III.3

Initial Review

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PURPOSE

1. The purpose of this policy and procedure is to describe the process of initial review of research proposals.

SCOPE

2. This policy and procedure is applicable to all investigators, CPHS members and ORSC staff.

POLICY

3. All human subject research proposals must be reviewed at a convened full board meeting unless they are determined to be exempt or qualify for expedited review. CPHS must receive and review adequate information to determine whether the criteria for approval have been met.

4. Criteria for Approval - In order for a research proposal to be approved, CPHS shall consider the following criteria:

1. Risks to subjects are minimized by using procedures which are:
   1. consistent with sound research design ,
   2. do not unnecessarily expose subjects to risk, and
   3. when appropriate, already being performed 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.
   1. CPHS shall consider only those risks and benefits that may result from the research (as distinguished from the risks and benefits of therapies participants would receive even if not participating in the research).
   2. CPHS shall not consider possible long-range effects of applying knowledge gained in the research as among those research risks (such as possible effects of the research on public policy) that fall within the purview of its responsibility.
      
      
3. Selection of Subjects is Equitable – In making this assessment, CPHS will take into account:
   1. the purposes of the research,
   2. the setting in which the research will be conducted, and
   3. special problems of research involving vulnerable populations, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons.
      
      
4. Informed consent will be sought from each prospective subject or the subject's legally acceptable representative, in accordance with, and to the extent required by, policy and procedure Informed Consent.
   
   
5. Informed consent will be appropriately documented, in accordance with, and to the extent required by, policy and procedure Informed Consent.
   
   
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.

PROCEDURE

5. Submission for Initial Review – CPHS members rely on the documentation submitted by Investigators for initial review. Therefore, the material submitted must provide CPHS members with adequate information about a research proposal to assess if it meets the CPHS criteria for approval, or the ORSC Staff/CPHS Member will request the Principal Investigator for additional information.

5.1. Essential documents:

1. Completed application form in iRIS
2. Protocol
3. Informed consent documents
4. Investigator Brochure
5. Recruitment materials
6. Appropriate HIPAA documents
7. Pediatric Risk Assessment form
8. Grant Application
9. Research Conflict of Interest Form
10. Data collection forms
11. CVs for the PI and Co-PIs
12. Documentation of Human Subjects Education for the PI and all Key Study Personnel
13. For Department of Health and Human Services (DHHS) – supported multicenter clinical trials:
    1. DHHS-approved sample ICF
    2. The complete DHHS-approved protocol

5.2. CPHS may also request the following additional documents:

1. Letters of Collaboration or Cooperation, including MOUs from other institutions and/or contact information
2. Letters of collaboration with departments
3. Letters of Support
4. IRB approval letters from other sites
5. Any other information necessary to conduct an adequate review of the proposed research.

6. CPHS Review Process – Scientific review will be conducted prior to IRB review by at least one of three processes. All proposals are signed off by the Departmental Chair. If the investigator is requesting for CRU services, the investigator submits a CRU Panel of the CPHS Application Form via iRIS. All iRIS applications to CPHS that include a CRU Application Form will be routed to the ISAC administrator and reviewed as described in the policy and procedure for Internal Scientific Advisory Committee. Protocols that do not involve the CRU are triaged for scientific pre-review based on information provided by the investigator in the application form as described in policy and procedure for Scientific Pre-review.

6.1. ORSC Staff will screen the proposal to ensure that the information provided is adequate. ORSC Staff will schedule a proposal for CPHS review only when it is determined that the information and materials submitted provide an adequate description of the proposed research. The ORSC Staff will assign the proposal to the first IRB panel that is scheduled to meet at least 10 days after the date of receipt of the complete proposal. If the first IRB panel has too many items on its agenda, the proposal is assigned to the next IRB panel.

6.2. The ORSC Director/Staff assigns the proposal to a subcommittee formed from CPHS Members of the IRB Panel that the proposal is assigned. The subcommittee consists of a Chairperson and two members. The subcommittee will conduct an in-depth review of all pertinent information provided by the investigator. The subcommittee will review the recommendations of the scientific advisory committee or the scientific pre-review expert. This review may include discussions with the investigator to clarify issues. The subcommittee may also call upon consultants for additional expertise. All the other members have access to complete documentation for all the protocols and are expected to review at least the protocol summary, consent documents and recruitment materials.

