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Tissue/Specimen Use & Repositories 

It is the responsibility of the IRB to review and approve research that involves the collection, use, storage, and re-use of all human tissue, blood, or genetic material that are generated within, transferred to, or transferred from the University of Utah and its covered entity. This guidance is based on the following regulations and guidance:

Please review the IRB guidance on tissue collection, use, and repositories according to the following topics:

Tissue Collection and Use

Tissue Repositories

Additional Resources and Guidance


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Definitions

Human Tissue: Any human biological specimen or byproduct obtained from a living or deceased individual that is sufficient in type and quantity to permit an analysis of its physical or biochemical properties. This definition includes solid tissues, cells, cell cultures, molecules derived from tissues (DNA, RNA, proteins, etc.) and body fluids, and associated data and information.

Tissue Bank(Repository): Tissue banks collect, store, and distribute human biological specimens for research purposes. Tissue bank activities involve three components: (a)the collection of samples and data; (b) the storage and data management center; and (c) the re-disclosure of tissues.


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Determining When Regulations Apply

Why would human subject research regulations apply to the research use of human biologic specimens?

OHRP interprets human biological specimens to be private information. If an investigator obtains a specimen from a living individual through a research intervention or interaction, the research involves human subjects. In addition, if an investigator obtains individually identifiable specimens about living individuals the research will also involve human subjects.

 

Is the research use of human biologic specimens always subject to the regulations?

No. The first objective of the IRB in evaluating research using human biological specimens (and other private information) for research purposes is to determine whether the particular activity meets the regulatory definition of research involving human subjects. If an activity meets the regulatory definition of research involving human subjects the DHHS regulations will apply.

The IRB will evaluate the project by answering the following questions in sequence:

  1. Does the activity involve research?
    Typically, these projects do involve research because there is a systematic investigation designed to develop or contribute to generalizable knowledge.
  2. Are human subjects involved in the activity?
    The definition of human subjects can mean either interaction with a living individual or interaction with their data. See below for more information regarding deceased individuals.

If the answer is no to either question 1 or 2 above, the DHHS regulations for the protection of human subjects in research do not apply. The activity is not considered human subjects research.

If the answer is yes to both questions 1 and 2 above, the DHHS regulations for the protection of human subjects in research do apply. The IRB review will proceed by looking next at whether the human subjects research activity is exempt under the regulations. The exemption most often used is Exemption #4. [See below]

What is an example of a research activity that DOES NOT involve human subjects?

The research would not not involve human subjects if 1) the research does not involve a researcher interacting or intervening with a living individual in order to obtain data or a specimen and 2) the investigator does not obtain individually identifiable information, private information or specimens from living individuals. For example, an investigator obtains data that was solely collected for clinical purposes. Before the investigator obtains the information, all the identifiers have been removed from the clinical data before being provided to the investigator. There was no research interaction or intervention to obtain the data because it was collected solely for clinical purposes. The investigator is obtaining anonymous information that would not allow for the investigator to identify the individuals from whom the data pertain.

Since the activity is research but does not involve human subjects, the DHHS regulations for the protection of human subjects in research do not apply.

When specimens or data are coded, are they individually identifiable?

Generally coded information is considered to be individually identifiable but there are exceptions. If a code exists, it would be possible to ascertain the identity of the individuals to whom the specimens or other private information pertain. Often, a code is retained with the information in order to allow someone to be able to re-identify the individuals from whom the specimens or the information pertain. However, the key is whether the investigator will be able to do so.

If there are mechanisms put into place that would prevent a recipient investigator from being able to readily ascertain the identity of the individuals to whom the specimens pertain, the investigator would not be considered to have individually identifiable information and human subjects would not be involved in this type of a research activity. An example that would meet this exception is when an agreement exists between the provider of the coded specimens and the recipient investigator in which the recipient investigator will not obtain the key to the code that would enable individuals to be re-identified under any circumstances. More OHRP guidance.

Who determines when regulations apply?

