Any institution engaged in federally conducted or supported human subjects research must commit itself in writing to the protection of those subjects.
This written commitment is called an Assurance of Compliance.
For human subjects research conducted or supported by the Department of Health and Human Services (HHS), the Office for Human Research Protections (OHRP) must approve an institution's Assurance before the human subjects research can begin. The Federalwide Assurance (FWA) is the only type of Assurance approved by OHRP.
The Institutional Official who signs the FWA, the reviewing Institutional Review Board(s) (IRBs), and the Human Protections Administrator or primary contact for human subjects protections at the institution should understand the responsibilities involved in an institutional program of human subjects protections.
The purpose of this tutorial is to explain these responsibilities, as well as the informed consent process.
The tutorial consists of three modules:
- Module 1: HHS Regulations and Institutional Responsibilities
- Module 2: Investigator Responsibilities and Informed Consent
- Module 3: Human Research Protections Program
Module 1: HHS Regulations and Institutional Responsibilities
This tutorial provides an introduction to the HHS Regulations for the Protection of Human Subjects at Title 45 Code of Federal Regulations Part 46. The HHS Regulations are intended to implement the basic ethical principles governing the conduction of human subjects research. These ethical principles are set forth in the report of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research entitled: Ethical Principles and Guidelines for the Protection of Human Subjects of Research (the “Belmont Report”).
The Belmont Report
The Belmont Report sets forth three basic ethical principles for the conduct of human subjects research:
- Respect for persons
- Respect individual autonomy
- Protect individuals with reduced autonomy
- Maximize benefits and minimize harms
- Equitable distribution of research burdens and benefits
Application of the general ethical principles to the conduct of human subjects research leads to the following requirements:
- Respect for persons
- Informed consent
- Protecting privacy and maintaining confidentiality
- Additional safeguards for protection of subjects likely to be vulnerable to coercion or undue influence
- IRB assessment of risk/benefit analysis, including study design
- Ensure that risks to subjects are minimized
- Risk justified by benefits of the research
- Ensure that selection of subjects is equitable
Food and Drug Administration
The Food and Drug Administration (FDA) has a separate set of regulation governing human subjects research (21 CFR Part 56 for IRBs and 21 CFR Part 50 for Informed Consent). The basic requirements for IRBs and for informed consent are congruent between the HHS and FDA regulations. Differences center on differences in applicability:
- HHS regulations at 45 CRF Part 46 apply to research conducted or supported by HHS
- FDA regulations apply to clinical investigations of FDA-regulated products: drugs, devices, or biologics
This tutorial focuses on the HHS regulations at 45 CFR Part 46. Institutions conducting research regulated by FDA should contact FDA for detailed guidance.
HHS regulations include additional protections for vulnerable populations as supbarts of 45 CFR Part 46:
Subpart B - Additional HHS Protections for Pregnant Women, Human Fetuses and Neonates involved in Research
Subpart C - Additional HHS Protections Pertaining to Biomedical and Behavioral Research Involving Prisoners as Subjects
Subpart D - Additional HHS Protections for Children Invovled as Subjects in Research
Subpart E - Registration of Institutional Review Boards
Research - A systematic investigation, including research development, testing, and evaluation, designed to develop or contribute to generalizable knowledge. Activities that meet this definition constitute research for pruposes of the HHS regulations, whether or not they are conducted or supported under a program, which is considered research for other purposes. For example, some demonstration and service programs may include research activities.
Human Subject - A living individual about whom an investigator (whether professional or student) conducting research obtains (1) data through intervention or interaction with the individual, or (2) identifiable private information.
Certain research is exempt from the requirements of the HHS regulations. A determination that research is exempt does not imply that investigators have no ethical responsibilities to subjects in such research; it means only that the regulatory requirements related to IRB review, informed consent, and assurance of compliance do not apply to the research. OHRP recommends that insitutions adopt clear procedures under which the IRB, or some authority other than the investigator, determines whether proposed research is exempt from the HHS regulations fro the protection of human subjects. OHRP's Exempt Research Determination FAQs say the following: "OHRP recommends that, because of the potential for conflict of interest, investigators should not be given teh authority to make an independent determination that human subjects research is exempt." (https://www.hhs.gov/ohrp/regulations-and-policy/guidance/faq/exempt-research-determination/index.html)
Basic Provisions of the HHS Regulations
The HHS regulations contain three basic provisions for the protection of human subjects:
- Insitutional assurances of compliance
- IRB review
- Informed consent
Institutional Assurances of Compliance
What is an Institutional Assurance of Compliance? Documentation of an institutional commitment to comply with HHS regulations for the protection of human subjects.
