January 10, 2025 – New York State Psychiatric Institute

Dear Dr. Smith:

This letter is in follow-up to OHRP’s October 15, 2024, letter to you, in which OHRP identified the conditions under which OHRP would remove the restriction on NYSPI’s FWA. On November 4, 2024, OHRP met with you, Dr. Ann Sullivan, Dr. Michael Lauer, and others from NYSPI and the New York State Office of Mental Health to discuss OHRP’s October 15, 2024, letter to NYSPI.

For the reasons discussed below, OHRP is removing the restriction it placed on the FWA ending in 6105 as of the date of this letter.¹

During the November 4, 2024, meeting, NYSPI verified that NYSPI will be relying on one or more external institutional review boards (IRBs) while NYPSI’s IRB is being reconfigured. We understand that NYSPI anticipates transferring all existing studies to an external IRB by December 31, 2024. Until the transfer of all studies is complete, NYSPI informed us that the NYSPI IRB will continue to review communications from investigators for paused studies. This will include review of unanticipated problems identified through ongoing quality improvement activities, changes in study personnel, modifications in studies where NYSPI served as the IRB of record for non-NYSPI sites (that were not subject to the FWA restriction) and protocol continuations/annual updates (and close-outs) for protocols that have yet to be fully transferred to an external IRB. NYSPI stated that no new protocols will be reviewed by the NYSPI IRB during this period.

NYSPI further informed OHRP that the NYSPI IRB will resume oversight over human subjects research conducted at NYSPI, only after NYSPI’s IRB has been reconfigured and the external Research Compliance Entity has provided verification to OHRP that: 1) the IRB members and staff have been trained in accordance with the NYSPI/RFMH Comprehensive Corrective Action Plan; 2) the IRB members have sufficient knowledge of the HHS regulatory requirements at 45 CFR part 46 to carry out their responsibility to review and oversee HHS-supported human subjects research; 3) NYSPI is adhering to its updated IRB written procedures which reflect the requirements of the HHS regulations at 45 CFR part 46; and 4) NYSPI has established a process to ensure that its IRB written procedures and policies reflect any future revisions to the HHS regulations at 45 CFR part 46.

OHRP acknowledges that NYSPI has informed OHRP of their plans for both internal and external monitoring of all studies involving human subjects, including those that are currently paused as well as new studies that NYSPI may conduct in the future. These plans include but are not limited to the following:

• Site initiation visits for every study prior to enrolling participants to check for consistency between the study team’s planned implementation of the protocol and what has been approved by the IRB; review of the protocol of all related procedures, regulatory documents, and study materials with the study team; and confirmation that any prior corrective and preventative action (CAPA) plans have been completed. Site initiation visits will be conducted by the NYSPI human subjects research protections program (HRPP) staff from the Quality Improvement and Education (QIE) team. Currently, these visits are planned to be conducted with the assistance of staff from NYSPI’s external monitors (Advarra Consulting), which will be providing training and oversight for the QIE team until such time as they can conduct these visits effectively on their own. Site Initiation Visit reports will be reviewed and approved by NYSPI’s external Human Subjects Research Governance Board before recruitment can begin.
• Post-Approval Monitoring – After the first subject is enrolled, HRPP staff along with an external monitor will conduct the first monitoring visit, focusing on consent and eligibility determination practices. The review team will produce a report to be reviewed by the external Research Compliance Entity. If the Research Compliance Entity has concerns, the PI will be asked to stop enrollment immediately and the study will be referred to the Human Subjects Research Governance Board for review and recommendations.
• Post-Approval Monitoring – After the third subject is enrolled, an external monitor will conduct the second monitoring visit assessing whether all study activities to date, including consent and eligibility processes, were conducted in compliance with the protocol and all applicable federal, state, and local regulations governing human subjects research. The monitor will produce a report to be reviewed by the external Research Compliance Entity. If the Research Compliance Entity has concerns, the PI will be asked to stop enrollment immediately and the study will be referred to the Human Subjects Research Governance Board for review and recommendations.
• Post-Approval Monitoring - Six months after the first subject is enrolled, an external monitor will conduct the third monitoring visit assessing whether all study activities to date, including consent and eligibility processes, were conducted in compliance with the protocol and all applicable federal, state, and local regulations governing human subjects research. The monitor will produce a report to be reviewed by the external Research Compliance Entity. If the Research Compliance Entity has concerns, the PI will be asked to stop enrollment immediately and the study will be referred to the Human Subjects Research Governance Board for review and recommendations.

OHRP concurs with the above procedures. We also recognize and appreciate the significant progress NYSPI has made to address OHRP’s concerns. We note that NYSPI has selected an external Research Compliance Entity that will audit and monitor multiple aspects of NYSPI’s HRPP to help ensure that NYSPI’s HRPP is adequately protecting human subjects enrolled in research at NYSPI.

As stated earlier in this letter, based on these and other safeguards that NYSPI has put in place, and NYSPI’s commitment to continue to protect human subjects in future research conducted at NYSPI, OHRP is removing the restriction it placed on the FWA ending in 6105.

OHRP expects that NYSPI will continue implementing NYSPI’s planned corrective actions that are not identified in this letter. OHRP will consider NYSPI’s implementation of these other corrective actions in determining when to close this investigation.

Sincerely,

Julie A. Kaneshiro, M.A.
Deputy Director, OHRP

cc:
Dr. Ann Sullivan, Commissioner, New York State Office of Mental Health
Dr. Karya Ottey, Director of the New York State Office of Mental Hygiene, Office of Human Research Protections Program
Dr. Rachel L. Levine, Admiral, United States Public Health Service, Assistant Secretary for Health
Dr. Michael Lauer, Deputy Director for Extramural Research, National Institutes of Health (NIH)
Ms. Theresa Jarosik, Chief Grants Management Officer, National Institute of Mental Health
Ms. Winifred Meeker-O’Connell, Director, Office of Clinical Policy, FDA
Dr. Michelle Bulls, Director, OPERA, Office of Extramural Research, NIH
Dr. Pamela Kearney, Director, Division of Human Subjects Research, Office of Extramural Research, NIH
Dr. Adam Berger, Director, Division of Clinical and Healthcare Research Policy, Office of Science Policy, NIH
Center for Devices and Radiological Health (CDRH) IRB: BIMO-CDRH@fda.hhs.gov
Center for Biologics Evaluation and Research (CBER): CBERBIMONotification@fda.hhs.gov
Office of Regulatory Affairs (ORA): orabimoinspectionpoc@fda.hhs.gov
Center for Drug Evaluation and Research (CDER): BIMO-CDEROSI@fda.hhs.gov

Endnotes

¹ Note: Separately, as previously discussed with NYSPI, NYSPI should be removed from the FWA ending in 6105 before conducting HHS-supported research under the FWA ending in 34910.