Guidelines for IRB Review of Tissue Banking Proposals - Institutional Review Board

Introduction
Definitions
Scope of Policy
IRB Information Requirements
Guidelines for IRB Review
Consent Form Guidelines
Form VI

I. Introduction

These guidelines addresses situations in which an investigator who wishes to enroll subjects in a particular research protocol under review by the IRB (the “primary research or underlying clinical trial”) also wishes to ask those same subjects to consent to the collection of biological materials for transfer to a central repository or “tissue bank” where the biological materials will be stored. Typically, the central repository accepts and stores biological materials in order to make future distribution of these materials to other investigators for other research uses beyond the scope of the underlying clinical trial, which uses are frequently described only in general terms (e.g., “for cancer research”). Hence, these guidelines address situations in which the underlying clinical trial under review by the IRB can be carried out whether or not subjects also give consent to the collection of their biological materials for tissue banking.

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II. Definitions

Human Biological Materials include the full range of specimens, from subcellular structures like DNA, to cells, tissue (e.g., blood, bone, muscle, connective tissue and skin), organs (e.g., liver, bladder, heart, kidney and placenta), and waste (e.g., hair or nail clippings, urine, feces and sweat, that often contain shed skin cells).

Collection of gametes and fetal tissues raise special issues that are outside the scope of these guidelines.

Note: This definition is taken from the 1999 report of the National Bioethics Advisory Commission entitled “Research Involving Human Biological Materials: Ethical Issues and Policy Guidance.”
A Tissue Bank is an entity that receives and stores human biological materials.
An Off-Site Tissue Bank is a tissue bank that is not under the exclusive control of Tufts Medical Center, Tufts University, or both.
Research is understood as defined in the Common Rule, that is, as a systematic investigation designed to develop or contribute to generalizable knowledge.
An Identifier is any one of the following types of information about the individual (or the relatives, employers, or household members of the individual) from whom the biological materials are collected:
1. Name
2. All geographic subdivisions smaller than a State, including street address, city, county, precinct, zip code, and their equivalent geocodes, except for the initial three digits of a zip code if, according to the current publicly available data from the Bureau of the Census:
  1. The geographic unit formed by combining all zip codes with the same three initial digits contains more than 20,000 people; and
  2. The initial three digits of a zip code for all such geographic units containing 20,000 or fewer people is changed to 000.
3. All elements of dates (except year) for dates directly related to an individual, including birth date, admission date, discharge date, date of death; and all ages over 89 and all elements of date (including year) indicative of such age, except that such ages and elements may be aggregated into a single category of age 90 or older.
4. Telephone numbers
5. Fax numbers
6. Electronic mail addresses
7. Social security numbers
8. Medical record numbers
9. Health plan beneficiary numbers
10. Account numbers
11. Certificate/license numbers
12. Vehicle identifiers and serial numbers, including license plate numbers
13. Device identifiers and serial numbers
14. Web Universal Resource Locators (URLs)
15. Internet Protocol (IP) address numbers
16. Biometric identifiers, including finger and voice prints
17. Full face photographic images and any comparable images
18. Any other unique identifying characteristic
Note: The above list is taken from the final federal regulations regarding the privacy of health information issued in December, 2000 under the Health Insurance Portability and Accountability Act (“HIPAA”).
De-Identified Biological Materials are biological materials from which all identifiers, as defined above, have been removed.

De-Identified Biological Materials are of two types:
1. Biological materials that are associated with a code that is linked to an identifier (“linked materials”)
2. Biological materials that are not associated with a code that is linked to an identifier (“unlinked materials”)
For example, an investigator may collect a blood specimen and store it with the patient’s diagnosis and medical record number. If the investigator subsequently removes the medical record number, the specimen has been de-identified. If the investigator then replaces the medical record number by a code that is linked to the medical record number, the specimen is still de-identified but linked. If the investigator removes the medical record number without affixing any code to the specimen (or affixes a code that is not linked to any identifiers), the specimen is de-identified and unlinked.
Medical Record Information means information in any medium, including paper and electronic form, that is derived from medical records maintained by Tufts Medical Center or Tufts University or from research records maintained by investigators, co-investigators, or sub-investigators on a clinical trial reviewed by the IRB.
De-Identified Medical Record Information is medical record information from which all identifiers have been removed.

