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IRB
Special Protection Issues
Special Considerations
Children:
The Federal regulations permit four categories of research involving
children. The categories are determined by the degree of risk and
prospect of benefit to the participating child-subject. For any
protocol involving children, the IRB, in consultation with the Principal
Investigator (PI), is responsible for determining in which of the
four categories of research the study belongs and for documenting
in the minutes the rationale for its choice. Therefore, it is desirable
for the PI to address these issues directly in the protocol in a
section entitled "The ethical and regulatory considerations
concerning the involvement of children" in which he/she identifies
which of the categories the study fits into and the rationale for
this categorization.
The four categories of research which may be approved by IRBs are:
Category 1: research that does not involve greater than
minimal risk to children.
Category 2: research involving greater than minimal risk but presenting
the prospect of direct benefit to the
Individual child- subject.
Category 3: research involving greater than minimal risk and no
prospect of benefit to the individual child-
subject. In order to approve research in this
category, an IRB must determine that the risk of
the research represents no more than a minor increase
over minimal risk; that the intervention or procedure
presents experiences to the child-subjects that are
reasonably commensurate with those inherent in their
actual, or expected medical, dental, psychological,
social, or educational situations; and the intervention
or procedure is likely to yield generalizable knowledge
about the subject's disorder or condition which is
of vital importance for understanding or amelioration
of the disorder or condition.
Category 4: research not otherwise approvable under one of the above
categories but the IRB determines that the study presents a reasonable
opportunity to further the understanding, prevention, or alleviation
of a serious problem affecting the health or welfare of children.
In these cases the IRB will forward the research for review by the
Deputy Director for Intramural Research (DDIR). If he/she agrees,
the study will be forwarded to the Secretary of HHS who may approve
the research after consultation with a panel of experts. The panel
must determine that the research presents a reasonable opportunity
to further the understanding, prevention, or alleviation of a serious
problem affecting the health or welfare of children, and that the
research will be conducted in accordance with sound ethical principles.
Federal regulation prohibits the use of children as subjects in
studies given exempt approval under the category 2 of exempt criteria.
In addition, research which would qualify for expedited review for
adult subjects may be judged to require full Board review when subjects
are less than 18 years old. The IRB Chair reserves the right to
require full Board review of any IRB application.
NIH Guidelines do now require that children be included in all research
studies unless there is scientific or ethical justification for
excluding them. Please refer to the "NIH Policy and Guidelines
on the Inclusion of Children as Participants in Research Involving
Research Subjects" for specific information regarding addressing
this issue in submissions.
Children who are wards of the state or any other agency, entity
or institution, can be included in approved research only if such
research is related to their status as wards or is conducted in
schools, camps, hospitals, institutions, or similar settings in
which the majority of children involved as subjects are not wards.
For each child who is a ward, an advocate must be appointed in addition
to any other individual acting on behalf of the child as guardian
or in loco parentis. One individual may serve as advocate for more
than one child. The advocate shall be an individual who has the
experience to act in, and agrees to act in, the best interest of
the child for the duration of the child's participation in the research
and who is not associated in any way (except in the role as advocate
or member of the IRB) with the research, the investigator(s), or
the guardian organization.
Consent Issues Regarding Children as Subjects
Unless one parent is deceased, unknown, incompetent, or not reasonably
available, or only one parent has legal responsibility for the care
and custody of the child, the consent of both parents is required
by regulation where the research involves greater than minimal risk
or will not directly benefit the individual child research subject.
Some studies include children as their only subjects. As such, the
consent forms should be addressed to the parent (e.g., Your child
will have. . . you have not waived any of your or your childs rights.
. . Emergency care for your child will be provided. . .). Other
studies could involve either children or consenting adults. In most
of these cases, two consent forms should be prepared, one for the
adult to sign and one for the adult to consent on behalf of the
child. The exception to this would be studies where there is very
little overlap between adult/child study populations (i.e. age range
1-19 or 17-99) in these cases, it is acceptable to do only one consent
form for either adult to sign on their behalf or on behalf of their
child. Please check with IRB office for specific instructions if
you feel that your study fits into this category.
