Section
19
Biological Specimens in Clinical (including Genetic) Research
A. Introduction
B. Definitions
C. Will Consent need to be obtained?
D. Levels of Physical and Non-physical Risk/Types of IRB Review associated with Biological Specimen Research
E. What about the information generated from specimen analysis?
F. General Issues to Consider in Biological Specimens Research
When dealing with the review of biological specimen use in research activities, CORIHS must balance two factors: the need for protection of the rights and welfare of the person from whom the specimen was/will be obtained, and the need to not impede the research activities conducted at Stony Brook University.
The reader should also review Section 18, which addresses research involving tissue registries/tissue banks.
Anonymous Samples: specimens lacking any code or identifier that would allow a link back to the subject who provided it. Sumbmission of a completed HIPAA de-identification form in required, and will attest to the anonymity of the samples being used.
Exempt Review Procedure: see section II.A.
Expedited Review Procedure: see section II.B.
Full Review Procedure: Involves review by CORIHS at a convened meeting. The schedule of meetings is available from the Office of Research Compliance.
Identifiable/Coded Samples: specimens that can be linked back to the subject who provided them.
Prospective Collection: proposed research involves specimens that do not exist 'on the shelf' when request is made to CORIHS for approval. The specimens will be collected once CORIHS approval has been granted.
Retrospective Collections: proposed research involves specimens that already exist, i.e., already collected and are 'on the shelf', stored or frozen at time of protocol submission to CORIHS. This type of research will often involve a ‘third party’, e.g., tissue bank or registry, Department of Pathology etc. In this instance the third party will likely have the tissue coded with respect to subject identity.
In many types of retrospective tissue collection research, it is not important to the aims of the research for the investigators to receive the code, or access to subject identity at any point. The specimens are therefore provided by the third party to the investigator anonymously, i.e., there is no way to link the subject's identity to the tissue once it is in the investigator's hands. When submitting the application materials to CORIHS, the investigator should include a written agreement between the third part entity and the investigator ensuring that the code will not be released to the investigator under any circumstances.
Sometimes the research aims require that the specimens be provided in an identifiable/coded manner, so that they can be linked to clinical information by the investigator (e.g., matching the results of the tissue analysis to the subjects’ outcome, linking specimens to information within medical records etc.). The investigator and the IRB must consider issues of added risk (e.g., confidentiality etc), of whether consent can be waived or if it must be obtained from the subject, and if the research activity meets the requirements consistent with HIPAA privacy regulations (see section E for further discussion on HIPAA implications in biological specimen research).
Whether an investigator is requesting anonymous or coded data, third parties should require proof of CORIHS approval prior to releasing biological specimens to the investigator.
C. Will consent need to be obtained?
CORIHS operates under the general rule that if an investigator can get consent from a possible subject, than s/he should get consent from that subject. This is the case in most instances of research proposing prospective collection of biological specimens. Exceptions to this general requirement (e.g., in the case of future discarded surgical specimen, etc.) can be granted only if the waiver criteria below are submitted, and deemed appropriate by CORIHS.
In general, if retrospective collection of specimens is proposed, a waiver from the consent requirement may be granted, so long as the investigator submits documentation that all of the following conditions are met:
and
Where consent from the subject will be required, see section D for text that will be relevant, depending upon factors
D. Levels of Physical and Nonphysical Risks/Types of IRB Review Associated with Biological Specimen Research:
The type of review that will be required, assuming that tissue collection/analysis constitutes the only involvement of human subjects in the activity, is dependent upon the level of risk associated with the activity, as determined by the IRB after review of the PI’s protocol submission. Answering the following questions will help with risk/benefit and review assessments of your research activity:
1. Will the biological samples be labeled such that they can be traced back, in any way, to the subject (via direct identifiers, or via codes)?
If the answer is NO, non-physical (e.g., breaches of confidentiality, etc) risks are deemed minimal. If the specimens were collected:
retrospectively:, study can undergo exempt review procedures.
prospectively: study will either undergo expedited or full committee review (depending on the physical risks associated with the collection procedure, e.g., blood drawing, biopsy, cheek swab, lumbar puncture etc). Research involving the prospective collection of anonymous specimens obtained from future, discarded clinical samples for non-genetic research qualifies for exempt status.
Regarding consent language (where consent is required), add to the end of the procedures OR confidentiality sections:
“Results from testing of your tissue will not be understood unless we pool it together with data from other study subjects. These tests will be conducted anonymously, that is, without knowing the identities of the individuals who contributed the tissue. Therefore, there will be no way to provide individual test results to you or your doctor."
Proceed to section E (no need to answer #2).
If the answer is YES: go to Question 2.
2. Will the test results be able to provide information that has known clinical significance for diagnosis or prediction of a disease state for either the subject or the subject’s family members?
