Internationally, modern concerns about the ethical treatment of human research subjects can be traced to the Nuremberg Military Tribunal which was convened to investigate the “research” performed under Nazi Germany during World War II. The people who conducted these experiments were tried separately from other Nazi war criminals because of their professional status as physicians and the heinous nature of their crimes. During the trial, fundamental ethical principles for the conduct of research involving humans were codified into the Nuremberg Code of 1947 (see Appendix A.6 of this manual), which sets forth ten conditions that must be met before research involving humans can be ethically permissible (e.g., the need for voluntary informed consent of subjects, a scientifically valid research design that could produce fruitful results for the good of society, etc.). The Nuremberg Code became the first international standard for the conduct of research. This was followed in 1964 by the initial Declaration of Helsinki (Appendix A.5) of the World Medical Association, which has been revised and updated several times since.
In the United States, several cases –in both the medical and social science arenas– of egregious violations of the principles of beneficence and respect for persons have caused great concern regarding the need for regulation and oversight of research projects involving human subjects. The Tuskegee Syphilis Study (1930s-1972), the Willowbrook State School studies (1963-66), and the Jewish Chronic Disease Hospital Study (1963) are just a few of the events which led, in 1974, to the passage of the National Research Act establishing the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. This Commission eventually published the Belmont Report (Appendix A.4) which articulated the ethical principles that were to guide the conduct of research with human subjects: respect for persons (to be applied by the obtaining of informed consent, consideration of privacy, confidentiality, and additional protections for vulnerable populations); beneficence (applied so that possible benefits are maximized and possible risks to the persons involved are minimized); and justice (as evidenced in the equitable selection of subjects). These same basic principles continue to serve as the basis for Title 45, Part 46 of the Code of Federal Regulations (45 CFR 46), the policy governing the approval, performance, and monitoring of all research on human subjects conducted, supported or otherwise subject to regulation by any Federal Department or Agency. Under 45 CFR 46, the mandate of Institutional Review Boards (IRBs) is to protect the rights and safeguard the welfare of human research subjects.
The Committee on Human Studies (CHS) is the administrative unit responsible for Federally mandated compliance review and oversight for all research protocols affiliated with the University of Hawai‘i (UH) that involve the use of human subjects. The CHS’s primary responsibility is to ensure that the rights, safety and welfare of human subjects are protected, and that human subject research is conducted ethically, and in compliance with all Federal regulations, the requirements of State law, and the UH’s policies. The CHS accomplishes this by way of prospective and continuing review of all human subject research that involves UH faculty, staff, students, facilities or resources. This includes the review of protocols, informed consent processes, and procedures used to enroll subjects. The CHS, by way of its several IRBs, has statutory authority to take any action necessary to protect the rights and welfare of human subjects in all UH related research programs.
The policies and procedures relating to human research subjects, as detailed in this manual, comprise the basic minimum procedures that the CHS uses in its review processes. These guidelines are written in accordance with the basic requirements of the Department of Health and Human Services (as set forth in 45 CFR 46) and are also in compliance with the principles of the Nuremberg Code, the Belmont Report and the Declaration of Helsinki, which laid out the ethical principles for the protection of human subjects.
Both the members of each CHS IRB and any prospective researchers who intend to use human subjects in their research are reminded that this manual constitutes a basic minimum of policies and procedures and does not include every possibility for the variation in protocols utilizing human research subjects.
It is important for IRB members to use these policies and procedures as a framework and guide to meet the minimum requirements for all research involving human subjects that is conducted at, by or under the auspices of the UH, no matter the source (or absence) of funding. In using the guidelines contained in this manual, it is important that IRB members exercise their judgment, within applicable laws and regulations, on how best to protect human subjects.
The purpose of this manual is threefold: 1) to assist researchers in planning to conduct research using human subjects; 2) to establish guidelines for IRB members, IRB Chairs, and other officials; and 3) to delineate the principles, authority, and responsibilities of the CHS. Researchers are urged to read this manual carefully to avoid unnecessary delay in obtaining IRB approval for their research.
