Federal Agencies Implementing the Final Rule

Note from Katherine Lerner: this summary was prepared for my own use as an aid to understanding the changes being implemented with this Final Rule – it is not a substitute for reading the Final Rule yourself, nor should this be relied upon as any form of advice or opinion. The summary below does not contain any analysis or opinion by me – it is intended to be descriptive, not analytical. Any errors below are my own.

Federal Agencies implementing the Final Rule:

In addition to the agencies that have already adopted the Common Rule in their regulations –

Dep't of Homeland Security is codifying this Final Rule into its regulations (DHS had previously been required by statute to comply with 45 CFR Part 46)

Social Security Administration is codifying the Final Rule into its own agency regulations

Dep't of Labor, which was not previously a signatory to the Common Rule, is now a signatory and is codifying the Final Rule into DOL regulations

Consumer Product Safety Commission intends to adopt this Final Rule through a separate rulemaking.

IRBs Not Operated by an Institution Holding a Federalwide Assurance – 46.101(a)(1)

(Authority to Enforce Compliance Directly Against IRBs not operated by an FWA-holding Institution):

Common Rule departments & agencies will now have authority to enforce compliance directly against IRBs that are not operated by an FWA-holding institution. Allows the federal gov't to avoid involving engaged research institutions in compliance enforcement activities if those activities are related to the responsibilities of the reviewing IRB (e.g., independent IRBs).

Application to non-federally funded research:

HHS plans to implement the non-regulatory change to the FWA mechanism to eliminate the option of voluntarily extending the FWA to non-federally funded research. Institutions can choose to establish an institutional policy that would require IRB review of research that is not funded by a Common rule agency/department.

Federal Department/Agency Head Discretion re applying the Common Rule:

Federal Common Rule department & agency heads retain final judgment about whether a particular activity is covered by the Common Rule – a new limitation is added that this discretionary decision must be consistent with the principles of the Belmont Report. Thus codifies the general practice that the ethical standards articulated in the Belmont Report are the ethical standards that Common Rule departments/agencies will use to determine whether an activity is covered under the Common Rule and whether to grant a waiver of the applicability of Common Rule provisions.

Common Rule impact on state & local laws that provide additional human subject research protections:

Consistent with the prior version of the Common Rule, keeps language providing that the Common Rule does not affect any state or local laws & regulations that may apply and that provide additional protections for human subjects. Adds clarifying language that state & local laws and regulations include tribal laws passed by the official governing body of an American Indian/Alaska Native tribe. Thus, if the official governing body of a tribe passes a tribal law that provides additional protections for human subjects, the Common Rule does not affect or alter the applicability of that tribal law.

Research conducted in foreign countries:

Removes the specific reference to the Declaration of Helsinki in the Common Rule, because ethical regulations/documents such as the Declaration of Helsinki are subject to change independent of the Common Rule agencies and therefore could be modified to contain provisions that are inconsistent with future U.S. laws and regulations. Does not affect the overall current Common Rule provision re "equivalence" – i.e., that if a Common Rule department head determines that procedures in place at an institution in a foreign country are at least equivalent to those in the Common Rule, the Common Rule department head may approve the substitution of those foreign procedures in lieu of the Common Rule's requirements.

Harmonization of Common Rule Department & Agency Guidance:

Guidance should be issued by Common Rule departments & agencies only after consultation among the Common Rule departments & agencies, but guidance is permitted to be issued without such consultation when it is not feasible. Largely codifies what has already been the working practice among Common Rule departments & agencies.

Compliance Dates and Transition Provisions:

Rule is effective on January 19, 2018. Compliance date for all provisions EXCEPT provision on cooperative research is 1/19/18. Compliance date for provision on cooperative research is January 20, 2020.

DEFAULT RULE: Research initially approved by an IRB, waived, or determined to be exempt before January 19, 2018 will NOT be subject to this Final Rule and will continue to be subject to the Common rule requirements that were in effect prior to 1/19/18.

HOWEVER, the Final Rule permits institutions to choose, on a study-by-study basis, whether research that was approved/waived/exempted before 1/19/18 will be subject to the pre-2018 Common Rule or to the provisions of this Final Rule. This is offered as additional flexibility for regulated entities. If an institution determines that it prefers to comply with the Final Rule for a particular study, that research will be subject to the Final Rule if the institutional formally makes a determination that the Final Rule applies to the research AND the IRB documents the decision. If these requirements are not met or the institution makes no decision, the pre-2018 Common Rule applies to that research.

Re cooperative research, institutions can use a single IRB to oversee cooperative research even before the Final Rule's compliance date re any research that institutions believe would benefit from that approach.

Severability

Adds language that if any provision of the Final Rule is held to be unenforceable in one set of circumstances, it should be construed to give maximum effect to the provision as applied to other persons or circumstances. Similarly, if a provision is held to be invalid or unenforceable, that provision should be severable from, and have no impact on the application of, the remainder of the rule.

Revisions to definitions, and new definitions, of key terms – 46.102

"Certification" – clarifies that notification by the institution that a proposed research study has been reviewed & approved is made to the supporting federal department/agency and that it might be a component of the agency/department that is notified rather than the entity as a whole.

"Clinical trial" – Adds a definition of clinical trial to the Common Rule. That definition is "a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of the interventions on biomedical or behavioral health-related outcomes." Expect this definition will be applied "harmoniously" with the definition of clinical trial recently promulgated in the ClinicalTrials.gov final rule.

This definition is relevant to the requirement for posting consent forms for clinical trials conducted by Federal departments/agencies.

"Department or Agency Head," "Federal Department or Agency," and "Institution" – inserts "Secretary of HHS" as an example to add clarity definition of Department or Agency Head.