As evidenced above, these determinations are complex. Research that does not meet the definition of research involving human subjects must be determined by the University of Utah IRB staff, not an individual investigator. Investigators must complete and submit a “Request for Non-Human Subject Research Review” which can be accessed by creating a new study application in ERICA. If the research does meet the definition of research involving human subjects and the regulations do apply, the IRB will proceed with the review of the project, evaluating whether the human subjects research activity is exempt under the regulations.

If the use of human biologic specimens is determined to be human subjects research, can it be exempt?

Yes. As mentioned earlier, the exemption criteria most often used for research involving human biologic specimens or data is exemption #4.

Research involving the collection or study of existing data, documents, record, pathological specimens or diagnostic specimens, if these sources are publicly available or the information is recorded by the investigator in such a manner that the subjects cannot be identified directly or through identifiers linked to the subjects. Research must not be subject to FDA regulations, research must not involve prisoners as participants and research must meet the University’s ethical standards governing the conduct of the research.

There are three factors that are important to focus on in determining whether exemption four is applicable to a human subjects research study.

  1. Are the specimens or data existing at the time the research is proposed for exemption?
  2. Are the specimens or data publicly available? Keep in mind that most human specimens would not be considered publicly available, meaning available without restriction.
  3. If not publicly available, are the data recorded by the investigators so subjects cannot be identified either directly or through identifiers linked to the subjects?

 

Research that meets the criteria for exemption #4 must be determined by the University of Utah IRB, not an individual investigator. Investigators must complete and submit an IRB new study application with any applicable documents.


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Review Process for Tissue Collection and Use

The IRB must review all research involving human tissue collection and use. As explained in the previous section, The IRB must make the determination of whether the activity is human subjects research. Additionally, if the project is determined to be human subjects research, the IRB will determine whether the project is exempt. In order to do so, investigators will be asked to respond to the following questions:

  1. What personal health information will accompany the sample for use in the proposed research?
    Any type of health information can accompany a sample, including identifying information. The type of information will depends on what the investigator is allowed to have access to during the study, based on IRB approval, consent and tissue source restrictions (e.g. lab sources, repository sources, etc.).
  2. Is the sample de-identified - i.e. will the investigator be able to identify the participant using the accompanying personal health information?
    'De-identified' means that there are no participant identifiers accompanying the sample, such as
    • name
    • medical record number
    • social security number
    • date of birth
    • address
    • telephone number

    'De-identified' also means that the sample cannot identify a specific group or family, based on the characteristics of the sample, such as genetic makeup.

    Other participant information may accompany the sample and still be considered 'de-identified.' Information that may accompany the sample includes, but is not limited to the following:
    • approximate date of collection (month/year)
    • approximate date of surgery (month/year)
    • type of specimen
    • diagnosis (*some exceptions)
    • stage of disease
    • gender
    • age
    • treatment status
    • outcome
    • race or ethnic group
    *Exceptions include when the diagnosis is rare and potentially identifiable

    The IRB reviews the list of information that will be included with the samples to assess how appropriate and necessary the information is to the research.

    The IRB recognizes that any combination of general information may provide a link to the personal information. We consider that good clinical judgment should be exercised in the provision of this information in select groups of patients. The IRB will determine whether there may be potential harm to the race or ethnic group being studied. If there is a question as to the use of certain information, the IRB should be consulted for advice prior to the use of such information.
  3. If the sample is de-identified, does a code or link exist to re-establish the identity of the sample? If yes, who created the code and who has access to the code?
    A sample may be de-identified, however, a code or link may still exist between the sample and the identity of the participant. It is important for the IRB to know if such a link exists and who has access to this link.

