UNIVERSITY OF MINNESOTA
ADVANCING HUMAN RESEARCH PROTECTION FINAL REPORT
Work Plan Section: For-Cause Investigations (External Review report recommendations: 3.2.8, 3.2.9, 3.2.10) Lead(s): Sarah Waldemar Date: September 30, 2015
Background and Introduction: The External Review stated that “one of the most challenging but critical functions of an IRB is addressing incidents of researcher noncompliance” and noted that “in alignment with these federal regulatory requirements, the U of M’s IRB has policies and procedures to address noncompliance. The IRB policies not only address the requirement that researchers report incidents of noncompliance to the IRB, but also outline the IRB’s processes for handling the incident reports once received”. However, it was noted that “neither of the active investigations to which it was privy during this evaluation had members with relevant expertise.” Further, the report noted external resources could have been used to help with the work of IRB investigation committees, but were not. The IRB has policies governing the process for investigating issues of non-compliance However, a basic principle of the University of Minnesota’s research oversight model is that: “Oversight is always separate from the operating unit that makes the decisions.” To that end the For Cause investigations will be managed by the Research Compliance Office. For purposes of this report, the following “for cause” definition is proposed: For-Cause Investigation (FCI) A compliance activity is considered “for-cause” when allegations, indications or suspicions of possible human or animal participant related non-compliance are received by OVPR, RCO, IRBs, IACUC, other regulatory committees or offices, faculty, research support staff, funding or regulatory agencies, research participants or via Fairview or other reporting options. For-Cause Investigations would include:
Issues forwarded from the IRB, IACUC, IBC, DURC or SCRO committee because the alleged failure exceeds in frequency or severity that which is typically handled in a post-approval review/monitoring activity. Issues arising from external complaints (U Report complaints, complaints from staff, other faculty, patients, outside the U, etc.)
To address the external review panel’s issues, the implementation team’s final report proposed the following:
Place responsibility for these investigations in a newly created Research Compliance Office in the OVPR.
UNIVERSITY OF MINNESOTA
ADVANCING HUMAN RESEARCH PROTECTION
The newly created Research Compliance Office in the OVPR will review and revise procedures related to the composition of the investigation panels to insure that membership includes members with relevant expertise. When a complaint is received, the complainant should promptly receive a response that includes information about what will happen next and a later response about the resolution. For a significant adverse event related to participation in a research study resulting in death, disability, or injury, the U of M must have a system for response to research participants and families that is prompt, empathetic, and informative. The principal investigator of the study must be an integral part of this process and should receive training on these types of discussions. This training should be incorporated into routine training for investigators.
Analysis and Recommendations Considerable consultation was undertaken to arrive at the conclusions included in this report. A list of those from whom counsel was sought is included in Appendix A. Recommendation 1: Review, revise or develop procedures to ensure the composition of the investigative panels related to for-cause investigations includes members with relevant expertise. Currently there exist three types of reviews within HRPP. 1) A standard PAR conducted on a sample of approved protocols. Information gleaned from these reviews is typically reported to the relevant IRB panel and, if required, any necessary actions are determined by the panel, communicated to the investigator and followed up by the PAR staff to ensure resolution. 2) A review carried out by the PAR team at the request of a convened IRB. This is typically a more “directed” review conducted due to concerns related to non-compliance which could be related to consenting, using inappropriate forms, enrollment levels being too high or too low, a higher than normal frequency of protocol revisions among other things. The result is a more extensive, deeper review of a protocol or an investigator’s portfolio. This investigation typically requires additional time to complete and report as well as more extensive requirements by the IRB to ensure resolution and mitigation of the problem. Findings from these reviews have the potential to be elevated to FCI. 3) A for-cause investigation is the most extreme of the reviews and can arise from a number of places. Findings from the directed review indicate where serious and continuing noncompliance may be discovered, concerns may be reported from a variety of sources as outlined in the proposed definition. It is at this point that an IRB panel or the IRB Executive Committee should request the intervention of the Research Compliance Office (RCO) Research Compliance Office in the OVPR (excerpted from separate Research Compliance Office report) The RCO once established should be expected to work closely with any involved compliance committee to ascertain facts, take advantage of topical expertise, and to determine whether there are qualified University or Fairview non-conflicted individuals who could serve on an investigative committee. In most cases, it would be expected that a member of an applicable compliance committee (IRB, IACUC, etc.) would serve as a full member or, at minimum, as an ex officio member of the investigative committee. Investigative committees should be comprised of internal members when sufficient qualified individuals are available to provide a
