Ongoing Discussions between Clinical Chairs and the IRB (March 1, 2004)

Memorandum

TO: Faculty, School of Medicine

FROM: Arthur S. Levine, MD
Senior Vice Chancellor and Dean, School of Medicine

Loren H. Roth, MD
Associate Senior Vice Chancellor for the Health Sciences and,
Senior Vice President Quality Care and Chief Medical Officer, UPMC

Randy P. Juhl, PhD
Vice Chancellor, Research Conduct and Compliance

DATE: March 1, 2004

Ongoing Discussions between Clinical Chairs and the IRB

Over the past several months we have been working together with the School of Medicine Clinical Chairs and representatives from our Institutional Review Board (IRB) Office to address emerging issues in our ongoing efforts to maintain a top flight clinical trials research enterprise that is fully compliant with human subjects protection regulations as well as with the ethical principles that underlie those regulations. Beginning in November we identified a number of areas wherein potential improvements could be made. In the following paragraphs we describe the current status of these discussions and the changes that have been and will be implemented in an attempt to make additional progress in achieving these mutually desirable goals.

I. HIPAA, the Common Rule and related medical record privacy considerations.

A focal point of our discussions has been the various issues and complex requirements surrounding the use of patients’ personal health information in the context of identifying and recruiting patients to become subjects in clinical research. There are three sets of regulations/policies that set forth obligations for investigators who wish to access and utilize patients’ personal health information for this research activity: HIPAA, the Federal Policy (Common Rule) regulations governing human research subject protections, and UPMC (or other health system) medical record privacy policies. In addition, there are ethical considerations related to the privacy of medical record information that must be weighed by our faculty colleagues and community volunteers who are members of the University IRB, the committee responsible for protecting the rights and welfare of individuals asked to participate in research studies.

Steering a proposal through the IRB requires that all of these regulations/policies and ethical considerations are adequately and appropriately addressed. Although there are nuances and subtle differences between the sets of requirements/policies, the common ethical premise is that the privacy and confidentiality of patients’ identifiable medical record information, when used for research purposes, must be respected.

The IRB has implemented several mechanisms that are available for investigators to utilize in identifying and recruiting subjects while maintaining regulatory and ethical compliance:

Model requests for waivers of written HIPAA authorization and/or informed consent. These model waiver requests, when appropriate to the situation, may be inserted into an IRB submission. They contain wording that has been pre-approved by the IRB as fulfilling the ethical (i.e., privacy and confidentiality) concerns and regulatory requirements for the specific situations described. These model requests for waivers can be found on the IRB web site along with an introductory guidance document: https://www.irb.pitt.edu/guidance-forms

Use of honest broker systems/processes. Researchers who are not involved in the care of the respective patients (and thus for whom the model request for a waiver of informed consent does not apply) may access and use medical record information for research subject identification and recruitment purposes through the use of an “honest broker” system/process. In this situation, the “honest broker ” (i.e., an individual [and/or a computer software system] who [which] is an agent of the health care provider and independent of the research project) reviews the medical record information on behalf of the researcher and provides the researcher with the de-identified medical record information of potentially eligible subjects based on inclusion/exclusion criteria initially provided by the researcher. The researcher subsequently identifies those medical record sets that appear to be eligible for study participation and communicates this back to the honest broker. The honest broker then provides the identities of the corresponding potentially eligible subjects to their primary physicians for subsequent contact to determine their interest in study participation. The forms for establishing an honest broker system at the school, department, division or center level can be found on the IRB web site (https://www.irb.pitt.edu/guidance-forms) and personalized assistance in establishing such a system can be obtained by calling the IRB Office (Teri Merolli Reiche or Patricia Orndoff @ 412-383-1480)

Research registries. Patients are asked to provide prospectively their written informed consent (authorization) to allow their identifiable medical record information related to their particular disease or condition to be placed in a research registry for the purpose of facilitating retrospective research studies and the identification and recruitment of potential, eligible subjects for participation in future research studies related to their disease. A model IRB protocol and informed consent document for establishing a research registry can be found on the IRB web site (https://www.irb.pitt.edu/guidance-forms). For additional information on establishing a research registry, call the IRB Office (Teri Merolli Reiche or Patricia Orndoff @ 412-383-1480)

Institution-wide registry. Work is underway between the UPMC and the IRB to implement a system-wide research registry that will involve obtaining prospectively the permission of all willing UPMC patients to permit the use of their medical record information for retrospective research studies and for prospective subject identification and recruitment purposes, and to permit researchers to contact them directly if it is determined that they may be eligible for participation in a research study.

