Recommendation Approved by SACHRP July 26, 2017
Guidance on Broad Consent under the Revised Common Rule
On January 19, 2017, the U.S. Department of Health and Human Services (HHS) and 15 other Federal Departments and Agencies promulgated regulations (the Final Rule) to revise the Federal Policy for the Protection of Human Subjects in Research (the Common Rule). Enacted in 1991, the Common Rule codified the ethical framework for the conduct of medical research involving human subjects conducted or supported by the federal government. The Final Rule establishes, among other things, a framework for “broad consent,” a new type of consent specifically defined in the regulation that is intended to serve as a substitute for traditional informed consent in certain circumstances. While the research community has relied on broad consent forms in a general sense for many years to allow institutions to collect, store, and use subjects’ data and identified biospecimens for unspecified future research, the Final Rule creates a new regulatory pathway for the use of broad consent and its legal implications. Specifically, the Final Rule establishes (i) two new exemption categories for the storage, maintenance, and research use involving identifiable information and biospecimens under which broad consent is a condition for the exception, and (ii) a regulatory pathway to obtain broad consent in lieu of traditional informed consent for non-exempt storage, maintenance, and research use involving identifiable information and biospecimens.
In the Notice of Proposed Rulemaking (NPRM), the Common Rule Agencies and Departments proposed that HHS would publish as part of the Final Rule broad consent templates that would contain all of the required elements of consent for future unspecified research. The Final Rule did not adopt that approach and instead, in the preamble, stated:
We agree with the public comments that favored allowing institutions to create their own broad consent forms that could be tailored to a variety of circumstances. Therefore, under the final rule, investigators and institutions may develop broad consent forms, which, provided specified conditions are satisfied, would meet the exemption for the storage and maintenance for secondary research use of identifiable biospecimens or identifiable private information . . . . At a later time, the Secretary of HHS expects to develop guidance on broad consent, which could include broad consent templates.
Consistent with the Final Rule preamble, the HHS Secretary’s Advisory Committee on Human Research Protections (SACHRP) has been charged with developing a proposed guidance document to provide recommendations for the interpretation and implementation of the broad consent provisions of the Final Rule.
SACHRP recognizes that the broad consent option makes it possible for potential subjects to control the uses of their identifiable biospecimens and identifiable data to some extent, but does not substantially change researchers’ preexisting ability to make use of de-identified biospecimens and data, or their access to identifiable biospecimens and identifiable data via waiver or other means. However, SACHRP is also aware that many potential subjects and members of the general public may not understand or agree with the limitations on their own control of biospecimens and data, especially when they have concerns about unspecified research uses. We hope that this guidance document and the broad consent template can be used to help educate potential subjects and the general public, and we also hope that in their consideration of broad consent, IRBs will take account of the potential ethical issues that may arise from the gap between public and professional understandings.
Final Rule Framework for Broad Consent
The Final Rule creates two new exemption categories under which research is excepted from compliance with the entire Common Rule if it satisfies certain abbreviated conditions, including obtaining the subject’s broad consent:
(i) Storage or maintenance of identifiable private information or identifiable biospecimens for potential secondary research use if an institutional review board (IRB) conducts a limited IRB review and makes certain determinations.
(ii) Research involving the use of identifiable private information or identifiable biospecimens for secondary research use, if the following criteria are met:
a. Documentation of informed consent or waiver of documentation of consent was obtained;
b. An IRB conducts a limited IRB review and makes certain determinations; and
c. The investigator does not include returning individual research results to subjects as part of the study plan (although the investigator is not prevented from abiding by any legal requirements to return individual research results).
The Final Rule also allows for broad consent to be obtained as an alternative to traditional informed consent for the non-exempt storage, maintenance, and secondary research use of identifiable private information or identifiable biospecimens (collected for either research studies other than the proposed research or nonresearch purposes).
Prior to the Final Rule, if researchers had not secured study-specific consent, the Common Rule contemplated only two alternatives for using identifiable data or biospecimens in a research study: obtaining an IRB waiver of consent or removing personal identifiers so that the research would not involve identifiable private information, therefore falling outside of the jurisdiction of the Common Rule. The Final Rule expressly permits researchers to obtain broad consent for the storage, maintenance, and secondary research use of identifiable biospecimens and data. If broad consent is obtained, any subsequent storage, maintenance, and secondary research uses of the individual’s identifiable biospecimens and data consistent with the broad consent would not require additional consent, so long as additional conditions are met, including limited review by an IRB.