HHS will conduct or support non-exempt research covered by the regulations only if:
- the institution has an OHRP-approved Assurance,
- the institution has certified to the HHS that the research has been reviewed and approved by an IRB, and
- the research will be subject to continuing review by an IRB.
Institutional Review Board (IRB)
The Institutional Review Board (IRB) is a committee established to protect the rights and welfare of human research subjects involved in research activities.
IRBs must have at least five members with varying backgrounds to promote complete and adequate review of research activities commonly conducted by the institution. The IRB must be sufficiently qualified through the experience and expertise of its members and the diversity of its members--including considerations of the race, gender, and cultural backgrounds and sensitivity to issues such as community attitudes--to promote respect for its advice and counsel in safeguarding the right and welfare of human subjects.
In addition to possessing the professional competence necessary to review specific research activities, the IRB shall be able to ascertain the acceptability of proposed research in terms of institutional commitments and regulations, applicable law, and standards of professional conduct and practice. The IRB shall therefore include persons knowledgeable in these areas. If an IRB regularly reviews research that involves a vulnverable catgory of subjects, such as children, prisoners, pregnant women, or handicapped or mentally disabled persons, consideration shall be given to the inclusion of one or more individuals who are knowledgeable about and experienced in working with these subjects.
Every nondiscriminatory effort must be made to ensure that the IRB does not consist entirely of men or entirely of women. No IRB may consist entirely of members of one profession. Each IRB shall include at least one member whose primary concerns are in scientific areas and at least one member whose primary concerns are in non-scientific areas. Each IRB shall include at least one member who is not otherwise affiliated with the institution and who is not part of the immediate family of a person who is affiliated with the institution.
No IRB may have a member participate in the review of any project in which the member has a conflicting interest.
An IRB may, at its discretion, invite individuals with competence in special areas to assist in the review of issues which require expertise beyond or in addition to that availableon the IRB. These individuals may not vote with the IRB.
Except when an expedited review procedure is used, the IRB must review research at convened IRB meetings at which a majority of the IRB members are present, including one member whose primary concerns are in nonscientific areas.
IRB Review of Research
An IRB must review all research activities covered by the HHS regulations, including proposed changes in previously approved human subjects research, and have the authority to approve, require modifications to secure approval, or disapprove any research activity. An IRB must conduct continuing review of approved research at intervals appropriate to the degree of risk, but not less than once per year. An IRB has the authority to suspend or terminate approved research that is not being conducted in accordance with the IRB's requirements, or that has been associated with unexpected serious harm to subjects. Any suspension or termination of approval must include a statement of the reason for the IRB action and must be reported promptly to the investigator, appropriate institutional officials, and HHS. Research approved by the IRB may be subject to further review and approval or disapproval by institutional officials. However, institutional officials may not approve the conduct of human subjects research covered by HHS regulations thta has not bene approved by the IRB.
Unless specifcially authorized by the IRB, no investigator may involve a human being as a subject in research covered by HHS regulations unless the investigator has obtained the legally effective informed consent of the subject or the subject's legally authorized representative. Informed consent is the voluntary choice of an individual to participate in research based on an accurate understanding of its purposes, procedures, risks, benefits, alternatives, and any other factors that may affect a person's decision to participate. Unless specifically waived by the IRB, informed consent must be documented by a written consent form approved by the IRB and signed by the subject or by the subject's legally authorized representative. Detailed information on the Informed Consent process may be found in Module 2.
The responsibility for the protection of human subjects does not rest solely with the IRB. It is a shared responsibility between the Institutional Official, the IRB, and the investigator. Each has a crucial, yet distinct, role to play.
