June 5, 2014 - New York Medical Center Queens
June 5, 2014
Stephen Rimar, M.D.
Senior Vice President and Chief Medical Officer
New York Medical Center Queens
56-45 Main St
Flushing, NY 11355
Re: Human Research Subject Protections Under Federalwide Assurance FWA-948
Research Project: Multiple protocols under the Gynecologic Oncology Group (GOG)
Principal Investigator: Manolis Tsatsas, M.D.
Dear Dr. Rimar:
Thank you for your November 12, 2012 report in response to our October 5, 2012 request that New York Medical Center Queens (NYMCQ) evaluate allegations of noncompliance 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 determinations:
A. Determinations regarding the above-referenced research
1) The complainant alleged that several subjects were confused about the nature of their disease, treatment options and what the study entailed, in violation of HHS regulations at 45 CFR 45.116. Based on the documentation provided in your October 5, 2012 correspondence, we have determined that the allegations of noncompliance are unproven. No evidence was presented to us indicating that there was failure to obtain legally effective informed consent of subjects. We note the following from your report:
a) The principal investigator stated that he spent over one hour discussing treatment with prospective subjects.
b) In one case where a subject withdrew after finding out she was randomized to the observation arm of the study, extensive documentation exists to indicate that the subject was fully aware of the study design and made an informed decision.
2) The complainant alleged that unanticipated problems in protocol GOG 0261 were not reported as required by HHS regulations at 45 CFR 46.103(a) and 46.103(b)(5). Based on the documentation provided in your October 5, 2012 correspondence, we have determined that the allegations of noncompliance are unproven. No evidence was presented to us indicating that there was failure to report unanticipated problems involving risks to subjects or others to the institutional review board (IRB), Institutional Officials, and OHRP. We note the following:
a) Two subjects were enrolled in GOG 0261.
b) One subject experienced severe neutropenia/thrombocytopenia following her last chemotherapy session. This event is listed as a possible side effect in the consent form.
c) Another subject experienced neuropathy and low blood cell counts. These events are listed as a potential side effect in the consent form.
d) These events were expected and therefore do not constitute unanticipated problems.
3) We have determined that there was no evidence that the subjects or the subjects’ legally authorized representative received a copy of the informed consent document as required by HHS regulations at 45 CFR 46.117(a), which requires that a copy of the informed consent document must be given to the person signing the form. We note the following from your report:
a) An audit revealed that while all subjects signed consent forms, there were some problems with documentation, such as signing the wrong version of the consent form and the principal investigator signing the consent form instead of the subject.
b) The audit also revealed no evidence that subjects were given a copy of the consent form.
Corrective Action: We acknowledge that NYMCQ has identified a medical record tool that will help ensure adequate documentation for each subject encounter. This form will be mandated for all encounters relating to obtaining informed consent and includes an entry for providing a copy of the informed consent document to subject or the authorized representative signing the informed consent document. . Additionally, as part of the continuing education of all investigators, all components of the informed consent process will be reviewed.
4) We have determined that the IRB failed to conduct continuing review of research at least once per year, in violation of HHS regulations at 45 CFR 46.109(e). We note the following from your report: An audit revealed that there were short lapses in IRB approval for protocols GOG 210, GOG 235, GOG 249, and GOG 261.
Corrective Action: We acknowledge that NYMCQ has initiated substantial changes in the human research protection program, including restructuring of the NYMCQ IRB, development of a quality assurance program, and contracting with an independent IRB to review all future clinical trials at NYMCQ.
5) The complainant alleged that amendments to the protocol, which included changes to the risk section, were submitted to the IRB over a year late while subjects were enrolled on older versions of the informed consent document that did not include an adequate description of risks, in violation of HHS regulations at 45 CFR 46.116(a)(2). Based on the documentation provided in your October 5, 2012 correspondence, we have determined that the allegations of noncompliance are unproven. No evidence was presented to us indicating that there was failure to disclose to subjects or their legally authorized representatives a description of reasonably foreseeable risks to the subjects. We note the following from your report:
a) There were no instances in which an amendment was found to be delayed over one year, and all amendments were submitted to and approved by the NYMCQ IRB.
b) Approval for revisions in GOG 258, and 261 were delayed greater than 90 days after the date of issue; these modifications did not result in any significant changes to the consent form.
c) For GOG 212, the delayed submission resulted in the use of a version of the consent form that would have been updated had the amendment been submitted on time. Language on pregnancy testing was added. The subject who was enrolled during this delay was age 77 at the time of enrollment. This language would therefore not have been a factor in a decision whether or not to participate, because it did not alter any aspect of the study that would have been relevant to that subject.
We make the following recommendations regarding NYMCQ’s human subject protection program:
We recommend that NYMCQ revise the IRB Policy and Procedures to include more operational details regarding how different procedures are carried out. Please see http://www.hhs.gov/ohrp/policy/irbgd107.html for guidance.
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 appreciate your institution’s continued commitment to the protection of human research subjects.
Kristina C. Borror, Ph.D.
Director, Division of Compliance Oversight
1101 Wootton Parkway, Suite 200
Rockville, Maryland 20852
Mr. Karen A. Hultberg, Administrator, New York Medical Center Queens
Dr. Michael Warhol, IRB Chair, New York Hospital Queens
Dr. Manolis Tsatsas, New York Medical Center Queens
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