HRPP Policy (June 2012)
Operations Manual - Part 3
This section describes the process by which HRPP policies are developed, approved and implemented, and articulates minimum requirements for IRB standard operating policies and procedures.
There is a hierarchy of rule making authority at the University: (i) the Bylaws of the Board of Regents (ii) rules initiated by subordinate 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.
The Vice President for Research (VPR) is the University authority delegated legislative powers for the Human Research Protection Program (HRPP). Chapter 303 in the University of Michigan Standard Practice Guide (SPG) is assigned to the VPR and is used for policy statements in general realms of authority and responsibility. The University policy statement on the UM HRPP is at SPG 303.05.
II. THE OPERATIONS MANUAL
The 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 Office of the Vice President for Research (OVPR).
At least once every five years, in conjunction with the AAHRPP reaccreditation cycle, OVPR 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 with notice to the VPR.
III. IRB STANDARD OPERATING POLICIES AND PROCEDURES
Each IRB designated by the University to review and monitor human research under the University's 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 Operations Manual, other central institutional policy (such as SPGs), and applicable laws and regulations. IRBs are free, however, to implement and enforce additional or more restrictive policies and procedures. All IRB SOPs (and substantive revisions) must be reviewed and approved by the office that provides resources and administrative oversight as well as the Vice President for Research prior to implementation. The VPR 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 Vice President for Research to ensure compliance with applicable laws or regulations or with University policy. SOPs and other guidance may require additional approvals at the unit level.
The SOPs must make provisions for SOP development, maintenance, update, and review. These activities may include:
- 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;
- Review at regular intervals, generally in conjunction with accreditation activities or revision of this Operations Manual; and
- Revision in response to comments by the IRB Council and the Vice President for Research or designee.
The SOPs may incorporate by reference elements of this Operations Manual, as appropriate. The SOPs, however, are intended to be descriptions of the actual procedures used by the IRB.
A. General Provisions
An IRB's SOPs must reference the authority under which the IRB is established, its relationship to the Vice President for Research 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, and the ethical principles under which it operates. The SOPs also must recite 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 Operations Manual (such as guidelines published by the International Conference on Harmonisation), these should be described in sufficient detail to apprise investigators of the standards against which their studies will be reviewed and monitored. This disclosure requirement does not apply to the concerns and considerations any individual reviewer may bring to his or her analysis of an application. Nor does it preclude the IRB from considering any given principles or rules beyond those formally articulated in its SOPs on an ad hoc basis.
B. Organization and Personnel
The SOPs must describe the membership of the IRB. For example, the description may include a discussion of the method by which the chair and IRB members are chosen or appointed, terms of service, duties and expectations, attendance requirements, and provisions for removal when necessary; and describe the duties and functions of IRB staff and their relationship with IRB members, researchers, and other stakeholders. Finally, the SOPs should describe any ethical expectations of these individuals in addition to those described in this Operations Manual.
The SOPs must provide that each IRB will have at least five members, with varying backgrounds to promote complete and adequate review of research activities commonly subject to that IRB's oversight. Accordingly, the 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 will include at least one member whose primary concerns are in scientific areas and at least one whose primary concerns are in nonscientific areas. According to OHRP guidance, "members whose training, background, and occupation would incline them to view scientific activities from the standpoint of someone within a behavioral or biomedical research discipline should be considered a scientist, while members whose training, background, and occupation would incline them to view research activities from a standpoint outside of any biomedical or behavioral scientific discipline should be considered a nonscientist. In addition, the IRB must have members with sufficient knowledge of the specific scientific discipline(s) relevant to the research that it reviews." No IRB may consist entirely of members of one profession.
- The IRB will include at least one member who is not otherwise affiliated with (or an immediate family member of a person affiliated with) the University. OHRP considers the following individuals affiliated: part-time employees, current students, members of any governing panel or board of the University, paid and unpaid consultants of the University, healthcare providers with medical staff membership or other credentials to practice at University clinical sites, and volunteers working at the University on business unrelated to the University. Payments to unaffiliated members at reasonable market rates for their services to an IRB do not render them affiliated. Otherwise unaffiliated individuals who are patients, research subjects, or former students are not considered affiliated. The University supports efforts of the IRBs to include additional unaffiliated members and many IRBs do include more than one.