If the answer is NO, the non-physical risks are deemed minimal, i.e., they are theoretical in that clinical significance may be determined in the future, with risks being a breach of confidentiality and the subject not knowing that this private information now exists. Study will qualify for expedited or full committee review, depending upon the physical risks of the collection procedure.
Regarding informing the subject of the test results, possible consent language in the procedures section (where consent is required) includes:
“Results from testing of your tissue will not be understood unless we pool it together with data from other study subjects. Because this is research, the clinical significance (if any) of your individual results may not be understood for years. Therefore, individual test results will not be shared with you or your doctor.”
If the PI wishes to contact subjects if and when the clinical significance of the results becomes clear, possible consent language includes:
If, in the future, findings from this study are confirmed by the scientific community and have definite implications for your health (or your children or future offspring), we will make a best effort to send you a letter describing the general results and offering ways to obtain care and/or counseling. If you initial here__________, it means you do not want to be contacted if future findings become relevant to you.”
If the answer is YES, the non-physical risks associated with this study constitute MORE THAN MINIMAL RISK. Study must be reviewed by the full committee, regardless of the physical risks associated with the specimen collection procedure. The non-physical risks, that are more than minimal, are as follows (and should be considered when drafting the foreseeable risks section of the consent document):
When subjects already have the disorder for which biological testing is being done: Risks may include possible breaches of confidentiality (affecting insurability, employability, etc) and (where applicable) unintentionally uncovering unintended incidental genetic information (e.g. non-paternity, hereditary risks, risks of future diseases). Benefits could include confirmation of clinical diagnosis, where applicable, or else indicate clearly that no direct benefit exists for the subject.
When subjects are not yet known to have the disorder for which biological testing is done: Risks include those above, as well as (where applicable) psychological risks, determination of the possible presence of a heritable disorder (in themselves or their current/future offspring, accordingly). This research activity could also be of direct benefit, e.g. giving the subject the ability to inform family and to make appropriate lifestyle and reproductive choices; offering the potential for more effective intervention).
Further:
E. What about the information generated from specimen analysis?
Another important aspect of specimen research to consider is that fact that the information that will be generated from analysis of the tissue will likely constitute ‘health information’, therefore requiring that the study be in compliance with privacy regulations, i.e., HIPAA. Section 25 must be reviewed to ensure that either:
OR
OR
OR
F. General Issues to Consider in Biological Specimens Research
1. If the banking of biological specimens is proposed within the context of a larger research study, the following issues can be addressed within the main research consent form, but the actual request for consent to bank the tissue should be separated out from the request to consent for the main study. This can be achieved by adding yes/no statements (with a signature or initial lines) right before the signature lines of the main consent.
For example:
1. Do you agree to allow use of extra blood obtained from this study/extra tumor from your surgery for use in future research, the purposes of which are unknown at this time? If you agree, any future studies using your sample will be subject to further regulatory review.
2. Do you agree to allow someone to contact you in the future to ask you questions about your health or to ask you to participate in more research?
2. At the time of the proposed activity, is it the intent of the investigator or the company collaborator/sponsor to produce a commercially valuable product? If yes, disclose in the consent form whether or not the subject or his/her heirs will receive a portion of the profits. Note that consent forms cannot contain language through which the subject is made to waive, or appear to waive, any of his/her legal rights. An acceptable example of consent language is:
“We may, in the future, be able to produce a commercially valuable product from the work done on samples collected from subjects in this study. It is not out intention to pay you or your heirs, for profits derived from such a product."
3. What happens to the specimen(s), and the data derived thereof, if the subject decides to withdraw from the study? Is the tissue removed from the study analysis or from the tissue bank? If so , state so in the consent. If it is not the intention to remove the sample or any data derived from it it, state so in the consent. What about cell lines that have been generated?
4. How long will the biological specimen be kept? (It is acceptable to indicate, in the consent form, that the specimen will be kept for an indefinite amount of time).
5. If a new study proposes secondary use of biological specimens, i.e., use of samples collected for a previously conducted study, an assessment will be made by CORIHS regarding whether or not the consent that was obtained for the first study is applicable to the second. If the purpose of the new study differs significantly from the purposes stated in the original study, and the specimens are identifiable, obtaining new consent will be required, unless the consent waiver criteria are met. CORIHS therefore recommends obtaining the initial consent for research with as broad a stated purpose as possible such as, e.g., “the causes and treatments of lung cancer” etc..
6. Given the study aims and risks, should the investigator obtain a study-specific Certificate of Confidentiality from the NIH to protect against disclosure required by issuance of a subpoena.. This is an extra protection for confidentiality if the study can potentially generate information that is particularly sensitive (ex. HIV status, history of alcoholism, possible mental illness, etc. For more information, visit: (http://www.nih.gov/grants/oprr/humansubjects/guidance/cert-con.htm)
Return to Human Subjects Research at SBU
Last Updated: 2007-05-01