Primary Reviewer Guidance for Initial Reviews

IRB Member Guidance--Version Date: August 11, 2008

General Guidance
Two primary reviewers are assigned to each new protocol undergoing review by the convened IRB.  A Primary Reviewer Form will be sent to each primary reviewer for each Application for Initial Review of Research Involving Human Subjects.  Many sections of this form will be pre-filled by the staff reviewer assigned to the protocol, including the Protocol Number, PI Name, Protocol Title, and Meeting Date.  Each section of this form should be completed and the form should be printed, signed, and returned at the IRB Meeting.  The forms can be handwritten or filled out electronically.

Section A. Reviewer Identification
Please fill in your name in this box.

Section B. Protocol Identification
This will be pre-filled by IRB staff.

Section C. Supplemental Review Forms
In addition to the Primary Reviewer Form, the following additional documents may be attached as they apply to the research study:
  • Informed Consent Checklist
  • Checklist for Research Involving Children
  • Checklist for Research Involving Prisoners
  • Checklist for Research Involving Pregnant Women, Fetuses, or Neonates
  • VA Checklist
These checklists should be reviewed tandem with the Primary Reviewer Form.  They will be filled out by the staff reviewer assigned to the study and may have questions embedded in them for the primary reviewer.

Section D. General Staff Notes to Primary Reviewers and IRB
This section allows the staff reviewer to provide an overall orientation to the review if needed.  This section may be left blank by the staff reviewer.

