All research projects with human participants conducted by faculty, staff, and students associated with The University of North Texas Health Science Center at Fort Worth (hereinafter referred to as UNTHSC) must receive ethical approval before the research is begun. The information in this Policies and Procedures document is designed to assist investigators with the process of achieving this approval. For more information about the Common Federal Policy for the Protection of Human Subjects, read 45 CFR, Part 46. For more information about basic ethical questions in the conduct of research, read The Belmont Report. These documents may be found on our web site at http://research.hsc.unt.edu/irb.html.

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 document will be informed about the National Institute of Health (NIH) rules and UNTHSC 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.

SECTION 1.2 BACKGROUND INFORMATION

SECTION 1.2.1 ETHICAL VIOLATIONS IN RESEARCH WITH HUMAN PARTICIPANTS

Human researchers have treated other humans inhumanely and unethically. The Nuremberg trials documented the unethical behavior of Nazi physicians. American researchers from the Public Health Service studied 400 African American men with syphilis in the Tuskegee syphilis study between 1933 and 1972. These men were not asked for their informed consent/authorization to be in the study and they were, in fact, given misinformation about their treatment. After penicillin became available and was known to be effective in the treatment of syphilis, it was withheld from these subjects because the researchers were interested in the natural history of the disease. Researchers from Harvard and MIT formed a "science club" of 19 mentally impaired boys at the Fernald State School between 1946 and 1956. These boys were fed forms of radioactive iron or calcium, sometimes in their milk, to enable the researchers to study the body's ability to digest minerals. Doctors at the Jewish Chronic Disease Hospital conducted studies of human transplant rejection using cancer cells. The subjects were not asked for informed consent/authorization and did not give written consent/authorization to participate in the study. Between 1963 and 1966, children at the Willowbrook State School, a state school for "mentally defective" youths were purposely infected with the hepatitis virus in a study of that disease. During the course of this study the institution closed its doors to new clients, claiming overcrowding. However, the wing housing the hepatitis program was willing to admit new clients if their parents agreed to allow their children to participate in the ongoing studies. (These descriptions of unethical research conduct are based on the NIH tutorial for ethical training. That training module is at http://ohsr.od.nih.gov/cbt/.)

Behavioral and social science researchers have exposed other humans to severe trauma and psychological stress in the name of scientific research. The participants in Milgram's "obedience" studies, conducted in the early 1960s, were told that they had to continue to participate in the study and shock another person at increasingly intense voltages. Studies supported by the Human Resources Research Office of the U.S. Army introduced severe stress to army recruits by threatening them with death from errant artillery rounds or by causing the recruits to think that they, by making a mistake in wiring an instrument, had caused the injury or death of others in their units.

SECTION 1.2.2 CODES OF RESEARCH ETHICS

Codes of research ethics have been developed, in part to address the disregard for human safety and dignity that these research projects reflect. The Nuremberg Code of 1947 was the first international code of research ethics. Its first principle is "The voluntary consent/authorization of the human subject is absolutely essential." The accompanying text made it clear that this voluntary consent/authorization should also be informed consent/authorization: "...the person involved ... should have sufficient knowledge and comprehension of the elements of the subject matter involved as to enable him to make an understanding and enlightened decision." This principle of "free and informed consent/authorization" remains the basic foundation of ethical research with human participants.

Another early code was the Helsinki Declaration, adopted by the World Medical Assembly at its meeting in Helsinki, Finland in 1964. Its second principle, "The design and performance of each experimental procedure involving human subjects should be clearly formulated in an experimental protocol which should be transmitted for consideration, comment and guidance to a specially appointed committee independent of the investigator and the sponsor..." established the concept of ethical review.

The first ethical code covering social and behavioral research was a set of 10 ethical principles adopted by the American Psychological Association in 1972, which has been updated effective June, 2003. The bases for these principles were critical incidents. Psychologists were asked to submit examples of research that they deemed unethical or of questionable ethics. The committee charged with developing ethical standards for psychological research then developed principles that would guide the conduct of researchers when conducting research that could pose ethical problems. The American Psychological Association's principles were the first to recognize the principle of confidentiality. Principle 10 states: "Information obtained about the research participants during the course of an investigation is confidential. When the possibility exists that others may obtain access to such information, ethical research practice requires that this possibility, together with the plans for protecting confidentiality, be explained to the participants as a part of the procedure for obtaining informed consent/authorization." Most professional organizations have ethical codes, and most require authors of manuscripts submitted to the journals of these organizations to state that they have followed these ethical principles in their research.

The U. S. Department of Health, Education, and Welfare issued ethical guidelines in 1971, which were codified into Federal Regulations in 1974. However, the primary impetus for current government ethical regulation began with the establishment of a National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research under the aegis of the Department of Health, Education, and Welfare in 1974. The Commission was charged with identifying the basic ethical principles that should underlie research with human subjects. The report of the Commission, called The Belmont Report because it was based on deliberations held at the Smithsonian Institution's Belmont Conference Center, was published in 1978. The Belmont Report identified three basic ethical principles. They are:

(1) Respect for Persons (autonomy): This principle acknowledges the dignity and freedom of every person. It requires obtaining informed consent/authorization from all potential research subjects (or their legally authorized representatives).

(2) Beneficence: This principle requires that researchers maximize benefits and minimize harms or risks associated with research. Research-related risks must be reasonable in light of expected benefits.

(3) Justice: This principle requires the equitable selection and recruitment and fair treatment of research subjects.

These three principles were the underpinnings of both an early (1980) version of a Common Federal Policy for the Protection of Human Research Subjects and the current version of that policy. The current version has been adopted by sixteen federal departments and agencies, including the Department of Health and Human Services, the National Science Foundation, the Department of Education, and the Central Intelligence Agency. The Food and Drug Administration (FDA) has concurred with the Federal Policy and has made changes in its IRB and informed consent/authorization regulations so that they correspond to the Federal Policy. This Federal Policy, sometimes called the Common Rule, is codified as the Common Federal Policy for the Protection of Human Subjects and was published in the Federal Register in 1991. It is referred to as 45 CFR 46 and its regulations underlie the decisions of IRBs. The regulations further require that each institution at which federally funded research is conducted adhere to the principles of The Belmont Report and set forth in writing its ethical principles, policies, and procedures. This institution's agreement to abide by the Belmont Report and by 45 CFR 46 (called a Federal Wide Assurance or FWA) is approved by the federal agency that oversees ethical issues in human research. Because UNTHSC has an FWA, UNTHSC can establish an IRB that can review all research projects involving human subjects.

SECTION 1.2.3 ADMINISTRATION OF RESEARCH ETHICS - FEDERAL

The audits conducted by the federal department responsible for human subject protection, now known as the Office for Human Research Protections (OHRP), of the performance of IRBs and the conduct of research with human participants at several medical schools have resulted in temporary injunctions of research with humans at those schools. The death of a participant in a gene therapy research study suggested a lapse of oversight at the site of that study. News reports of clinical trials have suggested that doctors may receive financial benefits by enrolling their patients in such trials and that the patients may not benefit or may be at risk.

