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- Operations Manual Part 3 - HRPP Policy
Operations Manual - Part 3
Rulemaking within the University of Michigan is divided three ways: (i) the Bylaws of the Board of Regents; (ii) rules initiated by University authorities that become effective only upon approval by the Board of Regents (Regents Policies); and (iii) rules adopted by subordinate University authorities, under delegated legislative powers, that become effective as provided by such subordinate authorities. Human Research Protection Program (HRPP) policies fall within the third class of rulemaking. In Standard Practice Guide (SPG) 303.05, the University has delegated to the Vice President for Research (VPR) general executive responsibility for the research programs of the University and, in that role, the responsibility for implementing the HRPP, including the legislative powers to adopt and enforce HRPP policy and procedures.
The HRPP Operations Manual (OM) is the primary location for compiling, organizing, integrating, and pointing to the rules, policies, practices, and guidance encompassing the University’s HRPP. The VPR has approved the OM and approves each substantial modification or amendment to it. Records of such approval are maintained in the U-M Office of Research (UMOR).
At least once every five years, typically in conjunction with the Association for the Accreditation of Human Research Protection Programs (AAHRPP) re-accreditation cycle, UMOR initiates a comprehensive review of the OM. Revisions may be made at any time, however, as required by changes in law, ethical standards, institutional policy, quality assurance activities or other considerations. Non-substantive revisions (e.g., to correct typographical errors, update links or incorporate summaries of new or revised laws or regulations governing the HRPP) may be made upon approval of the Deputy Institutional Official (DIO) with notice to the VPR.
Each Institutional Review Board (IRB) designated by the University to review and monitor human research under the University’s Federalwide Assurance (FWA) must adopt standard operating policies and procedures (SOPs) and may issue additional guidance as necessary to ensure appropriate review and oversight of University research and to facilitate compliance by investigators and research staff with applicable laws and regulations and with University policy, including IRB requirements.
The SOPs must be consistent with this OM, other central institutional policies (such as SPGs), and applicable laws and regulations. IRBs are free, however, to implement and enforce additional or more restrictive policies and procedures. SOPs may incorporate, by reference, elements of this OM, as appropriate. SOPs, however, are intended to be stand-alone descriptions of the actual procedures used by the IRB.
SOP Development, Review, Update, and Maintenance
The SOPs must describe the development, review, update, and maintenance processes, including the following activities:
- Responding to requests from the HRPP for new local policy development;
- Considering input from IRB chairs, members, and staff, as well as investigators and other stakeholders;
- Soliciting and considering input from standing and ad hoc research and advisory councils;
- Reviewing SOPs at regular intervals, generally in conjunction with accreditation activities or revision of this OM; and
- Revising in response to comments by the IRB Council and the Vice President for Research or designee.
When writing SOPs, IRBs should review Sections A through E, below, and include all applicable provisions.
SOP Approval Process
All IRB SOPs (and substantive revisions) must be reviewed and approved prior to implementation according to procedures outlined in that IRB’s SOPs and according to the procedures of the office that provides resources and administrative oversight as well as the HRPP Director.
The HRPP Director need not wait to approve revised SOPs in their entirety but instead may, at the request of the IRB and at his/her discretion, review and approve for implementation individual components as they are developed. Additional guidance may be issued without prior approval but must be revised or rescinded if directed by the HRPP Director to ensure compliance with applicable laws or regulations or with University policy. Guidance may require additional approvals at the unit level.
SOPs must describe:
- The authority under which the IRB is established;
- The relationship of the IRB to the VPR and other institutional leadership;
- The scope of its jurisdiction over human research conducted at the University of Michigan or by its faculty, staff or trainees;
- The ethical principles under which it operates; and
- The IRB’s purpose (i.e., to protect human research participants).
If the IRB, as a matter of policy, regularly applies ethical principles in addition to those described in the Belmont Report (such as the Nuremberg Code), or complies with laws, regulations or policies other than those described in this OM (such as guidelines published by the International Conference on Harmonisation), the SOPs must describe these additional guiding principles in sufficient detail to apprise investigators of the standards against which their studies will be reviewed and monitored. This requirement does not apply to the concerns and considerations that an individual reviewer may bring to his or her analysis of an application nor preclude the IRB from considering any principles or rules beyond those formally articulated in its SOPs on an ad hoc basis.
SOPs must describe each of the following:
- How the composition of the IRB is periodically evaluated and, when necessary, adjusted so that the membership and composition of the IRB meet legal or regulatory and organizational requirements.
- The selection, appointment, length of service, duties, attendance requirements, training, and evaluation of IRB chairs and members; and
- The duties and functions of IRB staff and their relationship with IRB chairs, members, researchers, and other stakeholders; and
- Any ethical expectations of these individuals in addition to those described in this OM.
Each IRB must have at least five members, with varying backgrounds to promote complete and adequate review of research activities commonly subject to that IRB’s oversight. SOPs must provide that:
- The IRB will be sufficiently qualified through the experience and expertise of its members, and their diversity (including consideration of race, gender, and cultural backgrounds and sensitivity to such issues as community attitudes), to promote respect for its advice and counsel in safeguarding the rights and welfare of human subjects.
- In addition to possessing the professional competence necessary to review specific research activities, the IRB will be able to determine the acceptability of proposed research in terms of institutional commitments and policies, applicable laws and regulations, and standards of professional conduct and practice. To this end, the SOPs will require the IRB to include members knowledgeable in these areas.
- For any IRB that regularly reviews research involving one or more vulnerable categories of subjects, such as children, prisoners, pregnant women or physically or mentally disabled individuals, consideration must be given to inclusion as members on the IRB of one or more individuals knowledgeable about and experienced in working with these subjects.
- When reviewing FDA-regulated studies, the IRB must include at least one physician.
