How to Review A New IRB Protocol

Per federal regulations, 45 CFR Part 46.111 (DHHS) and 21 CFR Part 56.111 (FDA), in order to approve research the IRB must determine that all of the following requirements are satisfied:

  1. Risks to subjects are minimized:
    1. by using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risk, and
    2. whenever appropriate, by using procedures already being performed on the subjects 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.

    In evaluating risks and benefits, the IRB should consider only those risks and benefits that may result from the research (as distinguished from risks and benefits of therapies subjects would receive even if not participating in the research).

    The IRB should not consider possible long-range effects of applying knowledge gained in the research (for example, the possible effects of the research on public policy) as among those research risks that fall within the purview of its responsibility.
  3. Selection of subjects is equitable. In making this assessment the IRB should take into account the purposes of the research and the setting in which the research will be conducted and should be particularly cognizant of the 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 authorized representative, in accordance with, and to the extent required by 45CFR Part 46.116.
  5. Informed consent will be appropriately documented, in accordance with, and to the extent required by 45 CFR Part 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.

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.

Before the full Committee Meeting:

  1. Read the assigned materials at least 2-3 days in advance of the meeting. UCI utilizes a primary reviewer system; therefore if you are assigned as either the primary or secondary reviewer it is your responsibility to thoroughly review the IRB application materials in advance of the meeting.
  2. Get all questions answered before the meeting. IRB Members are not expected to be the absolute experts about the protocols they are assigned to review. Talk with others as needed. Feel free to contact the:
    • IRB Chair
    • Co- reviewer
    • Informal Consultant* (e.g., colleague w/ expertise)
    • Research Protection staff (Administrator, Analyst)

    Furthermore, do not hesitate to contact the Lead Researcher if you have questions. Collegial interaction between researchers and IRB members facilitates the IRB review process and research compliance as well as fosters respect for human subjects protection.

  3. Contact the IRB Chair and Administrator if you have serious concerns about the protocol.
  4. Write comments and recommendations on the Reviewer's checklist and be prepared to present them to the Committee.
  5. Be organized (bring packet materials to the meeting).

* Informal verbal consultation is encouraged. However, IRB members must uphold the Members Standards by maintaining all committee proceedings and documents that contain personal, confidential and proprietary information in strict confidence. Such information may not be used for any purpose other than the IRB review and may not be disclosed to anyone outside of the IRB unless permission is granted in writing by the Vice Chancellor for Research.

The process of reviewing a new IRB protocol:

  1. Read the consent document first. The consent document should be in lay language and therefore, should provide a good introduction to the research.
    • First read the consent form for general information about the study;
      1. Can you clearly describe the study after reading the Consent Form?
      2. For studies involving medical treatments, can you distinguish standard-of-care from research procedures?
    • Then read it again for readability (6th—8th grade level);
      1. Did it seem easy, or did you have to re-read it for understanding?
      2. Can a junior-high school student explain the study after reading the consent form?
  2. Read the protocol narrative. Although the language may differ; the narrative and the consent form should be consistent in the description of the purpose of the study, the procedures, the study timeframe, the possible risks and potential benefits, compensation and costs, confidentiality of data, etc.

    Consider the following questions:

    • Background and Purpose of the Study
      1. Are the specific aims, hypotheses, and research questions clearly identified?
      2. Is there sufficient preliminary data to justify the research?
      3. If the study is a drug, biologic, or device trial, are the safety and efficacy data sufficient to warrant the proposed phase of testing?
    • Background And Expertise Of Study Team
      1. Is there sufficient expertise on the research team to conduct the study given the procedures and the study population(s)?
      2. Are the researchers' experience, specific roles and responsibilities clearly defined?
      3. Conflict of interest issues are considered by the Conflict of Interest Oversight Committee. The committee is charged with ensuring that a researcher's personal interest in, or commitment to, entities outside the University's purview does not compromise or appear to compromise his/her objectivity in performing a research project, in mentoring students involved in a research project, or in reporting the results of a research project conducted under the aegis of the University of California.
    • Research Methodology/Study Procedures
      1. Are the scientific design and research procedures adequately described and justified? Is the design appropriate to answer the research question? (Scientific merit should be considered in the context of whether individuals should be exposed to unnecessary risk).
      2. Does the description differentiate between standard-of-care procedures and research procedures, if applicable?
      3. Elements of the research design that need special attention (i.e. placebo control, washout periods, deviations from accepted standards of care). Does the researcher provide adequate justification for these elements?
      4. If drug, biologic, or device trial...
        • Is the status of the drug or device described (i.e., experimental)? Does the application include the FDA IND/IDE number?
        • Are the dosage and route of transmission justified and appropriate?
        • Is the significant or non-significant status of the device justified and appropriate?
    • Subjects (participants, charts, records and/or specimens)
      1. Is the proposed subject population appropriate given the research question?
      2. Are the inclusion and exclusion criteria explained and appropriate?
      3. Is the inclusion or exclusion of women, minorities, and minors justified?
      4. Does the proposed population include vulnerable participants (e.g., minors, prisoners, cognitively impaired, UCI students/staff)? If yes, consider special protections (e.g., parental permission, minor assent, surrogate consent, minimize undue influence or coercion to ensure voluntariness).
      5. Does the researcher include a projected sample size and appropriate justification? Is the projected sample sufficient to answer the research question, yet small enough to limit number of individuals placed at risk?
    • Recruitment/Informed Consent Process
      1. Are the recruitment procedures clearly described?
      2. Are the location and timing of the recruitment procedures appropriate considering the proposed populations?
      3. Are the recruitment procedures appropriate (ensure that they do not violate an individual's right to privacy)?
      4. Is the informed consent process sufficiently described?
      5. If requesting a waiver of informed consent (does not require researcher to obtain informed consent) or a waiver of documentation of informed consent (does not require a signed consent form, however still requires an informed consent discussion), does the researcher provide adequate justification? See the ORA website for guidance on when it is appropriate to grant a waiver.
      6. If recruiting minors, does the researcher address parental permission and minor assent procedures?
      7. If recruiting elderly subjects or potentially cognitively/emotionally impaired groups, does the researcher explain how competency will be determined and who will make the determination?
      8. Is the researcher requesting to obtain surrogate consent? Does the researcher adequately justify use of a surrogate? Does the researcher have a specific plan that will be employed to acquire and document surrogate consent? Is the plan appropriate?
      9. If recruiting minority groups or non-English speakers, does the researcher acknowledge that s/he will obtain inform consent or assent using a consent/assent form translated into the appropriate language?
    • Anticipated Risks/Risk Management
      1. Are the potential risks sufficiently identified, evaluated (probability and severity) and described?
      2. Are the risks minimized to the lowest level possible?
      3. After reviewing potential direct benefits to the participant and societal benefits, are the risks appropriate in relation to the anticipated benefits?
      4. If research includes vulnerable populations (e.g., minors, pregnant women, prisoners) determine which regulatory category of risk the research falls within and whether all the criteria within the category or Subpart are addressed?
    • Potential Benefits - Are the potential benefits (to participant and society) sufficiently identified, evaluated and described?
    • Adverse Event Reporting/Management
      1. Is there a data safety monitoring plan or board/committee in place?
      2. Does the protocol specify criteria for stopping (for a subject or for the project)?
      3. Does the researcher acknowledge that the research team will follow UCI's reporting policy on Adverse Events?
    • Costs - Is there sufficient justification for the participants to pay for costs associated with protocol (e.g., charge for standard-of-care procedures, FDA-approved device charge, parking fee, etc.)?
    • Compensation
      1. Is the amount and type of compensation reasonable (does not appear to unduly influence one to participate)?
      2. Does the researcher explain that compensation will be prorated and provides a schedule of payment?
    • Privacy and Confidentiality Of Research Data
      1. Are there appropriate procedures in place to protect the participant's privacy? How are participants being recruited? In what setting is the research being conducted?
      2. Does the researcher explain who will have access to the data?
      3. Are the security procedures regarding access and storage of the data adequate?
      4. Is the use of personal identifiers or codes linking the data to the participant justifiable? If yes, does the researcher explain at what point the data will be de-identified?
  3. Read the supporting documents (e.g., Investigator's Brochure, Sponsor Protocol, recruitment materials, etc.).
    • Investigator's Brochure provides the reviewer background information (animal data; preliminary human studies) about the investigational drug, biologic, or device.
    • Sponsor's Protocol provides a detailed description of study procedures including a power analysis justifying projected sample size, and the statistical methods to be used to analyze the data.
    • DHHS grant application (for DHHS funded research) - Does the IRB application match the grant application?
    • Recruitment materials/advertisements should be in lay language and describe the study to potential participants.
      1. SHOULD INCLUDE – Name of Institution and department Name of researcher and contact person along with contact information; purpose of research study; inclusion/exclusion criteria; procedures and time commitment involved; compensation and location of research.
      2. SHOULD NOT INCLUDE – emphasis on monetary compensation; misleading or exculpatory language; emphasis on "free" services (e.g., medical care).
  4. Re-read the consent document. Make changes or note questions for the researcher to address on the form and in the Reviewer Checklist. See How to Review the Consent Form
  5. Read the Reviewer Checklist: Write comments and recommendations on Reviewer's checklist and be prepared to present them to the Committee. Also, review the Administrator's Comments section and indicate your response to any questions posed to the Committee.

* Adapted from "Institutional Review Board Member Handbook"
by Robert Amdur, MD
Jones and Bartlett Publishers, 2003

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