The Final Rule prescribes the following elements for broad consent to be legally effective:
i. A description of any reasonably foreseeable risks or discomforts to the subject;
ii. A description of any benefits to the subject or to others that may reasonably be expected from the research;
iii. A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained;
iv. A statement that participation is voluntary, refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and the subject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled;
v. When appropriate, 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;
vi. When appropriate, 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);
vii. A general description of the types of research that may be conducted with the identifiable private information or identifiable biospecimens. This description must include sufficient information such that a reasonable person would expect that the Broad Consent would permit the types of research conducted;
viii. A description of the identifiable private information or identifiable biospecimens that might be used in research, whether sharing of identifiable private information or identifiable biospecimens might occur, and the types of institutions or researchers that might conduct research with the identifiable private information or identifiable biospecimens;
ix. A description of the period of time that the identifiable private information or identifiable biospecimens may be stored and maintained (which period of time could be indefinite), and a description of the period of time that the identifiable private information or identifiable biospecimens may be used for research purposes (which period of time could be indefinite);
x. Unless the subject or legally authorized representative will be provided details about specific research studies, a statement that they will not be informed of the details of any specific research studies that might be conducted using the subject’s identifiable private information or identifiable biospecimens, including the purposes of the research, and that they might have chosen not to consent to some of those specific research studies;
xi. Unless it is known that clinically relevant research results, including individual research results, will be disclosed to the subject in all circumstances, a statement that such results may not be disclosed to the subject; and
xii. An explanation of whom to contact for answers to questions about the subject’s rights and about storage and use of the subject’s identifiable private information or identifiable biospecimens, and whom to contact in the event of a research-related harm.
The Final Rule contains an important limitation on the ability of an IRB to waive consent for the future research uses of identifiable data and biospecimens of persons who have been offered a broad consent but have refused to give such consent: namely, if a researcher asks an individual to provide broad consent for the storage, maintenance, and secondary research use of identifiable private information or identifiable biospecimens, and the individual “refused to consent,” an IRB cannot waive consent for the storage, maintenance, or secondary research use of that person’s identifiable private information or identifiable biospecimens.
Under the Final Rule, therefore, researchers may opt to conduct secondary research on identifiable private information or identifiable biospecimens through one of the following mechanisms: (i) study specific consent and full or expedited IRB review, (ii) broad consent and limited IRB review (under the exemptions that rely on broad consent), (iii) waiver of consent and full or expedited IRB review, (iv) other exemptions, or (v) de-identification to remove the research activity from the scope of the Common Rule, which would not require consent or IRB review.
Final Rule Changes from the NPRM
In light of public comment, the Final Rule differs from the NPRM in several significant respects. The NPRM proposed that all biospecimens, regardless of their identifiability, be covered under the Common Rule, and thus would have required consent for secondary research of nonidentified biospecimens. In effect, researchers would have been required to obtain broad consent under the NPRM, because the proposed waiver criteria had been correspondingly narrowed, and de-identification of biospecimens to remove the research from the scope of the Common Rule would not have been available as a compliance strategy. Further, under the NPRM proposal, researchers would have been effectively forced to use broad consent for future research uses of identified data and of identified and de-identified biospecimens, because they could not, in most cases, have practicably undertaken the task of obtaining study-specific consent from subjects for each future research use. The Final Rule, however, declined to adopt these NPRM proposals, and instead has created a broad consent framework intended to provide flexibility to investigators for future research uses of identified data and biospecimens, which is intended to supplement the continued availability of undertaking secondary research through de-identification or coding of data and biospecimens, or seeking a waiver of consent from the IRB.
In the Final Rule’s preamble, the Common Rule Agencies and Departments “recognize public commenters’ concern that broad consent might not be as meaningful or informative as study-specific consent.” However, the preamble argues that when an investigator opts for broad consent, “doing so will generally provide increased protection to the autonomy of research subjects” by giving “them a choice to say no to such research, in contrast to most of the other routes by which an investigator might generally choose to conduct this type of research, such as with a waiver of informed consent, which allows research to take place regardless of the wishes of the person whose information or biospecimens are being studied, and without their knowledge.”
To address the public comments questioning the meaningfulness of broad consent, the Final Rule changed certain of the elements of broad consent proposed in the NPRM to require more specific information about the secondary research that may be conducted. In particular, the Final Rule revised the element of broad consent proposed in the NPRM regarding the provision of a general description of the types of research that may be conducted with identifiable private information and identifiable biospecimens. Under the Final Rule, this description must include sufficient information to allow a reasonable person to expect that the broad consent would permit the types of research conducted. The “reasonable person” standard appears to derive from that of the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule’s in its allowance of authorization for the use or disclosure of protected health information for future research purposes.
