November 21, 2014 - University of South Alabama

Dear Ms. Chronister:

Thank you for your June 20, 2014 and September 8, 2014 responses to our questions and concerns regarding allegations of University of South Alabama’s (USA) noncompliance with Department of Health and Human Services (HHS) regulations for the protection of human research subjects (45 CFR Part 46) in the studies referenced above.  Based on review of the documents you provided and your responses to the questions and concerns outlined in our letter dated May 14, 2014, we make the following determinations:

Determinations regarding protocols titled, "Evaluation of Mitochondrial Dysfunction in Severe Burn Patients" and "Microcirculatory Assessment in Patients with Trauma and Severe Burns"
(1) For the study titled, "Evaluation of Mitochondrial Dysfunction in Severe Burn Patients, "a complainant alleged that blood was being drawn from newly admitted patients in the surgical intensive care unit for research purposes without informed consent (3 to 4 times, for more than a cup of blood).

This study enrolls subjects in the USA’s Medical Center Burn Intensive Care Unit Blood is collected at the following intervals: baseline (at patient admittance to the unit), at 8 hours, 24 hours and 48 hours through an intravenous central line (for a total collection of 64cc).  The IRB approved the above referenced study and waived consent.

(2) For the study titled, "Microcirculatory Assessment in Patients with Trauma and Severe Burns, "a complainant alleged that tests involving probing the mouth and throat with a new device for research purposes only were being performed on newly admitted patients in the surgical intensive care unit without obtaining informed consent.

This study utilizes the same patient population (burn and trauma patients) as the study referenced above, but uses a device called a Sidestream Dark Field microscanner to measure microcirculation to reveal whether dysfunctional capillary density in this patient population can predict development of multiple organ failure.  The device is placed under the tongue or on the eye and takes images of microcirculation in external mucosa.  Based on the materials provided, the Sidestream Dark Field microscanner is approved by the Food and Drug Administration for this indication and classified as a non-significant risk device.  The IRB determined this to be non-invasive, minimal risk research. The IRB approved the study and waived consent.

Based on your response, at the time that the IRB approved these studies, the IRB would place a copy of the Secretary’s Advisory Committee on Human Research Protections’ letter to the HHS Secretary dated January 31, 2008 which outlined recommendations related to waiver of consent in study files to document waivers of consent.  Your response does not provide any other documentation to show that the IRB identified an appropriate basis for the findings required in order to waive informed consent.  OHRP does not agree that this process constitutes appropriate IRB documentation of a waiver of consent in compliance with the provisions specified under Health and Human Services (HHS) regulations at 45 CFR Part 46.  The regulations require the IRB to find and document that four waiver criteria have been satisfied in order for informed consent to be waived.  Specifically, 45 CFR 46.116(d) states:

[a]n IRB may… waive the requirements to obtain informed consent provided the IRB finds and documents that: 1) [t]he research involves no more than minimal risk to the subjects; 2) [t]he waiver… will not adversely affect the rights and welfare of the subjects; 3) [t]he research could not practicably be carried out without the waiver… and 4) [w]henever appropriate, the subjects will be provided with additional pertinent information after participation.

When waiving the requirement to obtain informed consent, OHRP recommends that the IRB document its findings in the minutes of the IRB meeting (including protocol-specific information justifying each IRB finding). For research reviewed under an expedited review procedure, these findings should be documented by the IRB Chairperson or other designated reviewer elsewhere in the IRB record (“Guidance on Written IRB Procedures” http://www.hhs.gov/ohrp/regulations-and-policy/guidance/guidance-on-written-irb-procedures-2011/index.html). We determine that the IRB failed to appropriately document its decision to waive consent for these studies.  

Corrective Action: We acknowledge that since the approval of these studies, USA has implemented an electronic IRB system and has updated  protocol application and reviewer forms to document that the four waiver criteria required by HHS regulations at 45 CFR 46.116(d) have been met for  protocols for which a waiver of consent is granted.  This corrective action adequately addresses this determination.

These corrective actions adequately address our determinations and are appropriate under the USA’s 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 determination.
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:
Ms. Dusty D Layton, Director of Research Compliance, University of South Alabama
Dr. William Green, University of South Alabama IRB #1

Dr. Margaret Hamburg, Commissioner, Food and Drug Administration (FDA)
Dr. Joanne Less, FDA