Human Research Protection Program: Policy

Initial Review of Research by Full IRB

Adopted By: All Campus IRB

Adoption Date: November 10, 2005

Revised: April 12, 2007

Revised: January 22, 2009

Purpose:  This document describes the policies and procedures of the UW-Madison IRBs for conducting initial review of protocols by the full IRB.

Policy

I.      All human subjects research must be reviewed and approved by an IRB, unless determined to be exempt, prior to the start of human subjects research activities.

II.     All new protocols that are not determined to be eligible for an exemption or for expedited review are reviewed by the full IRB.

A. Full IRB review is required for:

 

1.     all research projects involving the use of investigational drugs, devices, or biologics for which an Investigational New Drug (IND) or Investigational Device Exemptions (IDE) is required; see, Test Article Review Policy

 

2.     use of a Humanitarian Use Device; HUD Policy

 

3.     emergency use of a test article; Emergency Use of Test Article Policy

 

4.     research projects involving any of the following:

 

a.     deception

 

b.     collection of identifiable data concerning individuals engaged in illegal or

       stigmatizing behaviors (e.g., illicit drug use, child abuse, alcoholism, or gambling)

 

c.     interactions or interventions with prisoners, the cognitively impaired or

       institutionalized individuals (e.g., in a mental health facility, nursing home, or

       halfway house)

III.    Review Criteria

A.  To approve research involving human subjects, UW-Madison IRBs must determine that the following requirements are satisfied:

 

1.     Risks to subjects are minimized.

 

a.     Risks to participants are minimized by using procedures which are consistent with sound research design and which do not unnecessarily expose participants to risk, and

 

b.     Whenever appropriate, risks to participants are minimized by using procedures already being performed on the participants for diagnostic or treatment purposes.

 

2.     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 from the research.

 

3.     Selection of subjects is equitable.

 

4.     Informed consent will be sought from each prospective subject or the subject's legally authorized representative and will be appropriately documented as required by 45 CFR 46.116 and 46.117.

 

6.     When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects.

 

7.     When appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data.

 

8.     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, additional safeguards have been included in the study to protect the rights and welfare of these subjects. (45 CFR 46.111)

For additional information, see UW-Madison policies on Risk-Benefit Analysis, Equitable Selection, Informed Consent, Review of Data and Safety Monitoring, Protection of Privacy and Confidential Data, Research with Vulnerable Populations.   

Procedure

IV.   Preparing a Protocol for Initial Review by the Full IRB

A.  SBS IRB and ED IRB protocols: To apply for review of a new protocol, the investigator must submit to the appropriate IRB an Application for Initial Review of Research.

B.  HS IRB and MR IRB protocols: To apply for review of a new protocol, the investigator must submit to the appropriate IRB an Application for Initial Review of Research.

C.  Protocols may also be referred from one IRB to another IRB depending on the nature of the proposed research and the expertise of the IRB.  See, Review by Experts Policy.

V.    Screening of Protocols

A.  The IRB Office conducts a preliminary review of each protocol to determine whether the materials provided by the investigator are complete and contacts the investigator to obtain missing documents.  Incomplete submissions may be returned to the investigator. 

B.  Once all requested information is received, the IRB Director determines whether the protocol will be reviewed by the full IRB or is eligible for expedited or exempt review.  If the protocol is eligible for expedited or exempt review, the IRB Office will follow UW-Madison’s expedited and exempt review procedures. See, policies on Exempt Research and Expedited Review.

VI.   Review of Protocols

A.  If the IRB Director determines that a protocol will be reviewed by the full IRB, the review proceeds as follows:

 

1.     ED IRB and SBS IRB. Both the ED IRB and SBS IRB use a primary reviewer system for all initial reviews by the full IRB.

 

a.     For each IRB, at least two primary reviewers, who are members of the IRB, are assigned to each application for initial review to be reviewed by that IRB. See, Review by Expert Policy. The assignments are made by the ED/SBS IRB Director and reflect the expertise of the primary reviewers.  The IRB Office also checks for conflicts of interest between primary reviewers and research protocols. See, IRB Conflict of Interest Policy.

      

b.     The Education and Social and Behavioral Research Offices forward all of the materials submitted by the investigator to each IRB member, including any alternate substituting for an IRB member, except for any relevant grant application, any DHHS-approved sample consent document (when one existed) and the complete DHHS-approved protocol (when one existed), which are reviewed by one IRB member.  The grant application and any additional information provided to any primary reviewer are available from the Education and Social and Behavioral Research Offices to any IRB member who wishes to review it before or during the convened meeting.

