Attachment E - Transition Provisions and Informed Consent Req.

 

Informed Consent Requirements and Transitions Provisions of the Revised Common Ruel

SACHRP Recommendations, October 16, 2018

The U.S. Department of Health and Human Services (“HHS”) Secretary’s Advisory Committee on Human Research Protections (“SACHRP”) is aware of confusion in the regulated research community regarding application of the revisions to the Common Rule (45 C.F.R. Part 46, Subpart A) on research that is ongoing as of the revised Common Rule’s general compliance date of January 21, 2019.  SACHRP seeks to make recommendations to the HHS Secretary regarding the transition of ongoing studies to the revised Common Rule and also to identify related issues regarding which additional guidance from the HHS Office for Human Research Protections (“OHRP”).  Accordingly, in this letter, SACHRP describes the effects of the transition provisions and the relevant timing; identifies several specific revised Common Rule provisions that researchers and institutions have found difficult to navigate due to lack of guidance and clarity; and proposes guidance to assist the regulated research community. Certain aspects of the Common Rule’s transition provisions are currently in effect, and substantially all of the revised Common Rule’s substantive provisions will take effect in a few months, barring any further delay. This letter and its recommendations are therefore delivered with a sense of urgency and with the goal of avoiding administrative burden, confusion, and delay in human subjects research that is regulated by the Common Rule.

SACHRP is also mindful of certain related issues regarding the harmonization between the informed consent requirements set forth in U.S. Food and Drug Administration (“FDA”) regulations (21 C.F.R. Part 50) and those of the Common Rule, particularly in light of the revisions made to the requirements for informed consent in the revised Common Rule.  The lack of full consistency or identicality between the two sets of regulations has caused concern among many in the national research community, as changing and varied informed consent practices and inconsistencies created by the Common Rule transition process can increase administrative burdens associated with conducting research and can introduce confusion into the process of creating new informed consent forms.  SACHRP therefore makes certain recommendations regarding consent for research that falls under FDA jurisdiction, given that most research institutions will be migrating their informed consent forms and processes to conform to the requirements of the revised Common Rule.

  1. The Common Rule and its Transition Provisions

The Common Rule (45 C.F.R. Part 46, Subpart A.),[1] originally issued in 1991, was revised by a final rule promulgated by HHS and 16 other federal departments and agencies on January 19, 2017 (the “revised Common Rule”).  The promulgation of the revised Common Rule occurred over five years after the issuance of an advance notice of proposed rulemaking and over 16 months after the issuance of a notice of proposed rulemaking. 

The implementation of the revised Common Rule has been delayed two times, but is currently scheduled to take place on the rule’s general compliance date of January 21, 2019.[2]  The revised Common Rule’s transition provisions provide that research initiated on or after January 21, 2019 must comply with the requirements of the revised Common Rule in their entirety, with the exception of the requirement for use of a single IRB for all U.S. sites engaged in cooperative research, which becomes required as of January 20, 2020.[3][4] Research initiated before January 21, 2019 will remain subject to the prior version of the Common Rule (the “pre-2018 Rule”), with two exceptions.[5]

First, institutions were permitted to begin implementing in summer 2018 three “burden-reducing” provisions of the revised Common Rule.[6] Specifically, institutions have been able to elect to begin transitioning some or all studies to the new requirements after July 19, 2018, but before January 20, 2019 (the “delay period”) by implementing three “burden-reducing” transition provisions.[7] These three provisions include (i) the revised Common Rule’s change to the definition of “research,” which deems certain activities not to be research, (ii) elimination of the requirement for annual continuing review for certain categories of research, and (ii) removal of the requirement that IRBs review grant applications and funding proposals related to the research.[8] Once the decision to implement the three “burden-reducing” provisions has been made, this election may not be reversed.[9]  Additionally, each study for which these three burden-reducing provisions have been implemented must comply with the full suite of revised Common Rule requirements as of January 21, 2019, and institutions may make this voluntary determination to implement this limited portion of the revised Common Rule on a per-study basis or for a group of studies.[10]  However, studies initiated before January 21, 2019 for which an institution did not elect to use the burden-reducing transition provisions may continue adhering solely to the pre-2018 Common Rule provisions for the entirety of the study.[11]