An Adverse Event (AE) is defined as an event or occurrence not generally anticipated, including a change in the frequency or intensity of a reaction, as a consequence of the intervention being used in the research study.
Serious Adverse Events (SAEs) include, but are not necessarily limited to, events which:
An Unexpected Adverse Event is defined as any adverse experience that is not identified in nature or frequency in the risk information in the general investigational plan or elsewhere in the current research application.
Note: Investigators should be aware that drug company sponsors often use more inclusive definitions of Adverse Events; these definitions should be used if called for by the sponsor.
(From 45 CFR 46.402(b)) A child’s affirmative agreement to participate in research. Mere failure to object should not, absent affirmative agreement, be construed as assent.
Persons who have not attained the legal age for consent to treatments or procedures involved in the research, under the applicable law of the jurisdiction in which the research will be conducted. The legal age of consent in Hawaii is 18.
Projects which involve more than one institution.
The Committee on Human Studies, the administrative unit responsible for Federally mandated compliance review and oversight for all research protocols affiliated with the University of Hawai‘i that involve the use of human subjects.
· DHHS
U.S. Department of Health and Human Services, the United States government’s principal agency for protecting the health of all US citizens and providing essential human services.
· Emergency Use
(From 21 CFR 56.102(b)) Use of a test article on a human subject in a life-threatening situation in which no standard acceptable treatment is available, and in which there is not sufficient time to obtain IRB approval.
· Emergency Research
A narrow exception to the FDA requirement to obtain and document informed consent; applies to a limited class of research activities involving human subjects who are in need of emergency medical intervention but cannot provide legally effective informed consent. (See 21 CFR 50.24)
· Exempt Research
As defined at 45 CFR 46, Exempt Research encompasses categories of research that do not require full IRB Review and approval.
· Expedited Review
A procedure for review of certain categories of research which permits approval by the IRB Chair or by one or more experienced reviewers designated by the Chair from among members of the IRB.
· FDA
U.S. Food and Drug Administration, the United States government’s principal agency for regulating food, drugs, medical devices, biologics (vaccines, etc), animal feed and drugs, cosmetics, and radiation-emitting products.
· Fetus
The product of conception from the time of implantation (as evidenced by any of the presumptive signs of pregnancy), until a determination is made, following expulsion or extraction of the fetus, that it is viable. (See 45 CFR 46 Subpart B)
o Viable: being able to survive (given the benefit of available medical therapy) to the point of independently maintaining heartbeat and respiration; if a fetus is viable after delivery, it is a premature infant.
o Nonviable: a fetus ex utero which, although living, is not viable.
o Dead: a fetus ex utero which exhibits neither heartbeat, spontaneous respiratory activity, spontaneous movement of voluntary muscles, nor pulsation of the umbilical cord (if still attached).
· Guardian
An individual who is authorized under applicable State or local law to consent on behalf of a child to general medical care.
· Human Subject
(From 45 CFR 46.102(f)) A living individual about whom an investigator (professional or student) conducting research obtains:
o data through intervention or interaction with the individual; or
o identifiable private information.
(From 21 CFR 56.102(e) An individual who is or becomes a participant in research, either as a recipient of the test article or as a control. A subject may be either a healthy individual or a patient.
· Informed Consent
A key element in the protection of human research subjects. Broadly speaking, Informed Consent involves:
o disclosure to the subject of any and all information necessary for the subject to understand the procedures, purposes, risks, benefits, and alternatives involved in the research;
o assuring that the manner in which the information is presented to the subject is such as to optimize the subject’s understanding of the information and appropriate for that subject’s population;
o enabling the subject to weigh all known risks and benefits;
· Institutional Review Board (IRB)
(From 45 CFR 46.102(g)) An Institutional Review Board established in accord with and for the purposes expressed in this policy.