UNIVERSITY OF MINNESOTA
ADVANCING HUMAN RESEARCH PROTECTION
timely, fair and appropriate review. When applicable, a Compliance Committee would have first action responsibility to consider and act on the recommendations of a For-Cause Investigation. This would be followed by any additional action deemed necessary by the Vice President for Research. The current For Cause Policy is included as Appendix B. Once the recommendations are approved this policy will be revised to reflect those changes. Recommendation 2: Review, revise or develop procedures for conducting an FCI to include an assessment of expertise required, development of action plan, recruitment of either internal or external experts, collection, review and reporting of findings, and final resolution of the issue. It is recommended that a member of the RCO continue to serve in an ex officio role on the IRB Executive Committee. Through this relationship for-cause investigations can be identified, and assessed with the input of the IRB Executive Committee prior to undertaking any action. Potential investigation team members can be identified, consideration of the need for an external review discussed and the issue “handed off” to the RCO to undertake the actual investigation. Steps in the investigation would include: 1. Assessment of the complaint/issue/situation in collaboration with PAR and/or HRPP staff 2. Determination of next steps 3. Identify an investigative panel a. Is sufficient expertise available using University resources and researchers with training in human participant regulations and who have no conflict (reporting, collaborations, etc.)? b. If not, an external consultant will be enlisted to collaborate with the RCO throughout the investigation, University resources such as PAR staff will be enlisted as required. 4. Develop a communication plan to ensure that progress is reported in a timely and consistent manner with the person or entity which brought the issue forward as well as the IRB leadership. 5. Develop an investigation plan 6. Carry out the investigation 7. Develop a management plan that is presented to the IRB for final action related to regulatory findings and the Vice President for Research (VPR) if actions unrelated to regulatory findings are required or if additional escalation is required. 8. Provide notification of the resolution to those impacted. 9. Once all requirements of the action plan have been met, prepare and disseminate a final report to the IRB leadership, the VPR, and any others who need to be informed.
Recommendation 3: Develop a process to ensure that when a complaint is received, the complainant promptly receives a response that includes information about what will happen next and a later response about the resolution. This specific concern was expressed by a number of those consulted and needs to be implemented as quickly as possible. This is covered briefly in item 4, above, however it will be important for the RCO to carefully consider the best means for communicating with the reporting entity and the level of detail supplied. For example, should the reporter wish to remain anonymous sufficient care must be taken to ensure, to the greatest extent possible, that her/his identify not be revealed. Should it prove impossible to conduct the investigation without revealing the reporter’s identity consultation with the reporter must occur prior to the investigation moving forward. The RCO should build these processes in consultation with the Office of Institutional Compliance which has developed detailed procedures to be used when communicating with
UNIVERSITY OF MINNESOTA
ADVANCING HUMAN RESEARCH PROTECTION
reporters. No new technology will be required, rather a clearer focus on ensuring communication is a high priority.
Recommendation 4: Develop a system for response that is prompt, empathetic, and informative to research participants and families in case a significant adverse event related to participation in a research study (which could include but not be limited to death, disability, or injury) occurs. The principal investigator of the study must be an integral part of this process and should receive training on these types of discussions. This training should be incorporated into routine training for investigators. Several of the institutions consulted have initiated a “pre-enrollment orientation” with their investigators. During these sessions the protocol is reviewed, inclusion/exclusion criteria confirmed and processes related to enrollment and management of study participants discussed. If adopted, this meeting – researcher, staff and HRPP staff member (and/or a Fairview research compliance staff person if applicable) – would provide more direct training on managing significant adverse events such as those outlined above. This session would need to be no more than an hour so would represent little added administrative burden for researchers, but would be extremely useful for ensuring that a response plan has been put in place. Because it takes place after the approval process it does not extend the time from submission to review, rather it offers an opportunity, postapproval, to ensure research, clinical and HRPP staff are in step with one another regarding the management of information and communication to participants or their families.