Second, institutions may elect to transition a study initiated before January 21, 2019 to the regulations in the revised Common Rule on or after January 21, 2019.[12] This election may be done on a per-study basis or for a group of studies.[13] This election may be made even if the study or studies did not implement the three “burden-reducing” transition provisions during the delay period.[14] Once made, this election is irreversible.[15]

  1. Complexity Created by Transition Provisions

The transition provisions of the revised Common Rule are unclear in particular in regard to   studies that begin before the January 21, 2019 effective date and which the institution chooses voluntarily to transition to the requirements of the revised Common Rule.  We discuss here those ambiguities that appear to have generated the most confusion amongst the research community.

First, some confusion has arisen due to the change to the criteria under which an IRB may waive informed consent. Under the revised Common Rule, IRBs must determine when granting an informed consent waiver that the research could not practicably be carried out without use of biospecimens or information in an identifiable format.[16] This criterion is in addition to the requirements of the pre-2018 rule, under which the IRB must determine that the research involves no more than minimal risk to subjects, that the research could not be practicably carried out without a waiver, that the waiver will not adversely affect the rights and welfare of the subjects, and that subjects or legally authorized representatives will be provided with additional information after participation.[17]  It is unclear whether the revised waiver criteria should be applied to studies that transition to the revised Common Rule. For example, would a study for which a waiver of informed consent was obtained under the pre-2018 rules require, after transition to the revised Common Rule, a fresh waiver of informed consent satisfying the additional waiver criterion in the revised Rule?  Having reviewed this issue, SACHRP recommends that a study for which a waiver of informed consent was granted under the pre-2018 rule and that transitions to the revised Common Rule should be able to continue to rely on the existing waiver of informed consent following the transition. Requiring investigators in ongoing studies to apply for a new waiver of informed consent would cause delay to the research enterprise and create administrative burden for IRBs that are already expending significant resources in complying with the revised Common Rule.  SACHRP further believes that requiring investigators to obtain a new waiver of informed consent would add little in the way of additional protection for human subjects, given that all of the waiver criteria in the revised Common Rule, with one exception, are identical to those found in the pre-2018 rule. 

Second, the revised Common Rule includes a requirement that investigators engaging in research classified as “clinical trials” must post consent forms online, on a publicly available federal website.[18] The revised Common Rule defines “clinical trial” as a research study in which human subjects are prospectively assigned to one or more interventions to evaluate the effect of those interventions on biomedical or behavioral health outcomes.[19] The “final version” of the consent form is not required to be posted – rather, any IRB-approved consent form that was used when enrolling subjects into the study in question should be posted.[20] The form may be posted any time after the trial is closed to recruitment, so long as the posting is no later than 60 days after the last study visit by any subject.[21] The federal department or agency supporting the clinical trial may choose to permit redactions to the consent form if it determines certain information should not be made public.[22] This provision was intended to increase transparency regarding informed consent forms and processes and to facilitate the development of better informed consent forms. However, researchers may be confused by how the transition provisions interact with this new posting requirements. Specifically, with respect to studies begun prior to January 21, 2019 that transition to the revised rule, it is not clear for which studies consent forms must be posted online, and when the forms must be posted.  SACHRP recommends that research transitioning to the revised Common Rule should be required to comply with the consent form posting requirement but only if the transitioned study has used a consent form compliant with the revised Common Rule.  If the trial has already closed to recruitment at the time the transition is made, the posting should be made no later than 60 days after the last study visit by any subject, or no later than 60 days after the transition date, whichever is later.  If recruitment is ongoing at the time the transition is made, the researcher should be required to post a version of the consent form that is used after the general compliance date of the revised Common Rule so that the version posted reflects the additional consent elements required by the revised Common Rule. For studies beginning on and after January 21, 2019, the consent form should be posted following the end of recruitment and no later than 60 days after the last study visit by any subject.