(From 21 CFR 56.102(g)) Any board, committee, or other group formally designated by an institution to review, to approve the initiation of, and to conduct periodic review of, biomedical research involving human subjects. The primary purpose of such review is to assure the protection of the rights and welfare of the human subjects.
· Investigator
An individual who actually conducts an investigation (e.g., under whose immediate direction the test article is administered or dispensed to, or used involving, a subject). In the event of an investigation conducted by a team of individuals, the Investigator is the responsible leader of that team.
· Legally Authorized Representative
(From 45 CFR 46.102(c) and 21 CFR 50.3(l)) An individual or judicial or other body authorized under applicable law to consent on behalf of a prospective subject to the subject's participation in the procedure(s) involved in the research.
In Hawaii, there is no law that specifically addresses the use of an authorized representative to act on behalf of another individual for research consent. Under the Uniform Health-Care Decision Act (HRS 327E), a patient, or a guardian, or an agent under a power of attorney for healthcare, or a designated or non-designated surrogate can provide informed consent for “healthcare decisions” (i.e., “a decision made by an individual or the individual’s agent, guardian, or surrogate, regarding the individual’s health care.” (HRS 327E-2)). Healthcare, under the Revised Statute denotes:
any care, treatment, service, or procedure to maintain, diagnose, or otherwise affect an individual’s physical or mental condition, including:
(1) selection and discharge of health-care providers and institutions;
(2) approval or disapproval of diagnostic tests, surgical procedures, programs of medication, and orders not to resuscitate; and
(3) direction to provide, withhold, or withdraw artificial nutrition and hydration; provided that withholding or withdrawing artificial nutrition or hydration is in accord with generally accepted health care standards applicable to health-care providers or institutions.
Research activities, be they therapeutic or non-therapeutic, are not directly addressed by the statute. For therapeutic research, recourse may be made to any existing instructions for healthcare and/or agents designated in Advance Directives, though researchers should be cautioned to seek advice from their legal counsel and the CHS when considering research on decisionally incapacitated individuals.
· Minimal risk
Non-institutionalized Adults: (From 45 CFR 46.102(i)) Where the probability and magnitude of harm or discomfort anticipated in the proposed research are not greater, in and of themselves, than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. (e.g., the risk of drawing blood from a healthy individual for research purposes is no greater than the risk of doing so as part of routine physical examinations)
Institutionalized Adults/Prisoners: Risk of physical or psychological harm that is no greater in probability and severity than that ordinarily encountered in the daily lives, or in the routine medical, dental, or psychological examinations of healthy persons.
· OHRP
The Office for Human Research Protections (OHRP) fulfills responsibilities set forth in the Public Health Service Act. These include: (1) Providing leadership for human research subjects protections within the DHHS and for the U.S. Government in cooperation with other Federal Agencies; (2) developing and monitoring as well as exercising compliance oversight relative to DHHS regulations for the protection of human subjects in research conducted or supported by any component of the DHHS; (3) promoting and coordinating appropriate DHHS regulations, policies, and procedures both within the DHHS and in coordination with other Departments and Agencies in the Federal Government; (4) establishing criteria for approval of assurances of compliance for the protection of human subjects with both domestic and foreign institutions engaged in DHHS-conducted or supported research involving human subjects; (5) conducting programs of clarification and guidance for both the Federal and non-Federal sectors with respect to the involvement of humans in research; and directing the development and implementation of educational and instructional programs and generating educational resource materials; (6) evaluating the effectiveness of DHHS policies and programs for the protection of human subjects; (7) serving as liaison to Presidential, Departmental, Congressional, interagency, non-governmental, and international commissions and boards to examine ethical issues in medicine and research and exercises leadership in identifying and addressing such ethical issues; and (8) promoting the development of approaches to enhance and improve methods, particularly quality improvement at the institutional level, to avoid unwarranted risks to humans participating as subjects in research covered by applicable statutes.
· Parent
A child’s biological or adoptive parent.