Institutional Official Responsibilities
The Institutional Official is the individual authorized to act for the institution and, on behalf of the institution, obligates the institution to the Terms of the Assurance. Administratively, the Institutional Official is responsible for:
- Designating one or more IRBs that will review research covered by the institution's FWA
- Providing sufficient resources, space, and staff to support the IRB's review and record keeping duties
- Providing training and educational opporutnities for the IRB and investigators
- Depending on the organizational structure at a given institution, other administrative arrangements may be appropriate
- Setting the "tone" for an institutional culture of respsect for human subjects
- Ensuring effective institution-wide communication and guidance on human subjects research
- Ensuring that investigators fulfill their responsibilities as detailed in Module 2
- Encouraging that all staff engaged in the conduct or oversight of human subject research participate in education activities
- Serving as a knowledgeable point of contact for OHRP, or delegating this responsibility to another appropriate individual
The Institution bears full responsibility for all research invovling human subjects covered under its Assurance. For all HHS-conducted or supported research, all of the requirements of the HHS Regulations at 45 CFR Part 46, Subpart A, as well as Subparts B through E, must be met.
- Developing policies and procedures for effective and efficient administration of the Human Research Protections Program (HRPP).
- Ensuring that Assurances are in place and certifications of IRB review are submitted to the appropriate authorities for all HHS-sponsored research, not only for themselves, but also for collaborating performance sites for which the institution has agreed to accept oversight responsibility.
- Implementing appropriate oversight mechanisms to ensure compliance with HHS regulations and effective administration of the HRPP.
Institutions are responsible for ensuring that all institutions and investigators engaged in its HHS-supported human subject research operate under an appropriate OHRP-approved Assurance for the protection of human subjects. In some cases, one institution may operate under an Assurance issued to another institution through the Individual Investigator Agreement.
Module 2: Investigator Responsibilities and Informed Consent
Investigators have the primary responsibility for protecting the rights and welfare of human research subjects and are responsible for complying with all applicable provisions of their institution's Assurance.
Investigators are expected to be knowledgeable about the requirements of the HHS regulations, applicable state law, their institution's Assurance, and institutional policies and procedures for the protection of human subjects.
Investigators are responsible for:
- Conducting their research according to the IRB-approved protocol and complying with all IRB determinations;
- Obtaining and documenting the informed consent of each subject or each subject's legally authorized representative, unless the IRB has waived these requirements;
- Ensuring that each potential subject understands the nature of the research and participation;
- Providing a copy of the IRB-approved informed consent document to each subject or the subject's legally authorized representative at the time of consent, unless the IRB has specifically waived this requirement (all signed consent documents are to be retained for at least 3 years after the completion of the research and according to institutional policy);
- Promptly reporting proposed changes in previously approved human subject research activities to the IRB (the proposed changes may not be initiated without prior IRB review and approval, except where necessary to eliminate apparent immediate hazards to the subjects);
- Reporting progress of approved research to the IRB as often as, and in the manner, prescribed by the IRB; and
- Promptly reporting to the IRB any unanticipated problems involving risks to subjects or others or any serious or continuing non-compliance with the HHS regulations or determination of the IRB.
A physician may provide emergency medical care to a patient without prior IRB review and approval, to the extent permitted by applicable federal, state, or local law. However, such activities may not be considered research nor may the data be used in support of research, except to the extent required under FDA regulations. Investigators should consult with the IRB to ensure that activities that meet the regulatory definition of non-exempt human subject research undergo IRB review and approval prior to the initiation of the activities.
Unless specifically authorized by the IRB, no investigator may involve a human being as a subject in research covered by the HHS regulations unless the investigator has obtained the legally effective informed consent of the subject or the subject's legally authorized representative.
Informed consent refers to the voluntary choice of an individual to participate in research based on an accurate and complete understanding of, among other things, its purposes, procedures, risks, benefits, alternatives, and any other factors that may affect a person's decision to participate.
The Consent Process
Informed consent is not a single event or just a form to be signed. Rather, it is an ongoing process that takes place between the investigator and the subject.
The basic concepts of the consent process include:
- full disclosure of the nature of the research and the subject's participation, adequate comprehension on the part of the potential subject, and
- the subject's voluntary choice to participate.
Informed consent must be prospectively obtained from the subject or a legally authorized representative of the subject (if allowed by state law).
Information must be conveyed in language that is understandable to the subject or the subject's legally authorized representative.
The subject must be given sufficient opportunity to consider whether or not to participate.
Consent must be sought only under circumstances that minimize the possibility of coercion or undue influence.
Informed consent may not include any exculpatory language. For example, subjects must not be made to give up legal rights or be given the impression that they are being asked to do so.
Even though the IRB has approved a consent procedure, it is the investigator's responsibility to ensure that each potential subject understands the information and to take the appropriate steps necessary to gain that comprehension.