- Every nondiscriminatory effort will be made to ensure the IRB does not consist entirely of men or entirely of women. No selection will be made, however, solely on the basis of gender.
- The IRB must include at least one scientist member whose primary concerns are in scientific areas and at least one non-scientist member whose primary concerns are in nonscientific areas. The IRB also must have members with sufficient knowledge of the specific scientific discipline(s) relevant to the research that it reviews.
- A scientist is a member whose training, background, and occupation would incline him or her to view scientific activities from the standpoint of someone within a behavioral or biomedical research discipline.
- A nonscientist is a member whose training, background, and occupation would incline him or her to view research activities from a standpoint outside of any biomedical or behavioral scientific discipline.
- No IRB may consist entirely of members of one profession.
- The IRB must include at least one member who is not otherwise affiliated with (or an immediate family member of a person affiliated with) the University. The University supports efforts of the IRBs to include additional unaffiliated members.
- "Unaffiliated" individuals include:
- University patients or research subjects or former students of the University who have no other affiliation with the University are not considered affiliated
- Payments to unaffiliated members at reasonable market rates for their services to an IRB do not render them affiliated
- "Affiliated" individuals include:
- Part-time employees
- Current students
- Members of any governing panel or board of the University
- Healthcare providers with medical staff membership or other credentials to practice at University clinical sites
- Volunteers working at the University on business unrelated to the University
- "Unaffiliated" individuals include:
The IRB offices maintain IRB rosters. UMOR registers each IRB with OHRP and updates registrations as needed.
The IRB must possess sufficient knowledge of the local research context to fulfill its review responsibilities under federal regulations and this OM. To supplement this knowledge, the IRB may, in its discretion, invite individuals with competence in special areas to assist in the review of issues that require expertise beyond or in addition to that available on the IRB. SOPs must include provisions that:
- Describe when and how an IRB will use consultants to supplement the IRBs knowledge;
- Prohibit these consultants from voting with the IRB; and
- Require consultants to disclose any relevant conflicts of interest or commitment before agreeing to assist in a review.
SOPs may include provisions for designating alternate members to an IRB. If they do, each alternate IRB member should have experience, expertise, background, professional competence and knowledge comparable to that of the primary IRB member whom the alternate would replace. SOPs should include procedures for:
- Determining whether the primary member or his/her alternate is the official voting member of the IRB for review of protocols or applications (or any individual protocol or application); and
- Ensuring that only the vote of one is counted in any particular circumstance.
SOPs or other documents must describe:
- Any orientation procedures for new IRB chairs, members, and staff;
- Continuing education requirements and opportunities for IRB chairs, members, and staff;
- Available reference materials (e.g., library resources, internet sites, etc.); and
- Training and education requirements for researchers who plan to submit IRB applications and reports.
The SOPs or other policies or guidance developed by the administrative unit responsible for the IRB's operations must describe arrangements, if any, for compensating IRB chairs, members, and consultants for their IRB service. Liability coverage is a matter of institutional policy and is described in risk management policies. In brief, the University's self-insurance policies generally cover the actions of faculty, staff, students and non-affiliated volunteers performing authorized activities on behalf of the University (such as membership on an IRB). These policies do not cover acts of willful misconduct or illegal activities. Nor do they cover losses for personal property or for personal injury of non-employees sustained while engaged in the authorized activities.
The performance of each IRB chair, member, staff and regular consultant must be evaluated regularly. SOPs must:
- Describe the process that is used to conduct evaluations of IRB chairs, members, staff, and regular consultants;
- Indicate the frequency of the evaluations;
- Identify who conducts the evaluations; and
- Describe how the results of the evaluation are used.
SOPs must include:
- A statement that no IRB member or consultant may participate in the IRB’s initial or continuing review of any project in which the member has a conflicting interest (as defined in Part 9 of this OM), except to provide information requested by the IRB;
- A statement that any conflicted IRB member or consultant may not be present for, nor count for quorum, nor participate in the deliberations of, nor vote on the disposition of an application in which the member has a conflict. However, the member may be invited by the IRB to provide information relevant to the IRB’s consideration of the application;
- A description of the process used by IRB members and consultants to report conflicts of interest and commitment with any IRB application for review; and
- A description of the process the IRB will use to manage reported conflicts.
Part 9 of this OM provides further information on IRB member and consultant conflicts of interest.
SOPs must describe key IRB review policies and procedures in sufficient detail to inform IRB members and staff, researchers, and other stakeholders of the IRB's rules and expectations. These must include, at a minimum, the elements described below in Subsections 1 to 7. To the extent these elements are addressed through this OM or other institution-wide policy they need only be referenced in the IRB SOPs.
SOPs must describe:
- What types of studies are typically reviewed by the IRB;
- The authority of the IRB to approve, disapprove or require modifications for approval of human research under its jurisdiction;
- The IRB’s authority to suspend or terminate approval of a study, or to place restrictions on the performance of the study, and the circumstances under which these actions may be taken; and
- If the IRB issues a “not regulated” determination or notifies the investigator that research is exempt from review, the procedures that investigators must follow to request such determinations and the internal processes to perform them.
SOPs must acknowledge the principles that:
- Research approved by an IRB is subject to disapproval by the VPR and, as applicable, other institutional officials;
- No institutional official, including the VPR and the University President, is empowered to overrule an IRB’s disapproval.
The University has developed a web-based system for submission, routing, approval, and management of human research information. The system, called eResearch Regulatory Management (eRRM), is designed to help the University meet its obligation to conduct research in an ethical manner and in accord with laws and regulations governing research conduct. Access to eResearch is granted based on roles and oversight responsibilities.
