Human Research Protection Program - Faculty Handbook
This document is a compilation and description of the many components of Michigan State University's comprehensive Human Research Protection Program. It was approved by the Vice President for Research and Graduate Studies on April 21, 2005, after review by the Institutional Review Boards, University Research Council, University Graduate Council and MSU Legal Counsel. The document is included in the MSU Human Research Protection Manual as Section 3-1.
The Michigan State University (MSU) human research protection program's (HRPP) primary mission is the protection of individuals who are the subjects of research. MSU is committed to follow the ethical standards described in the Belmont Report, and all applicable federal, state and local regulations and university policies and procedures. The HRPP at MSU sets forth the structure, policies and procedures to implement this mission and commitment. The processes of education, review and monitoring described in the HRPP serve to ensure the safe and ethical conduct of research that will protect human subjects in an atmosphere of mutual trust and integrity in the pursuit of knowledge and human benefit.
The original MSU policies on protection of human research subjects are included here to emphasize MSU's long history of commitment. In the years following, Federal regulations and procedures were enacted that required many of the same activities that MSU had already instituted. MSU policy is to follow all applicable regulations.
Policies and Procedures for Protecting Human Subjects Used in Research, approved by Academic Council, January 23, 1979.
"The University's Institutional Review Board (known as UCRIHS) shall be responsible for the establishment of appropriate University review procedures so that all biomedical and behavioral research involving human subjects is adequately and effectively reviewed. This review should extend to such activities regardless of whether they are funded from external sources, internal sources or require no supplemental funding, and would also apply to research conducted by graduate and undergraduate students."
"MSU shall adopt a single code of ethics and behavior for the protection of human subjects engaged in biomedical and behavioral research. The uniform code of ethics will be developed by UCRIHS and reviewed by the University Graduate Council and the University Committee on Faculty Affairs before final approval by the Academic Council."
"The policies and procedures of the University and its units governing the use of human subjects in biomedical and behavioral research shall be consistent with federal and state laws and guidelines."
"The University Committee on Research Involving Human Subjects (UCRIHS) shall prepare a formal set of procedures and bylaws governing its operations. These shall be subject to review by the Academic Council and serve for any successor to UCRIHS."
Bylaws for Academic Governance, sections 4.47 and 4.87
The Vice President for Research and Graduate Studies and the Provost and/or the Dean of the Graduate School have the responsibility to present policies that pertain to research development to academic governance for advice and consultation: University Committee on Academic Policy and University Graduate Council respectively.
The Graduate School, Final Submission of Thesis/Dissertation
"Human or Animal Subjects Form - All students must complete and submit this form, even if no human or animal subjects were used. The form must be signed by the student and by the major professor and must include the UCRIHS or AUF number(s) as appropriate. In cases where the student's research involves human subjects, an approval letter from the University Committee on Research Involving Human Subjects (UCRIHS) must be submitted with the form." http://grad.msu.edu/current/formatfinal.pdf, http://grad.msu.edu/current/pacucrihs.pdf
Human Research Protection (HRP) Manual
Information regarding the structure of MSU's Institutional Review Boards, their policies and their formal procedures for reviewing human subject research for the protection of human subjects are set forth in the Human Research Protection (HRP) Manual which is available through the MSU Office of Vice President for Research and Graduate Studies (OVPRGS) and on the Internet at http://www.humanresearch.msu.edu/. The manual includes information regarding evaluation criteria for approval and initial and continuing review, as well as conflict of interest, unanticipated problems and noncompliance.
Federal Policy and Regulations
MSU is committed under its assurance to the federal Office for Human Research Protection (OHRP) to apply the federal Policy for the Protection of Human Subjects found in 45 CFR 46 and all of its subparts "to all of its human subject research regardless of source of support." MSU will also comply with any additional human subject research regulations and policies of supporting federal agencies, of the Food and Drug Administration (21 CFR 50 and 56) and the Standards for Privacy of Individually Identified Health Information (45 CFR 160 and 164).
The policies and procedures comprising the MSU HRPP apply to all of MSU's human subject research related activities regardless of funding support, and to all activities of its designated Institutional Review Boards (IRBs). The policies and procedures apply to the human subject research activities conducted by employees of MSU (faculty and staff), by students of MSU or by individuals who are members (employees) of entities that have a formal written agreement with MSU for review and approval of their human subject research. The MSU HRPP does not apply to clinical faculty who are not employees of MSU (volunteer faculty) unless they have a formal written agreement with MSU or are an employee of an entity that does have such an agreement.