      

c.     The assigned primary reviewers and the IRB member who is provided the grant application and DHHS-approved consent document and protocol, conduct the in-depth review of the application for continuing review and all provided materials, and lead the discussion of the application at the full IRB meeting.  All other IRB members, including any alternate substituting for an IRB member, are expected to review the provided materials in enough depth to be familiar with them and be prepared to discuss them at the convened meeting.

 

2.     HS IRB and MR IRB.  The HS IRB and MR IRB use both a staff reviewer and primary reviewer system for all initial reviews by the full IRB. 

 

       Staff reviewers [See, Review by Experts Policy] conduct the first review of a research protocol submitted to the HS IRB and MR IRB.  Protocols are assigned to staff reviewers by the IRB Director.

 

The IRB Office forwards all of the materials submitted by the investigator to the assigned staff reviewer.

 

The staff reviewer evaluates the research protocol, consent documents and any other accompanying materials for compliance with federal regulations, UW-Madison policies, and ethical principles relating to human subjects' protections, safety and potential medical concerns as well as compliance with the HIPAA Privacy Rule and may make recommendations to the primary reviewers and IRB. 

 

The staff reviewer sends the completed protocol evaluation and any written recommendations to the primary reviewers assigned to the protocol.  Copies of the staff review are also provided to all other IRB members, IRB legal counsel and IRB Office Director.  The staff reviewers guide the IRB through regulatory citations, e.g., for waiver of informed consent, waiver of documentation of informed consent, device regulations, IND regulations, regulations covering vulnerable populations (e.g., pregnant women, prisoners, children).

 

Assignments of primary reviewers, who are IRB members, are made by the IRB Director and reflect the expertise of the primary reviewers.  See, Review by Experts Policy.  The IRB Director also checks for conflicts of interest between primary reviewers and research protocols. See, IRB Conflict of Interest Policy.

 

The IRB Office forwards all of the materials submitted by the investigator, except for any relevant grant, to the primary reviewers, including any alternate substituting for an IRB member, who also receive the staff reviewer’s evaluation and recommendation regarding the protocol.  The primary reviewers are also provided with a reviewer sheet that contains guidance regarding relevant regulations and the criteria for review and approval of protocols.  The primary reviewers use the reviewer’s sheet to document their protocol review.

 

The assigned primary reviewers conduct the in-depth review of the protocol and all provided materials, and lead the discussion of the protocol at the full IRB meeting. All other IRB members, including any alternate substituting for an IRB member, are expected to review the provided materials in enough depth to be familiar with them and be prepared to discuss them at the convened meeting.

 

The IRB Office forwards the staff review and all of the materials submitted by the investigator to the other IRB members with the following exceptions:

 

Ÿ         any relevant grant application, DHHS-approved consent form and/or DHHS-approved protocol (when they exist) are reviewed only by one IRB member (any IRB member may request a copy of the grant for review)

 

Ÿ         any investigator’s drug brochure is sent only to the assigned staff

reviewer and primary reviewers

 

Additional information provided to any primary reviewer is available from the IRB Office to any IRB member who wishes to review it.

B.  After the full IRB discusses the protocol, the full IRB makes the determination whether to approve the protocol, require modifications in the protocol, defer the protocol until additional information is obtained, or disapprove the protocol.  [See, Section III, below]

C.  If, after discussion by the full IRB, questions remain unanswered, the IRB may request additional written information from the investigator and may invite the investigator to meet with the IRB during the next review to answer questions. 

D.  In reviewing a protocol, the full IRB may also consult with individuals representing areas of expertise not represented on the IRB. 

VII.   IRB Determinations

A.  On initial review of a protocol, the full IRB may:

1.     approve a protocol,

2.     approve a protocol pending resolution of required modifications,

3.     defer a protocol until additional information is obtained, or

4.     disapprove a protocol.

In each case, the IRB Office notifies the investigator in writing of the action taken and the reasons for that action.  Where necessary, the IRB Office also reports the IRB action to appropriate University officials or, where the protocol is submitted by an investigator from another institution for whom the IRB acts as the IRB of record (e.g., the Veterans Administration), to appropriate officials within that institution.

B.  To approve a protocol pending resolution of requested modifications:

 

1.     IRB members may agree during an appropriately convened meeting of the full IRB to approve a protocol pending resolution of requested modifications (contingent approval) if the requested modifications are non-substantive changes that are not relevant to the determinations required by the IRB under the Common Rule or its subparts (45 C.F.R. part 46) or, as applicable, FDA regulations (21 C.F.R. part 56).

 

Contingent approval also is permitted in situations where the IRB stipulates specific revisions requiring simple concurrence from the investigator.

 

If substantive clarifications or modifications regarding the protocol or informed consent documents are required as a condition of approval, approval must be deferred pending subsequent review by the convened IRB of responsive material (See, Section IV.C, below)

 

2.     The investigator will be notified of those modifications and must respond to these requests according to IRB directions.

