NIH

The Notice of Proposed Rulemaking (NPRM) for Revisions to the Common Rule

Questions & Answers

These Q&As are not meant to provide official interpretation or guidance on the NPRM but instead to highlight information in the NPRM that is relevant for members of the genomics community. Please see OHRP's NPRM page for more information: NPRM for Revisions to the Common Rule

Background

Research with biospecimens and private information

Informed Consent

New Privacy Safeguards

Proportional Oversight and IRB Review

Streamlining IRB Revew

Coverage of All Clnical Trials



Background

When would changes to the Final Rule come into effect?

Compliance with the new rules would begin one year after publication of the Final Rule with the exception of provisions .102(e) (redefining human subjects to include biospecimens) and .114(b)(1) (single IRB for cooperative research) that would be given three years.  Provisions that give additional flexibility and reduce burdens to researchers could be voluntarily implemented 90 days after publication of the Final Rule.

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Research with biospecimens and private information

Why would almost all research with biospecimens require consent under the proposed revisions?

For this proposed revision, the NPRM gives more weight to the principle of respect for persons than to beneficence (maximizing the benefits of research while minimizing harms). Because people have a strong autonomy interest in their biospecimens and wish to have some level of control over how their biospecimens are used, the NPRM proposes to elevate respect for persons by respecting their wishes and requiring informed consent.

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Is there a proposed grandfather clause on the requirement to obtain consent for biospecimens research?

Yes, the new requirements would be prospective and would only apply to research beginning three years after publication of the Final Rule.

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Could exemption .104(f) (for storage, maintenance, and study of biospecimens and identifiable private information with consent for future, unspecified research use) be used if a study plans to return research results to participants?

No; if a study plans to return results to research participants, the study would not qualify for the exemption under the NPRM. The study would have to undergo full IRB review.

However, there is an alternate proposal in the NPRM to create a panel of experts to make determinations about which unexpected findings and other data should be disclosed to participants. If this alternate proposal was implemented in the final rule, exemption .104(f) could be used to return approved information to participants without additional IRB review.

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Could exemption .104(f) (for storage, maintenance, and study of biospecimens and identifiable private information with consent for future, unspecified research use) be used to develop and share cell lines with other researchers?

Given that cell lines are a form of biospecimen, and given that the informed consent form includes information about this possible research use and future sharing, the exemption should apply to the creation and distribution of cell lines.

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Would the proposed changes apply to biospecimens from the deceased?

No, biospecimens from the deceased are not defined as human subjects under the NPRM or the current Common Rule.

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The primary proposal in the NPRM calls for changing the definition of human subjects to include biospecimens. What are the alternative proposals for changing the definition of human subjects?

Alternative A would expand the definition of human subject to include whole genome sequencing "or any part of the data generated as a consequence of whole genome sequencing." The NPRM notes that a significant difference between this proposal and the primary proposal is that under Alternative A, data produced by clinical whole genome sequencing (WGS) could only be used for research after additional consent, but under the primary proposal, clinical whole genome sequencing data could be used without additional consent (since, as currently defined by HHS, WGS data do not meet the definition of identifiable private information).

Alternative B is narrower than the primary proposal but broader than Alternative A. This proposal would expand the definition of human subjects to biospecimens based on the technology used to analyze that information. If the technology would make the data potentially identifiable, then the research would qualify as human subjects research. This information would be called "bio-unique information" and would include consent for sequencing "of even small portions of a person's genome," and for future technology that would qualify. A major concern with this proposal is that it would require continuous evaluation of new technologies to be included on the Secretary's list of information that is considered "bio-unique."

See a chart comparing the three proposals here

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What is the difference between de-identified information and non-identified information?

The term "non-identified" is used to distinguish it from the Health Insurance Portability and Accountability Act (HIPAA) term "de-identified." Non-identified biospecimens or data "have been stripped of identifiers such that an investigator cannot readily ascertain a human subject's identity" while HIPAA has specific requirements for what qualifies as de-identified.

In presentations by OHRP employees, presenters have been using the term "de-identified" for clarity and because this is an established and understood term.

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How is non-identified information treated under the NPRM?

Non-identified information is treated in the same way as it is under the current Common Rule. Non-identified data could continue to be used for secondary research without additional consent from the people from whom they came. 

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Informed Consent

What are the proposed new required elements of informed consent?

From the text of the NPRM:

  • "The proposed new element at §__.116(b)(7) would require that prospective subjects be informed that their biospecimens may be used for commercial profit and whether the subject will or will not share in this commercial profit."
  • "The proposed new element at §__.116(b)(8) would require that prospective subjects be informed of whether clinically relevant research results, including individual research results, will be disclosed to subjects, and if so, under what conditions."
  • "The proposed new element at §__.116(b)(9) would provide subjects or their legally authorized representatives with an option to consent, or refuse to consent, to investigators re-contacting the subject to seek additional information or biospecimens or to discuss participation in another research study."