- The IRB must possess sufficient knowledge of the local research context to fulfill its review responsibilities under federal regulations and this Operations Manual. 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. These consultants may not vote with the IRB and are expected to disclose any relevant conflicts of interest or commitment.
The 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. The SOPs should include procedures to determine 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 assure that only the vote of one is counted in any particular circumstance.
The SOPs or other policies or guidance developed by the administrative unit responsible for the IRB's operations must describe arrangements, if any, for compensation to chairs, members and consultants. Liability coverage is a matter of institutional policy and is described in risk management policies available on the internet at http://www.umich.edu/~riskmgmt/. 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.
C. IRB Functions and Operations
SOPs must include descriptions of key operational 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. To the extent these elements are addressed through this Operations Manual or other institution-wide policy they need only be referenced in the IRB SOPs.
The SOPs must describe what types of studies are typically reviewed by the IRB and the authority of the IRB to approve, disapprove, or require modifications in (to secure approval of) human research under its jurisdiction. They also must describe 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. Finally, if the IRB issues "human research/not human research" determinations or notifies the investigator that research is exempt from review, the SOPs must describe the procedures that investigators must follow to request such determinations and internal processes to perform them.
1. Application Submissions
The University has developed a web-based system for submission, routing, approval and management of human research information. The system, called eResearch Regulatory Management (eResearch RM), 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.
Within eResearch, the University's IRBs recognize only one principal investigator for each application. This policy has been adopted to ensure that the PI assuming full responsibility for a project and compliance with applicable laws and regulations and institutional policy is in fact knowledgeable about its existence, scope and progress.
Any submission (e.g., new project, continuing review, adverse event, other reportable information or occurrences, termination report) to the IRB must be overseen personally by the PI. Requiring the PI to execute the final command to submit the report or application (and in doing so to make certain attestations regarding the conduct of the project and his/her involvement in it) to the IRB ensures that the PI has reviewed the entire content of the submission and has approved all information submitted, including all supporting documentation. It also certifies that the PI is responsible for that information.
Due to possible time criticality associated with submitting an Adverse Event (AE), or Other Reportable Information or Occurrence (ORIO), the PI may specifically delegate the IRB submission of these reports to a co-investigator or the advisor. The PI is still ultimately responsible for these reports.
Exceptions to this policy are limited and must be approved by the Vice President for Research or designee.
2. General Review and Approval Procedures
The SOPs must describe specific procedures for (i) determining whether submitted applications describe research as defined in the Common Rule or FDA regulations, or other activities (such as Privacy Board activities) subject to IRB oversight; (ii) conducting initial and continuing review of research and reporting determinations to investigators and the University; (iii) determining which projects require review more often than annually (including specific criteria used to make these determinations); (iv) determining which projects need verification from sources other than the researchers that no material changes have occurred since previous IRB review; and (v) ensuring prompt reporting to the IRB of proposed changes in research activity and ensuring the changes are not made prior to IRB approval except when necessary to eliminate apparent immediate hazards to the subject.
(a) Determining Whether and Under What Authority the Research is Regulated
The SOPs describe the role of staff, consistent with the guidance provided at http://www.hhs.gov/ohrp/humansubjects/guidance/decisioncharts.htm and in consultation with IRB administrators or chairs as appropriate, in determining the following with respect to each application for initial or continuing review: (1) is the activity described in the application research as defined in the Common Rule; (2) is the activity human research as defined in FDA regulations; (3) is the University of Michigan engaged; and (4) is the research exempt from IRB oversight. If the research is not regulated (i.e., if the answer to question 1 and 2, or to question 3 is "no"), the SOPs must require the staff member to issue a "not regulated" determination through eResearch. If the research is exempt, the SOPs must direct the staff member to assure that the application seeks an exemption determination or direct the Principal Investigator to revise the application to do so.
(b) Initial and Continuing Review and Review of Other Applications
IRBs will obtain sufficient information (including protocols, sample informed consent documents, relevant grant applications, any investigators' brochures, and recruiting materials) prior to review of applications for initial or continuing review to apply and satisfy the requirements of 45 C.F.R. § 46.111 for approval of research.