SACHRP also recommends that when a consent form is posted in compliance with this requirement, that posting, regardless of where it occurs, should include some context for the form itself – e.g., the study name, the IRB approval date of the consent form, , the point in the study’s life cycle when the posted form was actually used.

There are, however, some distinct problems in interpreting and applying the posting requirement.  Some institutions have executed FWAs in which they have “checked the box,” thus applying the Common Rule requirements to all of the research in which they are engaged, regardless of source of funding.  However, the consent form posting requirement includes discretion on the part of the federal funding agency to allow redactions of the forms to protect, for example, commercially confidential information.  Yet for studies that are not federally funded, but whose forms must be posted because the institution has “checked the box,” there is no named authority to regulate or approve redactions to those posted forms. 

This dilemma also demonstrates the ambiguity in implementing the revised Common Rule’s termination of the practice of allowing institutions to apply the Common Rule voluntarily to all of the research in which they are engaged, regardless of funding source.  If an institution has executed an FWA and “checked the box” before the compliance date, but the FWA term extends past the compliance date, then it is unclear as to whether the regulatory obligations in regard to non-federally-funded studies will also extend past the compliance date. The lack of any named authority to approve redactions of posted consent forms in a non-federally-funded study is one example of how the revised Common Rule cannot be fully implemented for these non-federally-funded studies. 

At the same time, in some states, state laws may require that for research not conducted under federal jurisdiction, entities and researchers conducting studies must apply state research laws, which in some cases are less clear and less protective of subjects than federal law, or state laws may simply require compliance of all research with federal law.  In those states, research-intensive institutions have often “checked the box” on their FWAs in order to prevent application of state research laws or to demonstrate their federal law compliance.  But with the ending of the “check the box” FWA alternative, some institutions may no longer be able to avoid state research law obligations or may no longer be able to demonstrate their federal law adherence.  For this reason, and also taking into account the need to free other institutions from Common Rule jurisdiction so that they are not required to comply with requirements that are not implementable (e.g., the consent form posting requirement for non-federally-funded studies), SACHRP recommends the following:

Institutions that have “checked the box” on their FWAs to impose Common Rule jurisdiction on all their research should be allowed, after the compliance date, to choose, by written notification to OHRP, whether they wish to continue, as a regulatory matter, to impose Common Rule jurisdiction on all their research for the duration of their previously-executed FWA.

Institutions in Maryland and New York, for example, presumably will choose, by reason of their state laws, to continue to adhere to Common Rule standards for the duration of their FWAs, while entities in other states are more likely to choose to end Common Rule compliance obligations for their non-federally-funded studies, in order to avoid the uncertain implementation of the consent form posting requirement.[23]

For some entities, this choice to continue their FWA effectiveness past the compliance date will therefore mean that they will be subject to the consent form posting requirement, even though there is no funding authority to which to appeal for redaction permissions.  Because this new Common Rule requirement cannot meaningfully be implemented in this context, SACHRP suggests that OHRP exercise enforcement discretion for entities that continue to adhere to their “check the box” FWAs after the compliance date, not enforcing this posting requirement except in federally-funded studies. 

Third, confusion has arisen regarding when and how to implement the revised informed consent requirements.  If, for example, a multi-site study already has received IRB approval and has been initiated before January 21, 2019, it is possible that some study sites could require transition to informed consent forms compliant with the revised Common Rule whereas others will continue to use the older version of the forms, creating uncertainty and differences between consent forms used within the same study. Further, it is unclear whether ongoing studies that transition to the revised Common Rule will be required to obtain refreshed consents from current subjects that comply with the revised Common Rule consent requirements. Indeed, SACHRP is under the impression that some institutions have already started to implement certain of the new consent elements found in the revised Common Rule, as the preamble to the June 2018 rule delaying the general compliance date clarified that institutions may implement the requirements of the new Common Rule to the extent that those requirements do not conflict with the pre-2018 requirements.[24]  Some institutions therefore apparently already began at an early point to implement these non-conflicting new informed consent requirements.[25]