SOPs must describe the process used to submit applications and reports to the IRB and the Principal Investigator’s (PI) role and responsibilities for submission of IRB applications, including the following:
- The application is designed to allow only one PI for each application;
- The PI must assume full responsibility for a project and for compliance with applicable laws and regulations and institutional policy and must be knowledgeable about a project’s existence, scope, and progress;
- The PI is required to execute the final command to submit a report or application to ensure that the PI has reviewed the entire content of the submission and has approved all information submitted, including all supporting documentation (and in doing so to make certain attestations regarding the conduct of the project and his/her involvement in it and certify that the PI is responsible for that information);
- The PI may specifically delegate the responsibility to a co-investigator or the faculty mentor to submit reports of an Adverse Event (AE) or Other Reportable Information or Occurrence (ORIO) due to possible time-sensitive nature of these reports, although the PI is still ultimately responsible for these reports;
- Exceptions to this policy are limited and must be approved by the VPR or designee.
The SOPs must describe the procedures the IRB follows when making the determinations specified in Subsections (a) to (f) below.
The SOPs must describe the role of IRB staff in determining whether the research is regulated by the IRB. In making this determination, the IRB considers the following with respect to each application for initial, amendment or continuing review:
- Is the activity described in the application research as defined in the Common Rule?
- Is the activity human research as defined in FDA regulations?
- Is the University of Michigan engaged?
- Is the research exempt from IRB oversight?
These determinations are made consistent with the guidance provided at the U.S. Department of Health and Human Services Human Subject Regulations Decision Charts and in consultation with IRB administrators or chairs, as appropriate. If the research:
- Involves activities or data subject to other rules or regulations such as the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule, the Health Information Technology for Economic and Clinical Health Act (HITECH) Security Rule, the Family Educational Rights and Privacy Act (FERPA) or rules of other federal agencies, the SOPs describe the process for reviewing and ensuring compliance with these other regulations or rules.
- Is not regulated, the SOPs require that an IRB staff member issue a “not regulated” determination through eResearch.
- Is exempt, the SOPs direct an IRB staff member to ensure that the application indicates the request for an exemption determination or to direct the PI to revise the application to do so.
i. Information Required for IRB Review
IRBs must obtain sufficient information prior to review of applications for initial or continuing review so that it can apply and satisfy the requirements for approval of research. SOPs must describe what information the IRB must obtain prior to review of an application.
For protocols regulated by the Federal Common Rule, 45 CFR 46.111, the required information includes:
- IRB submission form
- Full protocol
- Full grant or contract application (if federally funded)
- Protocol summary
- Informed consent form
- Scientific review
- Recruitment material (e.g., advertisements, recruitment letters, scripts for telephone conversation or focus groups, etc.)
- Investigator’s qualifications [e.g., CV, medical license(s), etc.]
- Conflict of interest disclosure
- List of all investigators
- Other (Describe) Additional elements that may apply for biomedical research. Check all that apply.
- Investigator Brochure
- Package insert providing drug information
- Device manual
- Investigational New Drug Application (IND)/Investigational Device Exemption (IDE) number
- Copy of FDA 1572 form or Investigator Agreement (for device studies)
- Copy of case report forms
See the Office for Human Research Protections' (OHRP) QA Self Assessment Tool for more information.
For studies regulated by the FDA, (and, thus, subject to the provisions of 21 CFR 56.111), the required information includes:
- Description of the professional qualifications of the investigator conducting the research (including descriptions of necessary support services and facilities)
- Study protocols (addressing at least study title, purposes, risks and expected benefits, study sponsor, results of previous related research, subject inclusion/exclusion criteria including justifications for use of any vulnerable subject populations, and test article accountability procedures)
- A description of the study design (including, as needed, a discussion of the appropriateness of research methods)
- Description of the procedures to be performed
- Provisions for managing adverse reactions
- Consent procedures and issues to be addressed
- Subject compensation, if any
- Provisions for compensation for injuries resulting from the research
- Provisions for protecting subject privacy and confidentiality of data
- Extra costs to subjects or third-party payers anticipated resulting from participation in the study
- The investigator’s brochure, if any
- The case report form to be used, if any
- The proposed consent document, including translated versions
See FDA’s Information Sheet: A Self-Evaluation Checklist for IRBs for additional information.
ii. Review Process/Primary Reviewers
SOPs must describe the IRB’s review and approval process, including any primary reviewer process used for initial review, continuing review (see OHRP's Guidance on Continuing Review), review of protocol changes, or review of reports of unanticipated problems involving risks to subjects or others or of noncompliance, particularly serious and/or continuing noncompliance. SOPs must include all of the following:
- A list or description of specific documents and other information distributed or otherwise communicated to primary reviewers (if applicable), and to all other IRB members for each review
- The timing of the distribution
- Full grant or contract application (if federally funded)
- The regulatory criteria considered by the IRB and primary reviewers (if applicable)
- The range of possible actions taken by the IRB for protocols undergoing initial or continuing review and protocol changes undergoing review
iii. Timeliness of Submissions and Reviews
SOPs or other IRB guidance also should address the methods that will be employed to promote timely review (and approval, contingent approval, or disapproval) of applications submitted to the IRB. For example:
- How an IRB reminds investigators in advance of expiration that their approvals will expire and an explanation of the process for submitting renewals; and
- That the IRB may terminate studies when approvals have lapsed with proper notice to affected investigators.
iv. Notice and Appeal of IRB Determination
SOPs or other IRB guidance must describe:
- How the IRB will notify investigators and the University of IRB decisions
- The methods investigators can use to raise concerns with the IRB regarding its activities
- How investigators can appeal a specific IRB determination
SOPs must describe how IRBs determine the frequency of review of each study, including:
- IRBs review of all non-exempt University research at least once each year, except for qualifying University demonstration projects that allow for a different approval period by institutional policy (see HRPP Innovation and Demonstration Initiative). All federally sponsored research must be reviewed at least once a year.