SECTION 1.2.4 ADMINISTRATION OF RESEARCH ETHICS - THE UNIVERSITY OF NORTH TEXAS HEALTH SCIENCE CENTER AT FORT WORTH

The Office of the Executive Vice President of Academic Affairs and Research or designee is responsible for the administration of research ethics at UNTHSC. That office oversees the functioning of the Institutional Review Board (IRB), the University committee that reviews proposals for research with human participants. The IRB itself works out of the Office of IRB Services.

If there are questions about the rules or procedures for ethical review or the applicability of the information in this manual to a proposal, first contact the Departmental Chair. Chairs 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 the Chair cannot answer the questions, contact:

Brian Gladue, Ph.D. (Director - Office for the Protection of Human Subjects, Chair - UNTHCS IRB) [bgladue@hsc.unt.edu]
Phone: 817-735-5083
Fax: 817-735-0375

Debbie Ceron (Administrator – Biomedical Protocols) [dceron@hsc.unt.edu]
Phone: 817-735-5483
Fax: 817-735-0375

Sharon Tobola (Administrator – Behavioral and Social Science Protocols) [stobola@hsc.unt.edu]
Phone: 817-735-5457
Fax: 817-735-0375

SECTION 1.3 REVISION AND MAINTENANCE OF THE POLICIES AND PROCEDURES

All new or revised materials will be placed on the IRB web page by the Office of Research.

SECTION 2: DEFINITIONS

The following definitions are applicable to all sections of this document.

"Conflict of Interest:"
Growing interaction between for-profit enterprises and UNTHSC has created new possibilities for the occurrence of conflicts of interest. These conflicts arise when there are opportunities for faculty or staff members to benefit financially either from the outcome of research or from activities conducted in the course of responsibilities as an institutional research member.

UNTHSC believes that with clear guidelines and principles, in conjunction with appropriate supervision and monitoring, it is possible for interaction between industry and academic medicine to take place in a manner that is consistent with the highest traditions of medical and scientific research and in a way that energizes scientific creativity.

This Policy establishes guidelines for the appropriate structuring of relationships with industry and other outside ventures so as not to conflict with previously established responsibilities to UNTHSC. Investigators are expected to make reasonable inquiry as to whether their relationships and activities fall within the provisions of this Policy. It is not the intent of this Policy to eliminate or prohibit all situations involving a potential Conflict of Interest. This Policy is intended to enable Investigators to recognize situations that may pose a conflict of interest, to report these situations to the Conflict of Interest Committee, and to ensure that the Conflict of Interest Committee reviews these situations and, if necessary, supervises or monitors them. An integral part of this Policy is a disclosure mechanism whereby Investigators regularly review their activities. This Policy is intended to maintain the professional autonomy of scientists and physicians inherent in the self-regulation of science. This Policy should be viewed as complementing all institutional policies and procedures, including Sections 5.05 and 5.06 of UNTHSC’s Personnel and Procedures Manual.

Each Investigator shall disclose all significant financial interests:

of the Investigator including spouse and dependent children
that would reasonably appear to be affected by the research, educational, or service activities funded, or proposed for vending, by an external sponsor
in entities whose financial interests would reasonably appear to be affected by such activities.

What is covered?
Significant financial interests include:

Receipt of, or the right or expectation to receive monetary value, including but not limited to, salary or other payments for services (e.g., consulting fees, honoraria, payments for directorships or executive roles); equity interests (e.g. stocks, stock options, dividends or other ownership interests); and intellectual property rights (e.g., patents, copyrights and royalties from such rights); or
receipt of, or the right or expectation to receive other value, such as in the form of a forbearance, forgiveness, interest in real or personal property, rent, capital gain, real or personal property, or any other form of compensation, such as gifts.

The term does not include: interests held directly through funds such as mutual funds, pension funds, or other institutional investment fund in which the Investigator or the Investigator’s Family does not control the selection of investments.

Further, the following financial interests do not rise to the level of a Significant Financial Interest:

salary, royalties, or other remuneration received from UNTHSC;
standard royalties received for published scholarly work or other professional writings;
royalties or equities received under UNTHSC royalty-sharing policies (see UNTHSC Intellectual Property Policy);
consulting fees received from an entity in which neither the Investigator, the Investigator’s Family, an Associated Entity of the Investigator, nor UNTHSC have any other relationship, provided that the consulting relationship has been approved in accordance with the UNTHSC Outside Employment Policy, and subject to all other policy requirements including appropriate devotion of time to UNTHSC;
income from seminars, lectures, or teaching engagements sponsored by public entities; or
income from services on advisory committees or review panels for governmental entities.

"DHHS" means the Department of Health and Human Services.

"FDA" means the Food and Drug Administration.

"Federal Wide Assurance (FWA)" means a document that fulfills the requirements of 45 CFR Part 46 and is approved by the Secretary of Health and Human Services. The University of North Texas Health Science Center has an approved FWA on file with DHHS.

"HIPAA" is the Health Insurance and Portability and Accountability Act of 1996 (HIPAA) that protects the privacy of a research participant's health information. The three categories of IRB approval are maintained but the research protocol, and the activity conducted preparatory to the research, is required to meet additional qualifications more fully explained below.

"Human Subject" means a living individual about whom the investigator conducting research obtains (a) data through intervention or interaction with the individual or (b) identifiable private information.

Intervention includes both physical procedures, by which data are gathered (for example, venipuncture), and manipulations of the subject or the subject's environment that are performed for research purposes. Interaction includes communication or interpersonal contact between investigator and subject.

Private information includes information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, and information, which has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public (for example, a medical record). Private information must be individually identifiable (i.e., the identity of the subject is or may readily be ascertained by the investigator or associated with the information) in order for obtaining the information to constitute research involving human subjects.

"Informed Consent/authorization" means the knowing consent/authorization 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 4 of this manual.

"Institution" means any public or private institution or agency (including Federal, State and local Government agencies).

"Key Personnel" are defined as the principal investigators, co- investigators, and others specified within each project, as having decision-making power over the investigation.

· The principal investigator is that individual with signatory power on all documents related to the research project. This person has final authority over the project. The principal investigator accepts responsibility for training all personnel associated with the study in compliance with the human subject’s regulations of 45 CFR 46.

· The co-investigator is that individual who may be designated as a co-investigator in grant-related documents. The co-investigator reports to the principal investigator who is ultimately responsible for the conduct of the research.

· Others with decision-making power may include such persons as project managers, directors, trainers. These designations are not all-inclusive. Operationally, these individuals have some oversight responsibility for one or more portions of the project. Individuals in this category are determined uniquely for each project by the principal investigator.