Like de-identified human biological materials, de-identified medical record information is of two types:

Medical record information that is associated with a code that is linked to an identifier (“linked information”)
Medical record information that is not associated with a code that is linked to an identifier (“unlinked information”)

The Source Individual is the individual from whom the biological materials are collected.

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III. Scope of Policy

These guidelines are intended to cover situations in which subjects enrolling in a research protocol are also asked to consent to the collection of their biological materials for transfer to a tissue bank for storage and future research use. The policy does not address the mandatory collection and transfer of biological materials to a tissue bank as legally required under state law or regulation. The policy is limited to biological materials collected from living persons and does not address the use of biological materials obtained post-mortem.

The IRB has jurisdiction over such situations for the reason that they typically involve an interaction with the source individual to obtain the biological materials and/or the use of biological materials that can be identified with the source individual, either directly or with the help of a code.

Before the IRB will consider a proposed collection of biological materials that falls within the scope of these guidelines, the principal investigator for the underlying clinical trial (the “PI”) must provide the IRB with the following information:

The name, address, contact person and telephone number of the tissue bank responsible for maintaining the biological materials.
The types of biological materials to be transferred to the tissue bank, e.g., blood samples, tumor specimens, etc.
The manner in which the PI plans to collect the biological materials. For example, the PI may plan to collect the biological materials by means of an additional procedure, e.g., an additional blood draw or biopsy, which is not part of the primary research. Alternatively, the PI may plan to utilize a blood draw called for as part of the primary research. In this case, the IRB needs to know whether an additional volume of blood will be drawn for banking purposes or whether surplus blood leftover from the scheduled blood draw will be utilized for banking purposes.
Whether the biological materials that the PI proposes to transfer to the tissue bank will be de-identified. If de-identified, whether the materials will be linked (coded) or unlinked (uncoded).
If it is planned that the tissue bank will distribute the biological materials for research use by other investigators, whether the materials will be de-identified when they are distributed to the other investigators. If de-identified, whether the materials will be linked or unlinked.
If the biological materials are to be coded at any point in the process, who is responsible for maintaining the code and the circumstances, if any, under which the code may be broken.
Whether the PI also proposes to transfer to the tissue bank information from the medical records of the source individual. If so, a description of the specific information to be collected.
If medical record information is involved, whether the information (a) is limited to information that is available at the time the biological materials are transferred to the tissue bank or (b) may require ongoing access to the medical records of the source individual.
Whether the medical record information, if any, that the PI proposes to transfer to the tissue bank will be de-identified. If de-identified, whether the information will be linked or unlinked.
A copy of the tissue bank's written policies, if any, that govern (a) the types of investigators/entities to whom the biological materials may be distributed (b) the types of research for which the biological materials may be distributed, and (c) the measures taken to guard against disclosure of confidential information about the source individual.
Whether distribution of biological materials from the tissue bank to other investigators/entities is subject to oversight by an IRB or similar review body.
Whether or not the source individual can withdraw consent to research use of his/her biological materials/medical records information at any time, and the mechanism for withdrawal.
Whether there are any circumstances in which the tissue bank or individuals/entities to whom the tissue bank distributes biological materials might seek to contact the source individual.
Whether it is anticipated that the biological materials may be subjected to genetic testing or utilized to create a cell line.
Whether the tissue bank proposes to pay money or other remuneration to Tufts Medical Center, Tufts University or the PI in connection with the collection or use of the biological materials.
Whether it is anticipated that the biological materials may be utilized in the development of commercial products.
Whether the results of any research performed on the human biological materials will be conveyed to the source individual or his or her attending physician or placed in the individual’s medical records.