Section E. Application of Criteria for IRB Approval
Overall Guidance
This section represents the core of the IRB's work.  In order for non-exempt research involving human subjects to be approved by an IRB, all the criteria in this section must be satisfied.  Please fill out for each criterion whether you find that the materials submitted for the review satisfy the criterion as follows:
  • If the criterion appears to be satisfied, check "yes".
  • If additional changes or clarifications are needed before a study can be approved, check the "revisions or clarifications needed to satisfy this criterion" box.
  • If you cannot determine whether the criterion has been satisfied, check the "unable to judge at this time" box and explain in the notes section below the criterion why you do not find it to be satisfied and what changes or clarifications are needed from the research teams to address this criterion.
  • If you do not think any of the options provided express your determination, check the "other" box and explain your choice in the notes section below.
  • In some cases, the criterion will not apply and this can be noted.  "Not Applicable" is only an option where provided in the form.
Guidance Related to Specific Criteria
What follows is guidance regarding what factors should be considered when assessing whether a particular criterion has been satisfied.
  1. Determining whether the risks to subjects are minimized: (i) by using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risk, and (ii) whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes.  In making this assessment, please consider the following:
    • Whether adequate safeguards have been adopted to reduce risk exposure as much as possible.
    • Whether adequate measures have been taken to ensure that the occurrence of illness or injury will be detected and treated.
    • Whether the study procedures have been piggybacked onto procedures that would be performed for clinical purposes when possible.
    • Whether there are adequate means in place (e.g., data and safety oversight committee) such that if the research protocol needs to be modified, or changes in the risk level occur, they will be appropriately and timely brought to the attention of the IRB for review and approval.
    • Whether the data to be collected are adequately protected against the risk of break of confidentiality.
    • Whether the eligibility criteria will adequately reduce risks to subjects by excluding those who may be at higher risk from the study procedures.
  2. Determining whether the risks of the research are reasonable in relation to the benefits (i.e., the study has a reasonable risk/benefit ratio).  In making this assessment, please consider the following:
    • The purpose of the research.
    • Whether the research design is sufficiently robust to warrant the risks to the subject.
    • Whether the objectives of the study are appropriate and that study endpoints are clearly defined and likely to be met.
    • Whether the study design is sound such that the study will result in useful knowledge.
    • Whether the potential benefits to the subject and/or society outweigh the risks being incurred.
    • Whether there is reasonable justification for the protocol, especially if it presents more than minimal risk to subjects.
    • The types of risks the study may involve: physical, psychological, sociological, economic, or legal.
    • Potential risks to others, such as the risks related to disclosure of genetic information.
    • Potential reproductive risks.
    • Potential long-term effects.
    • Whether the potential risks and benefits have been clearly and accurately identified.
    • Qualifications of personnel to conduct research.
    • The setting in which the research will be conducted, including the adequacy of the facilities at which the research is conducted and the adequacy of the procedures in place should an emergency arise.
    • Whether the protocol should include a counseling or referral plan and, if so, whether these resources are adequate.
    • UW and national standards, especially in terms of institutional standards of care.
    • Whether additional protections are needed to ensure the protection of vulnerable populations.
    • How subject privacy and confidentiality are protected and whether this is adequate.
    • Data and tissue disposition (e.g., who will see the study data or receive samples, whether the data or samples with be destroyed or kept long-term, whether data/samples will be used for unspecified future research, whether the data/samples will leave this institution).
  3. Determining whether subject selection is equitable.  In making this assessment, please consider the following:
    • Whether inclusion or exclusion criteria are appropriate.
    • Whether a group will be targeted for inclusion or exclusion and whether this is justifiable.
    • Whether there is an adequate rationale or justification for sample size.
    • Whether recruitment methods are reasonable and will not bias subject selection or unduly influence subjects.
  4. 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.  In making this assessment, please consider the following:
    • Assess whether any of the following are included in the protocol: children, prisoners, pregnant women, mentally disabled persons, economically or educationally disadvantaged persons, VA subjects, critically ill patients, or others who may be vulnerable (which may include situationally vulnerable).
    • Whether vulnerable populations will be included and whether this is warranted.
    • Are additional measures needed to protect these subjects in terms of the recruitment process, payment, informed consent process, where the research occurs, how information is managed and protected and who conducts study procedures?
    • Is consent monitoring required or the presence of a subject advocate or witness during the consent procedure?
    • For children (Children: Regulations ), prisoners (Prisoners: Regulations ), pregnant women, fetuses, neonates of uncertain viability and nonviable neonates (Pregnant Women, Fetuses and Neonates: Regulations ), please refer to the additional guidance.
  5. 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 45 CFR 46.116, and, if applicable, 38 CFR 16.116 and 21 CFR 50.20 and 21 CFR 50.25.  In making this assessment, please consider the following:
    • Is the investigator requesting a waiver or alteration of informed consent?  If so, are the following conditions of a waiver or alteration of informed consent met: (1) research represents an emergency use of FDA-regulated drug or device; OR (2) the research presents no more than minimal risk to subjects; (3) the waiver or alteration will not adversely affect the rights and welfare of subjects; and (4) the research could not practicably be carried out without the waiver or alteration?  NOTE: With fes exceptions a waiver of informed consent cannot be granted for FDA-regulated research.
    • Will subjects or their legally authorized representatives be given sufficient time to consider the risks, benefits and alternatives to participation and whether they wish to participate?
    • Is consent monitoring warranted?