Individuals may not be involved as research subjects unless a) they understand the information that has been provided and informed consent has been obtained, or b) the IRB has approved a waiver for informed consent of the subject.
Elements of Informed Consent
HHS regulations detail specific elements of information that must be provided to each research subject unless the IRB has approved a waiver or alteration of these requirements. Basic elements of informed consent include a:
- statement that the study involves research, an explanation of the purposes of the research, the expected length of the subject's participation, a description of the procedures to be followed , and identification of procedures which are experimental in nature;
- description of any reasonably foreseeable risks or discomforts to the subject;
- description of any benefits, to the subject or others which may reasonably be expected from the research;
- disclosure of appropriate alternative procedures or courses of treatment, if any, that are available that might be advantageous to the subject;
- a statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained;
- for research involving more than minimal risk, an explanation as to whether any compensation or medical treatments, are available to the subject if injury occurs and if so, what that may consist of or when further information can be obtained;
- An explanation of whom to contact for pertinent questions about the research and research subjects rights;
- An explanation of whom to contact in the event the subject experiences a research-related injury; and
- A statement that participation is voluntary and refusal to participate will not result in penalty or loss of benefits to which the subject is otherwise entitle and the subject may withdraw at anytime without penalty or loss of benefits to which the subject is entitled.
Research and Procedures
The information provided to subjects should:
- make clear that the activity involves research and describe the overall experience that will be encountered;
- explain the procedures, including any parts that are experimental (e.g., a new drug, extra tests, separate research records, or nonstandard means of management, such as flipping a coin for random assignment or other design issues); and
- include the expected length of time it will take for study visits or scheduled procedures, as well as, the total expected length of participation.
All reasonably foreseeable risks, discomforts, inconveniences, and harms that are associated with the research activity should be described. Investigators should be forthcoming about risks and not understate or gloss over reasonably foreseeable risks. If additional risks are identified during the course of the research, the consent process and documentation will require revisions, and subjects previously consented may need to be re-contacted and informed of the additional risks.
Any benefits to subjects or others that may reasonably be expected from the research should be described. Investigators should be frank about benefits and not overestimate or magnify the possibility of benefit to the subject. If there is no reasonable expectation of benefit, the subject should be told this. Payment to subjects should not be listed or described as a benefit of participating in the research.
Alternatives to Participation
Appropriate alternatives to participating in the research project that might be advantageous to the subject should be described. For example, in drug studies, the medication(s) being studied may be available outside the research study from a physician without the need to volunteer for the research activity. Investigators should be reasonably specific about describing the nature and type of available alternatives. It is not sufficient simply to state "the researcher will discuss alternative treatments" with the subject.
HHS regulations require that subjects be told the extent, if any, to which confidentiality of research records identifying the subject will be maintained. For example, sponsors, funding agencies, regulatory agencies, and the IRB may review research records. Some studies may need sophisticated encryption techniques to prevent confidentiality breaches or may need a Certificate of Confidentiality to protect the investigator from being compelled to release (e.g., under subpoena) subjects' names or identifiable private information.
Compensation for Injury
If research-related injury (i.e., physical, psychological, social, financial, or otherwise) is possible in research that is more than minimal risk, an explanation must be given as to whether any compensation and treatment will be provided to an injured subject. If so, the compensation and treatment should be described, or the subject should be told where further information may be obtained. Note that the regulations do not limit injury to "physical injury." This is a common misinterpretation.
The regulations prohibit requiring subjects to waive or appear to waive any of their legal rights, and leading subjects to believe they are waiving their rights. Consent language regarding compensation for injury must be selected carefully so that subjects are not given the impression that they have no recourse to seek satisfaction beyond the institution's voluntarily chosen limits.
The regulations require that the subject be provided with information on who to contact to answer questions about the research and the rights of research subjects. Subjects must also be informed of whom to contact in the event of any research-related injuries. This information must be explicitly stated and addressed in the consent process and documentation.
A single contact person is not likely to be sufficient to answer all questions. This is in part because of real or apparent conflicts of interest. Questions about the research are frequently best answered by the investigator(s). However, questions about the rights of research subjects may best be referred to persons not on the research team. These questions could be addressed to the IRB, an ombudsperson, an ethics committee, or other informed individual or committee. Each consent document may have at least two names with local telephone numbers for contacts to answer questions in these specified areas.
The regulations require statements regarding voluntary participation and the right to withdraw at any time. Subjects must be informed that participation is voluntary, participation may be discontinued at any time, and there is no penalty or loss of benefits for refusing to participate or discontinuing participation.