"Legally authorized representative,” means an individual or judicial or other body authorized under applicable law to consent/authorization on behalf of a prospective subject to that subject's participation in the particular activity or procedure.

"Minimal Risk" means that the risks of harm anticipated in the proposed research are not greater than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. Please note the different definition for minimal risk for incarcerated persons: The probability and magnitude of physical or psychological harm that is normally encountered in the daily lives, or in the routine medical, dental, or psychological examination of healthy persons.

"OHRP" means the Office for Human Research Protections. This is an office in the Office of the Secretary of Health and Human Services that is responsible for regulatory oversight of human subject research.

"Research" means a systematic investigation, including research development, testing, and evaluation, designed to develop or contribute to generalizable knowledge. Research is defined by both the Common Rule of the Federal regulations and by the Privacy rule of HIPAA.

"Secretary" means the Secretary of Health and Human Services and/or any other officer or employee of the Department of Health and Human Services to whom authority has been delegated.

SECTION 3: THE INSTITUTIONAL REVIEW BOARD

SECTION 3.1 DESIGNATION OF THE INSTITUTIONAL REVIEW BOARD

The University of North Texas Health Science Center at Fort Worth has one (1) Institutional Review Board (hereinafter referred to as the IRB) that is responsible for conducting initial and continuing reviews 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 UNTHSC. The IRB will conduct initial and continuing reviews of research activities according to the procedures outlined in this document. All review procedures will meet or exceed the requirements set forth in 45 CFR 46.

To ensure compliance with the regulations, the University of North Texas Health Science Center has adopted an internal audit and/or self-assessment procedures designed to assure proper protocol and consent document preparation, protocol submission, review and approval by the IRB, and timely monitoring of protocol implementation. One example is the use of approval date stamps on consent documents and protocols to ensure that the Federal requirement of at least annual IRB review of each protocol is met. A second example is the use of standardized language endorsed by the institution, which meets the regulatory requirements and which is customized and elaborated upon by the investigator in creating an appropriate informed consent document.

Specification of quality standards in the conduct of research is an important function of the institutional leadership. Insistence upon well-conceived and well-conducted research should be evident both in written policies and in actions of institutional officials. Research that is conducted so poorly as to be invalid exposes subjects and the institution to unnecessary risk.

SECTION 3.2 CHARGE TO THE INSTITUTIONAL REVIEW BOARD

The University of North Texas Health Science Center (UNTHSC) has established a standing committee, Institutional Review Board (IRB), of members with the experience and expertise charged with the review of research involving the participation of human subjects and the protection of their rights and welfare. The IRB is charged with the responsibility to review and approve, disapprove or require modifications in all research involving the participation of human subjects that is:

SECTION 3.3 FACULTY BYLAWS

The IRB is a standing committee established under the Faculty Bylaws of UNTHSC. Therefore, the bylaws as a whole provide the basis and framework under which the UNTHSC bylaws operate. The IRB is addressed in Article XVI, Section H – Institutional Review Board:

1. Composition: The board shall consist of a minimum of nine members of the faculty appointed by the President of UNTHSC to serve for three years. The Chair will be elected from among the members of the Board, subject to approval of the President. The Chair may request additional faculty members to be appointed by the President as needed by increased workload. The President will appoint certain community members as mandated by federal regulations in addition to the above cited faculty members. The Associate Vice President for Research will be an ex-officio member.

2. Responsibilities: The IRB is responsible for review and approval of all research involving human subjects. Research involving human subjects cannot be conducted without the approval of the IRB. Federal guidelines for the conduct of research involving human subjects are provided by the United States Department of Health and Human Services.

3. Minutes: Copies of the minutes of the IRB are available to all faculty members.

SECTION 3.4 COMPOSITION OF THE INSTITUTIONAL REVIEW BOARD

The President of UNTHSC will solicit names for appointments from a variety of sources, e.g., past and present IRB members, and UNTHSC staff. The names of persons in ethics and healthcare, 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. As IRB members rotate off and new members are appointed, selections will be made to assure continuing compliance with the requirements of 45 CFR 46.107 regarding gender and diversity.

The committee must be sufficiently qualified through the maturity, experience, and expertise of their members and diversity of membership to insure respect for their advice and counsel specific to safeguarding the rights and welfare of human subjects. In addition to possessing the professional competence necessary to review specific activities, the committee must be able to ascertain the acceptability of proposals in terms of organizational commitments, regulations, applicable law, standards of professional conduct and practice, and community attitudes.

In addition to faculty members representing different disciplines, the IRB currently has three non-affiliated members who are deemed to represent non-scientific areas. 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.

Member files are kept in the IRB Services Office. They include 1) a letter of appointment, 2) a current curriculum vitae (as appropriate), and 3) documentation of a certificate that shows the member has completed the UNTHSC tutorial for IRB members and investigators.

Educational materials are generally distributed and discussed at each IRB meeting.

SECTION 3.5 CHAIRPERSON

It is the responsibility of the President to confirm the Chairperson. This appointment is made for a three-year period. In the absence of the Chair, the Vice Chair (an IRB member) has signatory authority.

SECTION 3.6 MEETINGS

The IRB shall hold one regularly scheduled meeting per month, at a time and place to be pre-determined (See Section 6 and 7 for specific details).

SECTION 3.7 CONFIDENTIALITY OF THE REVIEW PROCESS

During the process of initial or continuing review of an activity, material provided to the Institutional Review Board shall be considered privileged information and the Board shall assure the confidentiality of the data contained therein. All members of the IRB sign a Confidentiality Agreement.

SECTION 4: EDUCATION

SECTION 4.1 MEMBER EDUCATION

On appointment to the IRB, each member is given his or her own copy of the UNTHSC IRB Reference Manual. This manual contains the following material:

UNTHSC Multiple Project Assurance/Federal Wide Assurance
UNTHSC IRB Membership Roster
UNTHSC IRB Written Procedures
The Belmont Report
Nuremberg Code
Declaration of Helsinki
DHHS Regulations (45 CFR 46) and Miscellaneous OHRP Guidance
FDA Regulations (21CFR 50 & 56) and Select Information Sheet
UNTHSC Investigator’s Reference Manual Including Sample Documents & Key Policies
Research Ethics and Regulations, Education Resources

At most meetings pertinent articles regarding the participation of human subjects in research is distributed and discussed.

SECTION 4.2 REQUIRED EDUCATIONAL TRAINING

In accordance with federal regulations, it is necessary for all individuals identified as “key personnel” to complete required educational training on the protection of human research subjects. Key personnel include all individuals responsible for the design and conduct of the study.

When submitting a protocol for IRB review (both new and continuing review), the Principal Investigator must include written verification that each of the key personnel has successfully completed the online educational tutorial located on the UNTHSC web site (http://research.hsc.unt.edu/dhhs/irb.html). No protocols will be reviewed for new or continuing review that are not in compliance with this requirement.

