The collective effort of the University's Human Research
Protection Program, which acts on behalf of clinical research
subjects and clinical investigators, is designed to improve
the human condition through research. The diversity of both
the investigator community and the Institutional Review Board
membership occasionally results in differences of opinion
with respect to the local interpretation or implementation
of the regulatory process that governs clinical research.
These differences in opinion are commonly resolved by direct
communication between the investigator and the IRB leadership,
staff and/or committees. However, there are occasional disagreements
that cannot be resolved by this mechanism. The present document
is a policy that provides a formal process that (1) enables
investigators to formally register complaints, express concerns
and make constructive suggestions about the operation of the
IRB, and (2) identifies the mechanism of investigation of
complaints and disagreements between investigators and the
IRB. This process requires investigators to complete a web-based
form and submit appropriate documentation to support their
complaint. The Associate Vice Chancellor for Clinical Research,
Health Sciences and the Vice Chancellor for Research Conduct
and Compliance will evaluate and investigate the issues raised
and will determine what subsequent actions, if any, should
be taken by the IRB or the investigator to address the issues
and/or minimize the likelihood of their recurrence. The process
will include communication with all the relevant parties to
collect additional information as well as the transmittal
of the findings, recommendations and resultant actions back
to the investigator, the IRB, and the investigator's dean,
chair, director or chief, as is appropriate.
Introduction
The purpose of the University's Human Research Protection Program is to act on behalf of clinical research subjects to protect their rights and welfare and reduce their potential risks of study participation through a campus-wide program based upon education, regulation, peer review and the informed consent process. The University's Institutional Review Board (IRB) is an integral component of this program. Although one would hope for unanimity in our collective efforts to improve the human condition through research, given the diversity of both the investigator community and the volunteer faculty and non-faculty who serve as IRB members, differences of opinions will occur. That these differences of opinion occur is not in and of itself a problem. In fact the federal regulations governing human subject protections, by mandating a diverse IRB membership, encourage challenges of the proposed research.
Recently there have been productive discussions about methods to increase the effectiveness of communication for all parties. The following guide has emanated from those discussions.
The IRB Submission
Most problems with the IRB cited by investigators arise from a negative review of their human subject protection proposals which necessitates that the investigator re-work and re-submit their protocol for reconsideration at another convened meeting of an IRB committee. Although this happens with less than 25% of initial submissions requiring review by an IRB committee, the associated time delays and increased work for investigators, colleagues on the IRB and the IRB Office staff can be substantial.
A review of IRB records reveals that the primary reason IRB submissions are subjected to the requirement for reconsideration is because the initial submission was incomplete or addressed inadequately one or more of the required elements of human subject protection. Occasionally there are legitimate and spirited ethical discussions and disagreements between investigators and their colleagues on the IRB about the scientific validity or quality of the proposed research or about what constitutes current clinical care standards; however this is not the rule.
Thus, the important first step to navigating the IRB review and approval process is to prepare a complete and well-written initial human subject protection proposal. Over the past several years, the task of preparing an IRB submission has become more complex as a result of ever-increasing Federal regulatory requirements and the complexity of our research. We recognize that this places additional demands upon investigators and their research staffs; however it is unlikely that these trends will change in the future. Therefore, investigators are urged to refer to the IRB Reference Manual for the Use of Human Subjects in Research for guidance in the preparation of their IRB submissions. This Reference Manual is continually updated as new Federal and IRB policies are enacted and may be readily accessed via the IRB website (www.irb.pitt.edu). It is also recommended that, upon accessing the IRB web-site, investigators and their research staffs join the IRB's e-mail listing, which provides a mechanism for the IRB to direct new information and IRB submission requirements to clinical investigators.
In addition, it is not without purpose that the IRB submission is referred to as a "human subject protection proposal." It is tempting when preparing an IRB submission to simply cut-and-paste sections from a corresponding research grant or sponsor's clinical protocol. However, it must be remembered that the primary role and function of the IRB is the protection of the rights and welfare of research study participants. Thus, addressing only the scientific aspects of the proposed research will likely result in an incomplete or inadequate IRB submission.
The academic units (schools, departments, divisions and centers, as appropriate) are encouraged to make a pre-IRB submission review service available to their clinical investigators. Other unit faculty who are current or former IRB members can be a valuable resource in this regard. This task can be done concurrent with, or separate from, the unit's scientific review process. Human subject protection issues and omissions detected and corrected at the unit level will serve to reduce the chances for a negative review by the IRB; thus investigators are encouraged to take advantage of the unit's resources in the preparation of their IRB submissions.
Investigators are also encouraged to utilize the resources of the IRB Office. The IRB Office staff is more than willing, and in fact prefers, to work with investigators to develop a human subject protection proposal that will be acceptable to the IRB on initial submission rather than having to assist in the remedial action and deal with the consternation associated with a proposal requiring reconsideration.