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Consent and Authorization for Tissue Collection and Use

Informed consent and authorization (for samples collected within the covered entity) must be accounted for in one of the following ways:

  • Full informed consent and authorization (for samples collected within the covered entity)
  • Waiver of consent plus a method to account for authorization

Full informed consent and authorization must be obtained from participants or their legally authorized representatives for use and/or banking of their samples, except where waivers or non-human subject determinations apply. Consent and authorization documents should include the following information:

  • Tissue use description
    The consent form must describe how the sample will be collected and used for the proposed research.
    • For use that does not require tissue banking, the consent form must specify when the sample will be destroyed.
    • For use that involved tissue banking, see the information on Tissue Repositories below
    • If use of the sample involves genetic testing, the investigator must also include language regarding the disclosure of results as outlined in the IRB guidance on Genetic Research
  • Authorization language for use and disclosure of information
    Authorization determines who can have access to participants; personal health information. This language is outlined in the Biomedical Consent [DOC] and Parental Permission templates [DOC]on the IRB website. Some important considerations are as follows:
    • What protected health information (identifiable or non-identifiable) will accompany the samples?
    • Who will be allowed to receive the samples with the accompanying health information - only individuals within the University of Utah and its covered entity, or others from outside entities and institutions?
  • A waiver of consent may be requested for the use of tissues. The IRB will approve a waiver if the study meets the following 4 criteria, as outlined in 45 CFR 46.116(d):
    1. The research involves no more than minimal risk
    2. The waiver will not adversely affect the rights and welfare of the participants
    3. The research could not practicably be conducted without the waivers
    4. When appropriate, the participants will be provided with additional pertinent information
  • A method to account for authorizationmust be used in conjunction with a waiver of consent. The following methods may be used:

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Samples Collected for Non-Research Purposes (Pathology Samples)

Samples that have been collected or will be collected solely for non-research purposes, such as pathology samples, may be used and stored for research. The investigator must either obtain full consent and authorization from participants or provide justification for the use of a waiver of consent and other method to account for authorization.

The IRB will often request that these samples be de-identified without a link to identifiers to protect the privacy and confidentiality of the participants.


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Autopsy Samples

According to the Common Rule, deceased individuals do not meet the definition of a human subject; however, the IRB is still responsible for assuring HIPAA regulations are followed and must review research involving specimens collected from postmortem individuals. The IRB will also consider ethical issues concerning potential harm to the decedents’ families or other associated groups (e.g. race, sect, etc.).

Typically consent is not required to use and store autopsy specimens; however, if the research involves genetic testing of these samples for heritable traits, a consent form signed by the responsible family member(s) may be required. Written consent from the responsible family member(s) should be gained in conjunction with or following the autopsy consent process. Collection of autopsy specimens may not occur without IRB approval.

In addition to the new study application, the Research Using Decedents Information form must also be completed and attached to the new study application.


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Publicly Available Tissue Samples

There are few opportunities for tissue samples to be publicly available, but there may be limited circumstances of tissue samples being made available to qualified researchers for valid research purposes at a reasonable cost.

Publicly available samples must be characterized as de-identified samples. If the identity of the sample is known, the identity must be recognizable in the public domain and not entitled to a presumption of anonymity.


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Publicly Available Tissue Samples

There are few opportunities for tissue samples to be publicly available, but there may be limited circumstances of tissue samples being made available to qualified researchers for valid research purposes at a reasonable cost.

Publicly available samples must be characterized as de-identified samples. If the identity of the sample is known, the identity must be recognizable in the public domain and not entitled to a presumption of anonymity.


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Using Samples from a Tissue Bank

Tissue bank activities involve three components:

  1. the collector of samples and data;
  2. the bank storage and data management center; and
  3. the recipient investigators

An investigator who oversees a tissue bank must follow all of the requirements for tissue use when creating a tissue bank, including informed consent, authorization, sample coding, and de-identification. The investigator over the tissue bank may release samples to other investigators for future studies and may include specific identifiers according to the specific wishes of the participant as indicated on the signed informed consent document. The investigator over the tissue bank is responsible to perform the de-identification before releasing the samples.

The use of samples from a tissue bank requires the submission of a new study application to the IRB, disclosing the proposed use of the tissues, according to the requirements for tissue use. Samples may not be released until final IRB approval has been issued.


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Sharing Samples with Other Institutions

Tissue bank activities involve three components:

  • samples sent to other institutions/entities/investigators (including sponsors) from the University of Utah Covered Entity
  • samples received by the University of Utah Covered Entity from other institutions/entities/investigators

Identifying information can only be shared between institutions if the participant has given authorization to do so. The consent and authorization document must specify which outside institutions/entities/investigators the identifying information will be shared with. If the receiving institutions/entities/investigators are not listed in the authorization, the identifying information cannot be shared.