All IRB members have completed the required training.

SECTION 4.3 CHAIR AND STAFF EDUCATION

The Chair and staff members attend at least one national meeting each year that focuses on participation of human subjects in research. PRIM&R, ARENA, ACRP and specific workshops sponsored by OHRP are some of the resources of which they avail themselves.

SECTION 4.4 CONTINUING EDUCATION

In-services are given by the staff of the IRB Services Office as requested by Departments or Schools. The Office has scheduled three educational sessions for 2004 for general education for investigators and coordinators:

            February 10 - Informed Consent
            April 13 - HIPAA regulations
            June 8 - Continuing Review of Research

SECTION 5: GENERAL IRB POLICIES

SECTION 5.1 APPLICABILITY

The procedures set forth in this document are applicable to all faculty, staff, employees, and students at the University of North Texas Health Science Center who propose to use humans as subjects in research, development, and related activities.

SECTION 5.2 FUNCTIONS AND RESPONSIBILITIES

A. Safeguarding the rights and welfare of subjects at risk in any research activity, whether financially supported or not, and irrespective of the source of any supporting funds, is primarily the responsibility of the institution. In order to provide for the adequate discharge of the institutional responsibility, no research activity involving human subjects may be undertaken by any faculty, staff, employee or student at the University of North Texas Health Science Center unless our IRB has reviewed and approved the research prior to commencing the research activity.

B. The review will determine whether the subjects will be placed at risk and, if risk is involved, that:

1. Risks to subjects are minimized (This is an essential condition for approval);

2. The risks to the subject are so outweighed by the sum of the benefits to the subject and the importance of the knowledge to be gained as to warrant a decision to allow the subject to accept these risks;

3. The rights and welfare of any such subjects will be adequately protected;

4. Legally effective informed consent/authorization will be obtained by adequate and appropriate methods in accordance with the provisions of Section 4 of this manual; and

5. The conduct of the activity will be reviewed at intervals determined by the IRB, but not less than annually.

C. The determination of when an individual is at risk is a matter of the application of common sense and sound professional judgment as it relates to the circumstances of the research activity in question.

1. The IRB will carefully weigh the relative risks and benefits of the research procedures to be applied to the subject.

2. Research activities designed to yield fruitful results for the benefit of individual subjects or society in general may incur risks to the subjects provided such risks are outweighed by the benefit to be derived from activities.

3. The degree of risk involved in any activity should never exceed the humanitarian importance of the problems to be solved by that activity. Likewise, compensation to volunteers should never be such as to constitute an undue inducement to the subject.

4. There is a wide range of medical, social and behavioral research projects and activities in which no immediate physical risk to the subject is involved; e.g., those utilizing personality inventories, interviews, questionnaires, or the use of observation, photographs, taped records, or stored data. However, some of these procedures may involve varying degrees of discomfort, harassment, or invasion of privacy.

5. There may also be projects that involve tissues, body fluids, and other materials obtained from human subjects. The use of these materials obviously involves no element of physical risk to the subject. However, their use for research, training, and service purposes may present psychological, sociological, or legal risks to the subjects. In these instances, application of the policy requires IRB review to determine that the circumstances under which the materials are to be procured are appropriate and, if the subject is deemed to be at risk, that adequate and appropriate consent will or can be obtained for the use of these materials for research purposes.

6. Similarly, some studies depend upon stored data or information that was often obtained for quite different purposes. Here, the IRB will determine whether the use of these materials is within the scope of the original consent/authorization, or whether consent/authorization should be obtained or waived.

D. If the proposed activity involves an investigational drug, biological material, or device, it is the policy of the University of North Texas Health Science Center IRB that before these test articles may be tested on humans at this institution, or before an FDA-approved drug can be used for unapproved indications, the sponsor must obtain a Food and Drug Administration exemption [Investigational new Drug (IND) or Investigational Device Exemption (IDE)] before the activity will be approved by the IRB.

E. The Institutional Review Board shall not approve any activity involving human subjects unless the principal investigator is a faculty member, staff or student of The University of North Texas Health Science Center or unless a faculty member at the above institution agrees in writing to assume responsibility for the subjects involved.

F. Any activity involving the use of radioactive materials must have approval by the Radiation Safety Committee before it can receive final approval by the IRB.

G. Compliance with this policy or the procedures set forth herein will in no way render inapplicable pertinent laws of the State of Texas, any local law which may bear upon the proposed activity or the Rules and Regulations of the Board of Regents of the University of North Texas Health Science Center.

SECTION 5.3 TYPES OF PROTOCOL REVIEW

Three types of review may be conducted by the Institutional Review Board to ensure that all research involving human subjects conforms to Federal Regulations: (1) Ascertain that research meets the criteria for exemption from full board review; (2) Ascertain that research meets the criteria for expedited review; and (3) full Board review of research at a convened meeting.

SECTION 5.4 PROCEDURE TO BE FOLLOWED BY THE IRB FOR DETERMINING WHICH PROJECTS NEED VERIFICATION FROM SOURCES OTHER THAN THE INVESTIGATORS

A. To determine that no material changes have occurred in a project since previous IRB review, the IRB will utilize some or all of the following criteria;

1. Review of randomly selected projects;

2. Review of complex projects involving unusual levels or types of risk to subjects;

3. Review of projects conducted by investigators who previously have failed to comply with the requirements of the HHS regulations or the requirements or determinations of the IRB;

4. Review of projects where concerns about possible material changes occurring without IRB approval have been raised based upon information provided in continuing review reports or from other sources.

B. If it is determined that material changes have occurred in a project without IRB notification, review or approval, the IRB will meet and take appropriate action depending on the seriousness of the noncompliance.

C. Any action taken by the IRB shall be reported to the Executive Vice President of Academic Affairs and Research or designee, the Department Chair, the appropriate Dean, and if indicated, the President of UNTHSC. All material noncompliance will be reported to the cognizant federal agency.

Section 6: Initial IRB Review of Activities Proposing to Use Human Subjects in Research

SECTION 6.1 GOVERNING PRINCIPLES

The governing regulations for UNTHSC's IRB are 45 CFR Part 46 and 21 CFR Parts 50, 56, 312, and 812, and by HIPAA. The UNTHSC’s Federal Wide Assurance with OHRP specifies that the institution will follow 45 CFR 46 for all funded and non-funded research.

SECTION 6.2 REQUIREMENTS FOR INITIAL IRB REVIEW

Any faculty member, staff or student from UNTHSC who proposes to engage in any research activity involving the use of human subjects must submit the following to the IRB Office:

1. a completed original IRB Application Form with Principal Investigator and Departmental Chair's signature;

2. a protocol describing the rationale for the study, research questions to be answered, methods, procedures, data analysis plan, and other pertinent information.