For studies regulated by the FDA, (and, thus, subject to the provisions of 21 C.F.R. § 56.11), this information must include at least a description of the professional qualifications of the investigator to do 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), study design (including, as needed, a discussion of the appropriateness of research methods); a description of the procedures to be performed; provisions for managing adverse reactions; consent procedures and issues to be addressed; subject compensation and compensation for injuries resulting from the research; provisions for protecting subject privacy; extra costs to subjects or third party payors anticipated to result from participation in the study; the investigator's brochure (if any); the case report form to be used (if any); and the proposed consent document, including translated versions. (See FDA's Information Sheet: A Self-Evaluation Checklist for IRBs.).
In describing the IRB's review and approval procedures, the SOPs should discuss 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 or continuing noncompliance. The discussion should include 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 these activities and the timing of the distribution. It also should describe the regulatory criteria considered and the range of possible actions taken by the IRB for protocols undergoing initial or continuing review and protocol changes undergoing review.
The 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, and provide investigators with a method to raise concerns with the IRB regarding its activities; and to gain an audience with an IRB to appeal a specific determination. For example, the SOPs may describe how IRBs remind investigators in advance of expiration that their approvals will expire and explain the process for submitting renewals. Procedures should also provide that the IRBs may terminate studies where approvals have lapsed with proper notice to affected researchers.
(c) Frequency of Review
IRBs must provide for review of all non-exempt University research at least once each year except for projects qualifying for two-year approval according to University policy (see Innovation and Demonstration website). To ensure proper monitoring, the IRB must determine which projects require review more often than annually and its SOPs should include the criteria used 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. The University may undertake demonstration projects that allow for different approval periods.
(d) Monitoring and Verification
The IRB also must determine which projects need enhanced monitoring, such as verification from sources other than the investigators that no material changes have occurred since previous IRB review and its SOPs should include specific criteria used to make these determinations. For example, criteria might include any or all of the following: 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 or institutional or IRB requirements; projects where other concerns about possible material changes occurring without IRB approval have been raised.
(e) Reporting Changes in Research
The IRB requires prompt submission of proposed changes in research activity 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. The eResearch IRB application is the method by which investigators report and IRBs approve changes in research. In approving such changes, the IRB will apply applicable regulatory criteria, and require that any significant new findings that might relate to participants' willingness to continue participation are provide to them. The HRPP assures compliance with this requirement through its post-approval monitoring program and the IRB's internal monitoring activities.
(f) Lapses in Approval
It is the principal investigator's responsibility to submit a continuing review application before expiration of IRB approval, and in ample time for IRB review. 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 and 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, and the IRB will remind investigators that resources must not be expended for unallowable activities. The IRBs notify ORSP of lapses as needed.
3. Criteria for Expedited Review
The SOPs must describe 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 on an expedited basis, and the method for keeping all board members apprised of applications that have been approved on an expedited basis. An IRB generally may review using expedited procedures (through its chair or one or more experienced members designated by the chair) 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. 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 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.
IRB Chairs may deem that an IRB member is qualified with sufficient experience to conduct expedited review if they have acted in one or more of the following capacities: active or past IRB membership for at least six months, term of membership on a human ethics committee, principal investigator on federally sponsored human subjects research, scientific reviewer on one or more federal study sections, and any of the following for at least six months: administrative director of an IRB, administrative reviewer of research applications in an IRB office, project manager of a human subject research program, or study coordinator on a research project. Members may also be considered qualified by other experiences not listed here if the IRB Chair deems them equivalent. 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).
The IRB also may use expedited procedures to review minor changes in previously approved research during a period for which approval is authorized. For purposes of this policy, 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 do not fall into categories (1) Ð (7) of research that can be reviewed using expedited procedures.
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 unvalidated survey or interview 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
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.
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 Vice President for Research retains authority to require full-board review of any project or category of projects.