Compliance with the HIPAA rule, in interaction with the Common Rule, requires interpretation by the IRB and UPMC. Both entities are reviewing their regulatory approach to HIPAA and maintaining a watchful eye on national developments related to the potential for harmonization of regulatory interpretations of activities permitted by HIPAA as “preparatory to research.” The conditions under which researchers without a clinical care relationship to the prospective research subjects might access their records remain under discussion. Formulation of an additional model waiver possibly permitting greater latitude under both HIPAA and the Common Rule is under consideration. For now, however, faculty are advised to make use of the four options listed above to insure their work is in compliance with regulatory requirements. Assistance, in the form of individualized assistance or group workshops, is available through the IRB Office. Contact Teri Merolli Reiche or Patricia Orndoff @ 412-383-1480.

II. IRB Review of Protocol Reconsiderations, Renewals and Modifications

To clarify, for both investigators and IRB members, the IRB Executive Committee has defined the operational principles related to the scope of IRB review for research protocols submitted for Reconsideration, Renewal approval, and approval of Modifications. In general when protocols are returned to the IRB for reconsideration, the review process is focused at the deficiencies and concerns that were cited at the time of the initial review. When protocols are submitted to the IRB for renewal approval, the review is focused primarily on reports of Data Monitoring Plans, new information affecting the potential risks of study participation, and any new regulatory requirements. Review of modification requests will be focused at an assessment of the appropriateness of the requested modification(s) and its (their) impact on the risk to benefit ratio of study participation.

In all instances, the reviews may identify substantive issues affecting risk and regulatory compliance in any section of the protocol and consent, and a request for changes or additional information directed at addressing these substantive issues might result. The IRB vice chair who presides over the reviewing IRB committee has the prerogative and responsibility to determine whether the request for changes or additional information is sufficiently substantive to be disseminated to the principal investigator.

III. Review of Multi-Center Trials

In accordance with the University’s current assurance agreement with the Office of Human Research Protections, Department of Health and Human Services, multi-center clinical trials, even if they have been previously reviewed by a central IRB or scientific review entity, must still be reviewed and approved by the University IRB. Specific issues related to the conduct of research at this site and changes to the informed consent document as necessary to address local policies and/or standards are expected and generally accommodated by external sponsors of multi-center clinical trials. However, because of the scientific need for uniformity among the many sites involved in the conduct of multi-center trials and/or because of prior federal agency (e.g., FDA, NIH) acceptance of the design of the multi-center trial, requested changes by the local IRB in the basic elements of the protocol design will generally not be accepted by an external sponsor of the trial. Therefore, the University of Pittsburgh IRB will not request changes in the critical elements of design (as defined through communications with the investigator) of externally-sponsored, multi-center investigations. In those rare instances when the study, as viewed by a majority of the members of a University IRB committee, does not provide an acceptable risk-to-benefit ratio because of unchangeable study design elements, the protocol will be returned to the investigator as “Disapproved” with an explanation of the rationale for such action. Outside of this particular case, protocols will undergo a standard review.

IV. Deployment of IRB members’ expertise/Dispute resolution process

The primary functions of the IRB are to make a risk to benefit assessment of the proposed research on behalf of prospective research subjects and to ensure that individuals are fully informed of issues related to their rights and welfare as research subjects. As such, the IRB does not evaluate the underlying science of the proposal to the level of detail of an NIH study section, but there is a need (indeed there is a Federal requirement) that the members of the IRB understand the science in sufficient depth to make an informed risk to benefit assessment. The availability of the requisite scientific and clinical expertise is an important element in performing a proper review of an IRB submission. The availability of expertise is dependant upon a number of factors including the unique character of the research in question, the willingness of faculty with specific expertise to be IRB members, IRB members’ attendance at IRB meetings and the distribution of expertise among the IRB’s eight committees.