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IV. IRB Information Requirements

The name, address, contact person and telephone number of the tissue bank responsible for maintaining the biological materials.
The types of biological materials to be transferred to the tissue bank, e.g., blood samples, tumor specimens, etc.
The manner in which the PI plans to collect the biological materials. For example, the PI may plan to collect the biological materials by means of an additional procedure, e.g., an additional blood draw or biopsy, which is not part of the primary research. Alternatively, the PI may plan to utilize a blood draw called for as part of the primary research. In this case, the IRB needs to know whether an additional volume of blood will be drawn for banking purposes or whether surplus blood leftover from the scheduled blood draw will be utilized for banking purposes.
Whether the biological materials that the PI proposes to transfer to the tissue bank will be de-identified. If de-identified, whether the materials will be linked (coded) or unlinked (uncoded).
If it is planned that the tissue bank will distribute the biological materials for research use by other investigators, whether the materials will be de-identified when they are distributed to the other investigators. If de-identified, whether the materials will be linked or unlinked.
If the biological materials are to be coded at any point in the process, who is responsible for maintaining the code and the circumstances, if any, under which the code may be broken.
Whether the PI also proposes to transfer to the tissue bank information from the medical records of the source individual. If so, a description of the specific information to be collected.
If medical record information is involved, whether the information (a) is limited to information that is available at the time the biological materials are transferred to the tissue bank or (b) may require ongoing access to the medical records of the source individual.
Whether the medical record information, if any, that the PI proposes to transfer to the tissue bank will be de-identified. If de-identified, whether the information will be linked or unlinked.
A copy of the tissue bank's written policies, if any, that govern (a) the types of investigators/entities to whom the biological materials may be distributed (b) the types of research for which the biological materials may be distributed, and (c) the measures taken to guard against disclosure of confidential information about the source individual.
Whether distribution of biological materials from the tissue bank to other investigators/entities is subject to oversight by an IRB or similar review body.
Whether or not the source individual can withdraw consent to research use of his/her biological materials/medical records information at any time, and the mechanism for withdrawal.
Whether there are any circumstances in which the tissue bank or individuals/entities to whom the tissue bank distributes biological materials might seek to contact the source individual.
Whether it is anticipated that the biological materials may be subjected to genetic testing or utilized to create a cell line.
Whether the tissue bank proposes to pay money or other remuneration to Tufts Medical Center, Tufts University or the PI in connection with the collection or use of the biological materials.
Whether it is anticipated that the biological materials may be utilized in the development of commercial products.
Whether the results of any research performed on the human biological materials will be conveyed to the source individual or his or her attending physician or placed in the individual’s medical records.

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V. Guidelines for IRB Review

The IRB will utilize the following guidelines in reviewing a proposed collection of human biological materials and associated medical record information (“HBM/MRI”) for transfer to an off-site tissue bank:

