Research Project: A Therapeutic and Diagnostic Tool to Assess and Enable Spared Spinal Motor Function After Spinal Cord Injury
Protocol Number: IRB #14-000158
HHS Grant Number: 5R43EB018232

Dear Dr. Wakimoto:

Thank you for your March 14, 2017 letter and associated documentation in response to our February 6, 2017 request that University of California Los Angeles (UCLA) evaluate allegations of noncompliance with the Department of Health and Human Services (HHS) regulations for the protection of human research subjects (45 CFR part 46). We regret the amount of time it has taken us to respond. It is our understanding the activities described in your letter were initiated prior to January 21, 2019 and remain subject to the pre-2018 Requirements (i.e., the requirements published in the 2016 edition of the Code of Federal Regulations [CFR] at 45 CFR part 46, Subpart A). Please note that regulatory sections listed below refer to sections in the pre- 2018 Requirements. Based on our review of your responses, OHRP has made the following determinations regarding the allegations made by complainant:

1. The investigator failed to inform subjects of significant new findings developed during the course of the research. If proven, this allegation would represent a violation of the HHS regulations at 45 CFR 46.116(b)(5), which requires that significant new findings developed during the course of the research which may relate to the subject's willingness to continue participation be provided to the subject.

   The complainant alleges that certain injuries and associated pain that their son, the participant, suffered were related or possibly related to the electrical spinal cord stimulation that the participant underwent as part of the research. They further allege that the principal investigator (PI) failed to inform other research participants of these new risks associated with the intervention. However, based on the documentation provided by UCLA, the PI and an independent physician determined that the participant’s injuries and associated pain were unrelated to the research procedures. The requirement to inform other research participants of new risks of research participation applies to incidents related or possibly related to participation in the research. As such, OHRP has determined the claim that the investigator failed to inform subjects of significant new findings developed during the course of the research is unproven.

2. The study was not conducted as described in the IRB-approved protocol. If proven, this allegation would represent a violation of the HHS regulations at 45 CFR 46.103(b)(4)(iii), which requires that the IRB review and approve all proposed changes in a research activity, during the period for which IRB approval has already been given, prior to initiation of such changes, except when necessary to eliminate apparent immediate hazards to the subject.

   The complainant alleges that the participant did not receive appropriate follow-up or close observation to minimize the harms resulting from the intervention. The informed consent form states that potential anticipated research risks to participants would be minimized by close follow-up and ongoing observation by the PI and the research team. The documentation provided by UCLA supports that the PI closely followed up on and communicated on an ongoing basis with the participant and other physicians at UCLA who were treating the participant after the alleged injury.

   The complainant also alleges that the participant was not provided the medical care promised in the protocol in the event of an injury resulting from the research. Both the protocol and informed consent form state that in the event of any complications resulting from the research procedures, UCLA would provide the necessary medical care without any additional cost to the participant. Based on the documentation provided by UCLA, the PI and an independent physician determined that the participant’s injuries and associated pain were unrelated to the research procedures. Nonetheless, the participant was referred to and received care for such injuries at UCLA. Therefore, OHRP has determined the claim that the study was not conducted as described in the IRB-approved protocol is unproven.

3. The investigator failed to report unanticipated problems involving risks to subjects or others to appropriate institutional officials, the IRB, OHRP, and the head of the sponsoring Federal department or agency. If proven, this allegation would represent a violation of HHS regulations at 45 CFR 46.103(b)(5) which requires prompt reporting to the IRB, appropriate institutional officials, and the department or agency head of any unanticipated problems involving risks to subjects or others.

   The complainant alleges that the injuries and associated pain that the participant suffered were related or possibly related to the electrical spinal cord stimulation that the participant underwent as part of the research. They further allege that the PI failed to report this to the appropriate officials as an unanticipated problem involving risks to subjects. Based on the documentation provided by UCLA, the PI and an independent physician determined that the participant’s injuries and associated pain were unrelated to the research procedures. The requirement to report unanticipated problems involving risks to subjects or others only applies to incidents related or possibly related to participation in the research. As such, OHRP has determined the claim that the investigator failed to report unanticipated problems related to the research to the appropriate officials is unproven.

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 that might alter this conclusion.

We appreciate your institution’s continued commitment 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. Kristin Craun, Human Protections Administrator, UCLA
Ms. Winifred Meeker-O’Connell, Director, Office of Clinical Policy, Food and Drug Administration (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
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