Having reviewed the question of whether subjects who provided informed consent meeting the requirements of the pre-2018 Common Rule for a study that later transitions to the revised Common Rule should be given re-consent following the transition date, SACHRP recommends that re-consent should not be necessary in such a situation.  This is because the re-consent process is likely to cause confusion to research subjects who may not understand why they are being asked to provide new consent for a study in which they are already an active participant and for which they have already given consent. A requirement to obtain a new consent would also impose a large administrative burden on the research community but would not advance meaningfully the principle of respect for persons, given that the Common Rule’s additions to the elements of informed consent are unlikely to cause a subject to change his or her mind regarding participation in a study in which the subject is already actively enrolled.

There are other studies in which an IRB may require  at a point following the compliance date that all subjects be given an opportunity to re-consent for an independent reason (such as changes to material risks or benefits in the study).  In those cases, SACHRP recommends that the IRB should have broad discretion as to how the re-consent process should be undertaken or subjects who gave their initial consent before the compliance date. In those cases, for example, the IRB may:

  • Mandate re-consent using the new consent form compliant with the revised Common Rule; or
  • Mandate re-consent using the pre-compliance-date form amended with the requisite new information; or
  • Mandate a new supplemental form to present and highlight the new information alone.

The IRB decision among these alternatives should be made based on its judgment of the alternative that is most accurate, most informative and least confusing from the subject’s point of view.     

Despite our specific recommendations on each of the points discussed above, SACHRP recommends that given the uncertainty discussed above, the most prudent course for researchers, IRBs and institutions is not to transition ongoing studies to the revised Common Rule until legally required to do so.  Some institutions have, however, already begun to transition their studies to the standards of the revised Common Rule, and for those institutions, it is important that they understand as clearly and practically as possible how to implement that transition.  For those entities, IRBs and researchers that transition studies before legally required to do so, we discuss in this letter additional guidance that SACHRP recommends on these points, consistent with the issues identified above.

  1. Consent Requirement

In addition to the transition provisions discussed above, one of the aspects of the revised Common Rule that has received the most attention is a requirement at §____.116(a)(5)(i) that “informed consent must begin with a concise and focused presentation of the key information that is most likely to assist a prospective subject or legally authorized representative in understanding the reasons why one might or might not want to participate in the research.”[26] The revised Common Rule provides some additional guidance on the nature of this required statement, noting that such statements should be “relatively short” and that “in appropriate circumstances, [could] include a summary of relevant pieces of information that are explained in greater detail later.”[27] According to the revised Common Rule preamble, this statement could include concise explanations of: (i) the purpose of the consent and the voluntary nature of the research; (ii) the purposes of the research, expected duration of participation, and the research procedures; (iii) foreseeable risks to the prospective subject; (iv) expected benefits to the prospective subject or others; and (v) alternative procedures that might benefit the prospective subject.[28] This concise statement requirement is a response to concerns that informed consent forms had grown too long and difficult to understand, and that as a result, potential subjects were not making appropriately informed decisions about participation.[29]  The revised Common Rule notes that the purpose of this change is to enable regulated entities to pursue novel approaches to obtaining consent while ensuring that potential subjects receive all the information necessary for them to make informed decisions about research participation.[30]  This provision does not appear in the FDA regulations on informed consent.

In addition to the concise statement requirement the revised Common Rule has introduced four additional required elements of informed consent, none of which are currently found in the FDA regulations.  The first element, applicable to all research, requires a statement in the informed consent form that (i) identifiers might be removed from the data and that the non-identified data could be used for future research studies or distributed to another investigator for future research studies without additional informed consent from the subject, or (ii) the subject’s data collected as part of the research will not be used or distributed for future research studies, even in a non-identified form.  Three additional new requirements introduced by the revised Common Rule include:  (i) for research involving biospecimens, a statement that the subject’s biospecimens may be used for commercial profit and whether the subject will or will not share in this commercial profit, (ii) a statement regarding whether clinically relevant research results, including individual research results, will be disclosed to subjects, and if so, under what conditions, and (iii) 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).[31]