When study participants are children who are old enough to understand
what the study involves, the child must be given the opportunity
to assent to the study. For those children who can read a simple
document (typically age 7-17), a very simple assent form (one page
or less) may be appropriate. In complicated studies, a statement
like the following, at the end of the consent form is more appropriate:
Assent Statement:
I have explained the study to the subject in language appropriate
for his/her age and level of understanding. The subject has been
given the opportunity to ask questions and to decide about his/her
participation. The signature of the parent(s) and myself certifies
that the subject is agreeing to be a subject in the study.
Regardless of whether or not a separate assent form is included,
the child subject age 7-17 must provide an assent signature either
on the adult consent form (as a separate signature line specified
as an assent signature) or on the separate assent document.
A special note for studies conducted at elementary and high schools:
In most cases, the IRB requires affirmative, written consent (active
consent) from a parent/guardian for school-related studies. Procedurally,
this means that a consent form must be sent home with the child,
signed by the parent/guardian and returned to the school prior to
the studentâs enrollment in a study. It is our experience
that school districts prefer sending a letter home and having the
parent return it only if permission is not granted (passive consent).
Essentially, passive consent is not recognized in the Federal Guidelines.
Passive consent would only be allowed in such cases where the study
would otherwise qualify for a waiver of the consent process. There
are specific criteria which must be met for this to be approved
and this must be voted on by the Full Board. Therefore, the decision
on whether or not to require active consent will be determined by
this IRB on a case by case basis.
Inclusion of Women and Minorities
The following is taken from the NIH guidelines regarding the inclusion
of women and minorities in research studies. While NIH guidelines
may not specifically apply to drug company sponsored clinical trials,
the US Food and Drug Administration does support the NIH guidelines
and also expects for clinical trials to include women of all ages
in such testing of investigational drugs and devices. The Federal
Regulations (as well as this IRB) do not allow for exclusion of
women of childbearing simply because of potential harm to a fetus.
We expect for women to be informed of the risks involved with becoming
pregnant while on study as well as given specific options for using
proper contraception during study participation.
It is the policy of the NIH that women and members of minority groups
and their subpopulations must be included in all NIH-supported biomedical
and behavioral research projects involving human subjects, unless
a clear and compelling rationale and justification establishes to
the satisfaction of the relevant Institute or Center Director that
inclusion is inappropriate with respect to the health of the subjects
or the purpose of the research. Cost is not an acceptable reason
for exclusion except when the study would duplicate data from other
sources. Women of childbearing potential should not be routinely
excluded from participation in clinical research. All NIH-supported
biomedical and behavioral research involving human subjects is defined
as clinical research. This policy applies to research subjects of
all ages.
Pregnant Women and Fetuses
The following information is taken from the federal regulation (45
CFR 46) Additional Protections Pertaining to Research, Development
and Related Activities Involving Fetuses, Pregnant Women and Human
In-Vitro Fertilization.
I. General Limitations. A research project cannot be undertaken
unless:
A. appropriate studies on animals and non-pregnant women have been
completed;
B. except where the purpose of the research is to meet the needs
of the mother or the particular fetus, the risk to the fetus is
minimal and, in all cases, is the least possible risk for achieving
the objectives of the activity;
C. in the case of termination of a pregnancy, investigators engaged
in the research will have no part in any decisions as to the timing,
method and procedures used to terminate the pregnancy; in addition,
investigators will have no part in determining the viability of
the fetus at the termination of the pregnancy; and
D. in the case of termination of a pregnancy, no procedural changes
which may cause greater than minimal risk to the fetus or the pregnant
women will be introduced into the procedure for terminating the
pregnancy solely in the interest of the research project.
No inducements, monetary or otherwise, may be offered to terminate
pregnancy for the purposes of the research project.
I. Pregnant Women as Subjects
A. No pregnant women may be involved as a subject in a research
project unless: (i) the purpose of the research is to meet the health
needs of the mother and the fetus will be placed at risk only to
the minimum extent necessary to meet such needs, or (ii) the risk
of the fetus is minimal.
B. The research activity may be conducted only if the mother and
father are legally competent and have given their informed consent
after having been fully informed regarding possible impact on the
fetus, except that the father's informed consent need not be secured
if: (i) the purpose of the activity is to meet the health needs
of the mother; (ii) his identity or whereabouts cannot be reasonably
ascertained; (iii) he is not reasonably available; or (iv) the pregnancy
resulted from rape.