The proposal will be reviewed at a meeting of the IRB, rather than by expedited review.
There must be two separate informed consent documents, one for participation in the underlying clinical trial and another for consent to the collection and transfer of HBM/MRI. The subject’s willingness toconsent to the latter cannot be a condition for participation in the underlying clinical trial.
The collection and transfer of the biological materials must not compromise the medical care or safety of the source individual.
In situations in which the IRB determines that there is a potential for compromise of care or safety, the IRB may impose conditions to eliminate or minimize the potential. If, for example, the proposal involves biological materials that are “left over” after performance of diagnostic tests on a surgically removed tumor, the IRB may guard against removal of additional tissue by requiring that the surgeon not know whether or not the patient has consented to the research use of any surplus materials.
The IRB may approve proposals that involve the collection and transfer of de-identified unlinked HBM/MRI to an off-site tissue bank, provided:
1. The proposal sets out the information specified above in Part IV;
2. Informed consent will be obtained in accordance with the guidelines in Part VI;
3. If the tissue bank plans to distribute HBM/MRI to other investigators, the tissue bank has a written policy that governs the types of investigators/ entities to whom the HBM/MRI may be distributed and the types of research for which the HBM/MRI may be used, which policy must be made available to the IRB.
The IRB may approve proposals that involve the transfer and collection of de-identified linked HBM/MRI to an off-site tissue bank, provided:
1. The proposal sets out the information specified above in Part IV;
2. The HBM/MRI will be de-identified, i.e., stripped of all identifiers, before they leave Tufts Medical Center/Tufts University;
3. The key to the code will remain within the exclusive possession and control of a designated individual or individuals at Tufts Medical Center/Tufts University;
4. The proposal identifies a secure location in which the designated individual(s) will keep the key to the code and specifies that the key will not be divulged to the tissue bank, secondary recipients of the biological materials, or to anyone else except pursuant to IRB approval or as necessary for an audit to ensure that written informed consent was obtained;
5. Written informed consent will be obtained in accordance with the guidelines in Part VI;
6. The source individual is able to withdraw consent at any time to future use of HBM/MRI that have been transferred to the tissue bank, except where it is impossible to effectuate the withdrawal because:
7. If the tissue bank plans to distribute the HBM/MRI to other investigators, the tissue bank has a written policy that governs the types of investigators/ entities to whom the HBM/MRI may be distributed and the types of research for which the HBM/MRI may be used, which policy must be submitted to the IRB;
8. Once HBM/MRI have been transferred to the tissue bank, the results of research performed on those materials will not be communicated to the source individual or to the individual’s attending physician or placed in the individual’s medical record, except in extraordinary situations of compelling need, as determined on a case by case basis by the IRB.
In specific circumstances, the IRB may approve proposals that involve the collection and transfer of linked HBM/MRI that have not been stripped of identifiers, provided the requirements of Section V.6(1) and V.6(3) through V.6(8) above are met; and
1. The proposal is well designed as determined by the IRB;
2. The intended research uses of the HBM/MRI cannot reasonably be carried out if all identifiers are removed;
3. The IRB documents in the minutes and approval letter the specific identifier(s) that it has determined are necessary to the proposed research uses;
4. All other identifiers will be removed prior to transfer of HBM/MRI to the tissue bank;
5. The privacy risks to the source individuals are reasonable in relation to the importance of the knowledge that may be developed through the research uses of the HBM/MRI;
6. An IRB will review every occasion on which the tissue bank proposes to distribute the HBM/MRI to researchers;
7. The IRB submits the proposal and consent form for review by the relevant legal office for the purpose of determining the appropriateness of a written agreement between the institution and the tissue bank with respect to the tissue bank's policies for protection of patient confidentiality and indemnification of the institution in the event of harm resulting from loss of confidentiality;
8. The consent form explicitly describes the particular identifier(s) that will be disclosed to the tissue bank.
The IRB will not approve prospective collection of medical record information. Accordingly, IRB approval for the collection of associated medical record information will be limited to information that is available at the time the biological materials are transferred to the tissue bank. If the PI wishes to collect medical record information generated subsequent to that date, the PI must make a subsequent application to the IRB for the collection of updated medical record information, which application will be considered at a subsequent meeting of the IRB. In deciding whether or not to approve the application, the IRB will consider whether or not the additional information requested and the proposed research use of the information fall within the scope of the initial consent. See VI.18 below.
No HIV-test information may be collected, unless the source individual has provided the specific consent for disclosure of such information that is required under Massachusetts law.
The IRB may require the tissue bank to provide written assurance that it will not make any attempt, through use of other databases or other means, to ascertain the identity of the source individuals, and may require the tissue bank to agree to return to Tufts Medical Center/Tufts University any HBM/MRI that are inadvertently transferred to the tissue bank with identifiers.
The IRB may, with respect to particular proposals, impose any other conditions that it deems necessary or advisable for the protection of human subjects. For example, if the written policies of the tissue bank do not describe with sufficient specificity the research purposes for which the biological materials may be used, the IRB may condition approval upon written assurance that the tissue bank is subject to oversight by an IRB, ethics committee, or similar body, and that the recipient investigators are bound to abide by the conditions specified by that IRB.
The IRB will submit to the relevant legal office for its review any proposal that involves the transfer of money or other remuneration from the tissue bank to Tufts Medical Center, Tufts University or the principal investigator in connection with the use of the biological materials. The IRB will not consider the proposal for final approval until the IRB receives from the legal office written notification that all legal issues, if any, have been satisfactorily resolved.