The analogous provisions in the FDA regulations relating to informed consent are not aligned with these new elements required by the Final Rule. The FDA regulations, which have not yet been revised explicitly to reflect or accommodate these revised Common Rule informed consent requirements, do not mandate the concise statement required by the revised Common Rule or the additional new elements discussed above.  The informational elements required by FDA for an informed consent form are set forth in 21 C.F.R. section 50.25 and include such familiar elements as a statement of the purpose of the study, any benefits and risks to the subject, and other enumerated information.[32] FDA regulations call for the information provided during the consent process to be “in language understandable to the subject or the representative” but do not require the concise, up-front presentation described by the revised Common Rule.[33]

 

  1. Harmonization Between Revised Common Rule and FDA Regulations

Recognizing that the difference between the FDA human subjects research rules and those of the Common Rule can be confusing to the research community, in 2016, in Section 3022 of the 21st Century Cures Act,[34] Congress called for harmonization of the two regulatory regimes.  Specifically, the 21st Century Cures Act states:

In order to simplify and facilitate compliance by researchers with applicable regulations for the protection of human subjects in research, the Secretary of Health and Human Services (referred to in this section as the “Secretary”) shall, to the extent practicable and consistent with other statutory provisions, harmonize differences between the HHS Human Subject Regulations and the FDA Human Subject Regulations.[35]

The 21st Century Cures Act requires that HHS submit to Congress a progress report on harmonization efforts not later than December 13, 2018 and that harmonization efforts be completed not later than December 13, 2019.[36]  In addition, the preamble to the revised Common Rule includes a statement of intent to “consider the need for updates to FDA regulations.”[37]

In the June 2018 rulemaking delaying the general compliance date of the revised Common Rule to January 21, 2019, the Common Rule agencies stated in response to a comment that, “FDA is currently working to harmonize its human subjects regulations with the 2018 Requirements, to the extent permitted by FDA’s statutory authority and mandate,” suggesting that the harmonization process is actively in progress.[38] FDA, quite understandably, may be waiting to observe the effects of various of the revised Common Rule’s provisions – including those related to informed consent – before issuing its own revisions to its human subjects research rules.  The FDA also must, of course, analyze any changes to its human subjects regulations in light of its own regulatory mandates, which include protecting human subjects but also include assuring the integrity and accuracy of data used to make marketing approval decisions for drugs and devices.  Additionally, at the time of the passage of the 21st Century Cures Act in December 2016, near the end of President Obama’s administration, Congress was not aware of the details of the then-upcoming issuance of the revised Common Rule, and thus could not have realized that the harmonization process would be complicated by the extensive revisions to the Common Rule that were announced in early 2017.   Moreover, under this Congressional “harmonization” mandate, it is not even clear that FDA must adopt provisions identical to those of the revised Common Rule, as “harmonization” might be reasonably interpreted as requiring revisions to the extent that those revisions are necessary to allow parties to comply simultaneously with both FDA regulations and the revised Common Rule.  In that case, therefore, it is possible that the new informed consent requirements of the revised Common Rule may not be adopted at all by FDA, as it is even now possible to formulate an informed consent form that complies with both FDA and revised Common Rule provisions.

The Common Rule applies only to research funded by one of the federal Common Rule agencies.[39] As a regulatory matter, the Common Rule therefore does not apply directly to most industry-sponsored research, including most FDA-regulated clinical trials sponsored by pharmaceutical and medical device companies. Nevertheless, the Common Rule remains highly relevant for such industry-sponsored research, because many institutions that conduct industry-sponsored research apply the Common Rule as a matter of institutional practice to all human subjects research within the institution, regardless of funding source. Therefore, industry-sponsored research occurring at such institutions must comply with the Common Rule as a matter of practice, even if such research is not required to comply with the Common Rule as a regulatory matter.[40] For this reason, harmonization – or at least, a lack of inconsistency – between the Common Rule and FDA requirements is important both to investigators and to industry sponsors of research.