Further, the Final Rule requires that when subjects will not be informed about the details for any specific research studies that might be conducted using their identifiable private information or identifiable biospecimens, the broad consent must disclose this fact and inform subjects that they might have chosen not to consent to some specific future research studies. Importantly, the Final Rule does not adopt the NPRM’s proposed limitations on the research use of biospecimens or identifiable private information obtained for nonresearch purposes, that would have only permitted a broad consent to cover either or both of the following: (i) biospecimens or identifiable private information that exist at the time at which broad consent is sought; and (2) biospecimens or identifiable private information that will be collected up to 10 years after broad consent is obtained or until the child reaches the legal age of consent to the treatments or procedures involved in the research, whichever comes first. The Common Rule Agencies and Departments were persuaded by public comments objecting to the complexity and tracking burden required to implement the limitation, and the lack of a clear benefit conferred to subjects. In addition, the Final Rule does not include broad consent templates to be established by HHS Secretary, instead allowing institutions to develop their own broad consent forms specific to their institutional needs, as long as those forms contain the minimum required content.
Recommendations on the Interpretation and Implementation of Broad Consent
Broad consent permits researchers to engage in research use of identifiable biospecimens and identifiable data without the requirement to obtain additional consent for the future storage, maintenance, or research uses, so long as the future activities are within the scope of the broad consent. Broad consent may be the most suitable pathway for research involving identifiable private information or identifiable biospecimens in cases in which waiver of consent would not be available, based in part on the new criterion under the Final Rule requiring that an IRB grant a waiver only if, among other prerequisites, the research could not practicably be carried out without using such information or biospecimens in an identifiable format. However, under the Final Rule, as described above, researchers who seek broad consent are bound by the regulatory limitation that if an individual “refuses to consent,” the IRB cannot waive consent for the storage, maintenance, or secondary research use of the identifiable private information or identifiable biospecimens.
To implement fully a broad consent program, health care institutions would be required to install a system to track biospecimens and data for which individuals provide their broad consent, as well as the terms of the broad consent to determine which future research uses remain within scope. Notably, if an individual is offered to provide broad consent but refuses, the limitation only proscribes secondary research uses of the identifiable materials – meaning that researchers could simply choose to de-identify the subject’s data and biospecimens to conduct further research with them. A subject’s refusal to give broad consent also does not prevent the unconsented uses of their identifiable data and biospecimens for purposes that are not considered “research” under the revised Common Rule. For these reasons, if a person who is offered a broad consent refuses to give that consent, health care institutions have three basic options. First, if allowed by other law, they may simply destroy that person’s identifiable information and biospecimens. Second, they may de-identify the person’s information and biospecimens and use them for future research without restraint. Third, they may decide to retain the identifiable information and biospecimens, but allow their future use only for non-research purposes, such as quality improvement. In this third option, however, the institution must track that person’s information and biospecimens to ensure they are not used for future research purposes.
Extensive and seamless IT system capacity will be necessary for any institution or health system to implement fully a broad consent tracking system, as both broad consents as well as refusals to consent (unless the materials are destroyed) must be tracked over the lifetimes of persons who give broad consent and persons who refuse to give such consent. Due to these systems requirements for electronic tracking processes, SACHRP expects that, practically speaking, institutions or systems without interconnected, interfacing and fully interoperable medical records systems will not be able to implement and benefit from the broad consent regimen established in the Final Rule. A “confederated,” non-IT-unified health system will simply not be able, without significant error, to track these consents and refusals to consent. These logistical barriers will greatly limit the utility of the broad consent option.
The practical utility of the broad consent will probably include (1) an identified biorepository or databank study, whose defined purpose is to collect biospecimens and associated data from a well-defined set of individuals and for which the broad consent elements can be included in the study consent, thus giving researchers downstream access to the related exemptions, and (2) primary research studies in which the researchers seek to use an “add-on” or integrated broad consent to facilitate future research uses of the identified data and biospecimens collected as part of that primary study. In each of these cases, however, the use of broad consent would be specifically targeted to well-defined subject groups, rather than to a broad swath of all newly-admitted patients or all newly-enrolled clients.
Defining “Refusal to Consent”
The Final Rule does not delineate whether an individual’s silence, non-responsiveness, and/or express declination to give broad consent would constitute “refusal to consent” to broad consent for purposes of determining whether an IRB can later waive consent for the storage, maintenance, or secondary research use of an individual’s identifiable private information or identifiable biospecimens. While express declination to give broad consent is plainly “refusal to consent” under the Final Rule, the meaning and legal import of a person’s silence or non-responsiveness to a request to provide broad consent is less clear.
