________________________________________________________________________
NEBRASKA’S HEALTH SCIENCE CENTER
OFFICE OF REGULATORY
AFFAIRS (ORA)
Institutional Review Board (IRB)
ADDENDUM G
RESEARCH INVOLVING GENETIC TESTING
SECTION I
DATE:
IRB #:
TITLE OF PROTOCOL:
PRINCIPAL INVESTIGATOR:
SECTION II
Instructions: For the purpose of this application genetic testing means studies to identify or
characterize human DNA, RNA, chromosomes, proteins or other gene products to detect genotypes,
mutations, phenotypes, or karyotypes. Genetic testing may also include the creation of pedigrees for
the same purposes.
Research subjects require special protection when participating in studies which have a reasonable
possibility of producing information about that subject's genetic make-up, especially when there is a
possibility that such information, now or in the foreseeable future, could lead to diagnosis of a medical
or behavioral condition, prediction of risks for these conditions, or identification of carriers.
Investigators, therefore, must address specific issues relevant to protection of human subjects
participating in this type of research.
Investigators performing genetic testing must complete this addendum application, in addition to
appropriate IRB application. This addendum must be completed in order for the IRB to review the
research protocol. Information should be provided by site for all studies involving more than one site for
which the UNMC IRB or PedsIRB is the only IRB of record.
CHARACTERISTICS OF THE RESEARCH (1-3)
1. Is the genetic testing a portion of a more comprehensive therapeutic or non-therapeutic
study?
No
Yes. Respond to the following.
A. Is the genetic testing portion of this research directly relevant to the subject's
disease or condition?
Note: In most cases, it is expected that subjects who object to participation in studies involving
genetic testing will still be allowed to participate in associated therapeutic or non-therapeutic
studies. However, investigators may require subjects in a non-therapeutic study to participate
in an attached genetic testing protocol, especially if the genetic testing is an integral portion of
the research. In this case, if a potential subject objects to participation, he/she must refuse
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participation in the entire research project. Investigators may not require subjects in a
therapeutic study to participate in a genetic testing protocol unless the genetic testing is directly
relevant to the subject's disease and is an integral part of the protocol. Otherwise, if a potential
subject objects to participation, he/she must still be allowed to participate in the therapeutic
portion of the study.
2. Will identifiers (e.g., name, initials, patient identification number, or code) be maintained
which allow anyone to link the results of the genetic tests either directly or indirectly to the
subject?
No
Yes
3. Will potentially identifying information be obtained from, or about, family members?
Note: the investigator must consider whether individual persons will be identifiable based on the
results of genetic testing or creation of pedigrees performed during this research.
No
Yes
Note: If identifiers are not maintained (#2 above) and potentially identifying family information is not
obtained (#3 above) then no further information is required for this addendum application.
CHARACTERISTICS OF SUBJECT POPULATION (4-5)
4. Will children (i.e., 18 years of age or younger) be included in the genetic testing portion of the
research?
No
Yes. Provide justification.
Note: The inclusion of children in genetic research studies may entail risks over and above those
seen with adult subjects. The IRB generally supports the following principles regarding the
involvement of children in genetic research. These principles are based, in part on the statement
from the American Society of Human Genetics / American College of Medical Genetics (Am J Hum
Genet 57:1233, 1995)
1) The potential for timely medical benefit to the child should be the primary justification for
inclusion of children in studies involving genetic testing.
2) The potential for substantial psychosocial benefit to the competent adolescent may also be
justification for inclusion of adolescents in studies involving genetic testing.
3) If the potential medical or psychosocial benefits of genetic testing are not expected to accrue
until adulthood, as in the case of carrier status or adult onset diseases, children and adolescents
should not be included in studies involving genetic testing
5. Will cognitively or decisionally impaired persons be included in the genetic testing portion of
the research?
No
Yes. Provide justification.
METHODS AND PROCEDURES (6)
6. DESCRIBE THE GENETIC TESTS TO BE PERFORMED.
A. Is there a reasonable likelihood that these tests, now or in the foreseeable future, could
lead to diagnosis of a medical or behavioral condition, prediction of risks for these
conditions, or identification of carriers?
No
Yes
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B. Will pedigrees be obtained?
No
Yes. Describe the information to be obtained and how it will be obtained (e.g.,
interviews with subject or family member, review of family records, or review of medical
records).
DISCLOSURE OF RESULTS (7)
7. CRITERIA FOR DISCLOSURE OF STUDY RESULTS TO SUBJECTS
A. Will study results be made available to subjects, or, in the case of children or
incompetent subjects, to their parents or guardians?
No
Yes
B. Will incidental findings obtained in the course of the study be made available to
subjects?
No
Yes
C. If there are no plans to disclose results to subjects, provide justification.
Note: The investigator must carefully consider whether to make research results available to the
subjects. In general, the IRB supports the following recommendation made by the National
Bioethics Advisory Commission (NBAC): “the disclosure of research results to subjects
represents an exceptional circumstance. Such disclosure should occur only when all of the
following apply: a) the findings are scientifically valid and confirmed, b) the findings have
significant implications for the subject’s health concerns, and c) a course of action to ameliorate
or treat these concerns is readily available.”
