Recommendation 4. Before releasing coded and/or identified samples from its collection, a repository should require that the investigator requesting the samples either provide documentation from the investigator’s IRB that the research will be conducted in compliance with applicable federal regulations or explain in writing why the research is not subject to those regulations.
The Working Group concurs with Recommendation 4, which highlights the responsibility of repositories in protecting human subjects.
For those repositories operating under the Regulations, NBAC’s Recommendation 4 should work in concert with existing OHRP guidance, which states that repositories should operate under IRB oversight.11 It also provides for situations in which an investigator requesting coded samples signs an agreement with the repository indicating that he/she will not be provided with means to identify the samples. In such cases, the researcher is, in effect, working with anonymized samples and will have documentation to that effect.
It should be noted that there are situations in which the Federal Government has no jurisdiction over either the repository or the investigator. In such cases, where the parties are not governed by federal human subject protection regulations, opportunities for oversight may at best be limited. The Working Group urges that parties not subject to Federal oversight comply voluntarily with OHRP guidance.
The Working Group proposes that OHRP, in consultation with FDA, review for applicability and disseminate as appropriate its existing guidance on the type of information that repositories operating under the Regulations require in order to evaluate whether a proposed use of samples is in compliance with applicable federal regulations. These repositories should require all researchers to provide such information and documentation, use such information to determine whether and how to release samples, and retain records to document their procedures and decisions.
Recommendation 5. When reviewing and approving a protocol for research on human biological materials, IRBs should require the investigator to set forth
- a thorough justification of the research design, including a description of procedures used to minimize risk to subjects,
- a full description of the process by which samples will be obtained,
- any plans to obtain access to the medical records of the subjects, and
- a full description of the mechanisms that will be used to maximize the protection against inadvertent release of confidential information.
The Working Group concurs with Recommendation 5. Although the wording of this recommendation does not state so specifically, the recommendation addresses only research protocols involving the use of identified or coded samples since it appears, along with Recommendation 4, in a section that specifically addresses identified or coded human biological materials.
NBAC’s Recommendation 5 clearly articulates those issues that must be considered by an IRB when evaluating a proposal for research involving identified or coded human biological materials. These requirements are consistent with 45 CFR 46.111(a) and 21 CFR 56.111(a), which require the IRB to determine that research procedures are consistent with sound research design and do not unnecessarily expose subjects to risk. Guidance relevant to Recommendation 5 is contained in the Institutional Review Board Guidebook: Chapter 3a (Risk Benefit Analysis),12 Chapter 3d (Privacy and Confidentiality),13 Chapter 4 (Considerations of Research Design)14 and Chapter 5h (Human Genetic Research).15 The responsibility of IRBs to evaluate the investigator’s plan for maintenance of confidentiality is further elaborated in the memorandum “IRB Knowledge of Local Research Context”,16 which includes “method for protection of privacy of subjects” and “method for maintenance of confidentiality of data” as elements of the proposal that must be submitted to the IRB for review. Another provision of the memorandum requires IRBs to “determine and specifically document that provisions to protect the privacy of subjects and maintain the confidentiality of data are adequate.”
The Working Group calls attention to a strategy that can be used to protect research subjects from certain types of disclosures of sensitive information. Where appropriate and available, an investigator may obtain a Certificate of Confidentiality17 from DHHS. This permits the investigator to resist compulsory legal demands, such as subpoenas and court orders, for information identifying research subjects. Investigators and IRBs should be more aware of the potential value of these Certificates.
This Recommendation is directed at IRBs and is well covered by current OHRP guidance. However, the Working Group proposes that OHRP urge organizations such as Public Responsibility in Medicine and Research (PRIM&R) and the Applied Research Ethics National Association (ARENA) to increase awareness of pertinent guidance and educational materials that can assist IRBs in the review, and investigators in the preparation, of research protocols involving identified or coded samples.