which the IRB reviewed HHS-supported research that include a record of the votes on the actions taken by the IRB.  Please also provide OHRP with TMH’s written procedures for research involving HHS support for ensuring prompt reporting to appropriate institutional officials, any U.S. Federal Department or Agency head, and OHRP of (a) any unanticipated problems involving risks to subjects or others; (b) any serious or continuing noncompliance with 45 CFR Part 46 or the requirements or determinations of the IRB; and (c) any suspension or termination of IRB approval.

Please provide us with a response to the above required actions by March 1, 2013.  Feel free to contact me if you would like guidance in responding.

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: [email protected]

cc:
Dr. Rajendra A. Badwe, Director, Tata Memorial Centre
Dr. Madhuri Gore, Chairperson, Human Ethics Committee-I, Tata Memorial Hospital
Dr. Urmila Thatte, Chairperson, Human Ethics Committee-II, Tata Memorial Hospital
Dr. Surendra Srinivas Shastri, Tata Memorial Hospital

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. Harold Varmus, Director, National Cancer Institute, NIH