Clarifies that "federal department or agency" refers to the department or agency itself, not its bureaus, offices, or divisions.

Definition of institution revised to clarify that departments can be considered institutions for purposes of the Common Rule – gives HHS, Department of Defense, and the Central Intelligence Agency as examples.

"Human Subject" –

(NOTE: does NOT implement NPRM's proposed expansion of definition of "human subject" to include all biospecimens regardless of identifiability)

Revises definition of “human subject” to:

“a living individual about whom an investigator (whether professional or student) conducting research:

(i) Obtains information or biospecimens through intervention or interaction with the individual, and uses, studies, or analyzes the information or biospecimens; or

(ii) Obtains, uses, studies, analyzes, or generates identifiable private information or identifiable biospecimens.”

“Identifiable private information” and "Identifiable biospecimen" – 46.102(e)(5) and (e)(6)

Adds these new definitions to the Common Rule.

Identifiable private information is “private information for which the identity of the subject is or may readily be ascertained by the investigator or associated with the information.”

Identifiable biospecimen is “a biospecimen for which the identity of the subject is or may readily be ascertained by the investigator or associated with the biospecimen.”

Federal Common Rule departments & agencies must regularly, upon consultation with appropriate experts, re-examine the meaning of the terms "identifiable private information" and "identifiable biospecimen." This re-examination must take place at least every 4 years. Also at least every 4 years, Common Rule departments & agencies will assess whether there are analytic technologies and techniques that should be considered by researchers to generate identifiable private information or identifiable biospecimens. To the extent that this process leads to a determination that particular analytic technologies or techniques, when applies to information/biospecimens that are not identified, do lead to the generation of identifiable private information or identifiable biospecimens, those technologies/techniques will be placed on a list of technologies & techniques satisfying that determination, and recommendations might be made re relevant issues relating to consent and privacy and data security protections. The result "may be" that such technologies & techniques could therefore only be used in instances where the person has provided their consent (broad or study-specific) which meets Common Rule requirements, or where an IRB has waived consent. Notice & opportunity for public comment would occur before a technology or technique could be placed on this list. Whole genome sequencing is expected to be one of the first technologies that will be evaluated to determine whether it should be placed on this list.

Newborn Screening Saves Lives Reauthorization Act of 2014 will no longer be effective following this Final Rule's effective date – as a result, secondary research with non-identified newborn DBS would be treated in the same way as secondary research with any other type of non-identified biospecimen – such research is not considered research with human subjects.

"Legally Authorized Representative" – modifies definition of LAR to address situation where some jurisdictions have no applicable law authorizing an LAR to provide consent on behalf of a prospective research subject. In these jurisdictions, an individual recognized by institutional policy as acceptable for providing consent in the non-research context to the subjects' participation in the research procedures will be considered an LAR.

HHS expects that implementation will in large part rely on institutional policies for determining surrogates for clinical decision making. However, there could be some studies that do not relate to the types of decisions involved in clinical care, or don't involve procedures used in the clinical context. If the institution has a policy relating to who acts as a surrogate outside the research context for those types of decisions, such a policy could be applied in the research context to determine who is an LAR.

"Public health authority" – Adds definition of this term to the Common Rule. "Public health authority" means an agency or authority of the United States, a state, a territory, a political subdivision of a state or territory, an Indian tribe, or a foreign government, or a person or entity acting under a grant of authority from or contract with such public agency, including the employees or agents of the public agency or its contractors or persons or entities to whom it has granted authority, that is responsible for public health matters as part of its official mandate.

"Research" – keeps the current definition of "research."

Removes four categories of activities from the definition of research:

-- Certain scholarly and journalistic activities (e.g., oral history, journalism, biography, literary criticism, legal research, and historical scholarship)

-- Public health surveillance activities: Codifies the current interpretation that the definition of research does not include a category of activities that solely involve public health surveillance, including collecting and testing information or biospecimens in activities that are conducted, supported, requested, ordered, required, or authorized by a public health authority and that are limited to those necessary to allow the public health authority to identify, monitor, assess, or investigate potential public health signals, onsets of disease outbreaks, or conditions of public health importance.

"The line between public health surveillance and epidemiological research can be difficult to draw, as the same epidemiological techniques may be used in both. Generally, the difference between the activities is the purpose or context in which the investigation is being conducted and the role of the public health authority. … On the other hand, subsequent research using information collected during a public health surveillance activity, for instance, genetic analysis of biospecimens, would not be removed from the definition [of research]."

Research evaluations of public health surveillance activities fall within the definition of "research" because the nature of such evaluations is to create generalizable knowledge.

-- Criminal justice activities: clarifies that, consistent with current practice, data collection & analysis that enable the conduct of certain criminal justice activities is not "research" – the scope of these activities is collection & analysis of information, 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. Essentially codifies current federal interpretation

This category does not include social & behavioral studies of the causes of criminal behavior – such studies would be considered "research" under the Final Rule.

-- Authorized operational activities in support of national security missions: clarifies that definition of "research" does not include authorized operational activities (as determined by each agency) in support of intelligence, homeland security, defense, or other national security missions. Codifies the interpretation of the current Common Rule.

(these were proposed as "exclusions" in the NPRM, but the Final Rule drops the idea of exclusion categories)

Note: It is not the particular field that removes the activity from the definition of "research" but rather the particular activity's focus on specific individuals. "Studies using methods such as participant observation and ethnographic studies, in which investigators gather information from individuals in order to understand their beliefs, customs, and practices, and the findings apply to the studied community or group, and not just the individuals from whom the information was obtained, fall within the scope of the definition of research of the final rule."