The Review Summary
Within four working days of the IRB committee meeting, a summary of the committee's appraisal is transmitted to the principal investigator. The two most common verdicts are:
Approval with modifications - revisions can be reviewed and final approval granted by the IRB Chair or Vice Chair without re-review by the entire IRB committee, or
Reconsideration - unanswered questions remain which may materially affect the risk to benefit considerations. Thus, by regulation, the revisions must be re-reviewed by a full IRB committee.
Regardless of the category, investigators should respond thoughtfully to each item included in the IRB's appraisal. Much like dealing with a manuscript reviewer's comments, most requests for revisions are straightforward. However, it is acceptable to disagree with an item by clearly and authoritatively stating the countervailing case. The stated case may or may not be accepted, but communication about the disagreement is encouraged.
The IRB chairs and the IRB Office staff make every effort to insure that communications to investigators are clear and relevant. However, given the volume (nearly 5000 submissions/yr) and complexity of many of these communications, questions of interpretation are bound to arise. The IRB chairs and the IRB Office staff welcome the opportunity to clarify (via phone or email) the intent of the comments found in the IRB's appraisal and to assist the investigator in preparing their written response.
Mechanisms for Engaging Supplemental Expertise
Thoughtful and genuine efforts at each step of the IRB submission and review process should mitigate most disagreements. However, it is not uncommon for faculty colleagues who conduct research in related areas to have differences of opinion about the basic elements of the science and interpretation of findings. Thus it should not be surprising that faculty colleagues who serve on the IRB may have honest differences of opinion with basic scientific principles or study design features of a colleague's human subject protection proposal. On occasion, these differences raise questions that may impact the IRB committee's determination of the relative risks and benefits of participation in the clinical investigation. When this type of issue arises and persists, there are options for the investigator and the IRB to engage that may facilitate an understanding that serves both our collective regulatory responsibilities and the science embodied in the proposal.
If the IRB determines that an IRB submission must be reconsidered at a subsequent IRB meeting, the investigator will be invited to attend the subsequent meeting to address any outstanding issues. Furthermore, the investigator may bring, with prior notification of the IRB Chair or Vice Chair who will preside over the reviewing IRB committee, an expert in the area under discussion to address specific IRB concerns if he/she believes it would be helpful. Investigators are encouraged to take advantage of these opportunities.
The IRB has in place policies and procedures wherein an IRB committee may request, at any time, the involvement of additional expert consultants in its review of an IRB submission. The expert consultants may be one or more colleagues from a different IRB committee, faculty colleagues who are not IRB members or on rare occasions, a panel of outside experts. The experts will be considered advisors to the IRB, which, by regulation, retains the decision making responsibility.
As a result of preliminary (pre-submission) discussions, the IRB may seek additional expertise to review a protocol that appears to be controversial in one or several aspects. Similarly the investigator may enlist the assistance of colleagues with specific expertise to provide additional information as part of the submission. Both investigators and IRB chairs are encouraged to be pro-active in this regard as early recognition may lead to a speedier resolution.
Additional details regarding the specific procedures of the options listed above may be obtained by contacting the vice chair for the committee that reviewed the protocol.
The Complaint Process
The University's leadership, as well as the IRB leadership, recognizes that actions of the IRB are subject to scrutiny by the local research community as well as by the Federal regulatory bodies. The University's research community should be provided with an avenue to express concerns and make constructive suggestions about the operation of the IRB. Additionally, the IRB leadership would much prefer to learn of and respond to concerns as part of a formal process. The ultimate goal of protecting the rights and welfare of human research subjects according to our regulatory obligations is best served through open, honest, and respectful exchanges by all involved. Therefore the following process has been established to register complaints not resolved by the mechanisms described above, or to register other types of problems encountered with the IRB review and approval process, or to suggest improvements in our human research subject protection program.
A principal investigator wishing to raise an issue regarding the IRB should document his/her concerns or suggestions in writing according to the prescribed format http://www.clinicalresearch.pitt.edu/irbdisputes/. The completed document and supporting materials should be forwarded to the Office of Clinical Research, Health Sciences (OCR). The Associate Vice Chancellor for Clinical Research, Health Sciences and the Vice Chancellor for Research Conduct and Compliance will together evaluate the issues raised and will determine what subsequent actions, if any, should be taken by the IRB or the investigator to address the issues and/or minimize the likelihood of their recurrence. The process will include communication with all the relevant parties to collect additional information as well as the transmittal of the findings, recommendations and resultant actions back to the investigator, the IRB, and the investigator's dean, chair, director or chief, as is appropriate. Please note that neither the Vice Chancellor nor the Associate Vice Chancellor is permitted, by Federal regulation, to overrule a negative decision by the IRB.
The OCR will create and maintain a database to categorize and track complaints and suggestions and their disposition. The database will be used by the Associate Vice Chancellor for Clinical Research, Health Sciences and the Vice Chancellor for Research Conduct and Compliance to determine the frequency of various types of problems that are encountered by investigators, findings of investigations, and resultant actions that are taken as part of the ongoing process of improving our human subject protection program.
For additional details, please view the IRB website or call the OCR.
