January 28, 2016 - Baylor College of Medicine

Dear Dr. Berg:

The Office for Human Research Protections (OHRP) conducted an on-site evaluation of the human research protections program (HRPP) at Baylor College of Medicine (BCM) in Houston, TX from February 24-26, 2015.  The evaluation was conducted as part of our program to evaluate human research protection programs of institutions that receive Department of Health and Human Services (HHS) support for research in compliance with 45 CFR Part 46.

The evaluation, conducted by six OHRP staff and two expert consultants, included interviews with senior HRPP officials, institutional review board (IRB) Chairs and vice-chairs, IRB members, IRB staff and principal investigators who conduct HHS-supported research.  The site-visit team reviewed IRB records for over 45 HHS-supported research studies, IRB meeting minutes for the six months prior to the site visit and IRB written procedures.

We are pleased to note that BCM has a robust HRPP.  IRB leadership, chairs and members conveyed a sincere commitment and concern for their role in the protection of human research subjects.  On the last day of our visit, we shared with you several observations regarding the BCM’s HRPP.  Thank you for your reports (dated March 9, 2015, May 5, 2015 and May 8, 2015) in response to those observations.  We make the following determination:

A. Determination:

In protocol H-18112, titled “Perceptual Thresholds for Electrical Cortical Stimulation of Human Cerebral Cortex,” subjects are scheduled to undergo surgical placement of intracranial electrodes in order to determine in what part of the brain their seizures occur.  According to the IRB application for this research, additional electrodes, which were designed for research purposes, are embedded in the spaces between the standard electrodes.  Study investigators believe that the additional electrodes add no identifiable additional risks to the subjects. The intracranial electrodes are left in place until the subject has had enough seizures to allow epileptologists to reliably localize the epileptic region(s) of the brain, usually 7-10 days.  During this time subjects are hospitalized and monitored.

Based on the protocol, informed consent documents and IRB minutes that BCM provided for this study, the IRB assessed this study as more than minimal risk and the research appeared to enroll children.  We sought clarification regarding whether the IRB made the required findings under Subpart D and justification for why the informed consent document did not include information regarding research-related injuries.  

According to your response, at the time of initial IRB approval on December 27, 2005, the IRB assessed this study as minimal risk and approved a parental permission and child assent process but did not document Subpart D findings.  Because the research was assessed as minimal risk, the research-related injury language was not included in the informed consent document.

However, during the continuing review of this study in 2011, the IRB re-assessed this study and deemed it to be greater than minimal risk, but presenting the prospect of direct benefit to the individual subjects. The IRB failed to require that research-related injury language be added to the consent document.     

HHS funding began for this study on September 1, 2013.  On October 29, 2014, the protocol was revised by the PI to no longer include children as potential subjects and reported that “[s]ince inception, no children or adolescents have been enrolled as participants in this project.”

We determine that the informed consent documents reviewed and approved by the IRB failed to include or adequately address the following basic element required by HHS regulations at 45 CFR 46.116(a)(6):  “[f]or research involving more than minimal risk, an explanation as to whether any compensation and an explanation as to whether any medical treatments are available if injury occurs and, if so, what they consist of, or where further information may be obtained.”

Corrective action: We note that the following corrective actions have been taken by BCM:
1) The IRB's written procedures have been revised to require documentation of IRB findings pertaining to Subpart D; 2) the investigator was required to submit a revised consent form that includes an explanation as to whether any compensation and any medical treatments are available if injury occurs; 3) IRB members and staff received training to assure that when changes are made to previously approved research, any additional regulatory requirements are considered and implemented appropriately.  

B. Resolved concern:

1. HHS regulations at 45 CFR 46.305-306 require specific findings on the part of the IRB for approval of research involving prisoners.  However, we noted that the BCM Human Research Protections (HRP) Manual defined a “prisoner” as “. . . any individual involuntarily confined or detained in a penal institution.”  HHS’s regulations define “prisoner” as “any individual involuntarily confined or detained in a penal institution. The term is intended to encompass individuals sentenced to such an institution under a criminal or civil statute, individuals detained in other facilities by virtue of statutes or commitment procedures which provide alternatives to criminal prosecution or incarceration in a penal institution, and individuals detained pending arraignment, trial, or sentencing” (45 CFR 46.303(c)).  Concern was expressed that the limited definition of “prisoner” in the BMC’s HRP Manual could lead to IRB approval of prisoner research without adherence to the appropriate Subpart C requirements.  We acknowledge that the BCM HRP Manual has been revised to reflect the complete HHS definition of “prisoner” and that BCM’s online forms for submitting protocols to the IRB have been revised to include the complete definition for “prisoner.”

We recommend that IRB members and staff receive training on the revised definition to ensure that they are aware of which protocols may involve prisoners and make the appropriate findings to satisfy approval criteria outlined under Subpart C.

We determine that the corrective actions adequately address all of the determinations and are appropriate under your FWA.  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 which might alter this conclusion.

We appreciate the continued commitment of your institution to the protection of human research subjects.  Please do not hesitate to contact me should you have any questions.

Sincerely,

Lisa Buchanan, MAOM
Division of Compliance Oversight
1101 Wootton Parkway, Suite 200
Rockville, Maryland 20852
Telephone: 240-453-8298
FAX: 240-453-6909
E-mail: Lisa.Buchanan@HHS.gov

cc:
Mr. John Allen Wright, MPH, Human Protections Administrator, Baylor College of Medicine
Dr. Margaret Hamburg, Commissioner, Food and Drug Administration (FDA
Dr. Joanne Less, FDA
Dr. Michelle Bulls, Director of OPERA, Office of Extramural Research, National Institutes of Health (NIH)
Ms. Sarah Carr, Office Science Policy, NIH