 

3.     If a protocol is approved pending resolution of requested modifications, the IRB office will notify the investigator of those modifications and instruct the investigator that he or she must respond to these requests according to the IRB’s directions.

 

4.     An IRB member(s) reviews the investigator’s response and either

 

a.     approves the protocol, or

 

b.     if the investigator’s response is not consistent with the IRB’s directions, sends the response back to the full IRB.

 

If a staff reviewer process is used to review an IRB’s request for modifications, the staff reviewer works with the investigator to obtain the modifications requested by the IRB.  The staff reviewer then forwards the investigator’s response to an IRB member(s) for review along with a staff report and recommendation as to whether the investigator’s response has satisfied the IRB’s request for modifications. The IRB member(s) reviews both the investigator’s response and the staff report and recommendation before deciding to approve the protocol or to send it back to the full IRB as per Section IV.B.4.

 

5.     The full IRB will be provided, on a routine basis, a list of research protocols approved by the full IRB pending resolution of requested modifications that were subsequently granted final approval by an IRB director or IRB member(s) designated by the IRB office to conduct expedited reviews. IRB members shall be provided access to the IRB files for any research study in which they may have a concern.

 

6.     Notifications to investigators of requested modifications.

                                       

a.     SBS IRB and ED IRB: At intervals of 60 and 120 days from the date the modification request was first sent to the investigator, the electronic protocol management system automatically sends a reminder to the investigator of the need to respond to modification requests and obtain IRB approval of the research before research can begin.  If a response is not received from the investigator within 180 days of the first request for modifications, the electronic protocol management system automatically sends a notice to the investigator that the protocol has been closed and will need to be re-submitted for reconsideration before the research to proceed.

 

b.     HS IRB or MR IRB: The HS IRB and MR IRB do not send out automatic reminders.  However, if they fail to receive a response from the principal investigator to any modification requests, then the protocol is terminated.

C.  To defer a protocol until additional information is obtained:

 

1.     The IRB must defer approval of a protocol if, to approve  the protocol, the IRB requires substantive clarifications or modifications of the protocol or informed consent documents that are relevant to the determinations required by the IRB under the Common Rule or its subparts (45 C.F.R. part 46) or, as applicable, FDA regulations (21 C.F.R. part 56).

 

2.     The IRB will notify the investigator of the substantive clarifications or modifications needed to allow approval of the research.

 

32.   The investigator may supply the substantive clarifications or modifications or provide a rationale for not doing so. The protocol will then be re-reviewed by the full IRB.

 

·         For SBS IRB and ED IRB protocols, if the full IRB has determined in its deferral that the protocol is eligible for expedited review, the review of additional substantive clarifications or modifications supplied by the investigator may be done by an IRB subcommittee.

 

·         If a staff reviewer process is used to review an investigator’s response to an IRB’s request for substantive clarifications or modifications, the staff reviewer works with the investigator to obtain the substantive clarifications or modifications requested by the IRB.  The staff reviewer then forwards to the  IRB the investigator’s response along with a staff report and recommendation as to whether the investigator’s response has satisfied the IRB’s request for substantive clarifications or modifications. The IRB reviews both the investigator’s response and the staff report and recommendation before deciding whether to approve the protocol.

 

43.   At intervals of 60 and 120 days from the date of the notice requesting additional information was first sent to the investigator, the electronic protocol management system automatically sends a reminder to the investigator of the need to respond to information requests and obtain IRB approval of the research before research can begin.  If a response is not received from the investigator within 180 days of the first request for additional information, the electronic protocol management system automatically sends a notice to the investigator that the protocol has been closed and that a new application will need to be submitted and approved before the research can proceed.

D.  If an IRB decides to disapprove a protocol, the IRB gives the investigator an opportunity to respond in person or in writing.

E.  An IRB decision to disapprove or defer an application for initial review may be addressed by the investigator by re-submission of the protocol to the original IRB, accompanied by a cover letter detailing changes made or a justification of why recommended revisions were not made.  The IRB will approve or disapprove all responses. 

F.  An application for initial review that has been disapproved, deferred or for which modifications have been requested by an IRB cannot be resubmitted to a different IRB for review as an alternative to following the procedures as set forth in this Section.

VIII.  IRB Records on Initial Review

A.  The full IRB’s discussion, action and vote on each Application for Initial Review are documented in the minutes for each IRB meeting.

B.  Votes for and against approval of each Application for Initial Review and the name of any IRB member abstaining from the vote on each protocol or leaving the room before the vote due to a conflict of interest are recorded in the meeting minutes.  IRB meeting minutes are available from the IRB office for review by the Institutional Official at his or her request.