4. Criteria for IRB Approval
IRBs ensure research is approved only when all of the requirements in 45 C.F.R. § 46.111 or, for FDA-regulated research, 21 C.F.R. § 56.111 are met. These criteria are listed below. For research that is not federally supported and not subject to FDA regulations, an investigator or IRB may submit a request for an exception to any of the following criteria, to the Institutional Official or the Deputy Institutional Official, consistent with the provisions of 45 C.F.R. § 46.101(i), except that the IO or DIO assumes the role of the HHS Secretary in considering the request.
(a) Minimizing Risk
A research plan approved by an IRB must ensure that risks to subjects are minimized by using procedures consistent with 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.
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 the importance of the knowledge to be gained is sufficient to justify any risks associated with the conduct of the project. In ensuring 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.
(b) Risk-Benefit Analysis
Research may be approved only if 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.
(c) Equitable Subject Selection
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 decisionmaking capacity, or economically or educationally disadvantaged persons.
Additional guidelines on review of recruiting methods for FDA-regulated research are available on the FDA web site.
(d) Informed Consent
Information given to subjects as part of informed consent must meet applicable regulatory and institutional requirements, including those described in Part 6 of this Operations Manual. 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. In any event, the IRB must require all of the elements of informed consent and documentation of informed consent unless it waives, or alters, the requirement as provided in further detail below.
The IRB may approve a short form written consent document stating that the elements of informed consent required by HHS and/or FDA regulations have been presented orally to the subject or the subject's legally authorized representative. When this method is used, there shall be a witness to the oral presentation. Also, the IRB shall approve a written summary of what is to be said to the subject or the representative and assure that it includes the elements of informed consent required by HHS and/or FDA regulations. Only the short form itself is to be signed by the subject or the representative. However, the witness shall sign both the short form and a copy of the summary, and the person actually obtaining consent shall sign a copy of the summary. The IRB shall require that the short form document indicate the required signatures. A copy of the summary shall be given to the subject or the representative, in addition to a copy of the short form.
For subjects who do not speak English, the witness must be conversant in both English and the language of the subject.
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
i. Informed Consent Waivers, Alterations, Exceptions, and Substitutions
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(IV) for details.
An IRB may waive or alter the requirements for informed consent only if it finds and documents that:
- The research involves no more than minimal risk to the subjects;
- The waiver or alteration will not adversely affect the rights and welfare of the subjects;
- The research could not practicably (i.e., feasibly) be carried out without the waiver or alteration; and
- 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:
- The project is to be conducted by or subject to the approval of state or local government officials; and
- 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
- The project could not practicably be carried out without the waiver or alteration.
For research involving children as subjects, an IRB may waive the requirement to obtain parental permission if they determine that:
- The research involves no more than minimal risk to the subjects;
- The waiver or alteration did not adversely affect the rights and welfare of the subjects;
- The research cannot practicably be carried out without the waiver or alteration;
- When appropriate, the subjects will be provided with additional pertinent information after participation; and
- The research is not FDA-regulated.
- 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;
- An appropriate mechanism for protecting the children who will participate as subjects in the research is substituted; and
- The research is not FDA-regulated.
The IRB may waive the requirement for documentation of informed consent if it finds and documents either:
- 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
- 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 http://www.med.umich.edu/irbmed/guidance/EFIC.pdf.
ii. Studies Subject to FDA Regulations
An IRB may waive or alter the requirements for informed consent in an FDA-regulated study if it finds and documents that the following requirements have been met.
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 C.F.R. §§ 50.23 (a)-(c) apply. In circumstances where the IRB is informed after use of an investigational agent without informed consent the IRB will assess whether or not the regulatory criteria were followed. When criteria are met the IRB will so acknowledge via a notice of outcome in eResearch. If the IRB judges the criteria are not met, the IRB will require either that informed consent must be obtained prior to use or (if the IRB is notified after the use) 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
- Notify the FDA
See Part 12 for additional potential corrective action measures.
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 C.F.R. § 50.24, 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. January 11, 2007"
The IRB may waive the requirement for documentation of informed consent if it finds and documents that 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.
iii. Studies Subject to Both HHS and FDA Regulations
The following tables may be referenced when a study is regulated by both FDA and HHS regulations. [These tables compare the types of waivers or exceptions that may be requested by a researcher under one agency's regulations and determines if it can be approved if the other agency also has jurisdiction.]