Where appropriate, the following additional elements of informed consent must be provided to each subject:
- treatments or procedures that may involve risks to the subject, or to an embryo or fetus if the subject is or may become pregnant, that are currently unforeseeable;
- anticipated circumstances under which a subject's participation may be terminated by the investigator without regard to the subject's consent;
- any additional costs to subjects that may result from participation;
- the consequences of the subject's decision to withdraw from the research and procedures of orderly termination of participation by the subject;
- a statement that significant new findings developed during the course of the research which may relate to the subject's willingness to continue participation will be provided to the subject; and
- the approved number of subjects involved in the study.
Additional Protections for Vulnerable Populations
Incompetent adults cannot give consent. This may include the developmentally disabled, the cognitively-impaired elderly, and unconscious or inebriated individuals. Only legally authorized representatives in accordance with state law can give consent for incompetent adults to participate in research.
Additionally, when some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, mentally disabled persons or economically or educationally disadvantaged persons, additional safeguards shall be included in the study to protect the rights and welfare of these subjects.
Waiver of Consent
Under certain circumstances, HHS regulations specify that the IRB may approve a consent procedure that does not include, or which alters, some or all of the elements of informed consent, or waive the requirements to obtain informed consent provided the IRB finds and documents that the research or demonstration project is to be conducted by or subject to the approval of the state or local government officials and is designed to study, evaluate, or otherwise examine: public benefit or service programs, procedures for obtaining benefits or services under those programs, possible changes in or alternatives to those programs or procedures, or possible changes in methods or levels of payment for benefit or service under those programs, AND the research could not practicably be carried out without the waiver or alteration.
The IRB may approve a consent procedure that does not include, or which alters, some or all of the elements of informed consent, or waive the requirements to obtain informed consent provided the IRB finds and documents that the following four conditions have been met:
the research involves no more than minimal risk to the subjects;
the waiver or alteration will not adversely affect the rights and welfare of subjects;
the research could not practicably be carried out without the waiver or alteration; and
whenever appropriate, the subjects will be debriefed—provided with additional pertinent information—after they have participated in the study.
Documentation of Consent
Except as noted below, informed consent must be documented by use of a written consent form approved by the IRB and signed by the subject or the subject's legally authorized representative. A copy will be given to the person signing the form.
The purpose of the written presentation of information in the consent form is to document the basis for consent and provide the subject future reference. The consent document should be revised when deficiencies are noted or when additional information will improve the consent process. All revisions must be reviewed and approved by the IRB before a revised consent form may be used to enroll a subject.
The information that is given to the prospective subject, or his/her legally authorized representative, must be in language understandable to the subject or representative.
Consent forms should be written at a level appropriate to the understanding of the subjects to be enrolled; technical language should be avoided.
OHRP strongly discourages use of the "first person" statement in consent documents (using, "I have been fully informed about..."). Such statements unacceptably ask subjects to make statements that the subject is not in a position to verify (e.g., the subject has no way to verify that the investigator has provided full and complete information).
The consent form is merely the documentation of informed consent and does not, in and of itself, constitute informed consent.
The fact that a subject signed a consent form does not mean that he/she understood what was being agreed to or truly gave their voluntary consent.
Waiver of Documentation of Consent
The IRB may waive the requirement for written documentation of consent in cases where:
The principal risks are those associated with a breach of confidentiality concerning the subject's participation in the research; and the consent document is the only record linking the subject with the research. Each subject will be asked if they want documentation to remain with them or with the research records, and the subject's wishes will govern.
The research presents no more than minimal risk of harm to subjects and involves no procedures for which written consent is normally required outside the research context.
Please also review the following additional guidance:
Informed Consent Checklist (https://www.hhs.gov/ohrp/regulations-and-policy/guidance/checklists/index.html)
Informed Consent, Legally Effective and Prospectively Obtained (https://www.hhs.gov/ohrp/regulations-and-policy/guidance/legally-effective-and-prospectively-obtained/index.html)
Informed Consent of Subjects Who Do Not Speak English (https://www.hhs.gov/ohrp/regulations-and-policy/guidance/obtaining-and-documenting-infomed-consent-non-english-speakers/index.html)
Certificates of Confidentiality (https://www.hhs.gov/ohrp/regulations-and-policy/guidance/certificates-of-confidentiality/index.html)
Module 3: Human Research Protections Program
Administrative procedures related to an HRPP may be handled differently from one institution to another. The following describes responsibilities that are included in establishing an HRPP.
