The University of North Texas Health Science Center
at Fort
Worth
Institutional
Review Board
Policies and
Procedures Document
-Revised December
2007
Portions adapted with
permission from the University of Texas at Austin
PDF of Complete Policy (720
kbytes)
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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.
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.
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.
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.
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
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All new or revised
materials will be placed on the IRB web page by the Office of Research.
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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.
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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.
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:
Sponsored
by the UNTHSC;
Conducted
by or under the direction of any employee or agent of UNTHSC in connection with
his/her institutional responsibilities;
Conducted
by or under the direction of any employees or agent of UNTHSC using
institutional property or assets; or
Facilitated
by the use of the institution’s non-public information to identify or contact
subjects or prospective subjects.
The IRB may also review other
human subject research pursuant to formal affiliation agreements between UNTHSC
and other organizations.
The IRB is an administrative
body established to protect the rights and welfare of human research subjects
recruited to participate in research activities conducted under the auspices of
this institution.
The ethical framework for
this charge consists of the ethical principles regarding all research involving
humans as subjects, as set forth in the Nuremberg Code, the Declaration of
Helsinki, and the report of the National Commission for the Protection of Human
Subjects of Biomedical and Behavioral Research (entitled: Ethical Principles
and Guidelines for the Protection of Human Subjects of Research [the "Belmont Report"],
regardless of whether the research is subject to Federal regulation or with whom
conducted or source of support (i.e.,
sponsorship).
The IRB operates under
assurance of the Office for Human Research Protection (OHRP) and in accord with
the regulations of the Food and Drug Administration (FDA) and in compliance
with other State and federal regulations as applicable.
Federal Wide Assurance
(FWA)
covers the following entities:
Texas College of Osteopathic Medicine
Graduate School of Biomedical Sciences
School of Public
Health
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.
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.
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.
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).
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.
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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:
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UNTHSC Multiple
Project Assurance/Federal Wide Assurance
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UNTHSC IRB
Membership Roster
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UNTHSC IRB
Written Procedures
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The Belmont Report
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Nuremberg Code
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Declaration of Helsinki
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DHHS Regulations
(45 CFR 46) and Miscellaneous OHRP Guidance
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FDA Regulations
(21CFR 50 & 56) and Select Information Sheet
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UNTHSC
Investigator’s Reference Manual Including Sample Documents & Key
Policies
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Research
Ethics and Regulations, Education Resources
At most meetings pertinent
articles regarding the participation of human subjects in research is
distributed and discussed.
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.
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.
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
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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.
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.
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.
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.
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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.
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.
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.
* 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)).
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 1st). 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").
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.
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.
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.
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.
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.
By 5:00 p.m. on the 3rd 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.
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.
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.
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.
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.
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.
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The Investigational Device
Exemption (IDE) regulations (21 CFR part 812) describe two types of device
studies, “significant risk” (SR) and “nonsignificant risk” (NSR).
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.
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.
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.
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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, 4th Floor
Rockville, MD 20850
Phone: 301-827-2335
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.
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.
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.
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.
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
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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.
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 studies
involving drugs and devices should be explained. The means of disclosure of
information obtained during the study should be described, e.g., publication, entry
in medical records, or transmission to another physician.
7. An explanation
that only emergency medical treatment is available if a research-related injury
occurs. If a company or agency sponsoring the research agrees to provide for
additional treatment and/or monetary compensation for injuries and that
agreement has been approved by the UNTHSC legal counsel, this should be
included in the consent form.
8. A statement of
additional costs to the subject for research procedures.
9. A statement of the
amount of compensation for time and travel expenses associated with a subject’s
participation in the study. The compensation must not be contingent upon
completion of the entire study. The amount of the compensation must not be
coercive. The informed consent must indicate that compensation for subjects who
withdraw early or are removed from the study by the investigator will be
pro-rated accordingly. The UNTHSC legal counsel recommends that the following
statement also be included: “As applicable, reimbursement to you may be
withheld and credited to any outstanding debts you may have with the University
of North Texas Health Science Center at Fort
Worth or the State of Texas.
10. Identification
(full name[s] and 24 hour phone numbers) of the investigator(s) the subject may
contact for answers to questions about the research and the research subject's
rights, and whom to contact in the event the subject believed that he or she
has sustained a research-related injury. This | 