    • Are the individuals conducting the consent process the appropriate people to do so?
    • Are the consent documents written at an adequate reading level, is the length of the form appropriate for the complexity of the study, and is clear, concise, non-technical language used throughout?
    • Will the circumstances of the consent process minimize the potential for undue influence or coercion?
    • If potential subjects are unable to provide informed consent on their own behalf, are additional safeguards needed to protect their rights and welfare?
    • Is the consent language provided to potential subjects and/or their legally authorized representatives in language that is understandable to them?
    • Is the information being communicated to potential subjects or their representatives during the consent process free of exculpatory language (i.e., language that suggests the subjects or their legally authorized representatives are made to waive or appear to waive any of the subjects' legal rights or has released or appeared to release the investigator, the sponsor, the organization, or its agents from liability for negligence?)
    • Do the consent (not assent) documents contain the required information, including:
      • A statement that the protocol involves research
      • Explanation of the purpose of the research
      • The expected duration for subject's participation
      • The procedures to be followed
      • Identification of the experimental parts or procedures of the study
      • A description of the reasonably forseeable invasive or non-invasive risks or discomforts
      • Any potential benefits to subjects
      • Disclose appropriate alternative procedures, if any, that might be advantageous to the subject
      • Describe how confidentiality of the records identifying the subject will be maintained
      • A statement, if research is more than minimal risk, whether any compensation is available
      • Indicate whom to contact for questions about the research itself
      • Include a statement that participation is voluntary, that there are no penalties if one refuses to participate, and subjects can withdraw at any time without penalty
    • Are any of the following additional elements of consent appropriate and/or required?
      • A statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or fetus, if the subject is or may become pregnant) which are currently unforseeable
      • Anticipated circumstances under which the subject's participation may be terminated by the investigator without regard to the subject's consent
      • Any additional costs to the subject that may result from participation in the research
      • The consequences of a subject's decision to withdraw from the research and procedures for orderly termination of participation by the subject
      • A statement that significant new findings developed during the course of the research which may relate to the subject's willingness to continue participation will be provided to the subject
      • The approximate number of subjects involved in the study
    • If adults with impaired decision-making capacity will be enrolled, are there mechanisms for obtaining consent of surrogates?
    • If VA subjects are enrolled, does the consent document include the required VA language and is it on a VA 10-1086 form?
    • If minors will be enrolled:
      • Is an assent process and form needed?  Please take into account the ages, maturity, and psychological state of the children involved.
      • If an assent process is required, is the proposed assent process appropriate and does assent need to be documented?
      • How many parents need to provide permission for their participation according to the requirements of Subpart D?
      • Does parental permission need to be documented?
      • If parental/guardian permission needs to be waived because it is not a reasonable requirement to protect the subjects, what is an appropriate substitute mechanism for protecting the children who will participate as subjects in the research?
      • Can documentation of parental/guardian permission be waived and is it appropriate?
      • Are any children to be enrolled wards of the State?
    • If individuals who do not speak English will be included, does the consent process address this situation adequately?
    • Does the protocol involve deception?  If so, is this warranted and is there adequate debriefing planned?
  6. Informed consent will be appropriately documented, in accordance with, and to the extent required by 45 CFR 46.117, and, if applicable, 38 CFR 16.117 and 21 CFR 50.27.
    • Is the investigator asking for a waiver of written consent?  If so, does the protocol meet one of the following criteria: (1) the only record linking the subject and the research would be the consent document and the principal  risk would be potential harm resulting from a breach of confidentiality (NOTE: this criterion cannot be applied to FDA-regulated research); or (2) the research presents no more than minimal risk of harm to subjects and involves no procedures for which written consent is normally required outside of the research context.
    • Will an oral consent process be used?  If so:
      • Will the entire consent form be read to the subject or the subject's LAR or will a short form be used that is accompanied by a summary that contains the required elements of consent?
      • Will there be a witness to the oral presentation as required by the regulations, who is conversant in the language of the present and potential subject, and will witness sign and date the short form and copy of the summary presented to the subject?
      • Will a copy of the signed and dated summary be given to the subject or the subject's LAR?
    • Will the consent form(s) be signed?  If so:
      • Will they be signed by the subject or the subject's LAR?
      • Will the subject or the subject's LAR be asked to date the consent document(s)?
      • Will the person obtaining informed consent sign and date the consent document(s)?
      • Will copies of the signed and dated consent form(s) be given to the subject or the subject's LAR?
  7. When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects.  In making this assessment, please consider the following:
    • If the study presents minimal risk to subjects, a data and safety monitoring plan may not be required.
    • For research that presents more than minimal risk to subjects, consider whether the following are adequate:
      • How adverse events and unanticipated problems are defined in the protocol
      • How adverse events and unanticipated problems are monitored and whether they meet institutional and federal reporting requirements
      • Whether adverse events will be reviewed by an appropriate person/entity to ensure that new information that arises will be recognized and disseminated to relevant individuals (e.g., sponsor, investigators, subjects) promptly
      • Whether a formal Data Safety Monitoring Board or Data Monitoring Committee is required
      • If Data Safety Monitoring Board or Data Monitoring Committee is proposed, whether its composition adequate, meets sufficiently frequently, and reviews the appropriate information