I. Fetuses in Utero as Subjects
A. No fetus in utero may be involved as a subject in a research
project unless: (i) the purpose of the research is to meet the health
needs of the particular fetus and the fetus will be placed at risk
only to the minimum extent necessary to meet to meet such needs,
or (ii) the risk to the fetus imposed by the research is minimal
and the purpose of the research is the development of important
biomedical knowledge which cannot be obtained by other means.
B. Any research activity permitted under this section may be conducted
only if the mother and father are legally competent and have given
their informed consent. Exceptions to this requirement are specified
in Section 2(b) above.
Fetuses Ex Utero, Including Nonviable Fetuses, as Subjects
Research activities involving the dead fetus, macerated fetal material
or cells, tissue or organs excised from a dead fetus may be conducted
only in accordance with applicable state and local laws. The following
is taken from Oklahoma State Statute, Title 63, Section 1-730 and
1-735 (effective Oct. 1, 1978):
1-730. Definitions. As used in this article.
"Abortion" means the purposeful termination of a human
pregnancy, by any person with an intention other than to produce
a live birth or to remove a dead unborn child;
"Unborn child" means the unborn offspring of human beings
from the moment of conception, through pregnancy, and until live
birth, including the human conceptus, zygote, morula, blastocyst,
embryo and fetus.
1-735. Sale of child, unborn child or remains of child - Experiments
A. No person shall sell a child, an unborn child or the remains
of a child or an unborn child resulting from an abortion. No person
shall experiment upon a child or an unborn child resulting from
an abortion or which is intended to be aborted unless the experimentation
is therapeutic to the unborn child.
B. No person shall experiment upon the remains of a child or unborn
child resulting from an abortion. The term "experiment"
does not include autopsies performed according to law.
In brief, research conducted on fetal tissue resulting from an induced
abortion is strictly prohibited by Oklahoma State law. Research
on the remains from a spontaneous abortion (miscarriage) may be
permissible. Investigators with questions regarding the use of pregnant
women or fetuses in research are encouraged to contact the IRB Office.
Prisoners
This information is taken directly from 45 CFR 46, Protection of
Human Subjects.
The federal government requires additional protection for prisoners
inasmuch as prisoners may be under constraints because of their
incarceration which could affect their ability to make a truly voluntary
or uncoerced decision whether or not to participate as subjects
in research. For our purposes, prisoner means any individual involuntarily
confined or detained in a penal institution. This includes individuals
sentenced to such an institution under a criminal or civil statute,
individuals detained in other facilities by virtue of statutes or
commitment procedures which provide alternatives to criminal prosecution
in a penal institution and individuals detained pending arraignment,
trial or sentencing.
The Institutional Review Board must provide for this special protection
when reviewing research involving prisoners. The principal considerations
are as follows:
Any possible advantages accruing to the prisoner through his or
her participation in the research, when compared to the general
living conditions, medical care, quality of food, amenities and
opportunity for earnings in prison, are not of such a magnitude
that his or her ability to weigh the risks of the research against
the value of such advantages in the limited choice of the prison
is impaired;
The risks involved in the research are commensurate with risks that
would be accepted by non-prisoner volunteers;
Procedures for the selection of subjects within the prison are fair
to all prisoners and immune from arbitrary intervention by prison
authorities or prisoners;
Adequate assurance exists that parole boards will not take into
account a prisoner's participation in the research in making decisions
regarding parole, and each prisoner is clearly informed in advance
that participation in the research will have no effect on his or
her parole;
Where the IRB finds there may be need for follow-up examination
or care of participants after the end of their participation, adequate
provision has been made for such examination or care, taking into
account the varying lengths of individual prisoners' sentences,
and for informing participants of this fact.
Investigators who plan to use prisoners as research subjects should
contact the IRB Office for further guidance on this subject.