· Permission
The agreement of parent(s) or guardian to the participation of their child or ward in research.
· Pregnancy
Encompasses the period of time from confirmation of implantation (through any of the presumptive signs of pregnancy), until expulsion or extraction of the fetus.
· Prisoner
Any individual involuntarily confined or detained in a penal institution. The term is intended to encompass individuals:
o sentenced to such an institution under a criminal or civil statute;
o detained in other facilities by virtue of statutes or commitment procedures which provide alternatives to criminal prosecution or incarceration in a penal institution;
o detained pending arraignment, trial, or sentencing.
For the purposes of CHS review, institutionalized patients at the Hawaii State Hospital, the state’s public psychiatric facility, will be subject to the same degree of protection as those individuals who fall within one of the three criteria listed above. See §4.5.7 of this manual for more information on forensic patients
· Private Information
(From 45 CFR 46.102(f)) Information that is individually identifiable (i.e., the identity of the subject is or may be readily ascertained by the investigator or associated with the information):
o about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place; or
o which has been provided for specific purposes by an individual and which that individual can reasonably expect will not be made public (e.g., medical records).
· Research
A systematic investigation – including researching development, testing, and evaluation – designed to develop or contribute to generalizable knowledge. Generalizable knowledge refers to any systematically gathered data which is intended for dissemination beyond the institutional setting (e.g., program evaluation research for internal use does not usually need review), and which might reasonably be generalized beyond the research sample.
(From The Belmont Report) “research” designates an activity designed to test an hypothesis, permit conclusions to be drawn, and thereby to develop or contribute to generalizable knowledge (expressed, for example, in theories, principles, and statements of relationships). Research is usually described in a formal protocol that sets forth an objective and a set of procedures designed to reach that objective.
· Risk
The probability of harm or injury (physical, psychological, social, or economic) occurring as a result of participation in a research study, as distinguished from the risks of every day life and of therapies the subjects would receive even if not participating in the research. Both the probability and magnitude of possible harm may vary from minimal to significant. Note: Federal regulations define only “minimal risk.”
(From 21 CFR 56.102(j)) A person or other entity that initiates a clinical investigation, but that does not actually conduct the investigation, i.e., the test article is administered or dispensed to, or used involving, subjects under the immediate direction of another individual. A person other than an individual (e.g., a corporation or agency) that uses one or more of its own employees to conduct an investigation that it has initiated is considered to be a sponsor and the employees are considered to be investigators.
· Test Article
(From 21 CFR 56.102(l)) Any drug for human use, biological product for human use, medical device for human use, human food additive, color additive, electronic product, or any other article subject to regulation under sections 351 or 354-360F of the Public Health Services Act.
· UH
University of Hawai‘i: including all UH system community colleges and neighbor-island campuses.
The UH has assured that all of its activities related to human subject research, regardless of funding source will be guided by the ethical principles in the Belmont Report, and will comply with the Terms of Assurance for Protection of Human Subjects for Institutions Within the United States, 45 CFR 46 and all of its subparts (A,B,C,D) for all federally-conducted or -supported human subject research (Federalwide Assurance (FWA) number 03526). The CHS is the unit designated to function as the federally mandated Institutional Review Board for the UH system. This responsibility extends to all research involving human subjects by professors, researchers, students, and others affiliated with the UH or using UH facilities, personnel, staff, or students. This applies to all research involving human subjects whether funded or not.
The CHS has the authority to approve, disapprove, modify, suspend or terminate the enrollment and/or ongoing involvement of human subjects in the facility’s research as it determines necessary for the protection of those subjects. The CHS has the authority to observe and/or monitor the institution’s human subject research to whatever extent it considers necessary to protect human subjects. A decision of any CHS IRB to disapprove a study cannot be overridden by any State or institutional official.