      • Does the protocol outline sufficient monitoring of subject to ensure adequate safeguards are in place to prevent or identify and mitigate adverse effects of the study procedures?
      • For multisite research, whether the management of information relevant to the protection of subjects is adequate.
  8. When appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data.  In making this assessment, please consider the following:
    • Privacy can be defined in terms of having control over the extent, timing, and circumstances of sharing oneself (physically, behaviorally, or intellectually) with others.
    • Confidentiality pertains to the treatment of information that an individual has disclosed in a relationship of trust and with the expectation that it will not be divulged to others in ways that are inconsistent with the understanding of the original disclosure without permission.
    • Are research procedures conducted in a setting that helps ensure subject privacy?
    • Are the individuals accessing protected health information involved in their health care or have subjects given explicit permission for this information to be shared?
    • Is all information collected in the study or accessed by researchers necessary to answer the research question?
    • Is the plan for protecting the confidentiality of the data adequate?
    • When does the investigator plan on de-identifying the data?  Is this soon enough?
    • Do the application, protocol, and consent documents clearly identify all individuals or entities that may receive identifiable subject data?
    • If identifiable subject data will be shared with others, is this warranted and are the confidentiality protections sufficient?
    • How and where will the data be stored?  What mechanisms are used to secure the data?
    • Are any sensitive data collected such that additional protections (e.g., a Certificate of Confidentiality) are needed?
Section F.  Other Issues
In this section, the staff reviewer assigned to the protocol will note any additional considerations related to issues that do not directly fall under the criteria for IRB approval or additional regulatory considerations.
  • HIPAA Privacy Rule--this section is likely to comment on whether the HIPAA Privacy Role applies; the research team is requesting a waiver of authorization or an alteration of authorization; a Limited Data Set is being used; or the authorization form meets institutional Privacy Rule requirements.
  • Conflict of Interest (COI)--this will likely include either statement that there is no financial COI for the study or an explanation for how a COI will be handled (e.g., disclosure language in the CF).
  • Engagement and oversight issues--this section should address whether any action or requirements are needed due to engagement of sites or personnel not already covered by the UW IRB.  This includes indicating whether an IRB authorization agreement or independent investigator agreement will be needed or is in place.
  • FDA Issues--this section will typically address whether the FDA regulations apply.  If FDA regulations apply, likely issues raised include:
    • Whether an IND or IDE is present or whether the protocol represents a HUD or other type of non-research use of an experimental drug or device (e.g., treatment IND, "compassionate use").  For devices, SR/NSR determination would be included here.  For drugs, whether an IND is needed would be addressed.
    • If studies involve drugs or biologics, you may be asked to determine whether:
      • The research does not require an IND because only approved drugs are used within their FDA-approved indication.
      • The research does not require an IND because the study involves use of an FDA approved drug(s) used outside its approved indication and all the following are true:
        • There is no intention for the study to support FDA approval of a new indication or a significant change in labeling;
        • The study is not intended to support significant change in the advertising for the product;
        • The investigation does not involve a route of administration or dosage level or use in a patient population or other factor that significantly increases the risks (or decreases the acceptability of the risks) associated with the use of the drug product.
    • If studies involve devices, you may be asked to determine whether:
      • The research does not require an IDE because only approved of 510(k) cleared devices are used within their FDA-approved or FDA-cleared indications.
      • The research does not require an IDE because the device does not meet the definition of a "medical device" under federal regulations.
      • The device meets the FDA definition of non-significant risk.
      • The device is otherwise exempt from the IDE requirements pursuant to 21 CFR 812.2(c), because it:
        • Is noninvasive;
        • Does not require an invasive sampling procedure that presents significant risk;
        • Does not by design or intention introduce energy into a subject; and
        • Is not used as a diagnostic procedure without confirmation of the diagnosis by another, medically established diagnostic product or procedure.
  • VA Issues--this section will address VA-specific requirements, such as whether VA Research & Development Committee approval is needed or already in place; enrollment of incompetent subjects will occur and if this meets the VA regulations; and tissue banking will occur and whether it is allowed under VA regulations.
  • Other Issues--this is the section for anything that does not fit elsewhere in the review or for administrative issues.
  • Review Period Recommendation--under federal regulations, protocols must be reviewed at least once per year.  Examples of research that the IRB may review more frequently than once a year are non-therapeutic research that poses more than minimal risk to research subjects, locally investigator-initiated studies, and research that requires special monitoring of its consent procedures to ensure adequate informed consent is obtained.
  • Risk Level Recommendation--this section should indicate whether or not the study can be considered to be minimal risk or is greater than minimal risk.  Under the Common Rule, minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves that those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.  Risk determinations become relevant in consideration of waivers of informed consent, waivers of documentation of informed consent, when vulnerable populations are enrolled, and whether the study can be reviewed under expedited procedures in future.
Section G.  Overall Recommendation of Primary Reviewer
Indicate in this section your assessment of whether the application can be approved as submitted, approved after modifications or clarifications are made, meets criteria for exemption from IRB review under the federal regulations, needs to be deferred because not all of the IRB criteria for approval have been met or the submission lacks critical information, or should be disapproved because it does not appear that it can meet the criteria for IRB approval.