The current lack of harmonization creates several issues for researchers. An IRB transitioning informed consent forms to the new Common Rule requirements may require investigators conducting FDA-regulated research to use the Common Rule informed consent format, including the “concise and focused presentation of the key information” and the additional new elements discussed above, even though FDA-regulated research is only subject to the less proscriptive FDA informed consent regulations. In a multi-site study under FDA regulation, each institutional study site may seek to use its own template informed consent form, which in most cases will predictably conform to the requirements in the Final Rule.  Further, if each site is using its own designated IRB for such an FDA-regulated study, then permutations may multiply, as each IRB may require changes to the form that, in that IRB’s judgment, implements the new requirements of the Final Rule.  At the same time, industry sponsors may be offering, or even requiring use of, a study template form that conforms to FDA regulations but fails to conform to the requirements of the Final Rule.  While industry sponsors of studies today often require use by all sites of a central IRB, the lead investigator in a multi-site study may be required by his or her institution to use a consent form that complies with the Final Rule and is therefore not consistent with the template offered by the industry sponsor.

Even for studies that are not FDA-regulated, the transition of academic research, often funded by federal agencies, to these new Final Rule requirements may not be easy.  Different institutions in multi-site studies may interpret and apply differently the various new Final Rule informed consent requirements.  They may, for example, make different choices about the required statements relating to return of results or future uses of biospecimens for genomic sequencing.  In federally-funded multi-site research, even though use of a single IRB may be required, institutions collaborating in a study may have reached differing determinations, for example, about how their investigators must implement the “concise statement” requirement, or must provide for, or exclude, future use of biospecimens for genomic sequencing. In short, even aside from the current inconsistency of the informed consent provisions of the Final Rule and the FDA regulations, there will be predictable confusion in implementing these Final Rule requirements among the many sites in a multi-site study.

SACHRP understands that some industry sponsors may already have begun the process of conforming their template informed consent forms to the new Final Rule requirements, in anticipation that sites may demand such conformity, and in the expectation that the FDA eventually will duplicate these new requirements in FDA’s own revisions.  Nevertheless, some industry sponsors, just as predictably, will not have conformed their template informed consent forms to these Final Rule requirements.  For all these reasons, the offering by sponsors, sites and IRBs of varying informed consent forms, with each party deeming its own form compliant with the new regulatory requirements, will add complexity and confusion, especially in multi-site studies.  In addition to administrative burden and transaction costs of negotiating among competing forms, any major differences among consent forms used at sites could even have the potential to undermine the scientific integrity of studies by providing subjects at different sites with different understandings of the research.  Further, the complexity of this regulatory implementation must be considered in light of the other moving parts of the national research environment, including the transition to single IRBs, mandates for study registration and reporting of results, and efforts toward burden reduction in research.

The entire national research community must, SACHRP recommends, seek to avoid, insofar as possible while complying with law, a “battle of the forms” in which each academic institution, IRB (central or institutional), and each industry or foundation sponsor insists on use of its own template form that has been revised to accommodate these recent regulatory changes.  Each party may have its own understandable reasons for insisting on specific provisions in these forms – for example, how personal data are handled, or whether payment for medical services associated with a trial may be the responsibility of the site, sponsor or subject – and these details are worked out between sponsors, IRBs and institutions on a daily basis, according to a well-defined but often laborious process.  That system of reconciling positions on key issues must, and should, continue.  What is unnecessary, however, is a stand-off among parties due to the advent of these new Common Rule requirements for informed consent.  There is no legal requirement, for example, that research regulated by FDA and not by the Common Rule comply with the revised Common Rule standards for informed consent forms.  Similarly, in all or almost all cases, consent forms that have been crafted to comply with the revised Common Rule standards do not conflict with, or violate, FDA’s human subjects research regulations.  Indeed, some studies – for example, studies done under INDs or IDEs but funded by NIH – must comply with both FDA and revised Common Rule standards, and there should be no difficulty in satisfying both sets of standards. 