This discussion topic arose from an oft-expressed complaint that negative decisions by colleagues on the IRB occur because the committees lack sufficient expertise to understand the science underlying the proposals. However, a review of the IRB’s records reveals that the most common reason for a protocol to be “Reconsidered” is the omission, or incomplete explanation, of a required element necessary to define the risk to benefit ratio for the prospective research subjects. Reconsideration stemming from a disagreement about the underlying science or related standards of clinical care is not common. Thus, we have two groups of faculty (IRB members and investigators) viewing the same data but reaching different conclusions as to the source of the difficulties. Naturally, the proposed remedies vary depending on the respective definition of the problem.

Before implementing a solution to this problem – and several thoughtful and creative solutions were proposed, including expanding expertise in certain areas, for example cancer or neuroscience, into a smaller number of IRB committees – we believe that we first need to better define the issues. Thus, we will establish a dispute resolution mechanism, which will allow us to prospectively collect and categorize the difficulties investigators are having securing IRB approval. We expect that implementing this new process and collecting sufficient data to provide meaningful insight for both the IRB and the academic leadership will take no longer than six months.

This mechanism will also provide an avenue for present and future mediation in specific cases. It has been our experience that a calm discussion of the facts can often identify an alternate path for approval of the research while still maintaining our regulatory and ethical responsibilities. Please note that neither of us is empowered (nor inclined) to reverse or override an IRB decision not to approve a particular protocol. Ultimately it is the investigator and colleagues on the IRB who must come to an understanding that respects both the science and the rights and welfare of the human subjects. We will provide you with additional details of the dispute resolution process as it becomes available through the Senior Vice Chancellor’s Office of Clinical Research in the next few weeks.

V . Other Initiatives

In conclusion, we also note several ongoing initiatives which, when fully implemented, will assist investigators in various ways. These include:

A. Electronic Guided IRB Submission. The guided electronic submission of IRB proposals will provide an easier path to composing a complete IRB submission for investigators and a more efficient mechanism for the IRB Office to deal with its responsibilities (no more 26 copies of your submission). We have contracted with a company named Webridge to install their automated, web-based system for our IRB. There are a handful of other leading medical centers that have signed on with Webridge (U of Washington, Washington U, Hopkins, USC, etc). We have enhanced their standard package to provide a guided submission process for our investigators (ie: short answer, branching questions vs. the current term paper approach). The most common reason for a protocol to be reconsidered is that it lacks complete information to allow for the review of one or more of the required human subject protection elements. We believe the short-answer guided process will make it much easier to provide a complete package that can be approved on the first review. Our goal is to have fewer than 10% of the new, full-board review protocol submissions be reconsidered. Currently the rate is 27%.

B. Office of Research. The Office of the Provost and the Office of Research management are implementing a strategic plan for infrastructure improvement that includes process re-engineering, hiring of additional staff and implementation of enterprise IT solutions to enhance the research administration environment.

C. Clinical Trials Office. An innovative proposal to establish a Clinical Trials Office is under active consideration. The purpose of the office would be to coordinate all necessary approvals for privately sponsored clinical trials (contract negotiation, budgetary and reimbursement review, risk management assessment, IRB approval, etc.). Germane to the topic of this memo, faculty meeting certain qualifications would be able to employ the approval of an external IRB for their participation in many of our privately funded clinical trials.

D. IRB Accreditation. As a result of numerous reports and studies over the past four years, the call has been issued and responded to for increased public scrutiny of IRBs. There is near unanimous agreement that accreditation of IRBs is a desirable public policy strategy. Although accreditation of IRBs is a new (and as yet voluntary) process, it will become a de-facto standard that all institutions will need to meet. The University IRB is in the process of conducting a comprehensive self-study in advance of submitting our application for review by the American Association of Accreditation of Human Research Protection Programs (AAHRPP). This activity will insure we are competitive with other institutions and will provide useful, independent markers against which we may measure the quality of our university-wide human subjects protection program, as it operates both at the IRB level and within the academic units.

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Should you have questions individually or as a group we would be happy to meet with you to receive your thoughts on the preceding topics and issues.

cc: Chancellor Nordenberg
Provost Maher
UPMC President Romoff
Deans of the Health Sciences Schools

[Updated: December 2020 to provide current link to current Human Research Protection website (formerly Institutional Review Board.]

[Updated May 2021 to provide updated links to IRB forms.]