Recommendation 5: The IACUC was not included in the Implementation Team’s recommendations regarding FCI so this section has been added based on conversations with staff and other institutions. As part of the consultation done it was determined that inclusion of the RCO in significant issues found by the IACUC either through reports or PAM inspections is warranted. The IACUC procedures for reviewing concerns are as follows: Review concerns involving the care and use of animals at the Institution. Any individual may report concerns to the IO, IACUC Chair, Institutional Veterinarian, or any member of the IACUC. Concerns may be reported either verbally or in writing. Notices are located in the animal facilities advising individuals how and where to report animal welfare concerns and stating that any individual who, in good faith, reports an animal welfare concern will be protected against reprisals. All reported concerns will be brought to the attention of the full Committee. The Chair will involve other members of the Committee as needed and, if necessary, the IACUC Chair will convene a meeting to discuss, investigate, and address any reported concern. Reported concerns and all associated IACUC actions will be recorded in the IACUC meeting minutes. The Committee will report such actions, in writing, to the IO and, as warranted, to OLAW. Reports to the IO may be either via meeting minutes, semiannual report of IACUC evaluations, or separate letter. Reports to OLAW will be in writing and through the IO. Initial reports to both the IO and OLAW may be made verbal It would be appropriate going forward to include the RCO in any IACUC investigations which reach a level comparable to the FCI related to human participants. Given that animal subjects regulations differ significantly from those related to human participants it is unlikely that it would be necessary for the RCO to
UNIVERSITY OF MINNESOTA
ADVANCING HUMAN RESEARCH PROTECTION
assume responsibility for managing these investigations, however RCO involvement would ensure a level of transparency not currently available as well as resources for escalation when necessary.
Recommendation 6: It is recommended that the RCO be kept apprised of the second level PAR reviews. Tracking of the time required to resolve the issue as well as the number of such reviews required and the researchers involved could provide significant information regarding gaps in education, miscommunications between researchers and clinical staff or issues related billing processes (standard of care vs. research-related costs). A process for this data collection will need to be developed which does not impede the PAR work but provides sufficient data to allow the RCO to identify trends. These would become part of the Accountability Metrics requested by the Implementation Team.
Finally, the management of all For Cause investigations by the RCO will allow for a more robust review of any investigator. The financial oversight resources which will be a part of the RCO can be called upon to conduct a more thorough review of a given investigator (a repeat offender, or a “heavy hitter”) who seems to be struggling with one aspect of her/his research. It could prove to be an opportunity to assist the researcher by clarifying how all the pieces related to her/his research interact and the impact of protocol changes on budgets.
UNIVERSITY OF MINNESOTA
ADVANCING HUMAN RESEARCH PROTECTION
For Cause Investigations Advancing Human Research Protection Key Stakeholder Interviews and External Contacts Appendix A InstitutionAffiliation Harvard FTI Consulting University of Indiana Case Western Reserve University University of Maryland
Contact Ara Tahmassien, Chief Research Compliance Officer* and Pam Caudill, Chief of Research and Administrative Operations Scott Lipkin, Managing Director* John Baumann, Executive Director, Human Research Protection Program* Kim Volarcik, Executive Director, Research Compliance
Emory University
Joseph Smith, Manager, Research Compliance Office* Josie Lyan, Justin Snyder, IRB QA, Sarah Horn, IRB Director, Debra D. Thurley, J.D. Director of Research Compliance Office for Research Protections* Kerry Peluso, Assoc. VP-Research Administration
Duke University
Tina Tyson, Chief Ethics and Compliance Officer*
University of Iowa
University of Chicago
Michele Countryman, Interim Director, IRB Human Subjects Office Terry VandenBosch, Managing Director, Office of Human Research Compliance Review Mike Ludwig, Associate Vice President, Research
University of Connecticut
Wesley Bylerly, Associate Vice President for Research*
Wayne State University
Policy, procedure review
Creighton University
Policy, procedure review
Carilion Clinic
Policy, procedure review
Penn State
University of Michigan
*indicates in person or phone interview
University of Minnesota and Affiliates Interviews Internal Audits
Gail Klatt
Internal Audits
Al Willie
Internal Audits
Kelly Kuhns
Human Research Protection Program
Debry Dykhuis
Human Research Protection Program
Linnea Anderson
Human Research Protection Program
Felicia Mroczkowski
Institutional Animal Care and Use Committee
Cory Goracke Postle
Institutional Animal Care and Use Committee
Kristin Pilon
Institutional Review Board
Michelle Biros
Institutional Review Board
Michael Oakes
Center for Bioethics
Steve Miles
Research Compliance Advisory Committee
John Wagner
Implementation Team
Will Durfee
Vice President for Research
Frances Lawrenz
Office of General Counsel
Barb Shiels
Fairview Research Administration
Jill Cordes, Director
Fairview Health Services
Carolyn Williams, CEO
UNIVERSITY OF MINNESOTA
ADVANCING HUMAN RESEARCH PROTECTION
For Cause Investigations Advancing Human Research Protection IRB Policy number 408A – Current For Cause Policy Appendix B
IRB: Investigation Process Policy number: 408A
Date: 03/22/2014
References:
Policy Owner:
AAHRPP I.5.D
Executive Director, HRPP
Cross References: 408 Non-Compliance with Policies & Procedures
Definitions: None
1.0 Reason for Policy This policy describes the process for formal investigation of reports of possible serious or continuing noncompliance.