- To ensure proper monitoring of studies, the IRB may determine that some projects require review more often than annually. SOPs should include the criteria the IRB uses to make these determinations. For example, an IRB may set a shorter approval period for high-risk protocols or protocols with a high risk-to-potential benefit ratio.
- A statement that the expiration date is the last date the protocol is approved, and the method of calculating the expiration date. Effective dates of IRB approval and expiration dates are noted in the approval letters for initial review, continuing review, and amendments. The eResearch information management system uses the expiration date to calculate the end of the approval and the exact time at which the approval period ends is noted on the approval letter by the following statement: “Approval for this study expires on 11:59 p.m. on xx/xx/xxxx."
SOPs must describe how the IRB determines which projects need enhanced monitoring, such as verification from sources other than the investigators that no material changes have occurred since previous IRB review. SOPs should include specific criteria used to make these determinations, for example:
- Randomly selected projects
- Complex projects involving unusual levels or types of risk to subjects
- Projects conducted by investigators who previously have failed to comply with applicable regulations, institutional or IRB requirements
- Projects where other concerns have been raised about possible material changes occurring without IRB approval
SOPs must describe the process for submitting and approving changes to research projects, including all of the following:
- The eResearch IRB application is the method by which investigators report and IRBs approve changes in research
- The IRB requires prompt submission of proposed changes in research activity via an amendment prior to initiation of the change
- Changes may not be initiated until approved by the IRB except when necessary to eliminate apparent immediate hazards to the subject
- In approving such changes, the IRB will apply applicable regulatory criteria and will require that any significant new findings that might relate to willingness to continue participation are provided to participants
- The HRPP ensures compliance with this requirement through its post-approval monitoring program and the IRB’s internal monitoring activities
SOPs must describe the process used to prevent lapses of IRB approval of a study due to untimely submission of a continuing review application, including all of the following:
- The IRB requires investigators to submit a continuing review application before expiration of IRB approval, and in ample time for IRB review
- To assist the investigators in meeting this requirement, eResearch provides notification of impending expiration and directions for submitting a continuing review application.
- If an investigator fails to provide a continuing review application to the IRB, or the IRB has not reviewed and approved the continuing review application by the expiration date of the current approval (regardless of the reason or circumstances), the study will be considered lapsed.
- The research must stop unless the IRB finds it is in the best interest of individual subjects currently participating in the study to continue the research interventions or interactions.
- Enrollment of new subjects during a lapse is prohibited
- IRB will remind investigators that resources must not be expended for unallowable activities.
- The IRBs notify other University units of lapses, as needed.
SOPs must describe the expedited review process, including:
- Which categories of projects or applications may be eligible for expedited review
- The process (if any) for requesting expedited review
- The procedures for reviewing applications by expedited review, and
- The method for keeping all IRB members apprised of applications that have been approved on an expedited basis.
SOPs must describe the types of research that are eligible for expedited review as specified by OHRP’s Applicability Criteria and list of expedited review categories. An IRB generally may use expedited procedures (through its chair or one or more experienced members designated by the chair) to review research meeting the following criteria:
- The current and future research procedures present no more than minimal risk to participants
- The identification of the participants on their responses will not reasonably place them at risk of criminal or civil liability or be damaging to their financial standing, employability, insurability, reputation, or be stigmatizing, unless reasonable and appropriate protections will be implemented so that risks related to invasion of privacy and breach of confidentiality are no greater than minimal
- The research is not classified
- The research falls into one or more of the categories of projects or applications appearing on a list of expeditable studies published by the Secretary of the Department of Health and Human Services, and only in those categories (see 45 CFR 46.110 and 21 CFR 56.110).
The IRB also may use expedited procedures to review "minor" changes to research previously approved by the full committee. SOPs must provide that a proposed change in research is deemed “minor” if it does not significantly affect an assessment of the risks and benefits of the study and does not substantially change the aims or design of the study. A modification cannot be deemed "minor" if it involves the addition of procedures that involve more than minimal risk or does not fall into categories (1) - (7) of research published by the Secretary of the U.S. Department of Health and Human Services (HHS).
Examples of "minor" changes to a research study include, but are not limited to, the following:
- Addition or deletion of study team members
- Addition of procedures that do not significantly increase risk to subjects, considering the original purpose and study design of the approved study (i.e., new procedures that fall under any of the expedited categories can usually qualify as minimal risk)
- Removal of research procedures that would thereby reduce the risk to no more than minimal (i.e., procedures now meet expedited research categories)
- Addition of non-sensitive questions to a survey or interview, and procedures
- Addition of, or revision to, recruitment materials or strategies
- Change to improve the clarity of statements or to correct typographical errors provided that such changes do not alter the content or intent of the statement
The University may also undertake demonstration projects that allow for the addition of expedited review categories for research that is not federally sponsored.
SOPs must describe how expedited reviewers are chosen. Generally, IRB Chairs appoint experienced IRB members to serve as expediting reviewers. For purposes of this policy, a member is deemed experienced if he or she has completed all mandatory education for IRB members, has served on the IRB for a minimum of six (6) months or has described and documented the appropriate experience, and been approved by the IRB chairs as qualified to perform expedited reviews. The IRBs may adopt more restrictive criteria in their SOPs.
If the IRB employs expedited review procedures, the SOPs should address the method the IRB will use to ensure that expedited reviewers either approve or forward the application for full board review within a reasonable period of time. The expedited reviewer must review the same materials that the convened IRBs receive for protocols reviewed by the convened IRB. Applications may not be disapproved using expedited procedures; rather, full board action is required for disapproval.
SOPs must describe any limitations placed on the use of expedited review, including:
- The IRB Chair may limit the scope of expedited review to certain application types (i.e., only minor amendments or continuing reviews, but not initial reviews) or research fields (i.e., only social or behavioral, but not bio-medical).
- For federally supported or FDA-regulated research, the relevant department or agency head may restrict, suspend, terminate or choose not to authorize an institution's or IRB's use of expedited review procedures.
