National Heart, Lung, and Blood Institute
National Institutes of Health
Revised: April 14, 2000
Various issues regarding use of stored tissue are covered in a November 7, 1997 issuance from OPRR (http://grants.nih.gov/grants/oprr/humansubjects/guidance/reposit.htm). Research Involving Human Biological Materials: Ethical Issues and Policy Guidance). A draft of a document being developed by the NIH (Research on Human Specimens) also covers these issues (http://www-cdp.ims.nci.nih.gov/policy.html). NCI has developed sample consent documents for repository activities (http://www.napbc.org/napbc/consent.htm and http://www.napbc.org/napbc/q&a.htm).
Discussions of additional issues can be found in the August, 1999 report from the National Bioethics Advisory Commission. Go to the National Bioethics Advisory Commission page, select Reports, and scroll down to Ethical Issues in Human Stem Cell Research, September 1999. (All these files are in Adobe PDF format.)
The following operating principles and NHLBI staff responsibilities are consistent with these documents, in particular the OPRR regulations.
- The concept of a tissue repository may include two kinds of samples: a) those collected with the expressed purpose of distribution to investigators, and b) those collected by individual investigators, and not originally intended to be shared with others, but which are subsequently shared as part of a repository. Any collection which contains specimens that are potentially identifiable and are distributed to someone other than the investigator (or, in the case of a multi-investigator study, other than any of the identified investigators) making the collection, regardless of the original intent, may be considered to be a repository.
- Any identifiable tissue (included coded tissue) that is collected requires IRB review at the site of collection (even if different from the site of the repository) and, under most circumstances, written informed consent from the subject. Where possible, informed consent should include information about the repository and the conditions under which tissues will be shared. (For example, see NCI sample consent above.)
- Any tissue repository that distributes materials requires an IRB, convened under an OPRR-approved assurance, that lays out the conditions under which the tissue will be shared. These conditions must consider the privacy of the individuals from whom the tissue came, what the informed consent permitted, and the intent of the person to whom the tissue is sent.
- A committee, established under the repository IRB's guidelines, must evaluate each request for samples to see if the request is consistent with the IRB's conditions for sharing samples and with the original informed consent. The IRB at the repository institution may choose to perform this committee's functions itself.
- The recipient of the tissue samples must abide by the conditions specified by the repository IRB. This need not, but may, include review and approval by an IRB at the recipient's organization.
- Exemptions to the need for IRB review and informed consent may be made if the tissue samples are truly unable to be tied to an individual. Samples that are coded do not qualify for an exemption, as someone has the key to the code.
- Even if the samples do not formally constitute a repository, IRB approval at the institution where the samples are stored is required if the collector/distributor is an NIH employee or if the storage is for the purpose of sharing and that sharing is supported by funds from the Department of Health and Human Services. The need for IRB approval in other situations depends on the institution's OPRR-approved Assurance.
- The above Operating Principles will be broadly disseminated to the research community, including to investigators who do not currently distribute tissue samples, but might do so in the future. The Operating Principles would be put on the NHLBI public web site.
- NHLBI staff will ensure that any funded study involving the collection of specimens from human beings has IRB approval.
- NHLBI staff will ensure that any tissue repository has an approved IRB that has developed conditions for distribution of samples, which are consistent with the informed consents under which the tissue is collected.
- NHLBI staff will ensure that any tissue repository has a committee that reviews requests for samples.
- NHLBI staff are not responsible for ensuring that each individual sample that is distributed receives IRB approval when it is appropriate. That is the responsibility of the investigator and the IRB at the investigator's institution.
- The NHLBI funds an investigator to perform research on patients. Part of the research includes analysis of blood specimens. Aliquots of the specimens are stored, using some of the NHLBI grant money. Three colleagues of the investigator (from other institutions) learn of the specimens and ask for samples, as they would be useful for their own research.
This is not a formal repository. Whether or not the investigator needs IRB approval to provide the samples depends on her institution's OPRR-approved Assurance. If IRB approval is needed, the nature of the review may differ depending on factors such as what the informed consent says, the nature of the research that the colleagues wish to perform, and privacy protection for the patients. NHLBI staff would not be involved in these decisions.
- The NHLBI funds an investigator to perform research on patients. Part of the research involves storage of and special analyses on biopsy specimens. The investigator subsequently realizes that the collection of specimens from patients with a particular condition is larger than most and possibly important for future research. He applies to the NHLBI for additional support to maintain the collection and to distribute samples to other investigators. This would be considered as a repository. The investigator's IRB would need to review the conditions under which the specimens are distributed. A formal process for deciding on the appropriateness of providing specimens would need to be established. A factor in the process would be whether or not the specimens can be linked to individual patients. NHLBI staff would be involved in assuring that there is a process for specimen distribution.