6.3. The Chairman of the subcommittee, or his/her designee, shall provide an overview of the research proposal, identify the subcommittee’s specific concerns and make a motion to approve, approve pending, defer or disapprove. The Chairperson of the IRB Panel opens the research proposal for discussion by all attending CPHS members. For proposals that qualify for expedited review, see policy and procedure Expedited Review.

6.4. When a research proposal involves participants likely to be vulnerable to coercion or undue influence, the convened IRB will ensure that at least one member knowledgeable in working with the specific populations will be present at the meeting.

7. Independent Consultant – CPHS may, at its discretion, invite individuals with competence in special areas to assist in the role of consultants in the review of complex issues which require expertise beyond or in addition to that available on the CPHS. The IRB Chairperson, Subcommittee Chairperson or any member may request for Independent Consultant review. The ORSC Director works with the Subcommittee Chairperson, IRB Chairperson or Executive Chairperson to identify a suitable Independent Consultant.

7.1. The ORSC Staff will ensure that all material in the submission packet described in the policy on Initial Review is provided to the Independent consultant. This information may be provided via access to iRIS, electronic submission (email) or paper copy. The Independent Consultant will submit a written response via iRIS, email or written letter to the ORSC Staff. ORSC Staff will ensure that the Independent Consultant’s comments are posted in iRIS for review by all CPHS members. Independent Consultants may be invited to an IRB meeting to aid the discussion; however they may not participate in the voting process.

8. Possible Outcome of Review - After review, the IRB must take one of the following possible actions:

1. Approve - An approval is granted if the research activity meets the criteria for approval as stated above in Item 4 and no changes are recommended to the research proposal.
   
   
2. Approve Pending – CPHS may approve a protocol pending specific non substantive modifications. The Principal Investigator’s response may be reviewed through an expedited procedure.
   
   
3. Defer - When the convened board requests substantive modifications or clarifications directly relevant to the criteria of approval stated above in Item 4, IRB approval of the proposed research is deferred to review of the Principal Investigator’s responses by the Full Board.
   
   
4. Disapproval: CPHS may disapprove a research proposal if the proposal does not meet the criteria for approval as stated above in Item 4. If the IRB decides to disapprove a research activity, the ORSC staff will include in a written notification a statement of the reasons for the CPHS decision via iRIS and give the investigator an opportunity to respond in person or in writing.

8.2. A research proposal may be tabled until another meeting due to lack of review. In the event of a loss of quorum, all incomplete agenda items shall be considered tabled until quorum can be reconstituted at a convened meeting.

9. Period of Approval - In general, CPHS grants approval for one year. If the protocol under review involves a high degree of risk and/or the stage of the research is such that many of the potential risks are not yet known, CPHS will consider an approval period of less than one year. Examples of research projects where approval periods of less than one year may be appropriate include, but are not limited to:

1. Phase 1 drug trials
2. Gene therapy trials
3. Investigator initiated IND/IDE trials
4. Projects with limited background information
5. Projects where significant risks are expected and no direct benefits have been identified
6. Projects that specifically target vulnerable populations
7. Projects where the investigator has limited experience
8. Projects where there has been compliance related issues with the investigator.

9.1. When CPHS reviews and approves a protocol without any conditions at a convened meeting for a period of one year, the approval date is the date of the convened IRB meeting at which the protocol was approved. The expiry date is the last day of the month before the anniversary date of approval.

9.2. When CPHS reviews approves a protocol pending modifications for a period of one year, the approval date is the date of the convened IRB meeting at which the protocol was approved pending modifications. The expiry date remains the last date of the month before the anniversary of the date of the meeting at which approval pending was granted.

10. Reporting – The ORSC staff will convey the decisions and the stipulations requested by the CPHS promptly to the Principal Investigator via iRIS. The Institutional Officer has access to all protocols on iRIS and can review all CPHS decisions and stipulations.

Applicable Regulations and Guidelines

1. 45 CFR 46.111
2. 21 CFR 56.111
3. 45 CFR 46.109(f)
4. 21 CFR 56.109(f)
5. 45 CFR 46.103 (b)(4)
6. OHRP Compliance Oversight Activities: at http://www.hhs.gov/ohrp/compliance/findings.pdf

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