The CHS has three separate IRB Committees (each registered with the DHHS): one designated to review Bio-medical and related protocols (DHHS reg. No. 279); another focusing on Social Sciences and behavioral research projects (DHHS reg. No. 1353); and a third, Cooperative IRB (DHHS reg. No. 3433), designated to review exclusively those studies which are federally funded, non-pharmaceutical, multi-site studies in Hawaii. The purpose of this latter Committee is to serve as a single cooperative IRB —the members of which include representatives of those local institutions that have entered into a joint review arrangement with the UH to rely upon the findings of the CHS Cooperative IRB— in order to avoid duplication of effort. Committees currently each meet approximately once a month.
IRB membership for each Committee must satisfy the following requirements:
1. Be comprised of at least 5 members;
2. Possess varying professional backgrounds to promote complete and adequate review of research activities commonly conducted at the UH;
3. Be sufficiently diverse relative to race, gender, cultural background, and sensitivity to community attitudes so as to promote respect for the IRB’s advice and counsel in safeguarding the rights and welfare of human subjects;
4. Include persons able to ascertain the acceptability of proposed research in terms of institutional commitments, regulations, applicable law, and standards of professional conduct and practice;
5. Consist of qualified persons of both genders;
6. No IRB will consist entirely of members of one profession;
7. Include at least one member whose primary concerns are in scientific areas;
8. Have at least one member whose primary concerns are in non-scientific areas (this person must always be present to have a quorum);
9 Include at least one member who is not otherwise affiliated with the UH and who is not part of the immediate family of a person who is affiliated with the UH (this person must always be present to have a quorum).
As the Designated Institutional Official (as designated by the UH president) the University of Hawai‘i’s Vice President for Research ultimately is responsible for overseeing the protection of human subjects. The Institutional Official must ensure that open channels of communication are maintained between the CHS, research investigators, staff, and management. The CHS Executive Secretary serves as the conduit between the Institutional Official and the IRBs. The Executive Secretary may meet at least quarterly, and whenever necessary, to assure the Institutional Official is kept abreast of all issues involving human subjects. The Institutional Official is responsible for completing the necessary educational requirements.
The Executive Secretary facilitates communication between the IRB members, investigators and the Institutional Official. The Executive Secretary may meet with the Institutional Official at least quarterly to report on the activities of the CHS. Annually, the Executive Secretary may submit a report to the Institutional Official detailing the current human, financial, and physical resources utilization and any future resource requirements. The Executive Secretary has the authority to sign all correspondence relating to CHS activities, and to assign appropriately knowledgeable IRB members or consultants (when necessary) as primary and secondary reviewers.
In addition, the Executive Secretary is responsible for:
1. distributing the agenda and research activity documents, taking minutes, maintaining the roster and quorum requirements, assuring the minutes of IRB meetings are approved by the IRB, and that minutes are distributed, as appropriate;
2. organizing and providing an active program of educating deans, directors, faculty, students and staff on the regulations regarding the use of human subjects in research;
3. the dissemination of information regarding compliance with federally mandated policies and procedures, and specific guidelines received from federal agencies as well as University policies and procedures;
4. developing and recommending appropriate administrative procedures for compliance, consulting with appropriate offices at the OHRP, the Attorney General, the Ethics Commission, and other appropriate bodies;
5. keeping abreast of federal regulations governing human subject research and recipients of federal funds;
6. preparing the documents to renew the University’s Federalwide Assurance (FWA) with the DHHS;
7. communicating with federal agencies to clarify policies and guidelines, and to define agency requirements;
8. supervising the day to day operation of the CHS office and staff, and coordinating human subject matters with other institutional review committees of collaborating institutions;
9. reviewing all applications sent to the CHS and making independent judgment as to their disposition (i.e., whether they require full board review, Expedited review, Exemption, return for proper completion, or non-applicability);
10. notifying all PIs regarding the status of their applications;
11. sending letters of approvals and certifications to investigators and applicable agencies;
12. developing and maintaining a record-keeping database to assure the timely approval of the renewals of continuing projects;
13. attending human subjects workshops to keep abreast of current issues and regulations regarding human subjects;
14. performing other duties as detailed in other CHS related standard operating procedures.
