Health and Human Services Homepage

  U.S. Department of Health and Human Services | National Institutes of Health

Common Rule Bulletin #3: Biospecimens/Data Requirements in ICF

NIH OFFICE OF HUMAN SUBJECTS RESEARCH PROTECTIONS (OHSRP) GUIDANCE ON THE REVISED COMMON RULE

Common Rule Bulletin# 3: Informed Consent Requirements – “Biospecimen/Data Requirements”

The revised Common Rule (rCR), referred to as the “2018 requirements” or sometimes as “the Final Rule”, contains several new provisions that take effect for all new research reviewed on and after January 21, 2019. Note: This guidance is intended for use by the NIH Intramural Research Program (IRP) and may be superseded by future NIH guidance or policy, or guidance issued by the Office for Human Research Protections (OHRP).

A subset of the changes affects informed consent and this document aims to provide research teams with guidance on our current understanding of the new informed consent provisions and how to operationalize them so that informed consent documents achieve the intended aim of the revisions and are compliant with the regulations.

This guidance is focused on the consent elements regarding biospecimen/data to be included in a standard research informed consent. The rCR adds 1 new required element that must be included in all standard research consent documents, as well as 3 additional elements that must be included when appropriate for a specific research study. This guidance document does not discuss the biospecimen/data requirements necessary for broad consent. This will be discussed in a separate guidance document.

Summary of Biospecimen/Data Requirements for Informed Consent Documents

The original 8 required elements of informed consent at 45 CFR 46.116(b) were not changed by the rCR but 1 (one) new element is now included at 45 CFR 46.116(b)(9):

One of the following statements about any research that involves the collection of identifiable private information or identifiable biospecimens must be included in the informed consent document:

(i) A statement that identifiers might be removed from the identifiable private information or identifiable biospecimens and that, after such removal, the information or biospecimens could be used for future research studies or distributed to another investigator for future research studies without additional informed consent from the subject or the legally authorized representative, if this might be a possibility; or

(ii) A statement that the subject's information or biospecimens collected as part of the research, even if identifiers are removed, will not be used or distributed for future research studies.

In addition, 3 (three) new elements were added that must be included when they are appropriate for the research study:

45 CFR 46.116(c)(7) A statement that the subject's biospecimens (even if identifiers are removed) may be used for commercial profit and whether the subject will or will not share in this commercial profit;

45 CFR 46.116(c)( (8) A statement regarding whether clinically relevant research results, including individual research results, will be disclosed to subjects, and if so, under what conditions; and

45 CFR 46.116(c)( (9) For research involving biospecimens, whether the research will (if known) or might include whole genome sequencing (i.e., sequencing of a human germline or somatic specimen with the intent to generate the genome or exome sequence of that specimen).

Background

The new basic element at 45 CFR 46.116(b)(9) is required when the research will involve prospective collection of specimens or data. It is intended to inform the prospective subject whether their specimens collected on the proposed research, might have identifiers removed and used for future research or shared without any additional consent process. This makes transparent a process for sharing specimens/data of which subjects may not be aware.

The purpose of the additional 3 (three) new elements at 45 CFR 46.116(c)(7-9), is to be certain that subjects are informed of certain activities that are becoming increasingly commonplace in research and have not always been addressed in research informed consent documents.

45 CFR 46.116(c)(7) requires that if biospecimens will be used for commercial profit that this fact must be explained to subjects prospectively and that it should be made clear to the subject if s/he should expect to share in the profit or not. The Secretary’s Advisory Committee for Human Research Protections (SACHRP) spent significant effort on this topic, finalizing recommended edits to the biospecimen and data FAQs at their March 2018 meeting. The FAQ #25 on Commercialization further advises:

“The consent also should disclose sponsorship and address issues including (but not limited to) disposition of samples, who will have access, and how samples will be used. Subjects should be informed to what extent, if any, they can expect to control or receive compensation from future commercial uses...” (see References).

The additional element at 45 CFR 46.116(c)(8) discusses a topic that has been widely discussed in the research community, especially given the advances in genomic technology, namely the return of clinically relevant results. In the course of research, it is possible that results relevant to the health and welfare of a participant may be generated. These may be primary research findings or secondary findings not necessarily related to the aims of the study (sometimes termed incidental findings). The findings may or may not be anticipated by the research team.

This new requirement states that the subject should be prospectively informed whether these clinically relevant results obtained as part of the research will or will not be provided to the him/her. If they are to be provided, the subject must be told under what the circumstances these results will be provided. If return of research results is anticipated, the investigator will need to incorporate into the protocol a plan for returning the results. It is important to note that while much of the discussion on return of results has been related to genomic research, the regulation, applies to any clinically relevant results that might result from the research intervention or testing.

Note: CLIA regulations require that any result that might be used clinically must come from a CLIA certified laboratory environment. Results generated in non-CLIA labs may not be returned to participants or their provider. As part of the return of results plan, investigators should address whether the results are CLIA certified, and if not, how confirmatory CLIA testing will be done.

The additional element at 45 CFR 46.16(c)(9) requires investigators to inform participants if whole genome sequencing will or might be performed on their specimen. Empiric data suggests that many participants wish to be informed of this possibility in advance. Hence, the requirement for this new element.

All these new elements of consent are designed to increase the transparency of the research enterprise to those who enroll in our studies. While many of these activities seem routine to us as researchers, many members of the community are not aware of the nature of secondary research. Informing individuals as to what might or might not be done to their biospecimen in the future fulfills an important ethical obligation of respect for persons. It increases the level of public trust in research, which in turn can further future support.

How will these requirements be implemented at the NIH?

All informed consent documents for research collecting identifiable biospecimens or information from subjects, approved on or after January 21, 2019 must include the following information:

  • Research collecting identifiable private information and/or identifiable biospecimens must state that [45 CFR 46.116(b)(9)]:
    • Collected samples/data may be de-identified and used for future research or be given to another investigator for future research without consent; OR
    • Collected samples/data will not be used or distributed for future research even if deidentified.
  • And, as applicable to the research, these additional elements of consent are also required:
    • Statement that biospecimens, even if de-identified, may be used for commercial profit, and whether/if that profit will be shared. [45 CFR 46.116(c)(7)]
    • Statement regarding whether clinically relevant research results will be given to the participant and under what conditions. [45 CFR 46.116(c)(8)]
    • For research involving biospecimens, whether the research will or might include whole genome or exome sequencing. [45 CFR 46.116(c)(8)] 

NIH OHSRP recently updated the NIH informed consent template. The new NIH informed consent template must be used for studies conducted at the NIH Clinical Center (CC) to start but will be expanded for use across all NIH sites. The template comprises NIH required language, document headers, document footers, and section headings, as well as optional section headings and instructional language, and is consistent with NIH policies and the revised Common Rule (rCR). The template incorporates the new elements of informed consent as required by the rCR, including the new Key Information section (see Common Rule Bulletin# 1: Informed Consent Requirements – “Key Information) and sample language for: 1) the future/secondary use of biospecimens/data, 2) whether biospecimens may be used for commercial profit, 3) whether clinically relevant results will be shared and how, and 4) whether whole genome/exome sequencing will be performed.

References:

SACHRP Updated FAQs on Informed Consent for Use of Biospecimens and Data (March 2018): https://www.hhs.gov/ohrp/sachrp-committee/recommendations/attachment-c-faqsrecommendations-and-glossary-informed-consent-and-research-use-of-biospecimens-andassociated-data/index.html
Return to top