Guidance for UW Madison Health Sciences IRB & Minimal Risk IRB Primary Reviewers for Summarizing Initial Review Applications

Version Date: March 27, 2017

The HS IRBs assign two primary reviewers to each initial review submission. These reviewers are responsible for providing a brief but sufficiently detailed summary of the submission and analysis as to whether the protocol meets the criteria for IRB approval. Any changes needed to secure approval should be described. The first IRB member listed on an agenda is expected to summarize the study and provide their assessment of the submission. The second primary reviewer can then add his or her additional concerns or describe any disagreements with the first primary reviewer’s analysis. If the first primary reviewer is absent, the second primary reviewer will be asked to summarize the study.

All IRB members are expected to review submissions on an agenda in sufficient depth to participate in discussions and, consequently, the summary should be limited to:

  • The main objectives or purpose of the research
  • Primary subject population and noting whether any vulnerable populations will be enrolled (e.g., children, impaired decision-making, prisoners, pregnant women, low income, veterans)
  • Where the research will occur and whether it is a single- or multi-site study
  • Any unusual or significant risks to subjects
  • The study’s funding, especially noting if it is unfunded or federally funded
In their assessment of the submission IRB members should note whether the following section 111 criteria, which are outlined in the primary reviewer checklist, have been met and, if not, what changes are needed to secure IRB approval.  It is not necessary to recite that each of these has been met in the oral presentation at the meeting.  It is sufficient to state the areas that the committee needs to discuss further or needs to grant a waiver about. The reviewer can then state the other applicable section 111 criteria have been met.
  • Risks to subjects are minimized and whether the study presents minimal risk or more than minimal risk to subjects.
  • Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result.
  • Whether selection of subjects is equitable, there are any additional regulatory determinations needed (e.g., for children, prisoners, pregnant women, VA subjects), and the recruitment processes are acceptable.
  • When some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons, any additional safeguards have been included in the study to protect the rights and welfare of these subjects.
  • Whether the consent form and process are adequate and if any waivers of consent and/or documentation of consent need to be granted.
  • Whether the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects and is appropriate for the level of risk the study presents.
  • Whether the provisions to protect the privacy of subjects and to maintain the confidentiality of data are adequate.

Other issues that may need to be assessed include:

  • HIPAA Privacy Rule, such as waivers of authorization
  • Conflict of Interest that a study team member may have
  • FDA regulatory determinations required, such as a non-significant risk determination for devices
  • VA-specific determinations
  • Staff questions outlined in the staff review
It is not necessary to recite that each of these has been met in the oral presentation at the meeting. It is sufficient to state the areas that the committee needs to discuss further or required regulatory determinations (e.g., waivers of consent or non significant risk determinations for devices).

The primary reviewer should also recommend a review period (i.e., 1 year or less than a year) and propose a motion (e.g., approved as submitted, modifications requested, deferral).


Clinical study example summary

First Primary Reviewer: The purpose of this study is to compare an experimental drug, XY, to placebo for the prevention of progression of Alzheimer’s disease. This study involves adults aged 55-75 who have early onset Alzheimer’s disease. This study is federally funded and involves both the UW and the Medical College of Wisconsin. This study presents more than minimal risk to subjects. Although there are some risks to taking the study drug, I found the screening and monitoring of subjects adequately minimized these risks. Subjects may benefit directly from this study, so the risk/benefit ratio appears reasonable. Subject selection appears equitable as the subjects who will participate are those who are likely to benefit from this research. I also thought that the recruitment materials were approvable as submitted. Individuals with impaired decision-making capacity will be enrolled, but the study team has made adequate provisions for ensuring a legally authorized representative provides surrogate consent when capacity is lost and they will ensure the subjects’ dissent is respected. The consent form and process appear to be appropriate but I would like some specific revisions to the consent form that will help reduce the document’s reading level. I agree that a waiver of informed consent for record review is appropriate and meets the regulatory requirements for a waiver. Although the study does not have a formal data monitoring board, the data monitoring plan provided appears adequate to ensure subject safety. The privacy and confidentiality protections described are also adequate. The staff reviewer asked whether the wash out period for subjects was acceptable. Given that there is no effective treatment to prevent the progression of Alzheimer’s and the monitoring by the study team, this procedure seemed reasonable. I recommend approval for 1 year after the minor consent form modifications are addressed.