In order to ensure research project compliance, the Compliance Officer is responsible for:
1. assuring that CHS policies and procedures are accurate and are in compliance with Federal guidelines;
2. up-dating the human subjects policies and procedures in the CHS Policies and Procedures Manual;
3. performing “spot-check” audits of projects as needed;
4. ensuring that subgrantees and subcontractors comply with the appropriate policies, guidelines and requirements of the Federal agencies;
5. coordinating the insurance of cooperative agreements with other collaborating institutions which need to be approved by the OHRP;
6. keeping abreast of federal regulations governing human subject research and recipients of federal funds;
7. performing other duties as detailed in other CHS related standard operating procedures.
Selection and Appointment:
The IRB members nominate the Chair of their respective committees from among their membership. The nominee is then appointed as Chair by the Institutional Official. Examples of suggested criteria for selection of the Chair are:
1. Comprehensive knowledge of the Human Research Protection Program,
2. Experienced researcher (which can be validated by publications),
3. Uses sound ethical judgment which can be evidenced by past practices, and
4. Past experience as a Chair and/or member of a patient care committee.
Length of Term:
The Chair serves a 2-year term and may be reappointed.
Duties:
In addition to the responsibilities as a member, the Chair has primary responsibility for conducting IRB meetings and assuring the IRB operates within all applicable regulatory requirements. The duties of the Chair include:
The Vice Chair will assume all responsibilities of the Chair whenever the Chair is unavailable. If the Chair is unable to perform the duties attendant to that position, the Vice Chair will assume all responsibilities of the Chair, until the CHS appoints a replacement IRB Chair.
Selection and Appointment:
The CHS will solicit names for appointments from a variety of sources, e.g., the OHRP, consumer groups, past and present CHS IRB members, UH staff, etc. The names of persons in ethics, healthcare and advocacy, who have demonstrated experience and/or interest regarding the protection of the rights and welfare of human volunteers in research will be considered for possible contact and appointment. The Institutional Official appoints IRB members. Members who serve as designee to the Chair for the conduct of expedited and exempt reviews are selected based on the following qualifications and experience:
1. comprehensive knowledge of the Human Research Protection Program;
2. knowledge and understanding of the criteria for Expedited and Exempt Review
3. experience in the particular field of research.
Members do not receive financial compensation.
Length of Term:
Members serve 2-year terms, and are eligible for reappointment.
Duties:
Members and alternate members are responsible for reviewing and monitoring research involving human subjects and to protect the rights and welfare of subjects. Members vote to approve, require modifications in, disapprove, or defer research submitted to the IRB. Duties of members and alternate members include:
Attendance Requirements:
A fifty-percent quorum of voting members, including the Chair, must be represented at each meeting to vote on any research activity. Regular attendance at IRB meetings is essential.
If a member cannot attend a particular meeting, the Executive Secretary should be notified at least two weeks in advance of the meeting, barring emergencies. If an emergency occurs and the core member involved has already been assigned to serve as the primary reviewer for a protocol, the written review should be forwarded to the IRB Chair.
Removal:
Any IRB member may be removed for improper conduct, not acknowledging conflict-of-interest, and not maintaining confidentiality of the proceedings. In the event a member is charged with violating any of the above, the IRB will review the charges and the collected evidence and by a majority vote, not including the accused, will make a recommendation to retain or remove the member from the Board. The IRB Chair will notify the Executive Secretary in writing of the results of the IRB recommendation, before a final decision as to the removal is made. The Executive Secretary will, in turn, notify the Institutional Official. The Institutional official will ensure that the accused member will be notified in writing and a copy will be submitted to the CHS for filing.