2.0 Scope of Policy This policy applies to the IRB and HRPP staff.
UNIVERSITY OF MINNESOTA
ADVANCING HUMAN RESEARCH PROTECTION
3.0 Policy Statement
A formal investigation will be conducted under this policy if the Reviewing IRB committee initially reviewing an allegation of non-compliance requests a formal investigation (under Policy 408 Non-Compliance with Policies and Procedures.. Depending on the case, an investigation under this policy is expected to be completed within three months. However, the IRB Committee referring the matter for investigation may grant extensions if warranted and may request interim reports. The Executive Committee, IRB Reviewing Committee and Investigation Panel shall have access to the necessary resources and staff to conduct a thorough and fair review of allegations. Internal and external consultants may be called to assist in the review.
Panel Composition: The Chair of the IRB Executive Committee will designate a three person panel to conduct the investigation. The panel will be comprised of IRB members whose areas of expertise are suited to reviewing the allegation and area of study. Depending on the nature and scope of the allegation, panel members may be relieved of their regular IRB duties during the investigation so as not to be overburdened. As with all IRB processes, any IRB panel member or Executive Committee member who has a conflict of interest or commitment relating to the matter under review will excuse himself/herself from the proceedings and where necessary, an alternate will be designated by the Executive Committee chair.
Panel Charge and Scope of the Investigation:
The Investigation panel will review relevant materials, give the researcher an opportunity to respond to the allegations, interview witnesses as needed, and prepare a report of its conclusions and recommended actions. The panel’s findings and recommendations are advisory to the IRB and must be acted upon by a duly constituted IRB committee to become effective. The Reviewing IRB Committee will recommend the scope of the investigation, however, additional information may emerge during an investigation that justifies broadening the scope of the investigation beyond the initial allegations. The researcher shall be informed if new and different allegations are discovered during the course of the investigation.
Panel Role in Subjects Protection during Investigation: If the Reviewing IRB Committee has not suspended approval of the study prior to requesting a formal investigation, the Investigation Panel will evaluate the adequacy of subjects protection and determine whether a study under review may continue while the investigation is ongoing. As part of this assessment, the Investigation Panel will consider:
UNIVERSITY OF MINNESOTA
ADVANCING HUMAN RESEARCH PROTECTION
the adequacy of the protection plan whether changes are required in the plan or protocol to assure continued safety whether changes are required in the consent forms to be provided to new subjects whether information concerning the event should be shared with current or previous enrolled subjects as it may relate to their willingness to continue whether a formal re-consent of enrolled persons is in order as it may relate to their willingness to continue whether the time frame for continuing review reports should be modified whether additional information is required from the researcher or through a monitoring or audit mechanism.
If the Investigation Panel determines the study should be suspended to assure subjects protection, the panel will recommend suspension to the Reviewing IRB Committee. Depending on the timing of committee meetings and urgency of action needed, however, the investigation panel may refer the suspension recommendation to another duly constituted IRB committee that is able to act sooner on the recommendation. Except in cases of imminent harm to research subjects, the IRB will not suspend approval of a study until the researcher has had an opportunity to respond to the initial non-compliance concerns.