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VI. Consent Form Guidelines

The following information must be included in the consent form:

The name, address, contact person and telephone number of the tissue bank.
A description of the biological materials to be collected.
A description of the manner in which the biological materials will be collected, and in particular whether the involvement of the tissue bank will necessitate the performance of procedures in addition to, or taking of materials in a greater volume than, what would otherwise be done as part of the underlying clinical trial.
If associated medical record information will also be collected, a description of the specific information involved.
A statement that the source individual’s agreement to collection of HBM/MRI for transfer to a tissue bank is not a condition for enrollment in the underlying clinical trial or for future care and treatment at Tufts-NEMC.
A description of the measures that will be taken to guard against loss of confidentiality.
If the HBM/MRI will be coded, identification of the person(s) responsible for maintaining the key to the code, and the measures to be taken to safeguard the confidentiality of the key.
A description of the tissue bank’s written policies that govern (a) the types of investigators/entities to whom the HBM/MRI may be distributed and (b) the purposes for which the HBM/MRI may be used. The consent form should describe the intended purposes for the future use of the materials with as much specificity as possible.
If the HBM/MRI will be coded, a statement that the source individual can withdraw consent at any time to future use of the HBM/MRI, except where it is impossible to effectuate the withdrawal because the tissue bank has already distributed the HBM/MRI, or the code is no longer available. Include the name and telephone number of the person to contact in order to withdraw consent.
A statement that the subject will not be contacted by the tissue bank or by secondary recipients of HBM/MRI distributed by the tissue bank.
A statement, if applicable, that genetic tests will or may be performed on the biological materials.
A statement, if applicable, that the biological materials will or may be utilized in the development of commercial products, including the development of cell lines.
If the collection of biological materials involves the performance of procedures in addition to the procedures that would be performed as part of the underlying clinical trial, or involves the collection of materials in a greater volume than would be collected as part of the underlying clinical trial, an explanation of the associated risks, if any.
A statement that a risk of participation is the possible loss of confidentiality. If genetic testing is anticipated, include a statement to the effect that the results of genetic tests, if inadvertently disclosed, could negatively affect access to insurance or employment, or could have an impact upon social relationships.
A statement that the source individual will not receive any direct benefit from participation.
A statement that once the source individual’s biological materials have been transferred to the tissue bank, the results of research performed on those materials will not be communicated to the source individual or to the individual’s attending physician, or placed in the individual’s medical records.
An explanation, if applicable, that Tufts Medical Center/Tufts University/the principal investigator will receive money or other remuneration from the tissue bank for the collection or use of the biological materials. No explanation is necessary if the remuneration is intended solely as reimbursement for the direct costs of the collection of the materials and transfer to the tissue bank.
If it is anticipated that information will be needed from the medical records of the source individual on an ongoing basis, the consent form must:
1. Explicitly disclose that medical record information will continue to be collected from future medical records on an ongoing basis;
2. Describe the specific information to be collected;
3. State that the ongoing collection of medical record information will be subject to the further review and approval of the IRB;
4. State that the ongoing collection of medical record information will terminate once all research on the individual’s biological materials has been completed;
5. State that the individual can at any time revoke permission for the ongoing collection of information from his or her medical records.
If the IRB approves a proposal under Section V.7 above, the consent form should include the following additional elements:
1. An expiration date or expiration event;
2. A statement that once medical record information is disclosed to the tissue bank, the information is subject to redisclosure by the tissue bank that may not be protected by the federal privacy rule;
3. A statement that the patient may inspect or copy the medical record information to be disclosed to the tissue bank;
4. A statement describing the particular identifier(s) that will be disclosed to the tissue bank (for example, age, zip code, etc.).

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