February 28, 2022 - National Jewish Health

Dear Ms. Christensen,

OHRP conducted an on-site evaluation of National Jewish Health’s (HRPP) human research projections program in 2016. The evaluation was conducted as part of OHRP’s program for assessing compliance with 45 CFR Part 46 by routinely evaluating human subject protection programs at institutions that receive Department of Health and Human Services (HHS) support for research. As a result of concerns observed during that visit, OHRP conducted a follow-up visit in 2018, during which similar concerns were observed. Subsequently, NJH engaged the services of a human research consulting firm to address these concerns and elected to outsource the institutional review board oversight, as well as their IRB staff support.

I. Background

During the September 2016 not-for cause site visit, OHRP expressed concerns that NJH did not have adequately trained HRPP staff or sufficient IRB written procedures per regulatory requirement and as described in OHRP’s guidance titled, “Institutional Review Board Written Procedures: Guidance for Institutions and IRBs.” OHRP determined that a follow-up visit would be appropriate to re-evaluate NJH’s HRPP.

OHRP conducted a follow-up visit to NJH in September 2018 and noted that while NJH had made significant changes to address deficits in their HRPP, additional concerns related to their compliance with HHS regulations persisted. OHRP acknowledges that NJH was still in the process of hiring qualified staff to better manage their HRPP, in the beginning stages of implementing an electronic protocol management system, had updated their IRB written procedures, and implemented new IRB forms and checklists. However, OHRP observed little evidence of the HRPP’s preparation for the January 2019 implementation of the revised Common Rule. Further, interviews with the IRB members, staff and researchers revealed minimal knowledge of the revised Common Rule or plans to implement changes that would assure that the institution would be able to comply with the new requirements in the revised Common Rule. Additionally, through OHRP’s review of IRB records and observations made during an NJH IRB meeting, it appeared that significant IRB member training would be needed for the IRB to properly comply with HHS regulations. OHRP provided NJH with specific studies which appeared to illustrate compliance issues with the IRB’s review.

On August 6, 2020, September 8, 2020, and November 5, 2020, OHRP requested additional information from NJH to understand how OHRP’s concerns were being addressed by NJH. NJH quickly provided comprehensive responses that outline in detail actions they were taking to address OHRP’s concerns. Those actions are summarized below:

1. All research studies that were previously under the oversight of the NJH IRB were transferred to a n external IRB. The transfer was completed on May 28, 2020. NJH no longer has an internal IRB. The external IRB worked with NJH to obtain copies of all pertinent study records, including submission information, IRB review and approval documentation, and IRB minutes as applicable. An initial assessment of the IRB records received by the external IRB was completed to ensure the records were in order.
   1. The external IRB conducted a continuing review, comparable to an initial review, for transferred studies.
   2. For studies in which modifications were submitted to the external IRB for review right after transfer but before continuing review was due, the external IRB reviewed the modification while concurrently completing a review comparable to an initial review.
   3. For the remaining studies, qualified external IRB staff completed an administrative review of each transferred study to evaluate regulatory compliance and determine whether the external IRB should undertake IRB review sooner than the next continuing review date.
   4. A review comparable to an initial review was completed sooner than the next continuing review date for studies for which the administrative review indicated the need to document IRB determinations that were perhaps not clearly documented within the records transferred from the prior IRB.
   5. An initial review was conducted by the external IRB for transferred studies that had an initial review by NJH IRB, and the study was either deferred by, or received contingent approval from, NJH IRB and was transferred to the external IRB before the conditions of IRB approval were determined to be satisfied.
   6. For each transferred study requiring consent from the subject or the subject’s legally authorized representative, the external IRB provided the researcher with an IRB-approved consent form addendum to use to notify subjects of the change in IRB contact information.”
2. The HRPP office, which had four full-time staff, had only a single HRPP Administrator as of September 2020. Staff changes led to reconsideration of how to best administer the HRPP. While a search for a new human protections administrator was occurring, an HRPP consulting firm provided temporary staffing for the position of HRPP Interim Director. A consultant began serving as NJH’s Interim HRPP Director on March 30, 2020, and remains in place as of the date of this letter.
3. This HRPP Office provided regulatory and local context support for all researchers and coordinators regardless of study type or funding source. This support had previously been provided by the HRPP staff but in September 2020, it became the responsibility of the new Interim HRPP Director. The Interim Director was the liaison between researchers, coordinators, and the primary external IRB, as well as with other external IRBs.
4. After the 2018 OHRP site visit, NJH revised its standard operating procedures (SOP) to address the revised Common Rule, but further revisions were required to address the changes pertaining to the utilization of external IRBs. In September 2020, those SOP revisions were in progress.
5. NJH secured the use of an IRB electronic records management system, which had been implemented at NJH in September 2019. NJH used templates for submission forms and reviewer checklists customized with assistance from a consultant. However, since NJH was using an external IRB, all protocol submissions were entered directly into the external IRB system. NJH researchers were using the external IRB forms.
6. Training sessions for the NJH research community were conducted by a former HRPP Quality Assurance and Education Manager between August 2018 through March 2020 on topics such as the NJH SOPs, 2018 Common Rule revisions, submission forms, and onboarding with the new IRB electronic system.
7. Other programs supported NJH HRPP work in September 2020. The Clinical Research Services (CRS) is a research support unit that provides services for researchers conducting clinical trials at NJH. That support includes study coordination, regulatory support, and IRB submission support.
8. Documents attached in appendices to the September 2020 communication to OHRP show that NJH has developed procedures for registering all studies reviewed by outside IRBs, and NJH has developed procedures, specific to the particular outside IRB, to ensure both pre-review and post-approval review of such studies by NJH. Pre-review will include management of local context issues and NJH required training requirements for researchers. The post-review process will ensure that study documents comply with local context requirements before a study can start, will ensure that any allegations of non-compliance are reviewed by NJH, in addition to the external IRB, and all amendments will be reviewed for local context issues before submission to the external IRB.

II. Conclusion

NJH still recognizes its continuing institutional responsibility to maintain appropriate oversight over the human subjects research in which NJH is engaged. OHRP has determined that concerns identified during the two site evaluations have been adequately addressed.

We appreciate the continued commitment of NJH to the protection of human research subjects. Please feel free to contact me if you have any questions.

Sincerely,

Lisa Buchanan, MAOM
Director
Division of Compliance Oversight

cc:
Ms. Judy Matuk, Human Protections Administrator, NJH
Ms. Ann Meeker-O’Connell, Director, Office of Clinical Policy, Food and Drug Administration (FDA)
Dr. Quynh-Van Tran, FDA
Dr. Michelle Bulls, Director, OPERA, Office of Extramural Research, National Institutes of Health (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
Ms. Lydia Kline, Team Lead, Clinical Research Policy, Division of Clinical and Healthcare Research Policy, Office of Science Policy, NIH