Section H.  Staff Questions for IRB Members
The staff reviewer assigned to this study will include specific questions that he or she needs guidance from the IRB about.  Please indicate your response to these questions in this section.

Section I.  Modifications
The staff reviewer assigned to the study will propose modifications or clarifications that he or she thinks should be addressed before approval is finalized in this section.  Please indicate here any additional changes or clarifications you think should be addressed in order for the investigator to be granted approval or any disagreements with the points suggested by the review staff.

Section J.  Reviewer Certification
Please sign and date your reviewer form here.  This section includes a certification that the reviewer does not have a conflict of interest prohibiting him or her from serving as a reviewer for the protocol.  Please note that according to campus policy a UW-Madison IRB Member may not participate in the initial or continuing review of any research protocol in which the member has a conflict of interest except to provide information at the IRB's request.  Any IRB member with a conflict of interest in a research protocol under review bu the IRB must disclose the conflict of interest to the IRB Chair and leave the room during the discussion of the protocol and the related vote, except if the member is providing information at the IRB's request.  The meeting minutes will document the recusal (i.e., the temporary absence of the IRB member during the deliberation and vote on the protocol with respect to which the member has a conflict of interest).

An IRB member or IRB consultant has a conflict of interest with respect to a protocol when any of the following conditions occur:
  1. Members, or their immediate family, who have a professional interest as a principal investigator or co-investigator in the protocol.
  2. Members, or their immediate family, who have a financial interest in a business entity that (a) sponsors the study or (b) owns or licenses a technology tested in the study, and the IRB member's financial interest meets or exceeds one of the following thresholds:
    • Compensation of $20,000 or more in a calendar year from a business entity,
    • An ownership interest in a publicly traded business entity valued at $20,000 or more or a 5% or greater equity interest,
    • An ownership interest in a privately held business entity,
    • A leadership position in a business entity (e.g. service as an officer, member of the board of directors, or in any other position of trust, confidence, and responsibility for a business entity, whether or not the investigator receives compensation for such service).
  3. Members, or their immediate family, who have a personal relationship that may cause bias or create the appearance of bias by the member in the review of the protocol.
  4. Members, or their immediate family, who serve a principal investigator is responsible for planning, design, or publication of research or as a co-investigator who shares at least some of these responsibilities with a principal investigator.
NOTE: An "immediate family member" includes spouse, domestic partner, and/or dependent children.

Keywords:IR, IRBM, review   Doc ID:19683
Owner:Faye L.Group:Health Sciences IRBs
Created:2011-08-09 19:00 CDTUpdated:2015-10-13 15:10 CDT
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