Second Primary Reviewer: I agree with the primary reviewer’s comments about the study and agree that it can be approved after minor modifications are made. I had a question about the source of the placebo because this did not seem to be described in the IRB application. If the placebo is provided by the sponsor, this would address my concern. I also noted that the study team plans to test for APOE and plans to disclose the results of the testing to subjects and include this information in the medical record. Such disclosure does not seem consistent with previous IRB determinations. We generally have not allowed disclosure of APOE results because of the risks to subjects and no apparent benefit because the relationship of APOE to Alzheimer’s is still unknown. I agree with the staff reviewer’s recommendations that we disallow disclosure of APOE results. The initial review application will need to be updated to remove this information. I would like the study flyer revised to make it clearer that some subjects will receive placebo. Right now the flyer suggests that all subjects will receive an active treatment. Finally, I would like to see the study team add a neurologist who can provide consultation on some of the neurological testing performed for this study. I think Dr. Badger is the neurologist involved, but the study seems to have forgotten to list her on the IRB application.

Alternate Example Summary

First Primary Reviewer: The purpose of this study is to compare an experimental drug, XY, to placebo for the prevention of progression of Alzheimer’s disease. This study involves adults aged 55-75 who have early onset Alzheimer’s disease. This study is federally funded and involves both the UW and the Medical College of Wisconsin. This study presents more than minimal risk to subjects. The consent form and process appear to be appropriate but I would like some specific revisions to the consent form that will help reduce the document’s reading level. I agree that a waiver of informed consent for record review is appropriate and meets the regulatory requirements for a waiver. The staff reviewer asked whether the wash out period for subjects was acceptable. Given that there is no effective treatment to prevent the progression of Alzheimer’s and the monitoring by the study team, this procedure seemed reasonable. I find that all of the applicable section 111 criteria have been met for this study. I recommend approval for 1 year after the minor consent form modifications are addressed.

Second Primary Reviewer: I agree with the primary reviewer’s assessment and agree that it can be approved after minor modifications are made. I did not have any additional concerns or requests.

Minimal risk study example summary

First Primary Reviewer: The purpose of this study is to collect blood samples for a laboratory study of human T cells. This protocol will involve the prospective collection of blood samples as well as inclusion of existing samples from pathology that would otherwise be destroyed. Only samples from adults will be included. This protocol is unfunded. Although the application states that most samples will be used at UW, some samples will be sent to collaborators at other sites for future research. Given the amount of blood to be collected and the confidentiality measures in place, I think this research presents minimal risk to subjects. The study team provided a good plan for storing samples and keeping directly identifiable information separate from the samples and only sending coded samples with limited information outside of the UW. The risk/benefit ratio appears reasonable. Although subjects will not benefit directly from this research the risks of participation appear minimal. Subject selection appears equitable as the subjects who will participate are those who are likely to benefit from this research in future. No apparent vulnerable populations will be enrolled. The study team presented a combined consent and authorization form for the blood draws that was created through the consent form Wizard. This document and the consent process are fine, but I wanted to discuss with the committee the proposal to allow individuals working in the Department of Surgery to participate as blood donors. I agree that a waiver of informed consent for the inclusion of the leftover pathology samples is appropriate and meets the regulatory criteria for a waiver. I also agree that a partial waiver of authorization is needed for this group of subjects and the criteria for this waiver have been met. I recommend a review period of 1 year and would recommend minor modifications before final approval if the committee is comfortable with the recruitment of Department of Surgery employees.

Second Primary Reviewer: I agree with the primary reviewer’s comments about the study and think that because the study team will post flyers and not actively recruit employees that their inclusion is fine. However, I would ask the study team to confirm that the consent process will not be conducted by someone who is an employee’s direct supervisor. Given the confidentiality protections in place, I am fine with the blood samples being sent outside the UW, but I would like an assurance from the study in the IRB application that the samples will be either exhausted or returned to the UW. In regard to the request to use pathology samples, it does not appear that the study team needs identifiers for their research. I would like pathology to de-identify samples before providing them to the study team. This will require a revision to the IRB application.




Keywords:summary, IRBM   Doc ID:21771
Owner:Faye L.Group:Health Sciences IRBs
Created:2011-12-15 10:36 CDTUpdated:2017-03-27 13:10 CDT
Sites:Health Sciences IRBs
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