By James E. Valentine* & David C. Clissold –
On September 8, the U.S. Department of Health and Human Services (HHS) and fifteen other Federal departments and agencies announced a Notice of Proposed Rulemaking (NPRM) to revise the Federal Policy for the Protection of Human Subjects, known as the “Common Rule.” This 1991 set of regulations created a uniform set of human subject protections which are codified in each department or agency’s title or chapter of the Code of Federal Regulations (CFR) based on HHS’ regulations at 45 CFR part 45, subpart A.
The NPRM applies the same fundamental principles that underlie the Common Rule—respect for persons, beneficence, and justice—to the new contexts in which research is conducted in the 21st Century. The proposal is intended, among other things, to account for the change in volume and landscape of research involving human subjects, as well as the greater scale and more diverse nature of such research. The NPRM is also meant support efforts at HHS to harmonize human subjects policies between the HHS Office of Human Research Protection (OHRP) and FDA (e.g., see our previous post on FDA’s draft guidance on “Use of Electronic Informed Consent in Clinical Investigations,” which was developed as part of these efforts).
Below are some of the major proposed changes set forth in the NPRM.
Reforming the Informed Consent Process
Tightening Informed Consent Documents
In an attempt to focus the informed consent document on the information critical to a prospective subject’s decision about whether or not to participate in a research study, and reduce the document’s length and complexity, the NRPM would:
- Add new language to strengthen the informed consent requirements to make sure the most appropriate information is presented to prospective subjects in a sufficient detail and in a format that is tied to understandability;
- Add new language that would clarify that, when a HIPAA authorization is combined with consent, the HIPAA authorization elements must be part of the core elements of consent.
- State wehther indentifiers will be removed from data and data then provided to other investigators for future use without additional informed consent, or that it will not be used or distributed for further research.
- If appropriate, inform the subject: (1) that the subject’s biospecimens may be used for commercial profit and whether the subject will or will not share in this commercial profit; (2) whether clinically relevant research results, including individual research results, will be disclosed to subjects, and if so, under what conditions; and (3) 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.
The NPRM would also require that, for clinical trials conducted or supported by a Common Rule department or agency, a copy of the final version of a consent form to posted on a publicly available federal website within 60 days after the trial is closed for recruitment.
Creating Information Privacy Protections
Under the NPRM, HHS would create a list of specific measures that the institution or investigator can use that will be deemed to satisfy the requirement for “reasonable and appropriate safeguards” for the protection of identifiable private information and biospecimens. The regulations would also add limitations for the use and disclosure of identifiable private information and biospecimens.
Regulating Research Use of Identifiable Private Information & Biospecimens
The NPRM would now generally require informed consent for the use of identifiable private information and biospecimens in secondary research (e.g., information or biospecimens originally collected for clinical purposes or for use in research other than the proposed research). This new requirement would be accomplished by changing the definition of “human subject.” However, the consent would not need to be obtained for each specific subsequent study using the biospecimen, but could instead be obtained through “broad consent” for future unspecified research. This requirement would be only apply prospectively to research involving biospecimens that are collected in the future, with implementation delayed until three years after publication of the final rule.
HHS must publish a “template” for the broad consent and, unless such broad consent is altered, no IRB review is required. The proposal would only allow IRBs to waive the requirement for informed consent under a set of strict requirements so that waivers will only occur in rare circumstances.
Recalibrating the Review Process: Exclusions and Exemptions
The NPRM attempts to make the level of review more proportional to the seriousness of the harm or danger to be avoided. Some studies that currently require IRB approval would now become exempt, and others that are currently exempt would specifically become excluded.
An “exclusions” section would be created that would specify eleven types of activities that would be outside of the scope of the Common Rule (and would not be subject to any level of review):
Activities Deemed Not to be Research
- Program improvement activities (e.g., a survey of hospital patients to evaluate and improve the quality of meals delivered to hospital patients);
- Oral history, journalism, biography, and historical scholarship activities that focus on the specific individuals about whom the information is collected;
- Criminal justice activities (i.e., collection and analysis of data, biospecimens, or records by or for a criminal justice agency for activities authorized by law or court order solely for criminal justice or criminal investigative purposes);
- Quality assurance and quality improvement activities (e.g., evaluation of the implementation of an accepted practice, such as education, training, and procedures related to care or services);
- Public health surveillance activities (pursuant to or by a public health authority, limited to those necessary to fulfill its legal mandate);
- Intelligence surveillance activities (conducted by a defense, national security, or homeland security authority solely for authorized purposes).