- In addition, the VPR retains authority to require full-board review of any project or category of projects.
IRBs ensure research is approved only when all of the requirements in 45 CFR 46.111 or 21 CFR 56.111 (for FDA-regulated research) are met. SOPs must include all of these criteria as described below. For research that is not federally supported and not subject to FDA regulations, an investigator or IRB may submit a request to the Institutional Official (IO) or the Deputy Institutional Official (DIO) for an exception to any of the following criteria, consistent with the provisions of 45 CFR §46.101(i) except that the IO or DIO assumes the role of the HHS Secretary in considering the request.
In its review of research applications, the IRB considers whether research procedures are consistent with sound research design in order to yield the expected knowledge. Scientific merit is examined in relationship to the risks and benefits of the research. The IRB may fulfill its obligation to evaluate proposed research for scientific or scholarly validity by ensuring its membership includes individuals with appropriate scientific background to determine whether the research can reasonably be expected to answer its proposed question and whether the importance of the knowledge to be gained is sufficient to justify any risks associated with the conduct of the project.
A research plan approved by an IRB must ensure that risks to subjects are minimized by using procedures consistent with a sound research design that do not unnecessarily expose subjects to risk, and whenever appropriate, by using procedures already being performed on subjects for diagnostic and treatment purposes. When ensuring that risk is minimized, the IRB should evaluate the resources available at each site where research will be conducted, for example, by reviewing descriptions provided by investigators of facilities and personnel involved in the study.
Research may be approved only if the risks to subjects are reasonable in relation to any anticipated benefits to subjects and to 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 that 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 or benefits that fall within the purview of its responsibility.
An IRB must determine that recruitment and enrollment plans will promote equitable subject selection. In making this assessment, the IRB should review any proposed direct advertising to prospective subjects (i.e., communications intended to be seen or heard by potential subjects to solicit their participation in a study) and take into account the purposes of the research and the setting in which the research will be conducted. The IRB should be particularly cognizant of the special problems of research involving vulnerable populations, such as children, prisoners, pregnant women, persons who are cognitively impaired or lack decision-making capacity, or economically or educationally disadvantaged persons.
i. General Requirements
Information given to subjects as part of informed consent must meet applicable regulatory and institutional requirements, including those described in Part 6 of this OM. Generally, all of the elements of informed consent and documentation of informed consent required by HHS and/or FDA regulations must be satisfied before the IRB will approve a research study, unless the IRB waives or alters the requirements as provided in further detail below. An IRB may require that additional information be given to subjects when in the IRB’s judgment the information would meaningfully add to the protection of subject rights and welfare.
The IRB may approve a short form written consent document in certain circumstances. In a short form consent process, the elements of informed consent required by HHS and/or FDA regulations are presented orally to the subject or the subject’s legally authorized representative in the presence of a witness. The IRB must approve a short form and a written summary (oral script) of what is to be said to the subject or the representative and ensure that it includes the elements of informed consent required by HHS and/or FDA regulations. The short form must include the required signature lines. Table 3 summarizes short form consent requirements.
The subject or the representative signs only the short form itself. The witness signs both the original short form and a copy of the oral script, and the person actually obtaining consent signs a copy of the oral script. A copy of the signed short form and oral script is given to the subject or the representative, and the researcher retains the original signed short form and signed oral script for the protocol file.
For subjects who do not speak English, the witness must be conversant in both English and the language of the subject.
Table 3: Short Form Consent Requirements
Translator (when needed)
Forms Required to Sign
Recommended but not required UNLESS also serving as the witness or the researcher
Short form and oral script
Forms Required to Receive or Keep
A copy of the signed short form and oral script
Nothing UNLESS also serving as the researcher
Original signed short form and signed oral script
In some cases, an IRB may approve a consent procedure that does not include, or that alters, some or all of the required elements of informed consent, or may waive the requirement to obtain informed consent. The following standards apply to all federally and non-federally supported human research that does not involve vulnerable populations. Different rules for FDA-regulated studies are found further below. If vulnerable populations are included in the study, additional standards must be applied. See Part 7, Section IV in this OM for details.
Waiver or Alteration of Informed Consent
An IRB may waive or alter the requirements for informed consent only if it finds and documents that:
(a) The research involves no more than minimal risk to the subjects;
(b) The waiver or alteration will not adversely affect the rights and welfare of the subjects;
(c) The research could not practicably (i.e., feasibly) be carried out without the waiver of alternation; and
(d) Whenever appropriate, the subjects will be provided with additional pertinent information after participation.
Alternatively, the IRB may approve a waiver or alteration of consent if it finds and documents that:
(a) The project is to be conducted by or subject to the approval of state or local government officials; and
(b) The project is designed to study, evaluate or otherwise examine: (i) public benefit or service programs; (ii) procedures for obtaining benefits or services under those programs; (iii) possible changes in or alternatives to those programs or procedures; or (iv) possible changes in methods or levels of payment for benefits or services under those programs; and
(c) The project could not practicably be carried out without the waiver or alteration.
Waiver of Requirement for Parental Permission
For research involving children as subjects, an IRB may waive the requirement to obtain parental permission if it finds and documents that:
(a) The research involves no more than minimal risk to the subjects;
(b) The waiver or alteration does not adversely affect the rights and welfare of the subjects;
(c) The research cannot practicably be carried out without the waiver or alteration;
(d) When appropriate, the subjects will be provided with additional pertinent information after participation; and
(e) The research is not FDA-regulated.
Alternatively, the IRB may waive the requirement to obtain parental permission if it finds and documents that:
(a) The research is designated for conditions or for a subject population for which parental or guardian permission is not a reasonable requirement to protect the subjects;
(b) An appropriate mechanism for protecting the children who will participate as subjects in the research is substituted; and
(c) The research is not FDA-regulated.