If use of the samples is approved under a method other than full consent and authorization, the samples must be de-identified before they are shared. The samples may or may not have accompanying medical information. If a code exists to link the samples and the identity of the participants, it should remain with the home institution or entity and not be made available to the other institutions/entities/investigators.

Policy and procedures defining the handling, storage, and disposal of samples should be developed by the investigators and the process for the return of the tissue sample to the original requestor or the process of destruction of the sample(s) should be clearly defined.

IRB review must be conducted for both institutions before the data and samples are shared. The IRB requires all external IRB approvals to be submitted as part of the IRB application. One of the following agreements outlining tissue use and transfer must also be signed by officials representing each institution or entity before the transfer of data and samples may occur:

For more information about what elements a tissue use and transfer agreement should entail, please review the IRB guidance on Human Tissue Transfer.


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FDA Guidance for Testing In Vitro Diagnostic Devices

FDA regulation does not make provision for a full waiver of consent.  This means an IRB should not approve the use of samples for the testing of in vitro diagnostic devices without informed consent. However, the FDA has released a guidance document on this topic, indicating that they will exercise enforcement discretion in certain cases to allow for the use of samples without informed consent.

In order to qualify for a waiver of consent in this case, the following criteria must be met:

  1. The study uses an in vitro diagnostic device that meets the IDE exemption criteria described in 21 CFR 812.2(c)(3), which means the testing
    • is non-invasive
    • does not require an invasive sampling procedure that presents significant risk
    • does not by design or intention introduce energy into a subject
    • is not used as a diagnostic procedure without confirmation of the diagnosis by another, medically established diagnostic product or procedure
  2. The study uses leftover specimens collected for either (a) routine clinical care or analysis that would have been discarded, or (b) future use as part of a tissue bank.
  3. The specimens are de-identified to the investigator(s) who will be conducting the study.  This must be according to HIPAA standards.  Clinical information may be included with the samples, so long as it is de-identified.
  4. The individuals caring for the patients are different from and d not share information about the patient with those conducting the investigation. 

Investigators must attach a copy of the FDA Guidance on Informed Consent for In Vitro Diagnostic Device Studies Using Leftover Human Specimens that are Not Individually Identifiable to the IRB application when requesting such use.  


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 VA Policies for Tissue Collection

The VA designates human subject research to include both living and deceased individuals. Therefore, research involving human tissues from an autopsy or postmortem sampling requires full IRB approval as well as a signed informed consent document by a responsible family member that meets VA requirements.

Human biological specimens, as well as the linked clinical data collected as part of research projects conducted by VA investigators in VA facilities or approved off-site locations, must be maintained at VA-approved tissue banks. Full VA Policy on Tissue Banking [PDF].


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Why Create or Use a Research Tissue Repository?

The advantage to investigators of creating, maintaining, and/or using a research repository lies in the prospective intent of the repository’s organizers to control access to and use of human tissues by multiple investigators and/or of multiple research projects, most of which cannot be specifically described when the repository is created.

Given this focus on multiple, yet-to-be-described research projects, a repository’s operating procedures must include detailed mechanisms for controlling the collection, storage, use, and sharing of its information and tissues.

Investigators who collect information and tissues to be entered into the repository must agree in writing to specific conditions stipulated by the IRB exercising oversight of the repository. Tissue repositories may be maintained by an investigator or department within the University of Utah and its covered entity, an external investigator or institution, or a sponsor (industry, government agency, or non-profit organization).

Likewise, investigators receiving information and tissues from the repository must also agree in writing to specific conditions required by the repository’s IRB. Operators of the repository must implement physical and procedural mechanisms for the secure receipt, storage, and transmission of the information and tissues that the IRB finds sufficient to ensure the protection of participants’ privacy and the confidentiality of participants’ information.

When these protection mechanisms are sufficiently well-defined and implemented, the IRB can confidently approve relatively broad parameters for sharing the information and tissues with research investigators.


