July 31, 2026 – Vanderbilt University Medical Center

Study Title: Pubertal, Psychological and Physiological Development in Females with Autism
National Institutes of Health (NIH) Award Number: R01HD107695

Dear Dr. Rice:

Thank you for the responses to our requests that Vanderbilt University Medical Center (VUMC) evaluate allegations of noncompliance with Department of Health and Human Services (HHS) regulations for the protection of human research subjects (45 CFR part 46) that arose in the above-referenced NIH-funded study. The Office for Human Research Protections (OHRP) initiated this review in response to allegations of noncompliance from a complainant. In reviewing VUMC’s responses, OHRP learned that VUMC had already received a related complaint. OHRP reviewed the actions VUMC took in response to that complaint as they relate to 45 CFR part 46 and determined them to be sufficient. Therefore, OHRP makes no determination of noncompliance with 45 CFR part 46. We note the following:

In our May 1, 2025 letter to VUMC, we requested that VUMC investigate the following allegations of noncompliance with 45 CFR part 46 raised in a complaint about the referenced study:

1. Asking a child participant sensitive questions without disclosing that plan in the informed consent/parental permission process, which resulted in the child experiencing distress.
2. Discussing the child’s medical diagnostic information with the child against parental wishes.
3. Violating other guidelines, including by failing to report and provide care for research-related adverse events and not adhering to plans described in the NIH grant such as assessing participants for trauma and having licensed professionals conduct research assessments and exams.

OHRP has determined based on VUMC’s May 30, 2025 response that:

1. VUMC evaluated whether its actions complied with 45 CFR § 46.111, 46.116, and 46.408, based on the complainant’s allegations in item 1, above. VUMC’s response showed that the sensitive questions were included in the protocol approved by the institutional review board (IRB) at the time the subject was enrolled in the study, but the questions were not mentioned in the informed consent document (ICD). Thus, parents were not properly informed of the nature of the questions that investigators would pose to child participants. VUMC’s responses demonstrated that before OHRP initiated its inquiry, VUMC had already investigated the complaint it received and implemented corrective actions to: review and approve study changes, including changes to the protocol, consent process and ICD; recontact subjects to obtain additional consent; and institute appropriate monitoring and reporting to ensure the changes were implemented. OHRP determines that the corrective actions developed and implemented by VUMC adequately address item 1, above.
2. In January 2023, prior to the OHRP inquiry, VUMC initiated a prompt investigation into the related complaint referenced above, which included observation of the consent process and interviews. VUMC did not find evidence that medical diagnostic information was discussed with child participants against parental wishes, or in front of child participants. OHRP determines that based on the diverging factual descriptions in the complaint versus VUMC’s response, there is insufficient information for OHRP to conclude that the allegations described in item 2, above, constitute noncompliance with 45 CFR part 46.
3. The study’s principal investigator reported the complaint that the study team received to the human research protections program (HRPP) personnel and the IRB for investigation in a timely manner. VUMC’s investigation showed that the study team and institution followed the research protocol and procedures and used qualified researchers and personnel with respect to the allegations in item 3, above. OHRP makes no finding of noncompliance with 45 CFR part 46 with respect to these allegations.

Because the allegations described an event that potentially constituted an unanticipated problem involving risks to subjects or others (“unanticipated problem”) requiring prompt reporting to OHRP in accordance with 45 CFR § 46.108(a)(4)(i), upon receipt of the complaint, OHRP checked records for any related incident reports received from VUMC and found none. In a July 24, 2025 letter, OHRP asked VUMC why the incident described in the complaint was not reported to OHRP. VUMC explained that it did not report the incident because it was not a reportable unanticipated problem under the VUMC HRPP definition, which OHRP reviewed and found to diverge from OHRP guidance. Although the terms “unanticipated problem” or “unanticipated” are not defined in 45 CFR part 46, OHRP has explained our interpretation of the terms in guidance (https://www.hhs.gov/ohrp/regulations-and-policy/guidance/reviewing-unanticipated-problems/index.html)¹ and elsewhere (see, for example, https://www.hhs.gov/ohrp/compliance-and-reporting/guidance-on-reporting-incident/index.html and “Reporting to OHRP(1): Unanticipated Problems” section (time stamp 5:00) at https://www.hhs.gov/media/1690/modal). OHRP has also reminded assured institutions of the regulatory requirements to report certain events to OHRP.² VUMC subsequently revised its HRPP policies to reflect OHRP guidance.

The information provided by VUMC adequately addresses OHRP’s concerns. We note that OHRP did not conduct an all-inclusive review of VUMC’s HRPP. It is the institution’s responsibility to ensure adherence to each requirement of the relevant HHS regulations. This investigation is closed. We appreciate VUMC’s continued commitment to the protection of human subjects. Please contact me if you have any questions.

Sincerely,

Eric Fried, JD
Compliance Specialist
Division of Compliance Oversight
Office for Human Research Protections

CC (email only):
Human Protections Administrator, VUMC
Office of Clinical Policy, Food and Drug Administration (FDA)
Office of Policy for Extramural Research Administration, National Institutes of Health (NIH)
Office of Science Policy, NIH
Center for Devices and Radiological Health, FDA
Center for Biologics Evaluation and Research, FDA
Office of Inspections and Investigations, FDA
Center for Drug Evaluation and Research, FDA

Endnotes

¹ This guidance notes that OHRP considers unanticipated problems to include “any incident, experience, or outcome that meets all of the following criteria:
(1) unexpected (in terms of nature, severity, or frequency) given (a) the research procedures that are described in the protocol-related documents, such as the IRB approved research protocol and informed consent document; and (b) the characteristics of the subject population being studied;
(2) related or possibly related to participation in the research (in this guidance document, possibly related means there is a reasonable possibility that the incident, experience, or outcome may have been caused by the procedures involved in the research); and
(3) suggests that the research places subjects or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized.”

² See OHRP 2025 email posted at https://www.hhs.gov/ohrp/news/announcements-and-news-releases/2025/reminder-from-ohrp-about-reporting-requirements-fwa-holding-institutions-irbs-overseeing-hhs-supported-conducted-research.html