Waiver of Documentation of Informed Consent
The IRB may waive the requirement for documentation of informed consent if it finds and documents either of the following:
(a) That 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 (in which case each subject must be offered the opportunity to receive the documentation); or
(b) 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.
Even if the IRB approves a waiver of documentation of consent, the IRB may require the investigator to provide subjects with a written statement regarding the research.
For emergency research, the IRB may approve a waiver of consent consistent with the guidelines found at https://research.medicine.umich.edu/office-research/institutional-review-boards-irbmed/guidance.
Waiver of Alteration of Informed Consent
An IRB may waive or alter the requirements for informed consent in a FDA-regulated study if it finds and documents that the following requirements have been met:
(a) When the IRB receives a request to use an investigational agent without informed consent, the IRB will assess whether or not the regulatory criteria set forth in 21 CFR 50.23 (a)-(c) apply.
- If the IRB determines that the criteria are met, the IRB will issue a notice of outcome in eResearch.
- If the IRB determines that the criteria are not met, the IRB will require that informed consent must be obtained prior to use.
(b) Where the IRB is informed after the use of an investigational agent without informed consent, the IRB will assess whether or not regulatory criteria were followed.
- If the IRB determines that the criteria are met, the IRB will issue a notice of outcome in eResearch.
- If the IRB determines that the criteria are not met, the IRB will consider further action that may include, but not be limited to, any of the following:
- Require additional education for the administering physician;
- Require additional education for the department involved in administering the agent;
- Notify institutional officials;
- Notify the manufacturer/sponsor of the agent; and
- Notify the FDA.
Emergency Research Exception from Informed Consent
In reviewing a study that requests an "Exception from Informed Consent Requirements for Emergency Research," the IRB will assure that the criteria set forth in 21 CFR 50.24 described in the "Position Statement of the Medical School Institutional Review Board for Human Subject Research (IRBMED) on Allowing Exception From Informed Consent For Emergency Care Research" are met.
Waiver of Documentation of Informed Consent
The IRB may waive the requirement for documentation of informed consent if it finds and documents the following:
(a) That the research presents no more than minimal risk of harm to subjects; and
(b) That the research involves no procedures for which written consent is normally required outside of the research context.
The following tables may be referenced when a study is regulated by both FDA and HHS regulations. Tables 4 and 5 compare the types of waivers or exceptions that maybe requested by a researcher under one agency’s regulations and determine if it can be approved if the other agency also has jurisdiction.
Table 4: Comparison of FDA Criteria to HHS Criteria
HHS OHRP criteria are met
Waiver of requirement to obtain informed consent 45 CFR 46.116 (c).
Request for alteration of informed consent requirement 45 CFR 46.116 (d).
Substitute mechanism for parental permission 45 CFR 46.408 (c)
Waiver of documentation of informed consent 45 CFR 46.117 (c)
Applicability if the study is regulated by FDA 21 CFR 50, Subpart B
Alteration, or substitutions are not allowed. Waiver is not allowed for the aspects of the project that meets the FDA definition of research, however, the IRB may allow an HHS waiver of informed consent solely for recruitment, such that investigators may identify potential subjects.
Allowed if both apply:
21 CFR 56.109 (c)1
Table 5: Comparison of HHS Criteria to FDA Criteria
FDA criteria are met
FDA Emergency Use Exception 21 CFR 50.23 (a)
FDA Emergency Research Exception 21 CFR 50.24
FDA Terrorism/ Public Health Emergency Exception 21 CFR 50.23 (e)
FDA/DOD Presidential Waiver for Military 21 CFR 50.23 (d)
HHS OHRP applicability if the study is supported by federal funding
Agent can be administered but data collected cannot be used for research
Allowed if informed consent is obtained after the research is initiated
Allowed if 46.116(d) applies
HHS has not provided specific guidance. The IRB should consult with the IO or DIO in the event this waiver is requested.
Under HIPAA, researchers must obtain written authorization from a research subject for the release of protected health information that the researcher will collect, use or disclose for the study.
Waiver of HIPAA Authorization
The IRB may waive this requirement if the IRB finds and documents all of the following:
(a) The use or disclosure of protected health information involves no more than minimal risk to the subjects' privacy, as demonstrated by:
- An adequate plan to protect any identifiers from unauthorized use or disclosure;
- An adequate plan to destroy the identifiers at the earliest opportunity consistent with the conduct of the research (unless there is a health or research justification for retaining the identifiers or retention is required by law); and
- Adequate written assurances that the protected health information will not be reused or disclosed except as required by law or for research oversight or for other research approvable under a waiver; and
(b) The research could not practicably be conducted without the waiver; and
(c) The research could not practicably be conducted without access to and use of the protected health information.
SOPs must provide that the IRB will ensure, when appropriate, that research plans make adequate provision for monitoring data collected to ensure subject safety and describe how the IRB makes this determination. Additional information on data safety monitoring plans is available in Part 7 (II) of this OM.
“Privacy” refers to the willingness of research participants to allow access to themselves and their information. “Confidentiality” refers to the agreement between the researcher and participants on how the participants’ identifiable private information will be managed and used. SOPs must provide for all of the following:
- As part of the IRB's duty to protect the rights and welfare of study participants, the IRB must ensure that the research plan contains adequate provisions to protect the privacy of participants and maintain the confidentiality of their identifiable data for the duration of the study and, in the case of the confidentiality of the research data, after the study is finished;
- That the researcher must include a plan to protect participants' privacy and confidentiality in the eResearch application, protocol or other documents submitted to the IRB;
- A description of the types of privacy and confidentiality information that the researcher must include in its plan;
- That the IRB reviews the researcher's plan to protect participants' privacy and confidentiality to assess the adequacy of the protection;
- A description of the issues and points of interest that will be used to evaluate the protocol appropriately and adequately protects privacy and confidentiality;
- A description of the regulatory, institutional, and IRB policies, procedures, and guidance that will be used to confirm that the protocol appropriately and adequately protects privacy, including, but not limited to, the following:
- Code of Federal Regulations/Protection of Human Subjects (45 CFR 46)
- Food and Drug Administration (FDA)/Protection of Human Subjects (21 CFR 56)
- Health Insurance Portability and Accountability Act (45 CFR Parts 160 and 164)
- University of Michigan Website Guidance for Sensitive Human Subjects Data
Issues and points of interest considered when reviewing privacy protections include all of the following:
- The research setting, participant population, the manner in which participants will be approached and enrolled, and inclusion of any un-consented individuals about whom the primary participants will provide information.