Per 45 CFR 46.107(e), no IRB member may participate in the IRB’s initial or continuing review of any project in which that member has a conflicting interest, except to provide information requested by the IRB. The IRB members, including the Chair, who have conflicting interests are required to disclose such interests before the Board’s review of the protocol, and to absent themselves from deliberations, quorum counts, and votes on the relevant protocol. Such absences are recorded in the meeting’s minutes as absences, or as “excused,” not as abstentions. The IRB must maintain a quorum if votes are taken during absences.
Orientation:
Prior to assuming responsibility as a primary reviewer or a voting member of the IRB, newly appointed IRB members will participate in an orientation program that covers the history, structure, and mandate of an IRB; the Belmont Report and the applicable Federal regulations. Each new member will also be required to complete either the 8 hour seminar provided by CHS on “How to be an IRB Member,” or one of the web-based modules on human subjects protections provided by the OHRP at <http://137.187.206.145/cbttng_ohrp/cbts/assurance/login.asp>, the NIH at <http://ohsr.od.nih.gov/extramural/extramural_training.html> and elsewhere. New members will be given this manual (which documents the operations, policies, and procedures currently in effect for the CHS), and other relevant articles selected by the Executive Secretary and CHS staff.
Continuing Education:
As necessary, subcommittees may be formed to investigate selected topics, make informational presentations to the full IRB, and, if appropriate, offer recommendations for changes in policy, practice, or the published procedures.
Longer policy discussions or special topic seminars will be scheduled as needed. Updates of this manual will be provided to IRB members and placed on the CHS website.
IRB members will periodically receive copies of articles, newsletters and other information in electronic format or through materials distributed at IRB meetings. Special training sessions will be held as needed.
Reference Materials:
See appendices A and C of this manual.
Scheduling of Meetings:
Currently all three CHS IRB Committees meet approximately once a month.
Sample IRB Meeting Agenda:
I. Call to Order
II. Verification of quorum
III. Reading and Approval of Minutes
IV. General CHS business/announcements
V. Unfinished Business (previously deferred projects)
VI. New Business
VII. Adjourn
Distribution of Materials:
Review packets, which contain copies of each PI’s submitted research proposal (consisting of New Application Form, consent form(s) and supporting documentation), are sent to IRB members approximately one week in advance of a regularly scheduled meeting. The Executive Secretary assigns each project to a primary (and secondary, where required) reviewer who is provided with the complete protocol, and is responsible for presenting an in-depth critique at the meeting.
The Review Process:
Per 45 CFR 46.111(a), in order for an IRB to approve research, it must determine that the following requirements are satisfied:
1. risks to subjects are minimized;
2. risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result;
3. selection of subjects is equitable (i.e., the burdens and benefits of the research are fairly distributed and account has been taken for the purposes of the research, the setting in which the research is to take place, and any additional requirements when involving members of vulnerable populations);
4. informed consent will be sought from each prospective subject or the subject’s legally authorized representative;
5. informed consent will be appropriately documented;
6. when appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects;
7. when appropriate, there are adequate provisions to protect the privacy of subjects and to maintain confidentiality of data.
Voting Requirements:
Quorum Requirements:
1. A majority of the IRB members (or their designated alternates), including at least one member whose primary concerns are in nonscientific areas and at least one member who is a community representative (i.e., not affiliated or directly related to anyone from the UH), must be present to conduct a convened meeting. In order for research to be approved, it must receive the approval of a majority of those members present at the meeting.
2. Members may be present in person or audio (telephone) or audio-visual teleconference. Members present via teleconference are noted as such in the meeting minutes, which also indicates that the members received all pertinent information prior to the meeting and were able to actively and equally participate in all discussions. (This option is not allowed for FDA sponsored studies, and is not encouraged generally.)
3. IRB minutes include documentation of quorum and votes for each IRB action and determination by recording votes as follows: Total Number Voting ( ); Number voting for ( ); Number voting against ( ); Number abstaining ( )
4. Members absenting themselves due to conflicts of interest may not be counted toward quorum requirements (i.e., may not be counted among those voting or abstaining) or be counted as among the majority of members necessary to constitute a quorum.