Human Research Protections Program Administration
As part of the Assurance process, institutions are asked to provide contact information about its Human Protections Administrator or another staff member that can serve as a primary point of contact for OHRP. Depending on the size of an institution and the volume of research conducted, not all institutions will have a dedicated staff person as a Human Protections Administrator. What is most important is that OHRP have a reliable contact person for questions related to the institution's Assurance or other matters that may arise.
Administrative responsibilities for HRPP fall into three general areas:
- IRB Communication & Education
- Record keeping & Reporting
- Monitoring & Oversight
Communication & Education Responsibilities
The HRPP is responsible for:
- Promoting communication among the research administrators, department heads, investigators, clinical care staff, human subjects, and institutional officials to maintain a high level of awareness regarding the ethical conduct of research and safeguarding the rights and welfare of subjects.
- Maintaining access to the institution's Assurance; copies of pertinent Federal regulations, policies, and guidelines related to the involvement of human subjects in research; and institutional policies and procedures.
- Educating the members of its research community in order to establish and maintain a culture of compliance with Federal regulations and institutional policies relevant to the protection of human subjects.
Record Keeping & Reporting Responsibilities
The HRPP is responsible for:
- Ensuring that IRB records are being maintained per HHS regulations and that the records are accessible, upon request, to authorized HHS officials. For institutions relying on another IRB, records may be retained at the IRB site.
- Ensuring certification of IRB approval of proposed research to the appropriate HHS agency for HHS-conducted or supported research.
- Ensuring that changes in approved research, during the period for which IRB approval has already been given, are not initiated without IRB review and approval, except when necessary to eliminate apparent, immediate hazards to the subject.
- Ensuring prompt reporting to the IRB all proposed changes in a research activity.
- Ensuring the prompt reporting to the IRB, appropriate institutional officials, OHRP, and any sponsoring Federal department or agency head of:
- any unanticipated problems involving risks to subjects or others;
- any serious or continuing noncompliance with the regulations or requirements of the IRB, and
- any suspension or termination of IRB approval for research.
Monitoring & Oversight Responsibilities
The HRPP is responsible for:
- Ensuring that appropriate oversight mechanisms have been implemented to ensure compliance with the determinations of the IRB.
- Ensuring that all cooperating performance sites in HHS-conducted or supported research conducted primarily under the direction of the institution have appropriate OHRP-approved assurances and provide certifications of IRB approval to the appropriate federal authorities.
- Ensuring that cooperative IRB review arrangements are documented in writing, in accordance with OHRP guidance.
- Ensuring that all independent investigators that rely on the institution's IRB have documented, in accordance with OHRP guidance, their commitment to the institution's human subjects protections requirements and to the IRB's determinations.
Institutional Review Board Responsibilities
Review by an IRB is the cornerstone of an institution's program for the protection of human subjects. IRBs are responsible for ensuring that the rights and welfare of the subjects are adequately protected.
Although many institutions will have their own IRB, institutions have the option of relying on the IRB of another institution to review their research.
To approve, require modifications in to secure approval, or disapprove all research activities covered by the HHS regulations, including proposed changes in ongoing, previously approved, human subjects research. To suspend or terminate the approval of ongoing, previously approved research that is not being conducted in accordance with the IRB's requirements or that has been associated with unexpected, serious harm to subjects.
IRBs should be familiar with the requirements of the Federal regulations, applicable state law, their institution's Assurance, and institutional policies and procedures for the protection of human subjects.
IRBs should have effective knowledge of subject populations and other factors that can foreseeably contribute to a determination of risks and benefits to subjects and subjects' informed consent.
IRBs should be able to judge the adequacy and accuracy of information in the informed consent document, advertising, and any other materials to be presented to subjects.
An IRB that regularly reviews research that involves a vulnerable category of subjects such as children, prisoners, pregnant women, or handicapped or disabled persons, membership should include in its membership one or more individuals who are knowledgeable about and experienced in working with these subjects.
IRBs must have the professional competence necessary to review the specific research activities presented for approval.
IRBs may, in their discretion, invite individuals with competence in special areas to assist in the review of issues, which require expertise beyond, or in addition to, that available on the IRB.