If disclosure is to be made, then the investigator must also consider the CLIA-status of the
laboratory performing the testing. If the test was conducted in a CLIA non-approved lab and the
test is otherwise available at a CLIA-approved laboratory, the investigator should refer the
subject for verification of the test results.
If there are no plans to disclose testing results, but information arises during the course of the
study, or after it was completed, which suggests that these results are of material interest to the
subject, then the IRB should be consulted to develop a disclosure plan.
PROCESS OF DISCLOSURE (8)
8. IF THERE ARE PLANS TO DISCLOSE RESULTS TO SUBJECTS, THEN BRIEFLY DESCRIBE:
A. The plan for tracking subjects after participation in research.
B. The plans for contacting subjects if results or incidental findings become available.
Note: If written notification will be used, then this must be reviewed by the IRB.
C. The plans for disclosure of these results.
Note: If disclosure is planned the investigator must make a reasonable effort to contact the
subject and inform the subject that study results are available. The definition of Areasonable
effort@ will depend on the utility and value to the subject of the information to be provided. The
subject has the right to refuse to be informed of results of research. If the results of the
research would be, in the opinion of the investigator, of significant health benefit to the subject,
the investigator is obliged to ensure that a qualified person discusses fully with the subject the
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potential health effects of this non-disclosure. The process of disclosing either direct or
incidental results to the subject must be conducted by a person qualified in discussing the
significance, consequences and reliability of such results. In some cases, this qualified person
should be a genetic counselor. The investigator, or a trained genetic counselor, should remind
the subject of the risks associated with genetic testing prior to disclosing those results.
DISCLOSURE OF RESULTS TO CHILDREN (9-10)
9. If there are plans to disclose results to subjects, then will results of the study or of incidental
findings obtained in the course of the study be disclosed to children?
No
Yes. Briefly describe the process.
10. Will parental consent be required prior to disclosure of study results to children?
Yes
No
Note: Investigators must make a thoughtful analysis of the risks and potential benefits of disclosure
of study results to children. This analysis should consider the long term consequences of
information supplied to a subject and this analysis must consider the age and developmental
characteristics of the child. In general, if there is adequate justification to enroll children in the
research (i.e., findings are scientifically valid and confirmed and evidence-based risk-reduction
strategies or treatment interventions exist) then the presumption should be that results will be
disclosed.
POTENTIAL RISKS (11)
11. What are the risks associated with data obtained in the course of the genetic testing (either
as a direct result of the test, or as a result of incidental finding)?
Note: Potential harm may come to the subject as a consequence of data obtained from the
research. These risks include, but may not be limited to, psychological or emotional burden at being
informed of a potentially serious genetic defect or predisposition, impact on family relationships,
psychosocial impacts on other family members, discrimination in employment and insurability, risks
associated with disclosure of false negative or false positive results (i.e., foregoing potentially
preventive or therapeutic interventions, or undergoing potentially harmful preventive or therapeutic
interventions). Subjects must be informed that if the genetic testing is performed in a clinical
laboratory, then the results will be included in the subject's medical record. Risks associated with
genetic testing may be more significant in magnitude if children are to be included as subjects.
Note: The information included in this section is critical to the determination of a risk benefit
relationship of the research. The IRB requires the investigator to make a thoughtful and
comprehensive assessment of these risks.
MINIMIZATION OF RISKS (12-14)
12. PROTECTION AGAINST RISKS ASSOCIATED WITH RESULTS OF GENETIC TESTING
What procedure(s) will be used to prevent/minimize any potential risks associated with data
obtained in the course of the genetic testing (either as a direct result of the test, or as a result
of incidental finding)?
Note: The information included in this section is critical to the determination of a risk benefit
relationship of the research. The IRB requires the investigator to make a thoughtful and
comprehensive assessment of these risks, and how possible harms can be prevented or minimized.
13. CONFIDENTIALITY
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A.
What methods will be employed to assure confidentiality of results obtained?
B. Will other investigators at UNMC or at other locations have access to biological material
or data generated or obtained in the course of this study?
No
Yes. Describe the methods that will be employed to assure subject confidentiality?
Note: Methods to protect subject confidentiality include, but are not limited to, removal of
identifiers and substitution of codes, secure storage, and obtaining a Certificate of
Confidentiality. It is important to recognize that any tests performed in a clinical laboratory have
the potential of appearing in the subject's physical or electronic medical record, and therefore,
may be subject to future disclosure.
14. COUNSELING
What provisions have been made for the counseling of subjects prior to involvement in this
study, and at the time that study results are to be disclosed to subjects?
Note: Due to the sensitive and uncertain nature of genetic testing, the process of consent to
participate in such studies must include a thorough and knowledgeable discussion of the risks and
benefits associated with participation. In some cases, these discussions may be beyond the
capabilities of the principal investigator of the study. The investigator must give evidence of this
capability to the IRB, or make arrangements for another qualified party with experience in genetic
testing and counseling to represent him/her to the potential subjects. Similarly, the process of
disclosing either direct or incidental results to the subject must be conducted by a person qualified in
discussing the significance, consequences and reliability of such results.
It is the obligation the investigator to cover the costs associated with initial genetic counseling for the
subject (or, in the case of minors, for the subject and for their parents). However, if repeated or
longer term counseling is required, the financial obligation for such counseling belongs to the
patients. The investigator is not obligated to cover costs associated with genetic counseling of
family members of the subject, except as above.
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