3. four complete copies of the DHHS grant application, if applicable, and

4. an informed consent form in UNTHSC’s IRB approved format or justification for Waiver of Informed Consent or Waiver of Documentation of Consent;

5. if the study involves the use of questionnaires, surveys or similar instruments, copies of same must be submitted; and

6. In accordance with federal regulations, it is necessary for all individuals identified as “key personnel” to complete required educational training on the protection of human research subjects. Key personnel include all individuals responsible for the design and conduct of the study.

* A "human subject" is defined as a living individual about whom an investigator conducting research obtains (1) data through intervention or interaction with the individual, or (2) identifiable private information (45 CFR 46.102(f)).

SECTION 6.3 SUBMISSION SCHEDULE REQUIREMENTS

Presently, there is one IRB meeting per month. Meetings are held on the first Tuesday of each month. The meeting/submission schedule is distributed to every department and all investigators who conduct research before the beginning of the new fiscal year (September 1^st). Protocols must be submitted to the IRB office by 5 p.m. of the deadline date listed. The submission packets must have all individual forms stapled and collated. The deadline for submission packets is approximately two (2) weeks prior to the meeting date. An attempt is made to send the packets to the IRB members at least two weeks prior to the meeting date.

If the study is eligible for an "Expedited or Exempt Review" process, two copies of the list of materials described above should be submitted. Such protocols may be submitted at any time and will receive appropriate review and approval (See "IRB Review Process - Minimal Risk Protocols" below and for examples of research qualifying for "Expedited Review").

SECTION 6.4 REVIEW FOR EXEMPT STATUS

If requested by the Principal Investigator, the Chair of the IRB will determine whether a research proposal is exempt from review by the full Board. If a researcher believes their research meets the exempt criteria, they should submit two copies of the Statement by Principal Investigator (IRB Form 1) with a cover memo detailing the reason for the exemption (citing exemption number). Only the involvement of human subjects in one or more of the cited categories warrants an exemption.

SECTION 6.4.1 EXEMPT STATUS CRITERIA (as cited in 45 CFR 46.101 )

The following are the categories that qualify for exempt status:

#1. Research conducted in established or commonly accepted educational settings, involving normal educational practices, such as (i) research on regular and special education instructional strategies, or (ii) research on the effectiveness of or the comparison among instructional techniques, curricula, or classroom management methods.

#2. Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures or observation of public behavior, unless:

(i) information obtained is recorded in such a manner that human subjects can be identified, directly or through identifiers linked to the subjects; and

(ii) any disclosure of the human subjects’ responses outside the research could reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects’ financial standing, employability, or reputation.

#3. Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior that is not exempt under criteria #2 of this section, if:

(i) the human subjects are elected or appointed public officials or candidates for public office; or

(ii) Federal statute(s) require(s) without exception that the confidentiality of the personally identifiable information will be maintained throughout the research and thereafter.

#4. Research involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens, if these sources are publicly available or if the information is recorded by the investigator in such a manner that subjects cannot be identified, directly or through identifiers linked to the subjects.

The Principal Investigator will normally be notified within one week if the project meets the criteria for exempt status. It should be noted that the IRB has the authority to decline a request for exempt status based upon factors such as age of subjects (children), health of subjects, etc.

SECTION 6.5 EXPEDITED REVIEW

A research investigator may request that their proposal receive an expedited review by the board. An expedited review will consist of review by the Chair or by one or more members of the IRB designated by the Chair. If an expedited review is requested, two copies of the Statement by Principal Investigator (IRB Form 1), along with a cover memo detailing the justification for the expedited review (please cite the expedited review research category number), should be submitted. Investigators should allow two weeks for notification of expedited review results. It should be noted that the IRB has the authority to decline a request for expedited review, and require a full board review, based upon factors such as age of subjects (children), health of subjects, etc.

SECTION 6.5.1 APPLICABILITY:

A. Research activities that (1) present no more than minimal risk to human subjects, and (2) involve only procedures listed in one or more of the applicable research categories, may be reviewed by the IRB through the expedited review procedure. The activities listed should not be deemed to be of minimal risk simply because they are included on this list. Inclusion on this list merely means that the activity is eligible for review through the expedited review procedure when the specific circumstances of the proposed research involve no more than minimal risk to human subjects.

B. The categories in this list apply regardless of the age of subjects, except as noted.

C. The expedited review procedure may not be used where identification of the subjects and/or their responses would reasonably place them at risk of criminal or civil liability or be damaging to the subject’s financial standing, employability, insurability, reputation, or be stigmatizing, unless reasonable and appropriate protections will be implemented so that risks related to invasion of privacy and breach of confidentiality are no greater than minimal.

D. The expedited review procedure may not be used for classified research involving human subjects.

Research Categories:

#1. Clinical studies of drugs and medical devices only when condition (a) or (b) is met:

a. Research on drugs for which an investigational new drug application (21 CFR Part 312) is not required. NOTE: Research on marketed drugs that significantly increases the risks or decreases the acceptability of the risks associated with the use of the product is not eligible for expedited review.

b. Research on medical devices for which (i) an investigational device exemption application (21 CFR Part 812) is not required; or (ii) the medical device is cleared/approved for marketing and the medical device is being used in accordance with its cleared/approved labeling.

#2. Collection of blood samples by finger stick, heel stick, ear stick, or venipuncture as follows:

a. From healthy, nonpregnant adults who weigh at least 110 pounds. For these subjects, the amounts drawn may not exceed 550 ml in an 8 week period and collection may not occur more frequently than 2 times per week; or

b. From other adults and children, considering the age, weight, and health of the subjects, the collection procedure, the amount of blood to be collected, and the frequency with which it will be collected. For these subjects, the amount drawn may not exceed the lesser of 50 ml or 3 ml per kg in an 8 week period and collection may not occur more frequently than 2 times per week.

#3. Prospective collection of biological specimens for research purposes by noninvasive means. Examples:

a. Hair and nail clippings in a nondisfiguring manner;

b. Deciduous teeth at time of exfoliation or if routine patient care indicates a need for extraction;

c. Permanent teeth if routine patient care indicate a need for extraction;

d. Excreta and external secretions (including sweat);

e. Uncannulated saliva collected either in an unstimulated fashion or stimulated by chewing gumbase or wax or by applying a dilute citric solution to the tongue;

f. Placenta removed at delivery;

g. Amniotic fluid obtained at the time of rupture of the membrane prior to or during labor;

h. Supra- and subgingival dental plaque and calculus, provided the collection procedure is not more invasive than routine prophylactic scaling of the teeth and the process is accomplished in accordance with accepted prophylactic techniques;

i. Mucosal and skin cells collected by buccal scraping or swab, skin swab, or mouth washings;

j. sputum collected after saline mist nebulization.

