This policy describes the principles applied by UW–Madison IRBs in evaluating the scientific or scholarly merits of research protocols and how this evaluation is performed.
Adopted By: Chancellor, UW–Madison
Adoption Date: December 8, 2005
Revised: December 5, 2008
Revised: October 2011
Revised: March 1, 2012 by the HRPP Advisory Committee
UW–Madison IRBs are required to evaluate the merits of a proposed research design to the extent necessary to determine whether (a) the study is designed so that the risks to subjects are minimized, and (b) the risks to participants are reasonable in relation to anticipated benefits, if any, to participants, and the importance of the knowledge that may be expected to result. See, 45 CFR 46.111(a)(1); 21 CFR 56.111(a)(1).
UW–Madison’s IRBs use a variety of means for ensuring the adequacy of a protocol's study design.
Investigators are required to include information about study design in their IRB applications. The IRBs will request additional information from an investigator about study design if necessary to assure that the required IRB review can be performed.
The Health Sciences IRBs collect information via their initial review application regarding study design, including a summary of prior information or knowledge that exists in support of conducting the current study, alternatives to participation in the research study (if applicable), potential benefits of the research, expected risks of the research, an assessment of the risk/benefit ratio by the research team, and a rationale for the proposed number of subjects, including a formal statistical justification for sample size and analysis of results when the research appears to present more than minimal risk to participants.
For most research studies the Health Sciences IRBs require the provision of a formal protocol that describes the background and significance for the proposed study, the study aims/objectives, research design and methods (e.g., eligibility criteria, drug or device information), data safety monitoring plan, statistical considerations, and bibliography and references. The HS IRBs use this information to evaluate the adequacy of the study design.
The Education and Social & Behavioral IRBs (ED/SBS IRBs) collect information via their IRB applications regarding the purpose of the research, the study design and potential risks and benefits of the research.
To ensure that studies meet the criteria for minimal risk, the ED/SBS IRBs also collect additional information from the investigator for:
studies that take place at international sites to address current political, cultural or economic conditions that may relate to potential risk to participants
research that involves collection of any specimens (blood, saliva, body fluids), and
research that may involve participants with impaired decision making.
The IRBs may, when appropriate, collect additional information from investigators.
Study designs used in research protocols that present more than minimal risk receive scientific or scholarly review on the merits through a variety of mechanisms. The Health Sciences IRBs require review by an ancillary scientific review committee in the absence of prior adequate peer review of the scientific or scholarly merits of the research. An individual consultant with expertise in the study design also may be employed. See, Section III of this policy.
To the extent required by Section I of this policy, study designs used in minimal risk protocols, including those that are reviewed as expedited, receive a level of merit review commensurate with the lower level of risk. This may be accomplished solely through a review by the IRB where a committee member or members possess sufficient expertise on the subject matter, review by a consultant with specific expertise, review by an ancillary scientific review committee or funding agency (e.g., National Institutes of Health, National Science Foundation), per Section III, below. Review of study design related to human subjects research that qualifies for exemption is generally limited to feedback on components of study design that appear to raise ethical or regulatory concerns.
UW–Madison has established multiple IRBs, each of which specializes in reviewing particular types of research. Protocols are directed to the IRB with the expertise relevant to the particular protocol. An IRB reserves the right to refer a protocol to another IRB based on the IRBs’ evaluation of which one is best able to provide the necessary expertise.
All UW–Madison IRBs use a primary reviewer system for non-exempt research in which two IRB members are assigned to a protocol and assume responsibility for reviewing the protocol in detail, including an assessment of the merits of the study design to the extent required by this policy. Whenever possible, reviewers are chosen for their expertise in the subject matter(s) relevant to the protocol under review.
In addition, the IRBs may consider the assessments provided to them from ancillary committees, such as the UW Carbone Comprehensive Cancer Center Protocol Review & Monitoring Committee (PRMC) or the Institute for Clinical & Translational Research Scientific Review Committees (ICTR SRCs), to help ensure the adequacy of a protocol’s study design. Because protocols submitted to PRMC or ICTR SRC are usually higher risk studies, they are most often submitted to the HS IRBs. See, Section III of this policy.
If an IRB thinks that additional expertise is needed to evaluate a research proposal, the IRB may request the assistance of an independent consultant or refer non-oncology health sciences protocols for review by the ICTR SRC (oncology protocols are reviewed by the PRMC as described in Section III of this policy). The consultant may be a UW–Madison employee or an outside expert. The consultant’s review is communicated to the IRB as part of the process for review and approval.
Any consultant used by an IRB to evaluate the merits of a proposed study design must satisfy UW–Madison’s conflicts of interest policy applicable to IRB members and consultants. See, IRB Conflict of Interest Policy.
In some cases, the units within UW–Madison require that, in addition to review by an IRB, protocols be reviewed by other independent committees that review or contribute to the review of the scientific merit of the proposed research and the specific protocol procedures.
UW Carbone Comprehensive Cancer Center Protocol Review & Monitoring Committee (PRMC).
As part of National Cancer Institute requirements, all studies involving scientific questions that are cancer-related, that target cancer patients for enrollment, or involve the use or review of biological specimens, data, images, or records from cancer patients require review by the UW Carbone Comprehensive Cancer Center Protocol Review & Monitoring Committee (PRMC). The PRMC assesses the scientific or scholarly merits of all research studies that fall under its purview. The review includes an assessment of the qualifications of the research team to conduct the research, availability of resources to support the research, and the likelihood that the study can achieve its scientific and recruitment objectives.
The requirement for PRMC review encompasses exempt human subjects research and minimal risk research.
The IRBs may rely on the PRMC’s determinations as part of their assessment of the scientific or scholarly merits of a study.
The IRBs require PRMC approval per Sec. II.A.1 before a new protocol or a major change of protocol can be forwarded for IRB review.
Institute for Clinical & Translational Research (ICTR) Scientific Review Committees (SRCs).
ICTR SRCs were created to bolster the scientific review of biomedical protocols
The Health Sciences IRBs require ICTR SRC approval for research studies that meet certain criteria.
Non-oncology protocols that do not qualify for exemption and that do not meet at least one the following criteria are reviewed by the ICTR SRC:
The Health Sciences IRBs may rely on the ICTR SRCs’ determinations as part of its assessment of the scientific or scholarly merits of a study.
The Health Sciences IRBs require ICTR SRC approval before a new protocol can be forwarded for IRB review.
The ICTR SRC provides correspondence to the IRB that outlines any suggestions or issues for the IRB to consider in its review, but that the SRC did not find to invalidate the study design.
Notwithstanding the above, any UW–Madison IRB may request review of a protocol by the ICTR SRC if the IRB requires additional expertise to review the scientific merits of a protocol.
Clinical and Translational Research Core (CTRC) Protocol Implementation Review Committee (PIR).
Any research study that proposes to use ICTR Clinical and Translational Research Core (CTRC) services must undergo review by its Protocol Implementation Review Committee (PIR). The PIR reviews the research study to determine whether CTRC can accommodate the study and whether the research can be implemented as described in the protocol.
Madison VA’s Research & Development Committee.
Any research study that falls under the purview of the Madison VA requires review and endorsement by the Madison VA’s Research & Development Committee before review by the convened IRB can occur, for studies that require full board review, before a study reviewed under expedited procedures can receive final approval from the IRB, or before an IRB member grants an exemption determination for a project involving human subjects research.
If there is a question about the study design, the IRB may:
Ask the investigator to provide additional information to:
Explain and/or justify the design, or
Change the design to satisfy the IRB’s concerns;
Disapprove the research, if the concerns about study design cannot be resolved.
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