All parties in the research enterprise must realize that the only research that must comply with the new Common Rule standards for informed consent are federally-funded studies that are initiated on or after the compliance date of January 21, 2019. For all other studies, these new informed consent standards are both voluntary and, strictly speaking, unnecessary, even if desirable.  To prevent deadlock in the national and international research review and approval process, SACHRP recommends that all parties insist, during this transition time period, on consent form compliance with their true actual regulatory obligations, and yet that the parties tolerate, whenever possible, other parties’ efforts to improve their consent forms and processes consistent with the revised Common Rule standards.  As long as, for example, FDA regulations are respected, academic medical centers and IRBs should not deem it fatal if consent forms for studies only under FDA jurisdiction do not include the “concise statement” required by the revised Common Rule.  At the same time, when encountering, in FDA regulated studies, IRB- or institution-mandated consent forms that contain the “concise statement” and other features required by the revised Common Rule, industry sponsors of research would be wise to tolerate the use of such forms, as long as they do no misrepresent the sponsor’s position on key study issues.  It is critical, during this transition period, that all parties and categories of parties in the research enterprise be willing to compromise, to tolerate differences from their internal, non-regulatory standards and templates, and to insist, at the end of the day, only on those terms and conditions that are, in fact, required by regulation.  At some point, enterprise-wide experience with these revised informed consent standards will yield a system that handles consent form differences readily and well, but during this transition time, for the sake of the research enterprise and its participants, SACHRP believes that parties must avoid unnecessary conflicts.

As discussed above, SACHRP fully recognizes that given its different statutory mission from that of OHRP, FDA may choose not to make its consent requirements mirror precisely those of the Common Rule.  However, given the fact that much FDA-regulated research in the United States takes place at institutions that apply the Common Rule to all research as a matter of institutional practice, SACHRP recommends that HHS, including OHRP and FDA, endorse the position that compliance with the additional informed consent requirements found in the revised Common Rule is not inconsistent with FDA’s existing regulations on informed consent. .

Finally, in regard to enforcement by OHRP of the provisions of the revised Common Rule, and in regard to FDA’s future enforcement of its own impending revisions of its human subjects research regulations, SACHRP suggests that those agencies’ enforcement, for a decent interval after the regulatory compliance dates, be as accommodative and deferential as reasonably possible to good faith institutional, research, industry and IRB interpretations and implementations of these new requirements.  This is less because inherent ambiguities of regulations in this area may prevent any perfect compliance, than because there are varying ways in which entities and researchers may implement these new standards may illustrate and help define optimal ways in which these regulations themselves may be interpreted and applied.  The creativity of the regulated community may in fact help to define best interpretations and best practices under the new regulatory standards. 

  1. Conclusion

As described above, the lack of clarity regarding the application of the transition provisions in the revised Common Rule has created confusion within the regulated community.  SACHRP recommends that the HHS Secretary direct OHRP to issue guidance clarifying the application of the transition provisions in the Common Rule and how the revised Common Rule’s informed consent requirements may be read and applied to be consistent with existing FDA regulations.  SACHRP further recommends that the HHS Secretary ensure that FDA and OHRP consider the needs of all relevant stakeholders in harmonizing, or ensuring no inconsistency between their respective informed consent requirements, and that they proceed in this regard as rapidly as reasonably possible, to provide greater certainty to the research community, including research participants.



[1] 45 C.F.R. part 46.

[2] 83 Fed. Reg. 28,497, 28,502 (June 19, 2018).

[3] § ____.114(b), 83 Fed. Reg. at 28,502-03.

[4] For purposes of the Common Rule’s transition provisions, research is “initiated” when the research is initially approved by an IRB, when the government waives IRB review under §__.101(i), or when the research is determined to be exempt.

[5] 83 Fed. Reg. at 28,502-04.

[6] 83 Fed. Reg. at 28,503.

[7] 83 Fed. Reg. at 28,504.