Mentally Disabled
The primary ethical concern in research involving the mentally disabled
is that their disability may compromise their capacity to understand
the information presented and their ability to make a reasoned decision
about participation. The IRB Guidebook, published by the Office
of Protection from Research Risks, provides the following definitions
of mentally disabled and competence:
Mentally Disabled - Having either a psychiatric disorder (e.g. organic
and functional psychoses, neuroses, personality or behavioral disorders,
senility) or a developmental disorder (e.g. mental retardation).
Others, including persons under the influence of or dependent on
drugs or alcohol, those suffering from degenerative diseases affecting
the brain, terminally ill patients, and persons with severely disabling
physical handicaps may also be compromised in their ability to make
decisions in their best interest.
Competence - As a description of mental status, means an ability
to understand information presented, appreciate the consequences
of acting (or not acting) on that information and express a choice.
As a description of legal status, competence or incompetence pertains
to an adjudication in court proceedings that a person's abilities
are so diminished that his or her decisions or actions should have
no legal effect (e.g. writing a will). Such adjudications are often
determined by inability to manage business or monetary affairs and
do not necessarily reflect a person's ability to function in either
situation.
As a general rule, all adults regardless of their diagnosis or conditions
should be presumed competent to consent unless there is evidence
of serious mental disability that would impair reasoning or judgment.
Even those who do have a diagnosed mental disorder may be perfectly
able to understand the situation of being a research volunteer and
quite capable of consenting or refusing.
In the past, institutionalized individuals have been used as convenient
research subjects in drug and vaccine tests which were totally unrelated
to their disorders or institutionalization. This exploitation of
the vulnerable and "voiceless" led the National Commission
for the Protection of Human Subjects to recommend that, even in
research on mental disabilities, subjects should be recruited from
among the non-institutionalized whenever possible. The IRB strongly
supports this position. Investigators may contact the IRB Office
for more information.
Next of Kin Consent for Research Studies
Oklahoma law has recently been changed to allow for Family Members
consent in such cases where the potential subject is not capable
of consenting on their own behalf. There are some specific restrictions
within this law and certain guidelines which the IRB must follow
to allow for such consent. This law was essentially approved to
allow research on such diseases as Alzheimers, Head Trauma, Sepsis,
etc.
Family Member consent must be specifically addressed in the IRB
approval process. The Board must specifically approve a separate
consent form for the family member to sign and must specifically
state that the study is approved for use of Family Member Consent.
The IRB looks at a variety of issues when determining whether or
not Family Member Consent is appropriate. Some of these issues are:
Will participating in the study directly benefit the potential subject?
Are there alternate standard/approved treatments available for this
subject ?
Could this study be done without allowing Family Member Consent?
Based upon the answers found when addressing these questions, the
Board will make a determination regarding the appropriateness of
Family Member Consent. The Investigator will be notified as to the
approval/denial of this process and the Boards reason for such.
The Investigator is welcome to appeal this decision in writing to
the Board and provide documentation for such appeal. This will be
brought back to the Board for reconsideration.
Genetic Testing in Research Studies
Genetic testing in research studies is becoming more common and
presents a variety of factors to be considered. The IRB is giving
careful consideration to the use of genetic testing in research
and evaluates each use on a case by case basis. For the most part
the following criteria should serve as basic guidelines for submitting
genetic research to the IRB.
No research involving genetic testing will be approved under either
exempt or expedited process by this IRB at this time. All research
involving genetic testing must receive review and approval by the
Full Board prior to being started at this institution.
If material being prospectively collected is to be used or banked
for future use in genetic research, the research subject(s) must
be told specifically that their blood or tissue specimen will (or
may) be used for genetic testing. They must give active consent
for this process to take place. They must be given all information
available at the present time concerning the type of genetic research
that will take place on their sample. They must be told whether
information regarding the results of these studies will be made
available and why (or why not).
In most cases the Board feels that the results of the genetic testing
should not be made available to the subjects. The only acceptable
time to allow the patient access to the results are situations where
a positive result can be achieved by this information being released
(i.e. treatment available to them because of this information or
behavior modification recommendations that are appropriate for their
medical care) and where an approved genetic counseling program is
in place to help the patient deal with their access to this information.
In all cases where genetic testing is being done, the potential
risks must be covered in the consent form. Examples of appropriate
risks of genetic testing paragraphs are given in the sample consent
form.
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