Activities that are Low-Risk and Already Subject to Independent Controls
- Educational tests, survey procedures, interview procedures, or observation of public behavior (not including research activities where nay sort of intervention is used);
- Research involving the collection or study of information that has or will be collected (current Common Rule exemption category 4);
- Research conducted by a government agency using government-generated or government-collected data (if the information is collected and maintained in compliance with other certain Federal statutes);
- Certain activities subject to the HIPAA Privacy Rule whose risks relate only to privacy and confidentiality;
Activities that Do Not Meaningfully Diminish Subject Autonomy
- The secondary research use of non-identified biospecimens that are designed only to generate information about the individual that is already known (e.g., research to develop a diagnostic test for a condition using specimens from individuals known to have the condition and those known not to have the condition).
The NPRM also adds a number of “exemptions” to those currently set forth in the Common Rule, largely for categories of social and behavioral research. To assist in determining when a study is exempt, a web-based “decision tool” will be created, which can be relied upon by investigators as a “safe harbor” for this determination.
Mandating Single IRBs
With the goal of streamlining the review process by reducing inefficiencies, the NPRM would require all U.S. institutions engaged in a cooperative study to reply upon a single IRB for that study, with some exceptions (e.g., where more than single IRB review is required by law, such as FDA-regulated medical devices). In addition, the proposal extends regulatory requirements to IRBs that are not affiliated with an institution that is subject to the Common Rule if it reviews research covered by the Common Rule.
Changes to IRB Operational Requirements
The NPRM proposes a number of changes to the criteria for IRB approval of research, as well as IRB operations, functions, and membership, including:
- Eliminating the need for continuing review of research that has progressed to the data analysis or follow-up phase using data from procedures subjects would undergo as part of standard of care;
- Authorizing more limited IRB review of activities related to the storage or maintenance of biospecimens and identifiable private information for the purposes of doing secondary research;
- Have IRBs considering the equitable selection of subjects focus on issues related to coercion or undue influence in research with vulnerable populations;
- Allowing IRBs to consider both disabled persons and economically or educationally disadvantaged persons when determining that the selection of subjects is equitable and that they may be vulnerable to coercion or undue influence, as well as when considering IRB membership expertise;
- Making the default position that there is no need for additional IRB review of a research study’s privacy and security protections;
- Having IRBS, where a protocol calls for returning research results, determine whether the plan is appropriate; and
- Removing the provision regarding IRBs avoiding membership that consists entirely of individuals of one gender or profession since the requirements that IRB membership reflect members of varying backgrounds and diversity would accomplish the same goal.
Extending the Scope of the Regulations
Finally, one of the most significant proposals in the NPRM is with respect to the scope of clinical trials that are subject to the Common Rule. Currently, the Common Rule applies to all research involving human subjects that is conducted or supported by a Federal department or agency that has adopted the policy. The NPRM proposes an extension that would include clinical trials conducted at an institution in the United States that receives federal support for non-exempt and non-excluded human subjects research, regardless of the funding of the specific clinical trial. Because the intent of this proposal is to ensure that clinical trials that would not otherwise be covered by federal research ethics regulations are covered, research subjects to FDA regulation would not be included in this expansion. However, there might continue to be research that would be subject to both sets of regulations involving federal funding of research concerning an FDA-regulated product.
Questions to the Public
While the NPRM calls for input on each of its specific proposals, the notice calls out two overarching issues for which it is seeking comment:
- Will the proposed changes decrease the administrative burden, delay, and ambiguity for investigators, institutions, and IRBs?
- Will the proposed changes strengthen, modernize, and make the regulations more effective for protecting research subjects?
In addition, since FDA-regulated research remains exempt from the Common Rule under the NPRM, the notice considers whether there is the need for updates to FDA regulations where there is overlapping scope.
As noted in the title of this post, the NPRM lays out 88 questions it would like comments on with respect to these proposals. Comments are being accepted through December 7, 2015 here. To assist stakeholders in reviewing the NPRM, OHRP has just released a 6-part webinar series available here.
*Admitted only in Maryland. Work supervised by the Firm while D.C. application pending.