MSU is committed under its assurance to the federal OHRP to apply the ethical principles found in the Belmont Report to all of its activities related to human subject research, regardless of funding. The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research wrote the Belmont Report in 1979. The principles found in the Belmont Report are summarized as follows:
- Respect for Persons - Individuals should be treated as autonomous agents. They should voluntarily enter into research by being adequately informed. Special protection should be given to individuals with diminished autonomy and/or of special circumstances since they may not be able to make a considered judgment even if they are adequately informed. One group entitled to special protections is prisoners who may be subtly coerced or unduly influenced.
- Beneficence - Researchers are obligated to do no harm by maximizing possible benefits and reducing possible risks to subjects. In some cases where research may pose risk to individual subjects with no direct benefit to them the principle of beneficence requires careful assessment of the benefits to others or to society.
- Justice - The risks of research should be equally distributed and should not unduly involve persons from groups unlikely to be among the beneficiaries of the research. Selection of individuals or classes of individuals should be fair. Vulnerable classes of subjects should be given special protection and not be unduly selected as research subjects due to their ready availability or dependent status.
Institutional Official: Authority and Responsibility
The President of Michigan State University has designated Dr. J. Ian Gray, Vice President for Research and Graduate Studies, as the Institutional Official for the protection of human research subjects under its Federal Wide Assurance #00004556 with the U.S. Department of Health and Human Services, Office for Human Research Protections (OHRP).
In this federally mandated role, Dr. Gray shares responsibility with MSU's Institutional Review Boards and investigators for the protection of human research subjects. Dr. Gray is responsible for ensuring that all human subject research at Michigan State University, regardless of source of support, will follow the ethical principles as stated in the Belmont Report and will follow the laws and regulations governing human subjects research including 45 CFR 46 and all its subparts. He is also responsible for fostering open communication with regard to, and a culture of respect for, human subjects at the university.
The Institutional Official has the authority and responsibility to support the Institutional Review Boards for the review of human subjects research; to educate the IRB, researchers and staff on the ethical conduct of human subjects research; to monitor the human research protection program; and to delegate responsibilities to others as needed to carry out these duties.
The Institutional Official and other MSU officials may further review, approve or disapprove human subjects research that has been approved by an MSU IRB as appropriate. They may not, however, approve the research if it has not been approved by an MSU Institutional Review Board (45 CFR 46.112).
Institutional Review Boards: Authority and Responsibility
MSU has established two Institutional Review Boards (IRBs) that have oversight for all research conducted under its Federal Wide Assurance #00004556. The designated IRB's are:
- Michigan Ste U (University Committee on Research Involving Human Subjects or UCRIHS) - DHHS registration #00000297
- Community Research Institutional Review Board (CRIRB) - DHHS registration #00003392
UCRIHS is the original MSU IRB and reviews all human subject research protocols to which the MSU HRPP applies, with the exception of multi-community research. The CRIRB was recently designated as an MSU IRB in 2002 and reviews multi-community research protocols.
These IRBs have the authority and responsibility to approve, require modifications in, or disapprove all human subject research before it is initiated in order to comply with ethical principles and federal, state and local regulations (e.g., 45 CFR 46.109). Except for research that is exempted, all human subject research is subject to continuing oversight and review by the IRB at least annually. The IRBs have the authority to observe the consent process and the research (45 CFR 46.109(c)). The IRBs have the authority to suspend or terminate approval of research that is not being conducted in accordance with their requirements or that has been associated with unexpected serious harm to subjects. The IRBs are responsible for prompt reporting to appropriate officials and entities (university, federal or state agencies, regulatory bodies, OHRP, sponsor agency, reliant IRB, etc) of any unanticipated problems involving risks to subjects or others, of any serious or continuing noncompliance with federal regulations or IRB requirements, and of any suspension or termination of IRB approval (45 CFR 46.113). Details of the procedures for implementing these responsibilities are contained in the MSU HRP Manual available from the Office of the Vice President for Research and Graduate Studies (OVPRGS) and on the website http://www.humanresearch.msu.edu/.
Organization & Structure of IRBs
Details of the organization and structure of the MSU IRBs are contained in the MSU HRP Manual available from the Office of the Vice President for Research and Graduate Studies (OVPRGS) and on the website http://www.humanresearch.msu.edu/.
Administration and Contact Information
Each of the two MSU IRBs is chaired by an MSU faculty member appointed by the Vice President for Research and Graduate Studies. Each IRB has a staff administrator who upholds MSU's ethical standards and who is trained in the regulatory requirements and operations of human subject institutional review boards. The MSU IRB office is located in 202 Olds Hall and can be reached at (517) 355-2180 or by email: firstname.lastname@example.org, email@example.com, and/or firstname.lastname@example.org.
University Committee on Research Involving Human Subjects (UCRIHS) Membership
"The UCRIHS shall be composed of one representative from each of the following colleges: Social Science, Natural Science, Human Ecology, Human Medicine, Osteopathic Medicine, Communication Arts and Sciences, Education, Agriculture and Natural Resources, Veterinary Medicine, The School of Nursing, University College, Engineering, Arts and Letters. These college representatives shall be selected by the faculties of the respective colleges in accordance with college procedures. Up to five additional representatives may be appointed by the Vice President for Research and Graduate Studies to represent the Residence Halls Office or the Office of the Vice President for Student Affairs and areas of expertise not represented by the college selectees. Terms shall be for three years and members may serve for more than one term. The chairman of the UCRIHS shall be the Vice President for Research and Graduate Studies or his/her designee."
Polices and Procedures for Protecting Human Subjects Used in Research, approved by Academic Council, January 23, 1979 [Note: The names and organizational structure of the academic colleges and schools have changed since 1979.]
The UCRIHS membership must also include members as required by federal regulations: at least one member whose primary concern is nonscientific, at least one member who is not otherwise affiliated with the institution, and, if research reviewed regularly includes vulnerable subjects, one or more individuals who are knowledgeable about and experienced in working with vulnerable categories, e.g., children, prisoners, pregnant women, or handicapped or mentally disabled persons. 45 CFR 46.107 IRB membership
Community Research Institutional Review Board (CRIRB) Membership
The CRIRB is composed of a minimum of five members and a maximum of 25 members having representatives from each of the following: MSU-East Lansing, from the community campuses of MSU, IRBs from CRIRB affiliated hospitals and institutions, and non-affiliated and non-scientific members who may be from participating or centrally located communities. Details on CRIRB membership are in the HRP Manual. Like UCRIHS, the membership must comply with federal regulations found in 45 CFR 46.107.
CRIRB members and alternates are appointed for two-year terms with no limit to the number of two-year terms an individual may serve.
Relationship and Communication of MSU IRBs
- Research Protocols: The MSU IRBs differ in the types of research protocols that come under their jurisdiction. UCRIHS covers all human subject research protocols to which the MSU HRPP applies with the exception of multi-community research. The CRIRB covers these multi-community research protocols.
- Organizational Structure: The MSU IRB Chairs directly report to the same individual, the Vice President for Research and Graduate Studies (or his/her designee) as do the chairs or administrators of many related HRPP components, e.g., Conflict Review Committee, Institutional Biological Safety Committee, Chemical Safety Committee, Radiation Safety Committee, Chemical Hygiene Subcommittee and the Office of Regulatory Affairs (ORA). This structure promotes and requires direct communication of the IRB chairs with the Institutional Official and MSU Administration.
- Procedures: The MSU HRP Manual details the common procedures for the MSU IRBs. The exceptions to the shared procedures occur only when necessary to accommodate the specific structure or organization of each IRB and are included in the HRP Manual, e.g., meeting dates, protocols coming under their review.
- Physical Structure: Proximity of location promotes communication between the MSU IRBs and MSU administration. The offices of the IRB Chairs, administrators, support staff and files and the ORA staff are located in the same or adjacent offices in 201, 202, 204 and 205 Olds Hall. ORA staff include the Senior Assistant Vice President for Regulatory Affairs, the Educational Program Coordinator, the Director of Regulatory Affairs Operations (RAO), and additional support staff.
Relationship and Communication with External IRBs and Institutions
MSU IRBs enter into formal written agreements with other institutions in two ways: becoming the IRB of record for an external institution, or having a formal reliance agreement with an external IRB. In neither instance does the MSU IRB rely on an external IRB or institution for approval of human subject research conducted by MSU employees or students.
When the MSU IRB is the IRB of record for an external institution the MSU IRB assumes the review responsibilities for research protocols submitted to it by members of that institution. In these cases the external institution must formally register this arrangement with the federal Office for Human Research Protection (OHRP). The MSU IRB communication (e.g., approval letters, continuing review actions, etc) is directed to the researchers submitting protocols for review. Additional communications with the external institution are listed in the formal written agreement. An example of this type of relationship applies to Blue Cross Blue Shield of Michigan which lists UCRIHS (Michigan Ste U IRB #1) as their IRB of record on their FWA #00007636.
"The IRB will follow written procedures for reporting its findings and actions to appropriate officials at BCBSM. Relevant minutes of IRB meetings will be made available to BCBSM upon request. BCBSM remains responsible for ensuring compliance with the IRB's determinations and with the terms of any OHRP-approved Assurance." IRB Authorization Agreement
When the MSU IRB enters into a formal reliance agreement with an external institution the agreement is effective when that institution obtains their Federal Wide Assurance with OHRP. The MSU IRB communication (e.g., approval letters, continuing review actions, etc) is directed to the researchers submitting protocols for review. In addition, MSU IRB administrators communicate with the IRB administrators and chairs of the reliance institution informing them of the decisions and actions of the MSU IRB relative to research from their investigators. Examples of this type of relationship include the participating CRIRB members which rely on the MSU IRB #2 (CRIRB). This agreement defines the specific communication between the IRBs:
"Minutes of CRIRB meetings and individual project documentation shall be made available to Institution B. Institution B remains responsible for ensuring compliance with the CRIRB's determinations and with the terms of its OHRP-approved Federal Wide Assurance." IRB Collaborative Authorization Agreement with the Michigan State University Community Research Institutional Review Board
Communication with other MSU HRPP Components
- Conflict Review Committee: The Chair of the IRB communicates with the Chair of the CRC for advice, consultation and notification of IRB determinations of conflict of interest that affect the rights and welfare of participants. These may include but are not limited to instances of conflict of interest of IRB members, IRB consultants, investigators, students, sponsors or administrators. The CRC is responsible for developing and enforcing a management plan and informing the IRB of their decisions. The IRB has the authority to approve the research, to require modifications that incorporate the CRC management plan and/or additional IRB determined modifications, or to not approve the research. The CRC may not approve the research if it has not been approved by the IRB.
- University Intellectual Integrity Officer (UIIO): Any case of research misconduct or serious or continuing noncompliance with government regulations pertaining to research and/or university policy can be reported to the MSU University Intellectual Integrity Officer (UIIO) as an allegation of misconduct. These allegations can be presented to the UIIO by the chair of the IRB, any member of the IRB, IRB staff, human subject of the research, or any other individual.
- Office of Radiation, Chemical and Biological Safety (ORCBS): Acquisition, use and disposal of some research substances may require oversight by ORCBS. The administrative head of ORCBS is the Senior Assistant Vice President for Regulatory Affairs who also has a direct reporting line to the Institutional Official for MSU's HRPP. The Chair of the Chemical Safety Committee reports directly to the Senior Assistant Vice President for Regulatory Affairs. Communications occur regularly among these administrators as part of their reporting structure.
Jurisdiction of the IRB
The MSU IRB is responsible for review of all human subject research activities to which this HRPP applies (see section on Applicability). The definitions of "human subject" and "research" required by regulation are included in MSU's HRPP. MSU's HRPP, however, also applies to activities that may be more broadly defined by the MSU academic community as "research." These broader definitions are critical to protecting the human subjects with whom MSU investigators interact or about whom MSU investigators obtain private information. When there is a question about whether an activity constitutes human subject research subject to IRB review, MSU requires that "a qualified person or persons other than the investigator or research team" verify that the activity qualifies for exemption from IRB review. Terms of the Federal Wide Assurance for Institutions Within the United States, section 4.a.2. Details of the procedure are found in the MSU HRP Manual.
A "human subject means 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." 45 CFR 46.102(f).
A human subject for purposes of FDA-related research also "means 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 human (individual) or a patient". 21 CFR 50.3(g) and 21 CFR 56.102(e).
"Research means a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge. Activities which meet this definition constitute research for purposes of this policy, 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." 45 CFR 46.102(d)
Research also includes clinical investigation which is defined as "any experiment that involves a test article and one or more human subjects and that either is subject to requirements for prior submission to the Food and Drug Administration . . . or is not subject to requirements for prior submission to the Food and Drug Administration . . . but the results of which are intended to be submitted later to, or held for inspection by, the Food and Drug Administration as part of an application for a research or marketing permit. 21 CFR 50.3(c) and 21 CFR 56.102(c)
"The terms research, clinical research, clinical study, study, and clinical investigation are deemed to be synonymous for purposes of this part." 21 CFR 56.102(c)
[Note: These are definitions from the regulations. In academic settings these definitions are understood to be broader, e.g., behavioral studies and quality of care studies in a clinical setting may be understood as a clinical investigation by the investigators.]