#4. Collection of data through noninvasive procedures (not involving general anesthesia or sedation) routinely employed in clinical practice, excluding procedures involving x-rays or microwaves. Where medical devices are employed, they must be cleared/approved for marketing (studies intended to evaluate the safety and effectiveness of the medical device are not generally eligible for expedited review, including studies of cleared medical devices for new indications). Examples of permissible procedures include:

a. Physical sensors that are applied either to the surface of the body or at a distance and do not involve input of significant amounts of energy into the subject or an invasion of the subject’s privacy;

b. Weighing or testing sensory acuity;

c. Magnetic resonance imaging;

d. Electrocardiography, electroencephalography, thermography, detection of naturally occurring radioactivity, electroretinography, ultrasound, diagnostic infrared imaging, Doppler blood flow, and echocardiography;

e. Moderate exercise, muscular strength testing, body composition assessment, and flexibility testing where appropriate, given the age, weight and height of the individual.

#5. Research involving materials (data, documents, records, or specimens) that have been collected, or will be collected solely for non-research purposes (such as medical treatment or diagnosis). NOTE: Some research in this category may be exempt from the HHS regulations for the protection of human subjects. This listing refers only to research that is not exempt.

#6. Collection of data from voice, video, digital, or image recordings made for research purposes.

#7. Research on individual or group characteristics or behavior (including, but not limited to, research on perception, cognition, motivation, identity, language, communication, cultural beliefs or practices, and social behavior) or research employing survey, interview, oral history, focus group, program evaluation, human factors evaluation, or quality assurance methodologies. NOTE: Some research in this category may be exempt from the HHS regulations for the protection of human subjects. This listing refers only to research that is not exempt.

SECTION 6.6 FULL BOARD REVIEW

SECTION 6.6.1 INTRODUCTION

The Institutional Review Board (IRB) is responsible for protecting the welfare and rights of individuals who are subjects of any research, whether funded or unfunded, whether on or off campus, which is conducted by faculty, staff or students. If the proposed research does not satisfy the guidelines for exempt or expedited review, the IRB as a full committee will consider the proposal.

SECTION 6.6.2 PROCEDURES

By 5:00 p.m. on the 3^rd Monday of the month, the Principal Investigator will submit the original and 16 copies of IRB Form 1 to the IRB Office. If the project is a clinical trial, two complete copies of the pharmaceutical company protocol and the Investigator’s Brochure must be submitted for review. All other projects must be accompanied by two complete copies of the grant application (the title of the IRB submission must match the title of the grant application).

The administrative staff will collate the following information on each new full board review project for inclusion in the packets to be distributed to each IRB member approximately two weeks prior to the next convened meeting:

IRB Form 1 (Use of Human Subjects Statement by Principal Investigator)

NOTE: IRB Form 1 includes all elements of the protocol description, informed consent and any advertisements

The IRB Chair and Vice Chair, in addition to receiving each of the items listed above, will also receive:

Copy of the drug company protocol or grant application

Copy of the Investigator’s Brochure

NOTE: Upon receipt of their packets, members of the IRB are encouraged to contact the administrative staff for copies of any additional materials they will require to conduct their review.

When it is determined that consultants or experts will be required to advise the IRB in its review of a protocol, the research protocol will be distributed to the consultants or experts approximately two weeks prior to the next scheduled meeting.

SECTION 6.6.3 REVIEW

IRB review of research must be substantive and meaningful. Each project will be presented and discussed individually. Each project will be voted upon individually.

A majority of the membership of the IRB constitutes a quorum and is required in order to convene a meeting for the review of protocols. An IRB member whose concerns are primarily in non-scientific areas must be present at the convened meeting before the IRB can conduct its review. An IRB member who is not affiliated with UNTHSC must be present at the convened meeting before the IRB can conduct its review.

For a research protocol to be approved, it must receive the approval of a majority of those members present at the convened meeting. No IRB member may participate in the review of any project in which they have a conflicting interest, except to provide information requested by the IRB. That IRB member must leave the room during discussion and when the vote is taken.

The IRB will consider the following during their discussion of each new project:

Scientific Design in Relation to Subject Safety
Risks/Benefits
Subject Selection (populations to be studied and recruitment plan)
Additional Safeguards for Vulnerable Subjects
Minimization of Risks to Subjects
Privacy and Confidentiality
Informed Consent (assuring that all required elements are present)
Additional Considerations (e.g. collaborative research, international research, device study)

It is the responsibility of the IRB to determine whether or not vulnerable populations (e.g. children, pregnant women) may participate in the research.

The board must assign a level of risk. There are times when the risks associated with a particular project are such that continuing review should take place more frequently than annually. In these cases, the IRB will specify that the Principal Investigator reports to the IRB at a more frequent interval (e.g. 6 months).

The board will make one of the following recommendations regarding the disposition of the new project:

Protocol is approved as submitted

Protocol is approved contingent upon specific conditions (stipulations and/or recommendations)

Protocol is tabled pending substantial changes and resubmission

Protocol is disapproved

If the protocol is approved contingent upon specific conditions (stipulations and/or recommendations), the board must designate whether those stipulations and/or recommendations are to be reviewed by the IRB Chair, by a subcommittee of the IRB, or by the full IRB.

SECTION 6.6.4 PRINCIPAL INVESTIGATOR NOTIFICATION

After the convened IRB meeting, the disposition of the project is relayed to the Principal Investigator by IRB Form 2 (Board Action Form), normally within 3 working days. Any stipulations and/or recommendations will also be relayed.

Approval is granted for a period of not more than one year. Depending upon the degree of risk to subjects, approval may be given for less than one year. In addition, as a condition of approval, the IRB provides for the continuing review of all projects at least annually.

SECTION 6.7 MODIFICATION OF DECISIONS MADE BY THE INSTITUTIONAL REVIEW BOARD

Approvals, favorable actions, and recommendations made by the IRB are subject to review and further restriction by the institutional administration (HSC Deans, Executive Vice President of Academic Affairs and Research, President). For example, protocols could be approved by the IRB on a scientific and ethical basis, but be restricted or disapproved by institutional administration due to the potential for adverse public/community reaction. Protocol disapproval, restrictions or conditions imposed by the IRB upon any activity involving human subjects cannot be rescinded or removed except by subsequent action of the IRB.

SECTION 6.8 NON-ADHERENCE TO INSTITUTIONAL REVIEW BOARD DECISIONS

Any reported significant deviation in activities previously approved by the IRB would be the subject of further inquiry by the IRB. In the event that the IRB finds reasonable evidence that restrictions, stipulations or decisions of the IRB have not been adhered to, the Chairperson shall brief the IRB, at the next scheduled convened meeting or at a specially convened meeting, on the details of non-compliance. The IRB will then determine what restrictions, conditions, or other actions are necessary to resolve the non-compliance and what procedures will be required to prevent future occurrences. The PI will then be notified in writing of the requirements necessary to assure compliance with the restrictions and decisions of the IRB. All instances of non-compliance will be reported to the Executive Vice President of Academic Affairs and Research or designee. If serious or ongoing, instances of noncompliance must be reported to the regulating agency (OHRP, FDA, or both).

