May 16, 2025 – Children’s Mercy Hospital

Research Projects: TrialNet Studies:

• TN01: The TrialNet Pathway to Prevention (formerly Natural History Study of the Development of Type 1 Diabetes)
• TN07: Oral Insulin for Prevention of Diabetes in Relatives at Risk for Type 1 Diabetes Mellitus
• TN10: Anti-CD3 MAB (Teplizumab) for Prevention of Diabetes in Relatives at Risk for Type 1 Diabetes Mellitus
• TN16: Long-term Investigative Follow-up in TrialNet (LIFT)
• TN18: CTLA-4 Ig (Abatacept) for Prevention of Abnormal glucose Tolerance and Diabetes in Relatives at Risk for Type 1 Diabetes Mellitus

Dear Dr. Leeder,

The Office for Human Research Protections (OHRP) investigated the allegations lodged regarding the conduct of the above-referenced National Institute of Diabetes and Digestive and Kidney Diseases funded studies. OHRP acknowledges that Children’s Mercy Hospital (CMH) has taken appropriate corrective actions to address the alleged noncompliance that occurred in the studies. OHRP makes no determinations of noncompliance with the HHS regulations for the protection of human research subjects, and this investigation is closed.

All events related to these allegations occurred prior to January 21, 2019, and were subject to the Common Rule as it existed at that time (the “Pre-2018 Requirements”). Therefore, all citations in this letter refer to the Pre-2018 Requirements.

Background: In April 2015, OHRP received allegations against CMH of noncompliance with HHS regulations for the protection of human research subjects (subparts A – D of 45 CFR part 46). In summary, the complainant alleged that protocol changes were initiated without IRB approval; research procedures were performed prior to obtaining legally effective informed consent; and that the research team failed to ensure that privacy of subjects and confidentiality of records were maintained.

CMH investigated the above referenced allegations of noncompliance with the pre-2018 Requirements, and implemented the following corrective actions:

• Hired a new full-time employee to help implement corrective actions and to work with the PI of the TN01 study to increase oversight of the study conduct.
• Revised the study operations manual, revised study eligibility checklists, instituted a quality assurance process to ensure that all study-visit information has been obtained, logged, and recorded, and revised the TrialNet test result notification procedures.
• Trained new and existing staff on all new/updated policies, procedures, and practices.
• Required that the research team correct any informed consent, parental permission, or assent violations whenever possible. If violations could not be cured, study teams were instructed to withdraw the appropriate subject(s) from the research and remove their data from the TrialNet database.
• Submitted multiple incident reports to OHRP outlining instances of serious noncompliance found because of this investigation.

We regret the amount of time it has taken to close this investigation. The corrective actions developed and implemented by CMH adequately address the allegations presented.

We appreciate your institution’s continued commitment to the protection of human research participants. Please feel free to contact me if you have any questions.

Sincerely,

Crystal Kelly, MPH
Compliance Specialist
Division of Compliance Oversight

CC (email only):
Ms. Saskia Miller, Human Protections Administrator, CMH
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