- Whether the protocol proposes an invasion of privacy through observation or intrusion into situations where participants would otherwise have a reasonable expectation of privacy.
- Where there is a risk that privacy will be compromised, the IRB will evaluate:
- Whether reasonable people might be offended by the invasion of privacy;
- Whether the research can be redesigned to avoid the possible invasion of privacy;
- Whether the importance of the research objective justifies the invasion of privacy;
- Whether the participant will be informed of the invasion of privacy, its implications, and available protections; and
- Whether documentation of consent should be waived in order to protect participant privacy.
Issues and points of interest considered when reviewing confidentiality protections include all of the following:
- The research setting, participant population, the manner in which participants will be approached and enrolled, where private information will be collected, the nature of information, who will collect, receive and use the information and inclusion of any un-consented individuals about whom the primary participants will provide information or for whom the researchers will obtain information through record review or chart abstraction;
- Whether appropriate permission is sought for access to records when reviewing existing records for participant selection or to abstract data;
- Whether the protocol proposes the collection of sensitive individual information;
- Where the research includes the collection of sensitive individual information the IRB will evaluate:
- Whether adequate provisions have been identified to protect the confidentiality of the data through coding, destruction of identifying information, limiting access to the data, and any other methods that may be appropriate, given the context of the study;
- Whether the disclosure of the data might place the participant at legal, social, reputational, employability, or insurability risk;
- Where compelled disclosure of the data might place participants at risk, whether a Certificate of Confidentiality should be sought to protect the researcher from disclosure of the data under subpoena or other legal process;
- Where accidental disclosure of the data might place participants at risk, whether data management procedures ascribe to institutional policies and IRB guidance for appropriate and required data security measures;
- Whether disclosures to participants about confidentiality risks and protections are adequate; and
- Whether documentation of consent should be waived in order to protect confidentiality.
For more on privacy and confidentiality, see the OHRP IRB Guidebook – Chapter III (D), from which the above list of considerations was obtained.
SOPs must describe the different standards that apply to research involving vulnerable populations. These groups include but are not limited to: children, pregnant women and fetuses, prisoners, individuals who are cognitively impaired or lack decision-making capability, economically or educationally disadvantaged persons, or employees, students or patients of investigators. The IRBs will comply with the standards described in Part 7 (IV) of this OM for review and approval of research involving these populations. These standards limit the categories of research that may be performed and require, as appropriate, additional safeguards to protect subject rights and welfare when they do participate. Additional information is also available in Part 11 of this OM.
SOPs must provide that:
- The IRB may not approve an application for research involving drugs, biologics or devices unless it determines that the test articles will be used only in approved research protocols, under the direction of approved investigators, or in emergency circumstances, consistent with FDA requirements and University policies on emergency use;
- Protocols must describe local drug/biologic or device accountability procedures, if applicable, including procedures required by:
- University of Michigan Health System (UMHS) Research Pharmacy (formerly Investigational Drug Service (IDS)); and
- Biomedical Engineering Unit (BEU).
- Investigational drug management and accountability is performed according to Department of Pharmacy Services Policies 400.00-400.10;
- Investigational device accountability is performed in accordance with the UMHS Medical Equipment Management Plan, when applicable, and according to the plan approved by the IRB.
SOPs must include provisions requiring IRBs to determine that research studies have the resources necessary to protect subjects by evaluating all of the following:
- There is adequate time for the investigators to conduct and complete the research;
- There are an adequate number of qualified staff;
- The facilities where the research will be conducted are adequate;
- Investigators have access to a population that will allow recruitment of the necessary number of subjects; and
- Medical or psychosocial resources that subjects may need as a consequence of the research are available.
IRBs that review FDA-regulated studies must address additional items in their SOPs (details of which are provided in Part 8 of this OM). These include procedures and requirements for the following:
- Determining whether an IND or IDE is required;
- For device studies, making significant/non-significant risk determinations;
- Emergency use notification and reporting procedures;
- Procedures for reviewing protocols for anticipated additional use in emergency situations;
- Waiver of informed consent for certain emergency research, if permitted by the IRB;
- Adverse event reporting guidelines and procedures;
- Communications, if any, with sponsors (i.e. IND and IDE holders); and
- Test article accountability procedures (see Section C.6.i, above).
SOPs also may address any additional considerations for sponsor-investigators whose research activities will not be scrutinized by external sponsors, contract research organizations (CROs), or similar organizations. IRBs may choose to adopt policies and procedures to address and monitor, as appropriate, non-research expanded access to investigational drugs and devices.
SOPs must describe key IRB administrative functions and requirements in sufficient detail to inform IRB members and staff, researchers, and other stakeholders of the IRB’s rules and expectations. These must include, at a minimum, the elements described below in Subsections 1 to 4. To the extent these elements are addressed through this OM or other institution-wide policy they need only be referenced in the IRB SOPs.