Note: When no nonscientist member is present during the course of the meeting, the IRB may not take further actions or votes until a nonscientist member returns.
5. An individual who is not listed on the official IRB membership roster may not vote with the IRB. Proxy votes are not allowed.
6. Ad hoc consultants may not vote with the IRB.
7. A non-scientist member and a community representative member must always be present for a vote to be taken.
8. If research involving an FDA regulated article is involved, a licensed physician must be included in the quorum. If a quorum is not maintained, the proposal must be tabled or the meeting must be terminated.
Communication from the CHS:
1. The Executive Secretary will record concerns voiced by the committee, and will confirm what actions the committee believes are required. These actions are:
a. approval;
b. approval pending stipulated changes, in which the Chair is authorized to approve the revision(s) by Expedited Review criteria;
c. deferral of action pending receipt of additional information or because substantial changes are required. The convened committee will reconsider changes submitted.
d. disapproval.
(See §1.3.10 of this manual for a more detailed description of the types of CHS IRB action)
2. The CHS will draft a memorandum to the PI indicating the IRB’s decision.
a. In the case of approval, the PI will receive an approval number, duration of the approval, and list of responsibilities (e.g., to conduct the research as written; to inform the CHS immediately of any problems with the research pertaining to the rights of human participants).
b. In all other cases, the PI will receive a description of the IRB’s concerns and requests for modifications. The PI also will be invited to contact the CHS with concerns.
3. The Institutional Official will receive copies of the committee-approved minutes from each convened IRB meeting.
a. Included in the minutes is a listing of all protocols approved, approved with stipulations, deferred, and disapproved.
The IRB may take the following actions with respect to a research study submitted for review:
Approval:
Approval of the study as submitted without comments or contingencies. The study may begin once approval is received from the CHS.
Suggestions:
The IRB, in approving a study, may make suggestions for slight changes to protocols and/or informed consent documents. These suggestions are most often made to enhance protocol and/or informed consent document clarity, but (unlike “stipulations”) are not required changes.
Approval with Stipulations:
Acceptance of the protocol with requests for clarification and/or modifications (i.e., minor changes that can be reviewed using Expedited Review criteria and accepted by the Chair, a designated IRB member with relevant expertise, or a designated subcommittee of the IRB). The project cannot begin until the stipulations have been satisfied and reviewed (using Expedited Review procedures) by the Chair, a designated IRB member with relevant expertise, or a designated subcommittee of the IRB. No study may begin before receiving final Approval from the CHS.
Deferral:
Deferral of the application pending written responses to major or substantive questions raised by the IRB during the initial review (requires convening of the full IRB for a second deliberation meeting).
Disapproval:
Disapproval of the research application (proposal does not meet requisite standards; the study cannot be conducted).
Appeal of IRB Decisions:
See §3.7.1.5 of this manual for detailed information regarding appeal of IRB decisions.
Minutes of IRB Meetings:
The minutes of the IRB meetings reflect attendance, actions taken by the IRB, the vote on 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 discussion of controverted issues and their resolution (particular documentation must be made that proper review was made, and consideration taken, with regards to additional safeguards for (a) vulnerable subjects, and (b) waivers of informed consent and signed informed consent). The minutes should also clearly reflect any discussion and determinations regarding risk and approval period. All IRB actions must be documented separately for each individual protocol undergoing initial or continuing review. A quorum of members is necessary for IRB action.
All minutes of IRB meetings are confidential to the extend allowed by law.
Record Retention Requirements:
Per 45 CFR 56.115, the CHS must maintain adequate documentation of IRB activities, including:
In particular, CHS records must be sufficient to reconstruct a complete history of all IRB actions related to the review and approval of a given protocol.
Per 45 CFR 46.115(b), all CHS records and documents must be retained for at least three years. Records relating to research which is conducted must be retained for at least three years after completion of the research or termination of the protocol.
Written Policies and Procedures: