Section 1: Introduction
1.0 Purpose and Scope of this Manual
1.1 Applicability
1.2 Mission Statement
1.3 Administration of Research Ethics - Federal
1.4 Applicable State of Texas Laws
1.5 Administration of Research Ethics - University of Texas
1.6 Designation of the Institutional Review Board
1.7 The Institutional Review Board
1.8 Departmental Review Committees (DRC)
1.0 PURPOSE AND SCOPE OF MANUAL
The IRB documents its written procedures, according to (45 CFR 46.115(a)(6) (45 CFR 46.103(b)(4) and (45 CFR 46.103(b)(5). This manual contains current policies and procedures and will be regularly updated to reflect new standards, regulations and University of Texas at Austin policy. All research projects involving human participants1 conducted by faculty, staff, and students associated with The University of Texas at Austin must receive Institutional Review Board2 (IRB) approval prior to initiating the research. Some studies may be subject to FDA regulation and oversight; when in doubt contact the Office of Research Support ( ORS). The IRB has not reviewed investigational drugs3 (IND) granted by the FDA. The IRB does review research involving investigational devices. In the event that the IRB makes a determination of significant risk for an experimental device, the IRB will 1) document an Investigational Device Exemption (IDE) from the FDA, and 2) enlist a consultant with appropriate expertise as needed ato augment the expertise of the IRB. For more information about Federal Policy for the Protection of Human Subjects, read 45 CFR Part 46 and 21 CFR Part 50 & 56. For more information about basic ethical questions in the conduct of research consult The Belmont Report.
A brief review of these documents is provided here so that investigators may better understand the reasons for ethical review of research with human participants, the primary ethical principles that govern such research, and the statutory basis or enactment of these principles. This document also contains information that should be sufficient to allow researchers to submit an acceptable application for the review of a project involving human subjects. Investigators who read this manual will be informed about the National Institute of Health (NIH) rules and University of Texas at Austin requirement of education for all individuals responsible for the design and conduct of research projects with human subjects. Investigators will also be informed about their obligation to obtain an authorization from research participants for the disclosure of protected health information under the Health Insurance Portability and Accountability Act of 1996 (HIPAA), in what circumstances the authorization may be waived, and the process involved in creating de-identified information in compliance with the HIPAA privacy rule.
The contents of this document, including the cover sheets, the description of the information that must accompany an application for the review of a project involving human subjects, the sample consent4 forms, and the suggested wording for consent forms may be accessed from http://www.utexas.edu/research/rsc/
humansubjects/index.html
1.1 Applicability
The procedures set forth in this manual are applicable to all faculty, staff, employees, and students at University of Texas at Austin who propose to use humans as subjects in research, development, and related activities including research for which investigational devices or drugs are used. The University requires research investigators who are not its employees or agents a) to obtain the collaboration of a University faculty; b) to ensure all these investigators (internal and external to the institution) comply with all relevant (i) IRB determinations; (ii) federal and state regulatory requirements, and (iii) human participant protection standards.
The University of Texas at Austin’s IRB has a formal relationship with the University of Texas Health Sciences Center San Antonio (UTHSCSA), regarding human subjects research done by specific University of Texas at Austin pharmacy faculty (FWA #2030). For faculty identified annually by the College of Pharmacy, the process that will be followed involves the investigator sending copies of each (UTHSCSA) IRB approved action (new study, amendment, unanticipated problems, non-compliance, continuing reviews) to the ORS. The ORS will then enter the information into an electronic file, creating an IRB protocol number. The University of Texas at Austin will accept the IRB approval of the UTHSCSA; however, UTHSCSA will be required to submit copies of minutes from each IRB meeting to the ORS for their review. This review will determine whether appropriate due process occurred. At present UTHSCSA is not AAHRPP accredited.
When a site’s IRB requests the IRB to provide IRB review for a specific protocol, the IRB reviews the appropriateness of such request and if approved by the IRB, the site and IRB enter into an IRB Authorization Agreement. The site must indicate on their FWA that the site would rely on the IRB for review and continuing oversight of the specific protocol.
1.2 Mission Statement
The IRB and the human research participant protection program (HRPPP), are charged with the following mission:
“To determine and certify that all human subjects research projects (regardless of funding) conform to the regulations and policies regarding the health, welfare, safety, rights, and privileges of human subjects set forth by the Department of Health and Human Services (DHHS) in 45 CFR 46 and the Federal Drug Administration (FDA) in 21 CFR 50 and 56. These goals include ensuring that each research participant is informed of their rights and are able to give informed consent5. Researchers (faculty, staff and students) must assure through verified training that the welfare of their research participants is of paramount importance. It is noted that The University follows the ethical standards put forth in 45 CFR 46, 21 CFR 50 and 56, and relevant state and local regulations and procedures.”
The University of Texas at Austin, formally grants the IRB the following authorities, relative to the protection of human subjects:
- To approve, require modifications to secure approval, or disapprove all research activities overseen and conducted by the organization;
- To suspend or terminate approval of research that is not being conducted in accordance with requirements or that has been associated with unexpected serious harm to participants;
- To observe, or have a third party observe, the conduct of the research; and
- To indicate that officials of the organization may not approve a protocol that has not been approved by the Institutional Review Board.
1.3 Administration of Research Ethics -- Federal
The Office for Human Research Protections (OHRP) provides leadership on human research subject protections and implements a program of compliance oversight for Department of Health and Human Services (HHS) regulations for the protection of human subjects - Title 45, Part 46 of the Code of Federal Regulations (45 CFR Part 46). OHRP works to support and strengthen the nation's system for protecting those who volunteer to participate in research that is conducted or supported by agencies of HHS. To carry out its mission, OHRP has formal agreements with more than 10,000 federally funded universities, hospitals, and other medical and behavioral research institutions in the U.S. and abroad wherein they agree to abide by the human subject protection regulations found in the Code of Federal Regulations (45 CFR Part 46).
OHRP evaluates all written substantive allegations or indications of noncompliance with HHS regulations. The relevant institution is notified of the allegation and is asked to investigate the basis for the complaint. The institution then provides a written report of their investigation, along with relevant institutional IRB and research records, to OHRP which determines what, if any, regulatory action needs to be taken.
OHRP provides guidance to IRB members and staff as well as to scientists and research administrators on the complex ethical and regulatory issues relating to human subject protections in medical and behavioral research. The office conducts national educational workshops in partnership with other related federal agencies and organizations. OHRP also provides on-site technical assistance to institutions conducting HHS-sponsored6 research. In addition, OHRP helps institutions assess and improve their systemic protections for human subjects through a quality improvement program.
OHRP provides quality improvement consultation and research ethics training to domestic and foreign institutions involved in international biomedical and behavioral research to help ensure that recognized ethical protections are afforded to persons participating in research conducted in countries outside the United States. OHRP prepares policies and guidance documents as well as interpretations thereof on human subject protections and disseminates this information to the research community. In addition, every institution engaged in human subjects research conducted or supported by DHHS must obtain an assurance7 of compliance approved by OHRP. At the University of Texas at Austin, the criteria for determining whether the institution is engaged in human subjects research is articulated in the definition of “Human Research”. Refer to Appendix E for tools for making such determinations.
Within DHHS, the Food and Drug Administration (FDA) has oversight over FDA-regulated research (drugs, biologics, medical devices, foods). Title 21, Parts 50 and 56 of the Code of Federal Regulations (21 CFR Part 50 and 56) describe FDA oversight policies. The FDA is responsible for protecting the public health by assuring the safety, efficacy, and security of human and veterinary drugs, biological products, medical devices, our nation’s food supply, cosmetics, and products that emit radiation. Please contact ORS with questions about DHHS, OHRP, and FDA policies, jurisdiction, and oversight.
Office for Human Research Protections
1101 Wootton Parkway, Suite 200
Rockville, MD 20852
Toll-Free Telephone within the U.S. (866) 447-4777
Telephone: (301) 496-7005
Fax: (301) 402-0527
e-mail: ohrp@osophs.dhhs.gov
http://www.hhs.gov/ohrp/
Food and Drug Administration
5600 Fishers Lane
Rockville, Maryland 20857
1-888-INFO-FDA (1-888-463-6332)
http://www.fda.gov
1.4 Applicable State of Texas Laws
Reporting Requirement: Section 261.004 of the Texas Family Code provides that a person having cause to believe that a child's physical or mental health or welfare has been adversely affected by abuse or neglect by any person shall immediately make a report. The second clause of the statute addresses the reporting obligation of professionals, i.e., those licensed or employed by the state who have direct contact with children. The third clause waives any confidentiality privilege of an attorney, member of the clergy, medical practitioner, social worker, mental health professional or an employee of a clinic or health care facility that provided reproductive services who becomes aware of abuse or neglect of a child.
Under federal law a “Legally Authorized Representative” means an individual or judicial or other body authorized under applicable law to consent on behalf of a prospective participant to that subject's participation in the procedures involved in the research. [45 CFR §46.402(c)] [21 CFR §50.3(l)]. The individuals authorized under Texas law to consent on behalf of a prospective participant to participation in the procedures involved in the research are the parent or legal guardian8 if the patient is a child, a legal guardian if the individual has been adjudicated incapacitated9 to manage the individual’s personal affairs, an agent of the individual authorized under a durable power of attorney for health care, an attorney ad litem appointed for the individual, a guardian ad litem appointed for the individual, or an attorney retained by the individual [Section 241.151 Texas Health and Safety Code].
Under federal law “children” are persons who have not attained the legal age for consent to treatments or procedures involved in research or clinical investigations, under the applicable law of the jurisdiction in which the research or clinical investigation will occur. In Texas, individuals under the age of 18 are children unless emancipated by filing a petition and meeting the statutory requirements, or they have been adjudicated to be an adult for the purpose of criminal prosecution.
If research takes place outside the state of Texas, the IRB will consult with legal counsel; Legal counsel provides guidance and interpretation to the IRB.
1.5 Administration of Research Ethics - The University of Texas at Austin
The Office of the Vice President for Research is responsible for the administration and oversight of research ethics at University of Texas at Austin. It oversees the functioning of the Institutional Review Board (IRB). The Director of the Office of Research Support provides the IRB administrative support. Supervisors periodically evaluate administrative support staff regarding their knowledge and interpretation of relevant policies and procedures to human subjects research protection.
If you have questions about the rules or procedures for ethical review or the applicability of the information in this manual to your proposal, first contact your Departmental Review Committee (DRC). DRCs serve as the liaison between the IRB and the faculty, staff, and students in the departments and colleges where research is conducted with human participants. If your DRC representative cannot answer your questions, or your department does not have a DRC, contact:
Office of Research Support
North Office Bldg. A, Suite 5.200
Mail Code: A3200
Phone: 471-8871
Fax: 471-8873
e-mail: orsc@uts.cc.utexas.edu
http://www.utexas.edu/irb
1.6 Designation of The Instutional Review Board
The University of Texas at Austin has one IRB responsible for conducting initial and continuing reviews10 and providing oversight for all research activities involving the use of human subjects performed on the campus or at any location under the purview of University of Texas at Austin. The IRB will conduct initial and continuing reviews of research activities according to Sections 6 and 7 of this manual. All review procedures will meet or exceed the requirements set forth in 45 CFR 46 and 21 CFR 50 and 56.
1.7 The Instutional Review Board
The IRB is composed of regular voting members and alternate voting members. The IRB may use, as necessary, non-voting members and consultant reviewers’ considerations and discussions. The Common Rule, FDA regulations, and The University of Texas at Austin’s FWA require that the IRB have at least five regular voting members, including the Chair. At least one member on the IRB must have primarily scientific concerns, one must have primarily nonscientific concerns, and one must be unaffiliated with the University ("community or lay member") (45 CFR 46.107; 21 CFR 50 and 56.107). The University of Texas at Austin IRB maintains a roster of more than the minimum required number of members to ensure adequate and efficient review.
The IRB membership reflects expertise in both science and non-science fields. Scientific members of the IRB generally will have had experience in research involving human subjects, and will be recruited from among active members of the faculty of the Colleges of Pharmacy, Education, Liberal Arts, and The Schools of Nursing and Social Work or other others, as appropriate. Nonscientific members will be recruited from the faculty at large in areas such as the School of Law. Their appointment will reflect professional expertise in a non-scientific area, such as law, ethics, human or patient rights, etc. In addition to faculty members representing different disciplines, the IRB currently has three community members; one of whom represents non-scientific areas; one is a prisoner representative; and one is a radiologist. The community members will be knowledgeable about the local community and willing to discuss issues and research from that perspective. They are chosen from Austin and its vicinity. Neither they nor their immediate families may have an affiliation with The University of Texas at Austin. Candidates for these positions include but are not limited to, clergy, lawyers, teachers, state employees, and businesspersons.
At times, the IRB may not have the necessary expertise to judge the scientific soundness of a research protocol and may be unable to make a fair and accurate determination of the risk-benefit ratio. For these protocols, the IRB may call upon ad hoc consultants for assistance in review for scientific merit (See Sections 2.5 and 3.3).
The Institutional Official / Organizational Official (IO / OO; The Vice President for Research), Director of the ORS, and the IRB Chair annually review IRB membership and provide recommendations to the Vice President for Research, regarding the recruitment, retention or dismissal of members. This review includes examination of attendance, specialty, expertise, education, affiliation and diversity. Thus, the membership and composition of the IRB is periodically reviewed and adjusted to meet regulatory and organizational requirements. The Vice President for Research (both the IO and the OO, appointed by the President) formally appoints IRB members. The Vice President considers the following factors in the selection process: experience, expertise, racial, cultural, and gender diversity, and community involvement. Thus, the IRB will be able to ascertain the acceptability of proposed research in terms of institutional commitments, regulations, applicable law, and standards of professional conduct and practice (45 CFR. 46.107; 21 CFR 50 and 56.107).
Annually and as membership changes are made, the director of ORS will report any IRB membership changes to the Office of Human Research Protection (OHRPP). Administrative staff and / or faculty (e.g., legal counsel) at University of Texas at Austin may serve as non-voting members of the IRB should the Vice President for Research, the IO, the IRB Chair or the ORS Director decide that such persons would be of assistance to the IRB in conducting its duties. A non-voting member cannot be counted in the quorum and cannot vote, but can participate in discussions and deliberations. The Vice President for Research, the IO, IRB Chair, or ORS Director, may appoint a non-voting member who will serve for only as long as requested.
Generally, the IRB will have a Chair and a Vice Chair. The Chair and Vice Chair will be chosen from IRB members, and will typically be filled by members of the faculty of University of Texas at Austin knowledgeable in human subject research, including the federal and state regulations, University policies, and ethics relevant to such research. The Vice President for Research annually appoints The Chair and Vice Chair; however, subject to the discretion of the Vice-President for Research, this appointment may extend beyond one year. Whenever the Chair is not available, the Vice Chair will assume the responsibilities of the Chair during the period of his or her absence. Finally, any changes in IRB membership the ORS Director will promptly report in writing to OHRP.
1.8 The Departmental Review Committees (DRC)
The University allows each Department and/or distinct Research Unit to create a Departmental Review Committee (DRC) that best reflects its size and discipline. However, the IRB does not require all Departments engaged in human participants research to implement a DRC. Prior to submission to the IRB for review, the IRB requires applications from departments with DRCs are approved by the DRC. The purpose of the DRC is to provide first tier review of human subjects research by investigators of similar training. Thus, scientific merit, and relevant research design are considered important questions to be asked by the DRC. The DRC specifically addresses: does the research use procedures consistent with sound research design? Is the research design sound enough to reasonably expect the research to answer its proposed question? What is the importance of the knowledge expected to result from this research? By signature, the DRC is acknowledging and affirming the scientific merit and soundness of the methodology. In the absence of a DRC, these determinations are made by the IRB.