[8] 83 Fed. Reg. at 28,503-04.

[9] HHS guidance, Companion Q&As About the Revised Common Rule (July 24, 2018), https://www.hhs.gov/ohrp/sites/default/files/Revised-Common-Rule-Q%26As_07-27-2018.pdf.

[10] 83 Fed. Reg. at 28,503.

[11] 83 Fed. Reg. at 28,504.

[12] 83 Fed. Reg. at 28,503.

[13] 83 Fed. Reg. at 28,503.

[14] 83 Fed. Reg. at 28,504.

[15] 83 Fed. Reg. at 28,504.

[16] § ____.116(f)(3)(ii), 82 Fed. Reg. at 7,267.

[17] § ____.116(f)(3), 82 Fed. Reg. at 7,267.

[18] § ____.116(h), 82 Fed. Reg. 7,149, 7,229 (Jan. 19, 2017).

[19] § ____.116(h), 82 Fed. Reg. at 7,229.

[20] § ____.116(h), 82 Fed. Reg. at 7,229.

[21] §_____.116(h)(3), 82 Fed. Reg. at 7,229.

[22] § ____.116(h), 82 Fed. Reg. at 7,229.

[23] SACHRP notes institutions that elect to continue to self-impose Common Rule jurisdiction over all their research also will be conducting some research under FDA jurisdiction – and all FDA-regulated research they conduct will in fact be under Common Rule jurisdiction as well.  For those studies under both regulatory regimes, sponsors must accept consent forms that comply with the new Common Rule consent requirements. 

[24] 83 Fed. Reg. at 28,503.

[25] SACHRP also understands that some in the research community have expressed confusion as to how studies transitioning to the revised Common Rule will implement the regulatory broad consent provision found at ___.116(d), 82 Fed. Reg. at 7,266.  SACHRP’s understanding from its discussions with members of the research community, however, is that very few institutions intend to use the regulatory broad consent provision, at least in part due to the shortcomings with this provision that SACHRP previously addressed in its July 26, 2017 Guidance on Broad Consent under the Revised Common Rule.  Accordingly, we do not address the topic of transitioning to regulatory broad consent here.___

[26] 82 Fed. Reg. at 7,265.

[27] 82 Fed. Reg. at 7,213.

[28] 82 Fed. Reg. at 7,214.

[29] 82 Fed. Reg. at 7,211.

[30] 82 Fed. Reg. at 7,214.

[31]  __§.116(b)(9), __§.116(c), 82 Fed. Reg. at 7,265-67.

[32] 21 C.F.R. § 50.25.

[33] 21 C.F.R. § 50.20.

[34] 21st Century Cures Act, Pub. L. 114-255, § 3023(a) (2016).

[35] 21st Century Cures Act, Pub. L. 114-255, § 3023(a) (2016).

[36] 21st Century Cures Act, Pub. L. 114-255 § 3023(d), (e) (2016).

[37] 82 Fed. Reg. at 7,151.

[38] 83 Fed. Reg. at 28,497, 28,500.

[39] 82 Fed. Reg. at 7,259.

[40] Historically many U.S. institutions have “checked the box” on their Federal Wide Assurances submitted to OHRP, meaning that that the institution has elected voluntarily to apply the Common Rule to research conducted at that institution regardless of the funding source of the research.  45 C.F.R. §§ 46.101, 46.103(a). Unlike organizations that voluntarily apply the Common Rule as a matter of institutional policy to all of their human subjects research, organizations that “check the box” are subject to OHRP jurisdiction and enforcement for all of their human subjects research. Notably, however, the 2017 Final Rule preamble announced the elimination of the “check the box” option. No timeframe has been set for phasing out this option, but once the change is made, institutions will no longer be able to “check the box” to subject all of their research as a regulatory matter to the Common Rule, although such institutions will still be able voluntarily to apply the Common Rule to all of their research involving human subjects. 82 Fed. Reg. at 7,181.

 


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Content created by Office for Human Research Protections (OHRP)
Content last reviewed on November 20, 2018