SACHRP recommends that HHS interpret “refusal to consent” to include only a person’s express declination to give broad consent, as demonstrated by an individual’s unambiguous written or oral communication to that effect. SACHRP does not believe that silence or failure to respond in the face of a request for broad consent, or failure to communicate an unambiguous declination to give broad consent, should constitute “refusal to consent” for these purposes. This approach would not treat a person’s failure to respond to the offer of a broad consent as the granting of an actual broad consent. Instead, under this proposal, a non-response would be treated just for what it is – neither the granting of a broad consent nor an express refusal to give a broad consent.
Treating silence or non-responsiveness as a “refusal to consent” would imply that the individual objected to the use of his or her data and biospecimens, when in fact non-responsiveness obscures the intent of the individual. By failing to respond to a request for broad consent, an individual could be expressing indifference, inertia, ambivalence, uncertainty, or complete disinterest. In fact, an individual who strongly objects to a broad consent offer is likely to express affirmative declination on the form, especially if it describes the implications of an individual’s options (explicit agreement, silence, explicit declination). Further, an approach that equates non-responsiveness with refusal to consent may deprive researchers of complete, unbiased, and important data forever, as a refusal to consent would, as a practical matter, remove a person’s identifiable data from any possible use in future research. Moreover, an approach that equates non-responsiveness with refusal would incentivize researchers to prefer a waiver of consent over initially seeking broad consent, because of the potential that a significant percentage of individuals would not respond thereby causing their identifiable biospecimens and information to be unusable for non-exempt research. Because it would incentivize waiver of consent over a seeking of broad consent, interpreting non-responsiveness as refusal to consent would, in an unintentional but direct way, even operate to limit the choices of persons who actually wish to refuse their consent: with researchers more likely not to offer broad consent in order to avoid the harsh consequences of this approach, those who would opt out and expressly refuse consent would not have the opportunity to do so.
One objection that has been voiced to this approach is that in other instances in applying the Common Rule, we do not interpret a non-response to an offer of consent as permission to enroll the person in a study. This is true, and indeed, also under this proposed approach, a non-response to the offer of broad consent would similarly not be treated as that person’s agreement to a broad consent. Under the Common Rule, historically, when a prospective subject does not respond to an offer to consent to participation in a retrospective records review or registry study, then that person is not enrolled as a subject in that study. However, that person’s health records may well, at some not very much later point in time, be used in another study under a waiver of consent granted by an IRB. In other words, a person’s non-response to consent to a identified records study does not remove that person’s identified data from possible future use in other studies under an IRB-granted waiver of consent. The approach proposed here for the broad consent is analogous to our current and past practices, with a non-response to an offer of broad consent not being treated as a granting of broad consent, but also not treated as an absolute refusal of consent. Instead, under the approach proposed here by SACHRP, a person who is offered a broad consent and who simply does not respond, would be treated no worse, no better and no differently than if he or she had never been approached at all with the offer of broad consent. Importantly, the framework proposed by SACHRP in this specific and cabined context would not affect or change the current scheme requiring affirmative consent for interventional or interactional research.
To communicate clearly to persons who are offered broad consent the regulatory effects if they choose not to respond to that offer, SACHRP recommends that the broad consent form expressly state that failure to respond (i) will not be treated as a refusal to consent, (ii) will not prevent researchers from seeking a waiver of consent or pursuing an exemption, and (iii) will not act as affirmative broad consent. In an effort to ensure that the process is designed to afford the individual the opportunity to consider the broad consent request, SACHRP also recommends, as a best practice and one appropriately respectful of autonomy, that for persons who were offered broad consent through a medium other than face-to-face contact – e.g., by internet or mail -- researchers attempt to provide participants who have not responded within a reasonable timeframe with a second attempt to obtain broad consent, before interpreting their non-responsiveness consistent with this approach recommended by SACHRP.
If an individual neither expressly provides consent nor expressly declines consent, but instead does not respond in a specific way to a request to give broad consent, SACHRP recommends that an IRB continue to be able to waive consent under §___.116(f) for the future research uses of that person’s identifiable data or biospecimens. In addition, that person’s identifiable data or biospecimens would continue to be eligible for an exemption such as, for example, the new exemption provided under the Final Rule permitting the secondary research use of identifiable biospecimens or identifiable private information involving information collection and analysis of health information, when such use is otherwise regulated under HIPAA. To implement a protocol that would involve as subjects both a group of persons who gave their broad consent and those who failed to respond and for whom a waiver of consent is therefore required, researchers would need, under this approach, to describe the two separate subject populations in the study protocol. The protocol therefore would describe those subjects who provided broad consent, and those subjects for whom use of identifiable data or biospecimens would be based on a waiver or exemption, with details regarding the scope of collection, storage, and secondary research use permitted for each group. If an individual declines to provide consent by communicating the decision orally or in writing, the institutional staff or researcher who sought the broad consent from that person should document his or her refusal through appropriate notations, so that information about the refusal can be preserved and tracked.