SOPs must describe requirements for IRB meetings, including the following:
a. An IRB must review proposed research and conduct continuing reviews at convened meetings at which a majority of the members of the IRB are present.
b. At convened meetings at least one non-scientist member must be present in order to meet quorum; at least one unaffiliated member, who represents the general perspective of subjects, should be present at the majority of meetings in a given year. Attendance of all present members is recorded in the meeting minutes.
c. In order for the research to be approved, it must receive approval by majority vote of the quorum (as described above). If, during the course of the meeting, quorum is lost, votes may not be taken until it has been restored.
d. When convened-board review is not required, the SOPs must include details of any process, such as expedited review procedures (as described above) or subcommittee procedures, which may be used to supplement the IRB's review responsibilities.
e. IRB members may agree, during an appropriately convened meeting, to issue conditional approval for a project only if any requested clarifications or modifications are not relevant to the determinations required by the IRB under the Common Rule or its Subparts (45 CFR 46) or, as applicable, FDA regulations (21 CFR 56). 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 of responsive material by the convened IRB.
f. Although it is preferred that IRB meetings take place with all participating members physically present, an IRB may establish protocols to convene meetings via video conference, teleconference or similar means. Such protocols must provide a means for all participants to receive the meeting materials prior to the meeting and facilitate active and equal participation in the discussion of all protocols. The protocols must further provide that minutes from meetings convened in this manner will reflect that these two conditions have been met, in addition to other mandated information (e.g., presence of a quorum including at least one non-scientist, discussion, and resolution of problematic issues, final vote).
SOPs must describe requirements for how the IRB will notify investigators and the University of its decisions, including the following:
a. An IRB will notify investigators in writing of its decision to approve or disapprove a proposed research activity or of modifications to the proposal that are required to secure IRB approval.
b. If the IRB decides to disapprove a research activity, it must include a statement of the reasons for its decision in its written notification and must give the investigator an opportunity to respond in person or in writing.
c. An IRB will notify the IO or DIO and other institutional officials, when appropriate, of its decisions regarding proposed research activities by formal or informal means, such as through access to relevant electronic databases.
SOPs must also describe any process for reviewing and acting on investigator responses to IRB actions.
SOPs must require prompt reporting of Other Reportable Information or Occurrence (ORIO) to the IRBs, the IO or DIO and any other institutional officials, as appropriate, including:
a. Any unanticipated problems involving risks to subjects or others;
b. Any serious or continuing noncompliance with federal regulations, institutional policy, or IRB requirements; and
c. Any suspension or termination of IRB approval consistent with the requirements of Part 12 of this OM.
SOPs must describe the procedures that the IRB uses to receive, investigate, and address such reports, including the range of actions the IRB may take in response to such reports, consistent with the requirements of Part 12 of this OM. The process for making additional reports to sponsors and government authorities with jurisdiction outside of the institution is described in Part 12 of this OM.
SOPs must describe how the IRB documents its activities and decisions and maintains records of that documentation, including:
- Copies of all research proposals reviewed, scientific evaluations, if any, accompanying the proposals, approved sample consent documents, progress reports submitted by investigators, and reports of injuries to subjects;
- Records of continuing review activities;
- Statements of significant new findings provided to subjects;
- Copies of official correspondence between the IRB and investigators;
- A roster of IRB members;
- Standard Operating Procedures (SOPs);
- The justification for using an expedited procedure;
- Description of the action taken by the reviewer;
- Documentation of exemption determinations, including the category by which research was determined to be exempt;
- Documentation of approvals using the expedited procedure, including the applicable criteria by which the research was approved using the expedited procedure; and
- Minutes of IRB meetings sufficiently detailed to show:
- Attendance at meetings;
- Actions taken by the IRB;
- The vote on these actions including the number of members voting for, against, and abstaining;
- The basis for requiring changes in or disapproving research;
- A written summary of the discussion of problematic issues and their resolution;
- Separate deliberations for each action;
- When an alternate member replaces a primary member;
- For initial and continuing review, the approval period;
- The names of IRB members who leave the meeting because of a conflict of interest along with the fact that a conflict of interest is the reason for the absence;
- Unless documented in the IRB records, determinations required by the regulations and protocol-specific findings justifying those determinations for:
- Waiver or alteration of the consent process;
- Research involving pregnant women, fetuses, and neonates;
- Research involving prisoners; and
- Research involving children
- When following HHS regulations or guidance, documentation of justification of any deletion or substantive modification of information concerning risks or alternative procedures contained in a HHS-approved sample consent document; and
- When following FDA regulations or guidance, documentation of the rationale for significant risk/non-risk device determinations.
SOPs must describe IRB record retention mandates and destruction standards, including the following:
a. IRBs must maintain these records for at least three (3) years after the completion of the study;
b. If a protocol is terminated without subject enrollment, IRB records are maintained for at least three (3) years after termination.
c. If an IRB performs functions on behalf of a "covered entity" (such as the University of Michigan Hospitals and Health Centers) related to HIPAA and research, those records must be retained for at least seven (7) years, either by the IRB or by the covered entity; and
d. Administrative units responsible for IRB operations may impose longer retention and specific destruction standards.
All IRB records maintained must be maintained securely and made accessible for inspection and copying by authorized representatives of the University, relevant sponsors, and government authorities with jurisdiction (such as OHRP, FDA, and National Institutes of Health (NIH)) at reasonable times and in a reasonable manner.
At least once every five years, in conjunction with the AAHRPP accreditation cycle, the UM Office of Research initiates a comprehensive review of the HRPP OM. IRB SOPs must make provisions for such a review of SOPs on the same cycle or more frequently at the IRB’s discretion. Revisions to the SOPs may be made at any time, as required by changes in law, ethical standards, institutional policy, quality assurance activities or other considerations. Substantive revisions require advance approval by the HRPP Director. Additional requirements for quality assurance and quality improvement are described in Part 12 of this OM.
Other review units listed in Part 2 of this OM must develop, implement, and enforce their own standard operating procedures relevant to their role in the HRPP.