The HRPP provides for education on ethical principles, regulations and policies regarding human subject research for IRB members, IRB staff, investigators and their key personnel and appropriate administrators. The VPRGS provides resources for these activities as appropriate. All IRB members, staff, investigators and administrators have the responsibility to uphold the ethical standards upon which the MSU HRPP is based. The Graduate School also provides educational resources on the ethical and responsible conduct of research to graduate students.
IRB members and staff are instructed on an ongoing basis through a variety of means including but not limited to updates at regular meetings (IRB or staff), subscription to IRB publications, bi-annual IRB workshops and orientation (personal and tutorial).
Investigators and their research staff are required to complete an online tutorial on ethical principles, regulations and university policy on human subject research. Completion of the online tutorial is required for responsible investigators to submit human research applications to IRB #1. This requirement is scheduled for implementation for IRB #2 in the near future. Investigators are required to have their research staff complete the online tutorial.
Ongoing education for researchers is available through a variety of means including but not limited to "Crosstalk" meetings with the IRB chair and staff, an email "newsletter" from the IRB Chair to investigators, special workshops (e.g., audio-seminars on HIPAA issues), website postings, and formal seminars (RCR seminar series, individual course seminars). The Graduate School provides ongoing education through their publication, the Research Integrity Newsletter.
Education on human subject research is made available to participants via a participant's webpage: http://www.humanresearch.msu.edu/participants.html.
Evaluation of HRPP
Evaluation of the MSU HRPP is the shared responsibility of the Vice President for Research and Graduate Studies (VPRGS), the IRB Chairs, investigators and their administrators, sponsors and participants. This shared responsibility is implemented by several mechanisms to acquire and evaluate information regarding the human research protection program. The evaluation plan includes formal and informal elements.
Informal Evaluation Elements
Input is encouraged by wide publication of contact information asking for calls to answer questions.
IRB Office - The MSU IRB staff has a telephone number, fax number, address and email address that is included on consent documents, IRB applications, the human research website, etc. Consent documents also include contact information for the IRB Chair. Concerns and suggestions are welcomed and are discussed with the IRB Chair.
Office of Regulatory Affairs (ORA) - The contact information for ORA is available on the MSU Research website of the VPRGS. Concerns and suggestions are welcomed and are discussed with the IRB chair, the Senior Assistant Vice President for Regulatory Affairs and/or the VPRGS, and the Educational Program Coordinator, as appropriate.
Concerns and suggestions received during the presentation of seminars and other educational events are welcomed and are discussed with the IRB chair, the Senior Assistant Vice President for Regulatory Affairs and/or the VPRGS, and the Educational Program Coordinator, as appropriate.
Formal Evaluation Elements
- Audit of IRB protocols: ORA and/or the IRB staff conduct audits of IRB protocols in conjunction with IRB members and/or the IRB chair. Results of the audits are shared with the IRB members, the Senior Assistant Vice President for Regulatory Affairs and/or VPRGS as appropriate. Audits are conducted at least quarterly.
Evaluations of education events: Formal evaluation forms are used for workshops and request input on the specific event as well as suggestions for other events and/or concerns.
- Annual Report: The IRB Chair is requested to provide information on an annual basis to the Director of Regulatory Affairs Operations in order to develop plans for the coming fiscal year. This report can include an assessment and evaluation of physical space, staff resources and funding. The report is shared with the Assistant VPRGS and/or the VPRGS as appropriate.
- Human Research Protection Program (HRPP) Advisory Committee: The VPRGS has constituted an HRPP Advisory Committee to provide advice and consultation regarding the evaluation of MSU's HRPP. The committee consists of representative investigators, human subject participant groups, IRB members, sponsors and administrators. The committee includes individuals who are not affiliated with MSU. The Senior Assistant Vice President for Regulatory Affairs and Director of Regulatory Affairs Operations are ex-officio members.
- Staff Evaluations: IRB staff are evaluated on an annual basis following MSU Human Resource guidelines.
- IRB Member Evaluations: The IRB Chair provides input to the VPRGS or his/her designee on the participation of IRB members. This input includes but is not limited to an accounting of their attendance at scheduled meetings, the number and types of reviews conducted, the timeliness of reviews, participation in workshops, etc. This evaluation is done annually and input provided to appropriate administrators for MSU faculty who are IRB members.