A strategy for ensuring and improving the quality of the human subjects protection program is the implementation of an internal audit process. This is because an audit process can heighten investigator and IRB awareness of regulatory requirements and improve the ethical conduct of research. Authority for a research audit program is derived from federal regulation 45 CFR 46.109(e) and 21 CFR 56.109(f) which state that “an IRB … shall have the authority to observe or have a third party observe the consent process and the research.”
At the University, the “third party” is the Office of Regulatory Support and Quality Assurance (RSQA) previously known as the Office of Research Compliance Assessment (ORCA), which is supervised by the Vice Provost for Research. This Office has responsibility for:
1) Investigating allegations of non-compliance with federal and other regulations
2) Investigating allegations of non-compliance with the requirements or determinations of the IRB
3) Conducting audits to ensure that there is compliance with regulations and IRB decisions
Such investigations, whether routine or directed, shall have the involvement and/or consultation of the IRB and HSRO. The Associate Vice Provost for Human Subjects Research, or the Assistant Provost for IRB Affairs may also request an audit by the Office of Regulatory Support and Quality Assurance as may the IRB of any study it has approved. The request may be made by the full IRB or by the Chair or the Chair’s IRB-designee at his/her discretion. The Office of Regulatory Support and Quality Assurance may also initiate audits. Studies may be routinely chosen for audit or they may be selected for audit by predetermined criteria based on assessment of risk or they may be chosen for a particular reason such as funding source, number or type of studies being done by any one principal investigator or because the studies involve vulnerable populations. Investigators are expected to cooperate fully with the auditors.
When made aware that a routine or directed audit is being undertaken by the Office of Regulatory Support and Quality Assurance, no matter whether this audit is being conducted on a routine basis or in response to an allegation or problem requiring an audit, the HSRO shall compile file information and any other documentation and make these available to the officers of the Office of Regulatory Support and Regulatory Assurance. The IRB and HSRO shall have full and ongoing access to information pertaining to audits conducted by the Office of Regulatory Support and Quality Assurance. The IRB may also conduct its own inquiry or request materials/meetings in order to contribute to the investigation being conducted by the Office of Regulatory Support and Quality Assurance.
If warranted by findings of serious non-compliance or practices that may immediately jeopardize the safety and welfare of human subjects, the Office of Regulatory Support and Quality Assurance shall contact the Associate Vice Provost for Human Subjects Research before the audit is complete or before a response is requested from the Principal Investigator. The Vice Provost for Human Subjects Research may take any or all actions deemed necessary and within his/her authority (c.f. Policy 3.2) including suspension or termination of the study.
The Office of Regulatory Support and Quality Assurance shall document the outcome of its audits including communications, discussions and efforts to achieve resolution in writing, by either e-mail or paper memo with a copy to the files. Such documentation shall be factual and objective, and may include timelines for resolution if appropriate (e.g. meeting dates, response deadlines). All audits shall be reported to the IRB. If the documentation reveals non-compliance, this documentation shall be quickly forwarded to the HSRO for review by the IRB chair or IRB-designee who shall determine whether the practices cited in the report constitute relatively minor non-compliance or whether the practices may constitute serious or continuing non-compliance that may cause injury or any other unanticipated problems involving risks to subjects or others and/or that may adversely affect the rights, safety and/or welfare of human research subjects.
If the non-compliance is determined to be serious or continuing based on the definition above, the IRB Chair or designee shall forward the report for review and action by the convened IRB. If the IRB Chair or designee determines that there are serious or continuing non-compliance or practices that may immediately jeopardize the safety and welfare of human subjects, the IRB Chair or designee shall also contact the Associate Vice Provost for Human Subjects Research without waiting for review by the convened IRB.
If the IRB chair or IRB-designee forwards the audit report to the full IRB, the IRB may request that staff of the Office of Regulatory Support and Quality Assurance and/or the staff of the HSRO and/or the principal investigator or other key personnel provide information at the meeting. The IRB shall review the audit findings and determine by vote whether there shall be required corrective actions or sanctions which should be systematic in nature and may include (but are not limited to):
1) Additional, focused compliance audits
2) Suggestions or requirements for additional education/training in human subjects protections and regulations for investigators, staff and/or departments
3) Designating an IRB member or mentor to discuss compliance or other issues/concerns with the principal investigator
4) Notification to current or past participants of any modifications to the protocols or informed consent documents made in response to the audit
5) Modify the research protocol, consent process or consent documents
6) Send a letter of reprimand from the IRB to the principal investigator and/or recommend that a letter of reprimand be sent by the Associate Vice Provost for Human Subjects Research or the Provost
7) Termination or suspension of the research
8) Modify the continuing review timetable to require more frequent IRB review
9) Restrictions or disallowance on serving as an investigator in studies involving human subjects
10)Require the principal investigator to submit a corrective action plan to the IRB for review and approval
11)Noting that the audit served as an educational tool and that, based on the principal investigator's response to the audit, no further action is required
Following IRB review, the principal investigator shall be notified by the HSRO of the IRB decision. The principal investigator may submit a written request asking the IRB to reconsider its decision. The request should clearly indicate the facts or the interpretation in dispute and should provide supporting evidence where applicable. If a written request is received by the IRB, the IRB shall vote either to leave its decision unchanged or to reopen its review.
It is the responsibility of the IRB to ensure that changes and other mandates of the IRB are carried out by the principal investigator. To accomplish this, the IRB may request appropriate documentation from the principal investigator and/or the IRB may request that confirmatory site visits be performed, and reports made to the IRB, by the Office of Research Compliance Assessment or the HSRO.