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Developing and Maintaining a Tissue Repository

Under a repository protocol, the IRB can approve relatively broad parameters for collecting, storing, sharing, and using the repository’s information and tissues in research. A repository protocol may be submitted to the IRB to accomplish one of the following purposes:

  • Define the operating parameters for establishing and maintaining a new research repository.
  • Convert an existing non-research repository into a research repository.

Researchers who wish to develop or maintain a repository must submit an application for IRB review and receive IRB approval before initiating any repository-related activity.

In addition to the usual information contained in a human research protocol and an IRB application, the IRB expects that protocols for establishing and operating a research repository will include at least the following specific information:

  • The specific conditions under which tissues may be accepted into the repository, including a copy of each participant’s signed consent and authorization document.
  • A detailed description of the physical and procedural mechanisms for the secure receipt, storage, and transmission of information and tissues to ensure the protection of participants’ privacy and confidentiality.
  • The specific conditions under which information and tissues may be shared with or released to research investigators.

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Review Process for Tissue Repositories

IRB review is required for the creation of a tissue repository which is intended for research purposes. IRB approval and continued IRB oversight is required when the intended purpose of a tissue repository containing identifiable human tissues includes research, collecting, storing, sharing, and using the tissues.

As the creation of a tissue repository is considered ‘tissue use’, the review process for tissue repositories is the same as described above: Review Process for Tissue Use and Collection.


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Consent and Authorization for Tissue

Informed consent and authorization (for samples collected within the covered entity) must be accounted for in the one of the following ways:

  • Full informed consent and authorization
  • Waiver of consent plus a method to account for authorization

Full informed consent and authorization must be obtained from participants or their legally authorized representatives for the collection of their samples for repositories, except where waivers or non-human subject determinations apply. Consent and authorization documents should include the following information:

  • Tissue banking description
    For studies that involve tissue banking, the consent form should outline the requirements and options participants have regarding the future use of their samples. Please use the Tissue Banking Template Consent Language as a guide for the specific requirements.
  • Authorization language for use and disclosure of information
    Authorization determines who can have access to participants’ personal health information. This language is outlined in the Biomedical Consent and Parental Permission templates on the IRB website. It is important to consider authorization carefully when designing tissue banking studies, as this authorization will determine how each sample and the accompanying information can be disclosed in the future. Some important considerations are:
    • What protected health information (identifiable or non-identifiable) will accompany the samples?
    • Who will be allowed to receive the samples with the accompanying health information – only individuals within the University of Utah and its covered entity, or others from outside entities and institutions?
  • A waiver of consent may be requested for tissue use and banking studies. The IRB will approve a waiver if the study meets the following 4 criteria, as outlined in 45 CFR 46.116(d):
    1. The research involves no more than minimal risk
    2. The waiver will not adversely affect the rights and welfare of the participants
    3. The research could not practicably be conducted without the waivers
    4. When appropriate, the participants will be provided with additional pertinent information
  • A method to account for authorizationmust be used in conjunction with a waiver of consent. The following methods may be used:

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VA Policies for Tissue Repositories

Human biological specimens, as well as the linked clinical data collected as part of research projects conducted by VA investigators in VA facilities or approved off-site locations, must be maintained at VA-approved tissue banks. Full VA Policy on Tissue Banking [PDF].


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Using Samples from a Tissue Repository

The use of samples from a tissue repository typically requires the submission of a new study application to the IRB, disclosing the proposed use of the tissues, according to the requirements for tissue use. Samples may not be released until final IRB approval has been issued.

The use and disclosure of information and tissues from a repository are determined by the (a) IRB responsible for oversight of the repository, and (b) the IRB responsible for research at the site where the information and tissues are used.

The University of Utah IRB is responsible for any research repository maintained at the University of Utah or its affiliate institutions.

Information and tissues from these repositories may be accessed, used, shared, or disclosed in accordance with the IRB-approved repository protocol, informed consent and authorization document, and any additional conditions stipulated by the IRB. Once provided to investigators outside of the University of Utah, use and disclosure of the information and tissues must also comply with any additional requirements of the recipient institution and it’s IRB.

Last Updated: 10/17/16