Panel Materials, Interviews and Resources: The Investigation Panel may use any and all materials, reports and responses generated earlier in the review process, and may obtain additional documents and other records relevant to the investigation, such as researcher records, medical charts, grant applications and other scientific or scholarly data. The Investigation Panel will interview witnesses as needed and will summarize or audio record witness interviews. The Panel may draw on the resources of the institution, HRPP Post Approval Review Program, or external consultants to assist in the review of issues which require additional material verification mechanisms and/or expertise beyond or in addition to that available on the Investigation Panel. Researcher Considerations in the Investigation Process:
The researcher under investigation will be given an opportunity to submit written comments, and in cases where termination of IRB approval for research is under consideration, the researcher will have an opportunity to appear before the Panel in person on at least one occasion prior to the Panel issuing its report. The researcher may offer relevant information to the Panel and suggest other individuals to be interviewed.
UNIVERSITY OF MINNESOTA
ADVANCING HUMAN RESEARCH PROTECTION
The researcher also may be accompanied by an advisor, including an attorney, at any time the researcher appears before the Panel. The researcher shall give the Panel notice of the advisor's participation at least 48 hours prior to any interview.
Generally, the researcher under review should have access to the identity of complainant(s) and others who provide information. However, if such individuals are in a status subordinate to the researcher and wish to maintain their anonymity, the IRB will make every effort to protect their identities while at the same time affording the researcher access to the substance of the allegations and information presented against him/her. The IRB cannot guarantee absolute anonymity.
Panel Report: At the conclusion of its investigation, the Investigation Panel will prepare a report summarizing the information it considered and outlining its conclusions and recommended actions. The Investigation Panel will provide its report to:
a) the Reviewing IRB committee that referred the matter for investigation and b) to the researcher under review.
If the researcher disputes the panel’s conclusions or recommended actions, the researcher has 10 working days to submit comments to the Reviewing IRB Committee.
IRB Committee Decision and Notification to Researcher: The IRB Committee will base its decision on the report of the Investigation Panel and any comments submitted by the researcher. Actions the committee may take with respect to the investigation include, but are not limited to one or more of the following:
dismissal of the allegation as unjustified remediation or educational measures increased reporting by the researcher of his/her human subjects research activities restrictions on research practice, such as limiting the privilege to minimal risk or supervised projects suspension of approval for one or more of the researcher’s studies lifting suspension of approval for one or more of the researcher’s studies termination of approval for one or more of the researcher’s studies referral to other University officials or committees for possible further review and action by those bodies
UNIVERSITY OF MINNESOTA
ADVANCING HUMAN RESEARCH PROTECTION
The IRB Committee will issue the final investigative report in a timely manner and send it to the researcher via e-mail followed by a signed copy of the letter. The decision becomes final within 5 working days of release unless the researcher files a written statement of appeal within that time frame.
Appeals/Reconsideration: If the investigation results in a decision to suspend or terminate IRB approval for one or more of the researcher’s studies, the researcher may appeal the decision to the Executive Committee of the IRB under the terms of IRB Policy 410A Appeals of Suspension and Termination. Dissemination Of Findings: At the stage when the IRB’s decision becomes final, the IRB will release its findings to the investigator and to appropriate University and governmental officials as required by IRB Policy 409 Reporting Requirements. Further, it may be necessary to inform these same officials of the status of the proceedings while they are pending. Decisions whether to release the IRB's findings to the public will be made by institutional officials outside the IRB in conformance with the Minnesota Government Data Practices Act. The IRB will not initiate independently any public disclosure of findings.
Coordination with other Investigative Processes: Some complicated cases require review by other institutional or external entities. The IRB will cooperate in the review of allegations of research misconduct, financial mismanagement, FDA inspections, etc. In cases that appear to involve research misconduct, the Investigation Panel may report allegations of such misconduct to appropriate institutional officials. Where research misconduct and IRB investigations are pending against the same researcher, the IRB will coordinate or cooperate in the process to avoid duplication of effort and minimize competing use of resources.
4.0 Required approvals for this document
Title Executive Director, HRPP Counsel to the IRB
UNIVERSITY OF MINNESOTA
ADVANCING HUMAN RESEARCH PROTECTION
5.0 Revision History
Revision
Reason for change
Date of release
03/22/14 07/25/2013 11/03/09 07/10/09 06/16/08
Revision for clarity Revision Revision and update AAHRPP references Revision Revision
09/02/14 08/01/2013 11/09/09
05/16/07
Revision
04/26/07
Revision
09/30/06
Policy Development
To obtain a copy of a historical policy, e-mail the IRB at
[email protected] or call 612-626-5654.