The Executive Vice President of Academic Affairs and Research or designee will apprise appropriate members of the Administration, on a need to know basis. The Confidentiality of both research subjects and investigator will be protected as far as possible under current local, state and federal law.

If further action is necessary, the institutional policies and procedures relating to Misconduct in Science will be implemented.

SECTION 6.9 IRB MINUTES

The minutes of the prior meeting are approved at the subsequent IRB meeting. Minutes include a list of all studies that were voted on at the subsequent meeting, as well as a list of all actions that were taken administratively during the previous month. Minutes include separate deliberations, actions, and votes for each protocol undergoing initial or continuing review by the convened IRB. The vote on all IRB actions include the number of persons voting for, against, and abstaining, in order to document the continued existence of a quorum. The minutes include the documentation of risk, as well as any potential conflict of interest that an IRB member may have with a particular protocol.

SECTION 7: MEDICAL DEVICE STUDIES

The Investigational Device Exemption (IDE) regulations (21 CFR part 812) describe two types of device studies, “significant risk” (SR) and “nonsignificant risk” (NSR).

SECTION 7.1 SIGNIFICANT RISK DEVICE

A SR device study is defined (21 CFR 812.3(m)) as a study of a device that presents a potential for serious risk to the health, safety, or welfare of a subject and (1) is an implant; or (2) is used in supporting or sustaining human life; or (3) is of substantial importance in diagnosing, curing, mitigating or treating disease, or otherwise prevents impairment of human health; or (4) otherwise presents a potential for serious risk to the health, safety, or welfare of a subject.

SECTION 7.2 NON-SIGNIFICANT RISK DEVICE

A NSR device investigation is one that does not meet the definition for a significant risk study. NSR device studies, however, should not be confused with the concept of “minimal risk,” to identify a study that may be reviewed through the expedited review procedure.

SECTION 7.3 DETERMINATION AS TO CATEGORY OF RISK

The IRB, regardless of the classification (SR or NSR) of the device assessed by the sponsor, must make its own assessment of the classification based on the proposed use of the device in a study, and not on the device alone. This must be accomplished prior to submission for full board review. An investigator considering participation in a device study must provide the Chair of the IRB with the following information:

1. Reports of prior investigations conducted with the device.

2. The proposed investigational plan.

3. A description of subject selection criteria.

4. Monitoring procedures.
Information from the sponsor regarding risk assessment and the rationale used in making its risk determination.

5. If the device is already FDA approved, information on whether or not this is an “off-label” use of the device.

The IRB Chair may agree or disagree with the sponsor’s initial assessment. If the Chair agrees with the sponsor’s initial NSR assessment, the investigator will be notified in writing that the study may then be submitted for full board review (for confirmation of NSR classification and review of the study). If the Chair assesses the device as SR, the investigator and the sponsor will be notified in writing of the SR decision. The sponsor must notify the FDA that a SR determination has been made. The study can be submitted for full board review only after the sponsor has received FDA approval of an IDE application. If this is an investigational or “off-label” use of the device, the investigator must also comply with federal requirements for submission of an IDE, unless all of the conditions in 21 CFR 312.2(b)(1) are met.

SECTION 8: USE OF DRUGS IN INVESTIGATIONAL ACTIVTIES

SECTION 8.1 APPLICABILITY

This policy applies to ALL use of a drug in an investigational setting, whether FDA-approved or not, and whether used for clinical or research purposes.

The FDA (21 CFR 312.3) defines a clinical investigation as “any experiment in which a drug is administered to, or used involving, one or more human subjects.” Based on this definition, there are no exceptions to the requirement that any drug used in research with humans must be reviewed by the IRB and, in addition, is subject to FDA regulation.

This includes both Drugs and Biologic products.

SECTION 8.2 IND (INVESTIGATING NEW DRUG) APPLICATION

All drug use in research must include submission of an IND. The ONLY exception is if the marketed drug or biologic product meets ALL six of the following conditions:

It is not intended to be reported to the FDA in support of a new indication for use or to support any other significant change in the labeling for the drug;
It is not intended to support a significant change in the advertising for the product;
It does not involve a route of administration or dosage level, use in a subject population, or other factor that significantly increases the risks (or decreases the acceptability of the risks) associated with the use of the drug product;
It is conducted in compliance with the requirements for IRB review and informed consent (21 CFR parts 56 and 50, respectively);
It is conducted in compliance with the requirements concerning the promotion and sale of drugs (21 CFR 312.7); and
It does not intend to invoke 21 CFR 50.24 (this has to do with waiver of informed consent in an emergency room setting).

If your study does not meet ALL six of these conditions, or is an unapproved drug or unapproved use of a new drug, you must submit and IND, or provide written evidence from the FDA that an IND is not required. Because of the potential risk involved, the IRB will require an IND submission if there is any doubt that your study meets these six criteria.

Refer to the FDA website for instructions.

Currently, we have two contact numbers available.

A             Food and Drug Administration
                Division of Drug Information, HFD-240
                5600 Fishers Lane, Rockville, MD 20857
                Fax number: 301-827-4577
                Email: druginfor@cder.fda.gov
                Contact at the FDA: Barry Poole at 301-827-4570

Send:

Your name, address, phone number, fax number, Email address, and affiliation.
The name and a brief description of the substance to be administered, the source ( e.g., animal, synthetic, etc.), dosage form, sterility (if applicable) and supplier
A brief summary of the study including the purpose, hypothesis, number of subjects, patient population, condition or disease (if applicable), dose, route, and duration of substance administration.
A brief explanation of why you consider the substance safe for administration to human subjects under the conditions of the study (append references, if necessary).

B. The FDA has also established a Pre-IND consultation Program that you may contact for guidance and instructions:

                U.S. Food and Drug Administration

                Office of Drug Evaluation IV (HFD-104)

                Pare-IND Consultation Program

                ATN: Sylvia D. Lynche, PharmD

                9201 Corporate Blvd, 4^th Floor

                Rockville, MD 20850

                Phone: 301-827-2335

SECTION 8.3 RESEARCH INVOLVING AN FDA-APPROVED USE

If the proposed use of a drug in a study is fully within the guidelines for use approved by the FDA, and meets the six criteria listed in Section 8.2, then an IND is not required.

However, the protocol submission should contain a summary of known risks and precautions associated with the drug, including any new data that has emerged the drug or biologic received FDA approval.

SECTION 8.4 RESEARCH INVOLVING AN OFF-LABEL USE OF AN APPROVED DRUG.