A list of recommended training references for DRCs is provided in Section 4.6. While DRC’s are encouraged to provide direct review of the research protocol and informed consent process, the DRCs do not make final decisions about research determinations. Applications listing DRCs must have DRC approval prior to IRB submission. Final decisions about human subjects research are made by the IRB in the Office of Resarch Support and Compliance. For a list of DRCs: http://www.utexas.edu/research/rsc/humanresearch/users_guide/DRClist.php
Notes:
1) The University of Texas at Austin defines, “research projects involving human participants” to include all activities that are “research,” and involve, “human participants” according to The Common Rule, and to include all activities that are “research” according to FDA regulation. According to The Common Rule, “research” is a systematic investigation, including clinical investigations, research development, testing and evaluation, designed to develop or contribute to generalizable knowledge and “human participants” are living individuals about whom the investigator conducting research obtains a.) data through intervention or interaction with the individual or b.) identifiable private information (45 CFR 46). According to FDA regulations “research” is any experiment that involves: a.) “test article,” that is any drug or biological product for human use, a medical device for human use, a food additive or color additive intended for human use, an electronic product or any other article subject to regulation by the Food, Drug, and Cosmetic Act; and one or more individuals who are either recipients of the test article or controls; and that either involves a drug or medical device (other than the use of an approved drug or device in the course of medical practice) or the results of the research are intended to be later submitted to, or held for inspection by, the Food and Drug Administration as part of an application for a research or marketing permit. For specific University of Texas at Austin IRB positions on Oral History, Journalism, or Program Evaluation see http://www.utexas.edu/research/rsc/humansubjects/special_topics/policy_updates.html.
2)“Institutional Review Board” (IRB) is an independent committee comprised of scientific, non-scientific, and non-affiliated members established according to the requirements of federal regulations. Any board, committee, or other group formally designated by an organization to review research involving humans as participants, to approve the initiation of and conduct periodic review of such research. The term includes, but is not limited to Institutional Review Boards, Investigational Review Boards, Central Review Boards, Independent Review Boards, and Cooperative Research Boards. [45 CFR §46.402(g)] [21 CFR §50.3(i)]
3) “Investigational New Drug” (IND) An investigational drug or biologic application by which the FDA allows testing in human beings of a substance having an effect in the body. (21 CFR part 312, subpart B)
4) “Consent/Permission is the agreement of participant or the parent(s) of or guardian to their, their child’s, or ward’s participation in the research/clinical investigation.
5) “Informed Consent” means the agreement to participate in research that is made voluntarily by an individual with legal and mental competence and the requisite decision-making capacity, after disclosure of all material information about the research. Informed Consent means the knowing consent of an individual or his legally authorized representative, so situated as to be able to exercise free power of choice without undue inducement or any element of force, fraud, deceit, duress, or other form of constraint or coercion. Information conveyed in the informed consent/ authorization procedure must include all essential elements listed in Section 5 of this manual.
6) “Sponsor” is an entity who takes responsibility for and initiates research, but who may not conduct the investigation. A person other than an individual (e.g., corporation or agency) that uses one or more of its own employees to conduct research it has initiated is considered to be a sponsor, and the employees are considered to be investigators. [21 CFR §50.3(k)] [21 CFR §56.102(j)] [21 CFR §312.3]
7) “Assurance” is an agreement between an Organization and a federal agency that stipulates that the Organization will comply with regulatory requirements. [45 CFR §46.103]
8)Pursuant to Section 601 of the Texas Probate Code, a "guardian" means a person who is appointed guardian of the person and/or the estate of an incapacitated person under a court order issued pursuant to Section 693 of the Texas Probate Code.
9) Incapacitated persons include "minors", that is, persons under the age of 18 years and who have never been married or who have not had the disablements of a minor removed for general purposes; and adult individuals who, because of a physical or mental condition, is substantially unable to provide food, clothing, or shelter for themselves, or to care for their own physical health, or to manage their own financial affairs.
10) “Continuing Review” is the periodic review of a research study by an IRB to evaluate whether the study continues to meet organizational and regulatory requirements. Federal regulations stipulate that continuing review should be conducted at intervals appropriate to the level of risk involved in the study, and not less than once per year. [45 CFR §46.109 (e)] [21 CFR §56.109 (f)]