November, 19, 2015 - MetroHealth System

Dear Dr. Connors:

Thank you for your January 12, 2015 report in response to our December 1, 2014 letter with questions regarding allegations of noncompliance with Department of Health and Human Services (HHS) regulations for the protection of human research subjects (45 CFR part 46).

1. The complainant alleged that 45 CFR part 46 was violated when the following events occurred:
   1. Investigators conducted two research studies without institutional review board (IRB) review and approval.
   2. For another study, the investigator failed to obtain the legally effective informed consent of subjects prior to research procedures being performed.
   3. Changes to research in several studies were made by investigators prior to IRB review and approval.
   4. There was failure in numerous studies to conduct continuing review at least once per year.
2. We note that MetroHealth investigated these alleged incidents prior to our office opening an evaluation into this potential noncompliance.  MetroHealth advised us that it reached the following conclusions with respect to the alleged incidents:
   1. One of the two research studies that were alleged to have been conducted without IRB review and approval involved a non-exempt chart review and was conducted prior to IRB review and approval; there is no evidence that the other study was started before IRB review and approval.
   2. An IRB quality assurance audit revealed that minimal risk, non-invasive study procedures (manual muscle testing and surveys) were performed on 5 subjects prior to consent; the investigator mistakenly thought that consent had already been obtained from the subjects.
   3. There were two studies with protocol deviations related to subjects being asked for consent using administratively incorrect consent forms that had been reported to the IRB. However, these consent forms were only incorrect in that they had expired or missing IRB approval stamps.
   4. A routine quality assurance audit of one study revealed numerous consent documentation deviations from the approved protocol and consent form (e.g., failure to document in the record that subjects were given a signed copy of the consent form, and the person obtaining consent completed the date for the parent/guardian and printed the name of the minor subject and the subject’s age when this should have been completed by the parent/guardian.)
   5. Numerous studies had expired IRB approval, but investigators either had submitted renewal requests or closed the study; there is no evidence that research was conducted during the lapses.

We understand that MetroHealth determined that some of the above-described incidents constituted noncompliance with 45 CFR part 46. Based on the information you provided, MetroHealth took numerous corrective actions to address the above noncompliance prior to OHRP sending a letter regarding the allegations. For the study that did not have IRB review and approval, MetroHealth required the investigator to submit the protocol to the IRB for review. For the study in which procedures were conducted prior to obtaining consent, the principal investigator obtained informed consent from those subjects and agreed to review the HIPAA and consent forms before initiating study procedures in the future.  Investigators were educated about the definition of research vs. QA and the importance of following approved consent procedures. To prevent use of expired consent forms, stamped consent documents are locked and study staff can only access approved, stamped documents and the only location in the eIRB that stamped documents can be printed from is under the approved/stamped documents tab. To address problems with expiration of IRB approval and noticing that many expired studies had residents as principal investigators, as of December 2013, residents are no longer permitted to be principal investigators. In addition, the eIRB system will automatically close expired studies and a notice to the investigator, department chair, and research team will automatically be generated by the eIRB system 30 days post study expiration.

In view of the information you provided, including the above corrective actions, and because it appears that the institution had already adequately addressed the problems before OHRP sent its letter, as a matter of policy OHRP will take no further action regarding this matter.

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 your institution’s continued commitment to the protection of human research subjects.

Sincerely,

Kristina C. Borror, Ph.D.
Director, Division of Compliance Oversight

cc:
Ms. Rachel Phetteplace, Manager, Human Research Protection Program MHS
Dr. Ann Avery, MHS IRB Chairperson
Dr. Joanne Less, Food and Drug Administration (FDA)
Ms. Bridget Foltz, FDA