An off-label use of a drug in experimental setting will generally require submission of an IND. Again, refer to section 8.2. THIS IS TRUE EVEN IF THE DRUG IS COMMONLY USED IN A CLINICAL SETTING FOR THE “OFF LABEL” CONDITION OR DOSAGE.

Purely clinical, non-research use of a drug in an off-label manner is outside the jurisdiction of the IRB and is covered by other regulations of the UNTHSC and the physician's license.

SECTION 8.5 RESEARCH INVOLVING A NEW OR UNAPPROVED DRUG

Any investigation involving the use of a new drug, or any drug that does not have formal FDA approval, will require an IND. NO EXCEPTION will be made without written documentation from the FDA.

SECTION 8.6 SUBMISSION AND REVIEW PROCEDURES

IN ADDITION to the requirements of the IRB contained in other policies and procedures, the following procedures apply.

A. For ON-LABEL, approved use:

Submit the study protocol as usual, but include:

Information supporting your use as an approved use
Updated safety and efficacy information. You are responsible for conducting a current literature review as outlined in section 8.6.

B. For ALL other uses, the submission should include:

The IND number and name of the sponsor (if different than the investigator)
The generic, chemical, and trade name of the drug and its structural formula.
An abstract of the available information concerning the animal pharmacology and toxicology.
A summary of previous clinical studies. This should include any adverse effects or toxicity. Pertinent references should be included. See Section 8.6 for guidelines.
A specific indication of the Phase (i.e., I, II, III, or post-marketing surveillance) should be included.

C. The UNTHSC-IRB will review the project in two parts.

1. Upon submission for full-board review, the chair will assign the protocol to a member of the board who has specific training in pharmacology; of an appropriate member is not available, it will be assigned to an outside consultant.

2. The reviewer will conduct a Pharmacy and Therapeutics (P&T) review to evaluate the protocol and drug for safety for the proposed use, and make one of three recommendations: approval, modification, or disapproval. If the reviewer recommends modifications or disapproval, the investigator must satisfy the recommendations of the reviewer. NO STUDY will be approved until cleared for approval by the pharmacy and therapeutics reviewer.

3. The IRB will then conduct a full board review.

D. Since the UNTHSC does not have a separate pharmacy and therapeutics committee, there is no time estimate for this review process. Since the study cannot go forward until cleared, the investigator is strongly advised to submit the study as early as possible.

SECTION 8.7 DOCUMENTATION GUIDELINES

The following guidelines are adapted from those in place at Johns Hopkins University.

When a study involving a drug or biologic is submitted for review, the IRB must have access to sufficient information to determine if the drug is sufficiently safe to use in the subjects of the study. The standard the investigator must reach has been raised in recent years due to situations where negligent documentation by investigators and negligent review by IRBs have resulted in the death of otherwise healthy research subjects. The investigator should strive to provide more than the minimum data and be prepared for careful scrutiny of any use of drugs or biologics with humans.

This means the investigator must conduct and provide evidence of a thorough review of the literature for safety of the proposed agent. What this means in practice will vary widely. For example, sponsored drug trials are usually presented to the local investigator with extensive, current documentation, so that the local investigator's obligation will be to be familiar with the data, be prepared to report to the IRB (and sponsor) any additional safety data, and transmit the materials to the IRB for review. This is normally also a requirement by the sponsor. A study involving an established, approved use of an approved drug will also require a simple updated literature review to supplement that available from the drug manufacturer. At the other extreme, an agent that has not been approved by the FDA for any use will require an extensive and comprehensive review of the literature. If the study is investigator-initiated, then the ENTIRE responsibility for that documentation falls to the investigator.

The standards given here apply to the latter case, that is, where the study is of an off-label or unapproved use or use of an unapproved drug. However, the IRB and the P&T reviewer have the responsibility of assessing whether the submitted documentation is adequate and have the obligation to request additional documentation if, in their judgment, the provided documentation is inadequate or incomplete. The IRB members and the P&T reviewer also have the option to conduct an independent literature review.

The investigator should conduct a thorough and complete review of the literature. It is NOT SUFFICIENT to simply order a computerized search. The search may include reviews, textbooks, abstracts, meeting notes, meeting synopses, and advertisements but are not sufficient. It should also include primary peer reviewed publications.

The investigator should also remember that a substantial amount of information may be unpublished, and other information may predate the years covered by an automated search. The investigator is responsible for showing that an active effort was made to search out those sources. For example, a published paper may not contain all the data from a study, and direct contact with the study authors might reveal information affecting subject safety. Investigators have been cited when auditors believed that the investigator knew or should have known about such unpublished data.

The investigator should provide three sets of information:

A. A summary of the literature review, detailing the findings regarding the safety and toxicity of the agent, including data from both human and animal studies.

B. A Literature Search Log showing the information sources used as well as the search paths that have led to that information. The search log should include information showing:

Date search conducted
Name of database
Host
Latest update available
Years searched
Print-out of your search strategy (not a retyped form, but rather the original strategy)

C. Bibliography

Johns Hopkins recommends the following search strategy be used as a general guideline:

Identify the drug
Check for alternate names of the drug
Define the research setting in which the drug will be used
Consult reference or tertiary sources as a starting point
Consult secondary sources (abstracting and indexing services) for comprehensiveness and quality assurance.
Choose the most appropriate sources of evidence of safety/adverse effects
Create a bibliography

Section 9: Informed Consent

SECTION 9.1 GENERAL REQUIREMENTS

Principal investigators are responsible for obtaining written informed consent in accordance with federal regulations and for ensuring human subjects will not be involved in research prior to obtaining consent. Each of the following points MUST be included in the consent document, except where the point is irrelevant to the research.

SECTION 9.2 ELEMENTS OF INFORMED CONSENT/ASSENT FORMS

1. A statement that the study involves research, an explanation of the purpose of the research and why the subject is asked to participate.

2. A description of the procedures and identification of any procedures which are experimental. For example, the description of procedures should include the length and frequency of hospitalizations; number, length and frequency of clinic visits; total amount of time a subject should expect to devote to the study; names and types of medication; types and number of tests; amount of blood to be drawn noted in tablespoons or teaspoons; use of questionnaires; special diets; withholding of standard treatment; follow-up studies; and randomization, use of placebo, double-blind, or cross-over methods. In the case of patient subjects, state clearly which procedures are experimental and which procedures would be performed for medical reasons if the patient were not a research subject.

3. A description of any reasonable risks or discomforts to the subject. These may include drug side effects, hazards of procedures, or withholding therapy of proven value. Describe what will be done to minimize the risks, counteract side effects, and which side effects might be irreversible.

4. A description of any benefits to the subject or to others which may reasonably be expected from the research.

5. A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject. It is not necessary to provide a full account of the risks and benefits of standard alternative treatments in the consent form.

6. A statement describing the extent to which confidentiality of records identifying the subject will be maintained. FDA and sponsor inspection of records in