Review of Performance Sites
IRB rosters submitted to OHRP should include members knowledgeable about any other institution for which the IRB regularly conducts reviews. For performance sites for which the IRB does not regularly conduct reviews, the IRB must obtain effective input on the local research context from knowledgeable persons other than those conducting the research.
Note: IRB rosters will no longer be submitted to OHRP as of the effective date of the final rule (January 19, 2018). Instead, institutions must keep IRB membership/roster information in their records.
IRBs must provide the investigators and the institution with written notification of decisions to approve or disapprove research and of modifications required to secure IRB approval of the research activity. If the IRB decides to disapprove a research activity, the written notification must include reasons for the decision and give the investigator an opportunity to respond in person or in writing.
Criteria for IRB approval of research:
In order to approve research, IRBs must find that:
- risks to subjects are minimized by using procedures which are consistent with sound research design and do not unnecessarily expose subjects to risks, and whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes;
- risks to subjects are reasonable in relation to anticipated benefits, if any, to the 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;
- selection of subjects is equitable; in making this assessment the IRB should take into account the purposes of the research and the setting in which the research will be conducted and should be particularly cognizant of the special problems of research involving vulnerable populations; and
- informed consent will be sought from each subject or the subject's legally authorized representative; informed consent will be appropriately documented, in accordance with, and to the extent required by the HHS regulations.
Additional criteria for IRB approval as appropriate:
- the research plan makes adequate provision for monitoring the data collected to ensure subject safety;
- there are adequate provisions to protect the privacy of the subjects and confidentiality of data;
- when some of all of the subjects are likely to be vulnerable to coercion or undue influence, additional safeguards are included to protect the rights and welfare of these subjects.
HHS regulations allow some categories of minimal risk research to be reviewed by the IRB through an expedited review procedure. Expedited review may be carried out by the IRB chairperson or by one or more experienced IRB members designated by the chairperson. All of the requirements for IRB approval of research apply to expedited review. Expedited review should not be viewed as a less rigorous review. Under expedited review, the reviewers may exercise all of the authorities of the IRB, except that the reviewers may not disapprove the research.
Expedited review procedures may be used for:
- research appearing in the published list of eligible research, per HHS regulations, and found by the reviewer to involve no more than minimal risk, and
- minor changes in previously approved research during the authorized approval period.
The IRB observes the following requirements for convened meetings:
A majority of the members of the IRB must be present including at least one member whose primary concerns are in non-scientific areas. If the required number and type of members is lost during a meeting, no action may be taken until a quorum is restored. In order for research to be approved, it must receive the approval of a majority of those members present at the meeting.
Scheduled meetings of the IRB should occur at intervals appropriate to the level of reviewed research and with sufficient frequency so that the IRB can adequately oversee the progress of the research it has approved.
Convened meetings may be conducted by telephone conference call, provided that each participating IRB member has received all pertinent material prior to the meeting and can actively and equally participate in the discussion of all protocols.
Minutes of such meetings must clearly document which members were present via conference call and that the criteria for a member's participation via conference call have been satisfied.
Minutes of IRB meetings must include:
- a list of attendees at the meeting;
- 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; and
- a written summary of the discussion of controverted issues and their resolution.
IRB Record Keeping
An institution, or when appropriate an IRB, shall prepare and maintain adequate documentation of IRB activities, including the following:
- Copies of all research proposals reviewed; scientific evaluations, if any, that accompany the proposals; approved sample consent documents; progress reports submitted by investigators; and reports of injuries to subjects;
- Minutes of IRB meetings;
- Records of continuing review activities;
- Copies of all correspondence between the IRB and the investigators;
- A list of IRB members;
- Written procedures for the IRB; and
- Statements of significant new findings provided to subjects.
An IRB must conduct continuing review of ongoing approved research at intervals appropriate to the degree of risk, but not less than once per year. For approved research, the IRB determines which activities require continuing review more frequently than every 12 months. Continuing IRB reviews are preceded by receipt of appropriate progress reports from the investigator, including available study-wide findings. Continuing review must be substantive and meaningful.
Relying on Another IRB
An institution relying on another IRB has the following responsibilities:
- To ensure that the reviewing IRB is in compliance with the IRB requirements in the Federal regulations; and
- To ensure that the particular characteristics of the institution's local research context are considered, either through knowledge of its local context by the reviewing IRB; or through subsequent review by appropriate designated institutional officials.
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Content last reviewed on August 23, 2017