While not determinative of SACHRP’s position, SACHRP is cognizant that an interpretation of “refusal to consent” that would extend to non-responsiveness could adversely impact the volume of identifiable biospecimens and data available for scientific and clinical research. Appreciating that a sizable population will not respond to a notice of broad consent for a variety of reasons unrelated to an actual objection to participate, researchers could lose access to a significant volume of identifiable biospecimens and data. Under an approach that views non-responsiveness as “refusal to consent,” secondary research on the non-responsive individuals’ materials and information would require study-specific consent, which in many cases, with the passage of time and dispersion of persons, may be impracticable or infeasible, or an exemption, for which the proposed research may not be eligible.
In contrast, the position offered by SACHRP would allow researchers to pursue a waiver of consent, in addition to study-specific consent or an exemption, for proposed secondary research. A waiver of consent would not be guaranteed, however, because an IRB must determine, among other things, that “the research could not practicably be carried out without the requested waiver . . .” If, for example, individuals are provided with an in-person opportunity to provide broad consent, obtaining consent would not be impracticable at that time. But obtaining consent may become impracticable if circumstances materially change, such as if, after a considerable amount of time, the individuals are no longer present at the institution and are not expected to return in the near future, and the research protocol involves biospecimens or information from a large number of individuals such that it would not be practicable for the researchers to locate and contact all of the individuals to seek their consent.
Parties Bound by a Person’s Refusal to Give Broad Consent
The Final Rule does not identify the party(ies) bound by an individual’s refusal to consent. Instead, the Final Rule prevents “an IRB” from waiving consent based on an individual’s refusal to provide broad consent. Without more limitation or explanation, however, such a prohibition could apply to all U.S. IRBs, investigators, and institutions with respect to that individual’s identifiable biospecimens and identifiable private information. This approach would ignore the possibility that an individual may refuse broad consent at one institution or for one investigator but provide broad consent, or even decline to respond to a request for broad consent, at another institution or when asked by a different investigator. Differing personal reactions to an offer to give broad consent could be based on a variety of factors, such as the purpose of the primary study, the type of identifiable biospecimens or private information to be collected, the anticipated future research purposes, personal confidence or lack of confidence in a particular researcher or institution, or changing preferences and values of the person himself or herself over time. Further, refusal to provide broad consent presumably would not prevent the same researcher or other researchers from contacting or recontacting the individual at a future time to request broad consent, as long as such requests were neither insistent nor abusive. It is possible that an individual who expressly has refused an offer of broad consent might be approached later from the same institution, entity or researcher with another offer of broad consent. When an individual previously refused broad consent (which refusal would be express and unambiguous, as defined in this guidance document), then that individual’s failure to respond to any additional offers should not “revoke” that person’s prior refusal of broad consent. In other words, non-responsiveness to additional offers of broad consent would not serve to move that individual from the “refused broad consent” category into the “failure to respond to broad consent” category.
Importantly, if an institution, academic medical center or health care system functions under a corporate model that involves loosely organized or decentralized medical and research operations, SACHRP recommends that the entire entity takes steps to assure that an individual who refused to provide broad consent at one organizational unit not be approached shortly thereafter to provide broad consent by staff at other organizational units under the same leadership or governance. To that end, institutions structured in such a manner should establish and maintain systems to track and respect across all its organizational units an individual’s refusal to provide broad consent.
In any event, the scope of the effect of a refusal to give broad consent will be critical in understanding and applying broad consent, and clarity on this point will be essential. SACHRP therefore recommends that the broad consent form clearly delineate which party(ies) would be able under that broad consent to use the data and biospecimens for secondary research purposes. By negative implication, a refusal to provide broad consent would deny those identified party(ies) the ability to access and use for secondary research purposes the individual’s data and biospecimens. Because the refusal of broad consent will bind those entities or institutions that have offered the broad consent, extreme care must be taken to define and specify exactly those entities, institutions and researchers covered by the broad consent.
Refusal of an individual to provide broad consent should, however, (i) not prevent those researchers or their institution from recontacting the individual to re-request broad consent (as defined by institutional policies designed to assure non-abusiveness in any subsequent recontact efforts), (ii) not prevent other institutions and researchers not identified in the initial broad consent from requesting the individual’s broad consent provided that they agree not to share the information and biospecimens with the institutions and researchers initially denied broad consent unless the individual expressly consents to the sharing, and (iii) not prevent an IRB from waiving informed consent for future research uses of that person’s identifiable data and biospecimens, based on a waiver application from a research team unaffiliated with, and not acting on or behalf of, those researchers whose previous request for broad consent had been refused by that person.