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The NPRM only refers to written consent. Would e-consent satisfy this requirement?

Yes; just as under the current Common Rule, electronic informed consent would be permitted. No changes have been proposed regarding this.

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Under the proposed changes, would consent forms for all clnical trials have to be made publically available?

Yes; under the proposed revisions, there would be a one-time posting requirement for consent forms for clinical trials so that they could be made available for public scrutiny.

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What is the difference between informed consent requirements in NIH's Genomic Data Sharing (GDS) Policy and those in the proposed revisions to the Common Rule?

NIH's informed consent requirements under the GDS Policy are more stringent with regard to genomic data than those under the proposed revisions to the Common Rule. The GDS Policy expects investigators to obtain consent for genomic and phenotypic data to be used in future research and to be shared broadly, irrespective of the source of the data. The data are also expected to be de-identified. In contrast, the proposed revisions of the NPRM would require consent for all secondary use of biospecimens and identifiable personal information for research but not for genomic (or other) data obtained from clinical encounters that are subsequently de-identified. There are also no expectations outlined in the NPRM for de- (or non-) identification or broad data sharing.

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New Privacy Safeguards

To what would the new privacy safeguard provisions apply?

The new privacy safeguard Provisions would apply to all non-excluded research with biospecimens and identifiable information.

All non-exempt research and certain exempt research would also be subject to the new privacy safeguards of the NPRM. The exempt research that would require safeguards includes:

  • Benign interventions with adult subjects
  • Research involving educational tests, surveys, interviews, or observations of public behavior when sensitive information may be collected
  • Secondary research use of identifiable private information originally collected as part of a non-research activity, where notice of possible use was given
  • Storage, maintenance, and study of biospecimens and identifiable private information for future, unspecified research use

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Proportional oversight and IRB review

What is the difference between an exclusion and an exemption?

Exclusions are a new category created under the NPRM for activities that would not be subject to the regulations and would require no review because they either 1) are deemed not to be research, 2) are inherently low risk and have adequate protections otherwise mandated, or 3) include secondary research use of biospecimens that will not reveal new information about an individual. There are 11 proposed exclusions.

See a flowchart of the 11 proposed exclusions here

Exemptions under the NPRM would have limited oversight requirements commensurate to the level of risk posed by the studies. There are 3 proposed categories of exemptions: 1) low-risk interventions that would require only documentation of exemption, 2) research that may involve sensitive information that would require documentation of exemption and the application of privacy safeguards for identifiable private information and biospecimens, and 3) secondary research with biospecimens and identifiable private information that would require exemption documentation, application of privacy safeguards, use of  the Secretary's broad consent template, and limited IRB review. There are 8 proposed exemptions.

See a flowchart of the 8 proposed exemptions here 

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What is the difference between program improvement activities and quality assurance and improvement activities as defined by the NPRM?

Program Improvement Activities would involve "data collection and analysis, including the use of biospecimens, for an institution's own internal operational monitoring and program improvement purposes, if the data collection and analysis is limited to the use of data or biospecimens originally collected for any purpose other than the currently proposed activity, or is obtained through oral or written communications with individuals." These activities would be excluded because they are not designed to produce generalizable knowledge.

Example from NPRM: a survey of hospital patients to evaluate and improve the quality of meals.

Quality Assurance and Quality Improvement Activities would involve "the implementation of an accepted practice to improve the delivery or quality of care or services (including, but not limited to, education, training, and changing procedures related to care services) if the purposes are limited to altering the utilization of the accepted practice and collecting data or biospecimens to evaluate the effects on the utilization of the practice."

Example from NPRM: Assume there is an accepted practice for insertion of a central line that reduces the likelihood of an infection. A randomized study to determine whether an educational intervention with staff can increase adoption of this practice would qualify under this exclusion; the activity would only be designed to assess whether the intervention results in greater use of the accepted practice and not to evaluate the practice itself.

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Streamlining IRB Review

Under the porposed changes, would single IRBs have to be used for multisite studies? What about for multisite studies conducted in whole or part outside of the United States?

Under the NPRM, single IRBs would have to be used for multisite trials. For trials conducted in whole or part outside of the United States, a local IRB could be used.

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Coverage of All Clinical Trials

How would the porposed changes extend the Common Rule to virtually all clinical trials in the United States?

Only federally-funded clinical trials are subject to the requirements of the current Common Rule. The proposed revisions would extend the Common Rule to cover all clinical trials, regardless of their funding source, if the research is conducted at a US institution that receives federal funding for non-exempt and non-excluded human subjects research.

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Last Updated: December 22, 2015