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)
FDA applicability if the study is under FDA oversight
Alteration, or substitutions are not allowed. Waiver is not allowed for the aspects of the project that meet 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
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.
iv. Studies Subject to HIPAA Regulations
If the IRB is also being asked to waive the requirement under HIPAA for written authorization for release of protected health information to be collected, used or disclosed for the study, the IRB must also find and document that:
- The use or disclosure of protected health information involves no more than minimal risk to the subjects' privacy, as demonstrated by: (i) an adequate plan to protect any identifiers from unauthorized use or disclosure; (ii) 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 (iii) 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
- The research could not practicably be conducted without access to and use of the protected health information.
(e) Data Monitoring
The IRB must ensure that, when appropriate, research plans make adequate provision for monitoring data collected to ensure subject safety. Additional information on data safety monitoring plans is available in Part 7 of this Operations Manual
(f) Privacy and Confidentiality Protection
The IRB must ensure that the research plan contains adequate provisions to protect the privacy of subjects and maintain the confidentiality of data. IRB procedures may describe the types of information addressing provisions to protect privacy that investigators may be asked to provide in the protocol or other documents; and describe the circumstances under which the IRB will consider proposed privacy protections to be appropriate and adequate. Points the IRB should consider in determining whether a protocol includes plans sufficient to address privacy and confidentiality concerns include:
- Does the research involve observation or intrusion in situations where the subjects have a reasonable expectation of privacy? Would reasonable people be offended by such an intrusion? Can the research be redesigned to avoid the intrusion?
- If privacy is to be invaded, does the importance of the research objective justify the intrusion? What if anything, will the subject be told later?
- If the investigators want to review existing records to select subjects for further study, whose permission should be sought for access to those records (the physician, the institution maintaining the records, the subjects)? How should the subjects be approached (through their physician, the medical records department, the institution)?
- Will the investigator(s) be collecting sensitive information about individuals? If so, have they made adequate provisions for protecting the confidentiality of the data through coding, destruction of identifying information, limiting access to the data, or whatever methods that may be appropriate to the study? If the information obtained about subjects might interest law enforcement or other government agencies to the extent that they might demand personally identifiable information, can a Certificate of Confidentiality be sought from a federal or state agency to protect the research data and the identity of the subjects from subpoena or other legal process?
- Are the investigator's disclosures to subjects about confidentiality adequate? Should documentation of consent 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 is borrowed.
(g) Vulnerable Subjects
Different standards 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 decisionmaking 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) 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.
(h) Institutional Approval
Research approved by the IRB is still subject to disapproval by the Vice President for Research and, as applicable, other institutional officials. However, no institutional official, including the Vice President, is empowered to approve research previously disapproved by an IRB.
(i) Test Article Accountability Procedures
Protocols must describe local drug/biologic or device accountability procedures, including, if applicable, procedures required by the Investigational Drug Service (IDS) and the Biomedical Engineering Unit (BEU). 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.
The IRBs must 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 is 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.
5. IRB Meetings
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.
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 (e.g. 10 out of 12 meetings per year). Attendance of all present members is recorded in the meeting minutes.
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.
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.
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 C.F.R. part 46) or, as applicable, FDA regulations (21 C.F.R. part 56). If substantiveclarifications or modifications regarding the protocol orinformed consent documentsare required as a condition of approval, approval must be deferred pending subsequent review by the convened IRB of responsive material.
Although it is preferred that IRB meetings take place with all participating members physically present, an IRB may establish protocols to convene meetings via videoconference, 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).
6. Notification of Decisions
An IRB will notify investigators in writing, as well as the Institutional Official or Deputy Institutional Official and other institutional officials as appropriate, of its decision to approve or disapprove proposed research activity, or of modifications required to secure IRB approval. Notification to the IO/DIO and other institutional officials may be by formal or informal means, such as through access to relevant electronic databases. If the IRB decides to disapprove a research activity, it must include in its written notification a statement of the reasons for its decision and give the investigator an opportunity to respond in person or in writing. The SOPs should also describe any process for reviewing and acting on investigator responses to IRB actions.