Broad Consent Description of the Consequences of Responding/Not Responding to the Offer of Broad Consent
As described above, an individual’s response, or lack thereof, to a request for broad consent will affect whether researchers can (i) store, maintain, and conduct secondary research use on the individual’s identifiable data and biospecimens, (ii) waive consent to conduct those activities, or (iii) seek an exemption to conduct those activities (which may or may not require consent). To ensure that individuals understand the full range of implications of their decision, SACHRP recommends that a broad consent form describe the three available options for responses (express agreement, express declination, or non-responsiveness) and the regulatory consequences of each response.
Specificity of Description of Future Uses
Broad consent forms must contain a general description of the types of research that may be conducted with the identifiable private information or identifiable biospecimens (§___.116(d)(2)). As a consequence, broad consent forms may be general in nature to cover a wide swath of research uses, or may be specific to a defined category of research (e.g., diabetes research). Institutions must track the permissible scope of collected identifiable information and biospecimens, and ensure that any access to, and use of, them be consistent with the terms of the executed broad consent.
Institutions offering broad consent will need to describe the range of future research uses to which the person is giving his or her broad consent. These purposes may be described generally, but should also contain some illustrative examples, especially listing any controversial areas of potential research uses (e.g., creation of cell lines, abortion/induced termination of pregnancy) and the areas for which specific mention is required by applicable laws (e.g., genetic testing, drug abuse/alcoholism, HIV/STDs, mental health). Attempts should not be made to present an exhaustive list of research areas or issues, as such a list cannot be comprehensive and could, in fact, mislead the individual considering the broad consent.
Continuing Research after Withdrawal of Broad Consent
Guidance accompanying the adoption of the revised Common Rule suggests that if an individual gives broad consent but later withdraws it, investigators may continue to use that person’s collected and stored data and biospecimens so long as they have been subsequently stripped of identifiers so as to not be subject to the Common Rule. 82 Fed. Reg. 7217 (Jan. 19, 2017). That same guidance also indicates, however, that if an investigator promises – most likely in the informed consent form – that withdrawal of a broad consent would mean that there would be no future research use of that person’s information and biospecimens, then the promise should be honored, and future use of that information and those biospecimens even in de-identified form would not be allowed. In either case, however, the consequences of a withdrawal or revocation of informed consent should be carefully specified in the broad consent itself, and those representations must be honored by those researchers and entities that sought and initially received the broad consent.
To anticipate that a person might withdraw his or her broad consent in the middle of a study that has already begun to use that person’s identifiable data and biospecimens, broad consent forms should describe that withdrawal of broad consent would not prevent the completion of use of that person’s data and biospecimens in a study already commenced when the request to withdraw was received, and would not prevent the continued storage and use, for research integrity purposes, of identifiable information and biospecimens already used for research purposes. However, after withdrawal, no further data collection and storage should occur, and the existing identifiable data and biospecimens should not be used for any new research purposes. Further, when in reliance on the broad consent, identifiable information and biospecimens have been distributed outside of the institution or research team covered by the broad consent, then it may be difficult to recall the information and biospecimens or to interdict their future use. Subjects should be informed of this in the broad consent.
IRB’s Responsibilities in Performing Limited Review
Under the Final Rule §___.104(d)(7), storage or maintenance of identifiable private information or identifiable biospecimens for potential secondary research use shall be exempt, if, inter alia, an IRB conducts a limited review. Specifically, the IRB must determine that:
i. Broad consent for storage, maintenance, and secondary research use of identifiable private information or identifiable biospecimens is obtained in accordance with the applicable informed consent and broad consent requirements;
ii. Broad consent is appropriately documented or waiver of documentation is appropriate; and
iii. If there is a change made for research purposes in the way the identifiable private information or identifiable biospecimens are stored or maintained, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data.
The Final Rule does not describe the extent of diligence required by an IRB to certify that broad consent has been obtained and documented appropriately. SACHRP believes that a limited assessment of the broad consent process would meet the intent and letter of the Final Rule. To that end, SACHRP recommends that a limited IRB review to assess whether broad consent is obtained in accordance with the applicable requirements would require an evaluation by the IRB of the broad consent form used and a review of the process used to secure such consent, to ensure that the form and process meet the applicable requirements and contains the requisite elements. To satisfy the requirement that the IRB ensure that broad consent is appropriately documented, SACHRP recommends that the investigator certify (i) that he or she has obtained such a consent from the subjects, or otherwise has assured that those subjects have in fact given such broad consent; (ii) that the broad consent is documented and available and will remain available for IRB review during the entire period of the study, if the IRB determines that such review is appropriate; and (iii) that the investigator provide a summary of the process used to seek broad consent, including the use of requests made in-person and by mail, telephone, and/or email. SACHRP believes that these activities, in addition to satisfying §___.111(a)(8)(iii), would be sufficient for meeting IRBs’ due diligence obligation. Importantly, a limited IRB review process can be conducted by a full IRB or through an expedited review process, consistent with §___.110(b)(1)(iii). Likewise, institutions and researchers who obtain broad consent should have an obligation to maintain those consents during their entire period of effectiveness, to assure that the use of such consents can be effectively monitored.
In addition, under § ___.104(d)(8)(iii), an IRB must determine that a secondary research use of identifiable private information and identifiable biospecimens falls within the four corners of the broad consent, among other determinations, before the secondary research use may be exempted from the Common Rule. In particular, the IRB must determine that the research to be conducted is “within the scope of the broad consent,” but the Final Rule is silent as to what degree of diligence an IRB must expend to satisfy the criterion. On one extreme, an IRB could theoretically be required to review every signed broad consent to ensure that the proposed secondary research use of the individual’s data or biospecimens is permitted under the broad consent. On the other extreme, an IRB could be expected only to request a certification from the investigator that the proposed secondary research use is within the scope of the broad consent. SACHRP would recommend, instead, that an IRB review the broad consent form(s) used or relied upon, to assess whether the proposed secondary research use falls within its scope. The IRB also should request a written certification from the investigator that all identifiable biospecimens and identifiable private information to be used for the secondary research purpose have documented and legally effective broad consents from the human sources.
Finally, an IRB in its limited review would optimally assure that the proposed research would not be fundamentally shocking to or fundamentally inconsistent with prevailing community attitudes among those who have given their broad consent. Although such a role for the IRB is not required or directed by the Final Rule, institutions that host IRBs may apply their own standards of appropriateness to research allowed to proceed, and may assign to an IRB the discretion to make such determinations. Such a substantive review process would, if implemented on an institutional basis, be respectful to communities from which broad consents have been gained and would tend to assure beneficence in research to be conducted under those consents. Importantly, researchers themselves also have an ethical responsibility to assure that the research being proposed under the broad consent is appropriate, scientifically sound, and respectful of the populations from whom the broad consents have been obtained.
Return of Research Results
In the Final Rule under § ___.104(d)(8)(iv), secondary research use of identifiable biospecimens and identifiable private information is exempt from the Common Rule, if, inter alia, “[t]he investigator does not include returning individual research results to subjects as part of the study plan.” The Final Rule is silent as to whether the plan to return individual research results must be intended to apply to each and every subject, or only to at least one subject, for the research to be excluded from the exemption. If the exemption is not available, the proposed research would be subject to regular IRB review. Note, however, that the return of general or aggregate research findings would not preclude use of this exemption, which applies only to return of individual research results. Further, this provision does not prevent an investigator from abiding by any legal requirements to return individual research results.
However, returning individual research results may be beneficial not only to the subjects, but to research in general by enhancing public trust and subjects’ willingness to participate. In fact, SACHRP previously recommended a rebuttable presumption in favor of returning individual results to be used in clinical research and other areas such as genomics research and social behavioral research. Therefore, we recommend that in developing the study plan, sponsors and investigators carefully balance the utility of returning individual research results against the increased regulatory requirements resulting from not meeting the exemption criteria.
The return of individual research results could be made to a single subject, a subset of the subjects, or to all of the subjects. This exemption does not require that the return of individual research results actually occur, but rather that the intention to return individual research results be part of the study plan—that is, that the return of results is a planned. premeditated activity contemplated in the protocol. If, for example, a study plan were to provide for the return of individual research results only to a subset of subjects who may be discovered to have a significant finding, that study plan should be considered to include the anticipated return of individual research results to subjects under § ___.104(d)(8)(iv), and thus not be eligible for an exemption from the Common Rule. Under this proposed interpretation, however, a study plan would continue to meet the exemption criterion if it allows for reporting or disclosure to subjects of incidental findings, which are clinically meaningful risks unrelated to the study’s design or endpoints.
Effect of Consent for Future Research Uses of Identifiable Data and Biospecimens
While the Final Rule creates a new regulatory scheme for “broad consent,” the research community has long relied on consent for future uses in the general sense to allow institutions to collect, store, and use subject data and leftover biospecimens for future research. SACHRP believes that future research consent forms signed before and after the effective date of the Final Rule (January 19, 2018) will continue to be effective. After the effective date of the Final Rule, a consent for future research using identifiable data and/or biospecimens must be analyzed as before, to assure that the consent has sufficiently detailed the future research uses, even if that consent would not be sufficient to meet “broad consent” as used in the Final Rule for purposes of the exemptions at §§___.104(d)(7) and (d)(8) or the broad consent framework under §___.116(d).
Use of a Single Combined Form for Primary Study Consent and Broad Consent
The Final Rule does not require that broad consent be obtained on a form separate from that of a primary study-specific consent, so long as the content and other requirements for broad consent are satisfied. In particular, the broad consent form must be offered to a prospective subject only under circumstances that provide the prospective subject sufficient opportunity to discuss and consider whether or not to participate, and that minimize the possibility of coercion or undue influence. In primary studies, a broad consent, if offered, presumptively should be offered as an adjunct to the primary study consent, so that the participant may participate in the primary study without agreeing to the broad consent as well. However, there are a number of studies – such as registry or biobanking studies, or studies in which biospecimens and data to be gathered are recognized from the outset as essential to future studies of, for example, the compound or agent tested – in which a broad consent is appropriately required in order to enroll in the primary study. SACHRP recommends that a broad consent therefore be able to be combined with a consent form for a primary study in appropriate, carefully defined, necessary circumstances. However, we recommend that a clinical consent form not be combined with a broad consent form in order to clarify to prospective participants the difference between research and medical treatment, and that receiving the clinical procedure does not depend on providing broad consent.
SACHRP recommends that when broad consent is not an integral part of the primary study design, the single combined consent form should include an option for an individual to affirm or decline expressly whether to provide broad consent – either as a signature line or an initials box. As such, the consent form would allow an individual to consent to a primary study but at the same time refuse to provide broad consent. The effect of such a choice would allow the subject to participate in the primary study but also communicate an express declination to a broad consent, which therefore would prohibit the reviewing IRB from waiving consent for the secondary research use of that subject’s identifiable biospecimens and identifiable private information.
In general, providing subjects with the ability to communicate an express declination to broad consent in a combined consent form, where appropriate, is consistent with the HIPAA Privacy Rule, which permits a researcher within a HIPAA-covered entity to seek authorization for the use or disclosure of protected health information for a “conditioned” research-related treatment activity (i.e., the primary study) and other “unconditioned” research activities (e.g., future, unspecified research) in a single, combined authorization form. The HIPAA Privacy Rule requires that where the provider “has conditioned the provision of research related treatment on the provision of one of the authorizations,” such compound authorization “must clearly differentiate between the conditioned and unconditioned” consents and must provide the individual with an opportunity to opt in to the authorization to any unconditioned research. However, there may be research studies in which the collection and storage of relevant identifiable biospecimens or data is so integral or important to the study objectives, that the researcher will allow participation only from individuals who agree to provide broad consent in addition to primary study consent. SACHRP recommends that IRBs review any such combined consents that lack the ability for the subject to opt out of the broad consent, in order to assure that the broad consent purpose indeed is important to the primary research aims. As an alternative, SACHRP recommends that sponsors and investigators consider incorporating broad consent activities and procedures into the primary study protocol itself, if those broad consent processes are essential or critical to the scientific purposes of the primary study. Somewhat analogously, the HIPAA Privacy Rule allows a covered health care provider to condition the provision of research-related treatment on an individual providing his or her authorization for the use or disclosure of PHI for such research. For any primary study consent that also requires the individual to provide broad consent, SACHRP recommends, similar to the HIPAA Privacy Rule, that the purpose(s) of the broad consent be integral to the primary study aims, such that the data or biospecimen collection, storage, and secondary research use could arguably be considered part of the same research project. Importantly, SACHRP does not believe that a clinical procedure should ever be conditioned on the provision of broad consent.
Summary of Proposed Consequences of Individual’s Response to Notice of Broad Consent
See Table 1.0 below describing SACHRP’s proposed consequences of an individual’s decision with respect to broad consent:
|Response to Notice of Broad Consent
||Storage, Maintenance, and Secondary Research Use of Identifiable Biospecimens & Information
||Storage, Maintenance, and Secondary Research Use of De-Identified Biospecimens & Information
||Ability to Withdraw Consent
||IRB Waiver of Consent
||Yes, consistent with the terms of the broad consent
||Yes, consistent wit hthe terms of the broad consent
||Not applicable (N/A)
||Yes, unless expressly prohibited by consent
||Yes, after decent interval or by other entities not covered by broad consent
||Only under waiver or applicable excemptions, which would not include the "broad consent" exemptions
||Yes, after decent interval or by other entities not covered by the offered broad consent
|Withdrawal after Express Agreement
||No, except (i) to complete ongoing research and (ii) for research integrity purposes
||Yes, after decent interval or by other entities not covered by broad consent