7. Response to Complaints and Allegations of Noncompliance and Related Reporting Requirements
An IRB will receive, investigate and address complaints and allegations of noncompliance, consistent with the requirements of Part 12 of this Operations Manual. The SOPs also must require prompt reporting to the IRBs, the Institutional Official or Deputy Institutional Official, and any other institutional officials as appropriate of (i) any unanticipated problems involving risks to subjects or others; (ii) any serious or continuing noncompliance with federal regulations, institutional policy, or IRB requirements; and (iii) any suspension or termination of IRB approval consistent with the requirements of Part 12 of this Operations Manual. In addition, the SOPs must address the range of actions the IRB may take in response to such reports, again consistent with the requirements of Part 12 of this Operations Manual. The process for making additional reports outside the institution to sponsors and government authorities with jurisdiction is described in Part 12 of this Operations Manual.
D. IRBs Reviewing and Monitoring FDA-Regulated Research
IRBs whose responsibilities include reviewing FDA-regulated studies must address additional items in their SOPs. Additional details are provided in Part 8 of this Operations Manual. These include procedures and requirements for determining whether an IND or IDE is required and, for device studies, for making significant/non-significant risk determinations; emergency use notification and reporting procedures and 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; and communications, if any, with sponsors (i.e., IND and IDE holders). SOPs also may address any additional considerations for sponsor-investigators whose research activities will not be scrutinized by external sponsors, CROs, or similar organizations. Finally, IRBs may choose to adopt policies and procedures to address and monitor, as appropriate, non-research expanded access to investigational drugs and devices.
E. IRB Member and Consultant Conflicts of Interest
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 Operations Manual), except to provide information requested by the IRB.
Any conflicted IRB member or consultant may not be present for, nor count for quorum, nor participate in the deliberations or vote on the disposition of an application in which the member has a conflict. The member may, however, be invited by the IRB to provide information relevant to the BoardÃ•s consideration of the application. Part 9 of this Operations Manual provides further information on IRB member and consultant conflicts of interest.
F. Records and Reports
Each IRB is responsible for preparing and maintaining records adequate to document its activities, 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 list 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 alternation of the consent process;
- Research involving pregnant women, fetuses, and neonates;
- Research involving prisoners; and
- Research involving children.
- When following DHHS regulations or guidance, documentation of justification of any deletion or substantive modification of information concerning risks or alternative procedures contained in a DHHS-approved sample consent document; and
- When following FDA regulations or guidance, documentation of the rationale for significant risk/non-risk device determinations.
The IRB's SOPs must address these requirements, as well as related retention mandates. IRBs must maintain these records for at least three (3) years. 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 six (6) years, either by the IRB or by the covered entity. Administrative units responsible for IRB operations may impose longer retention and specific destruction standards.
If a protocol is terminated without subject enrollment, IRB records are maintained for at least three years after termination.
All 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 NIH) at reasonable times and in a reasonable manner.
G. Educational Activities
SOPs or other documents should describe any orientation procedures for new chairs and members, continuing education requirements and opportunities for chairs, members, staff, investigators and other stakeholders, and available reference materials (e.g., library resources, internet sites, etc.).
H. Quality Assurance and Quality Improvement
The SOPs or other processes within each IRB should make provisions for responding to requests from the HRPP for new local policy development.
At least once every five years, in conjunction with the AAHRPP accreditation cycle, the Office of the Vice President for Research initiates a comprehensive review of the OM. IRB SOPs must make provisions for such a review, on the same cycle or more frequently at the IRB's discretion. Revisions to the SOPs may be made at any time, however, as required by changes in law, ethical standards, institutional policy, quality assurance activities, or other considerations. Substantive revisions require advance approval by the Vice President for Research.
The SOPs should provide for solicitation of input from IRB chairs, members, staff and affiliated investigators, and from standing and ad hoc research advisory councils within the jurisdiction of the IRB; and for periodic evaluations of chairs, members, staff, and regular consultants.
Additional requirements for quality assurance and quality improvement are described in Part 12 of this Operations Manual.
I. Other Review Units
Other review units listed in Part 2 of this Operations Manual must develop, implement, and enforce their own standard operating procedures relevant the their role in the HRPP.