the re-use of existing information and materials can be an efficient
mechanism for conducting research without presenting additional
physical or psychological risks to the individual, it seemed prudent to
consider changes to current regulations relating to those issues.
2. NPRM Proposals
    The NPRM proposed to allow broad consent to cover the storage or
maintenance for secondary research use of all biospecimens (regardless
of identifiability) and identifiable private information. Broad consent
would be permissible for the storage or maintenance for secondary
research of such information and biospecimens that were originally
collected for either research studies other than the proposed research
or nonresearch purposes. The broad consent document would also meet the
consent requirement for the use of such stored biospecimens and
information for individual research studies. The NPRM made a separate
case for nonidentified private information than it did for
biospecimens, stating that consent would not be required for the
secondary research use of nonidentified private information, such as
the research use of medical records that have had all identifiers
removed. Because the NPRM proposed that the definition of human subject
be expanded to include all biospecimens, it also proposed to facilitate
research using biospecimens by permitting broad consent to be obtained
for their storage or maintenance for secondary research.
    It was envisioned that the proposed broad consent provision would
be used by institutions and investigators to give individuals the
choice to either allow or disallow the use of their biospecimens and
identifiable private information for secondary research. In some cases,
institutions would be expected to seek broad consent as part of a
research protocol to create a research repository of biospecimens or
information. However, in other cases it was expected that institutions,
particularly those that do not typically conduct human subjects
research, might not develop a research protocol to create a research
repository, but still choose to seek broad consent from individuals for
the research use of their biospecimens or identifiable private
information. In such cases, these institutions might simply ``tag''
biospecimens and information as either available or not available for
secondary research.
    Because broad consent is a different form of consent than the
consent that is obtained for a specific research study, the NPRM
proposed required elements for broad consent that would include several
of the basic and additional elements of informed consent, but not all,
and would include several additional required elements. The NPRM
proposed to require that the information included in broad consent
describe the biospecimens and identifiable private information that
would be covered by the consent, recognizing that the biospecimens and
information to be used in future research studies might be collected
after the consent was obtained. Further, the NPRM proposed that broad
consent for the research use of biospecimens or identifiable private
information obtained for nonresearch purposes would be limited to
covering either or both of the following: (1) 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 for adult subjects, and, for research involving children as
subjects, 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 NPRM proposed to include the standard concerning who is a child
based upon the definition of ``children'' as defined at 45 CFR
46.402(a). At the time the child becomes an adult, the broad consent or
permission would no longer be valid and either broad consent would need
to be sought from the child-turned-adult, or the investigator would
need to seek a waiver of informed consent in order to use the
individual's biospecimens or identifiable private information for
research, unless one of the exclusions or exemptions were applicable.
    A proposed element of broad consent in the NPRM included a
requirement that subjects be informed that they may withdraw consent,
if feasible, for research use or distribution of the subject's
information or biospecimens at any time without penalty or loss of
benefits to which the subject is otherwise entitled. However,
information that has been stripped of identifiers might not be
traceable. Thus, it might not be feasible to withdraw consent for
future use or distribution in this case. If, however, an investigator
committed to permitting a subject to discontinue the use of such
information, it was expected that the investigator would honor this
commitment by not stripping identifiers and using the information or
biospecimens in research. The proposed regulations would not require
investigators to make such a commitment.
    Another proposed element of broad consent in the NPRM related to
the public posting of nonidentified data about a subject. This proposed
element of broad consent would include an option, when relevant, for an
adult subject or the subject's legally authorized representative to
consent or refuse to consent to the inclusion of the subject's data
with removal of the identifiers listed in the HIPAA Privacy Rule at 45
CFR 164.514(b)(2)(i)(A) through (Q), in a database that is publicly
available and openly accessible to anyone. This provision was proposed
in the context of increasing interest in inviting study participants to
allow their study data, in some cases including genomic data, to be
made publicly available in order to maximize the potential for research
that spurs increased understanding of disease processes. Under this
provision, the consent document would be required to prominently note
the option for the participant to allow the investigator to publically
post (e.g., on a Web site) the participant's genomic or other
potentially identifiable sensitive information, and to include a

description of the risks associated with public access to the data.
    To facilitate the use of broad consent, the NPRM proposed that the
Secretary of HHS would publish in the Federal Register templates for
broad consent that would contain all of the required elements of
consent in these situations. It was envisioned that at least two broad
consent templates would be developed: one for information and
biospecimens originally collected in the research context, and another
for information and biospecimens originally collected in the
nonresearch context.
    Public comment was sought on whether broad consent to secondary
research use of information and biospecimens collected for nonresearch
purposes should be permissible without a boundary, or whether a time
limitation or some other type of limitation should be imposed on
information and biospecimens collected in the future that could be
included in the broad consent as proposed in the NPRM. If a time limit
should be required, public comment was sought on whether the NPRM
proposal of up to 10 years was a reasonable limitation and whether a
limitation related to an identified clinical encounter would better
inform individuals of the clinical information and biospecimens that
would be covered by a broad consent. Public comment was also sought on
whether all of the elements of broad consent proposed in the NPRM
should be required for the secondary use of biospecimens or
identifiable private information originally collected as part of a
research study that was conducted without consent because (1) either
the original research study met an exclusion or exempt category of
research, or (2) a waiver of consent was approved by an IRB.
    Public comment was sought on how likely investigators are to seek
broad consent for the use of identifiable private information (as
contrasted with biospecimens), given that provisions within the NPRM
would make it easier to do such research without consent. In this
regard, the NPRM proposal to prohibit waiver of consent by an IRB if a
person has been asked for broad consent and refused to provide it could
create a disincentive on the part of investigators from choosing to
seek broad consent for research involving secondary use of identifiable
private information. Given the costs and time and effort involved in
implementing the system for obtaining broad consent for the use of
identifiable private information and tracking when people provide
consent or refuse to do so, the public was asked to comment on whether
the benefits to the system were likely to outweigh the costs, and if
so, whether the broad consent provisions should be limited to obtaining
broad consent for research use of biospecimens.
3. Public Comments
    Approximately 475 comments addressed broad consent, a majority of
which expressed opposition to broad consent as proposed and discussed
in the NPRM. The basis of this opposition was largely related to the
NPRM proposal that some type of consent (broad or specific) would be
required for research with nonidentified biospecimens. A smaller number
of comments (approximately 150) addressed the adequacy or inadequacy of
broad consent as a concept, or the proposed broad consent templates to
be created by HHS.
    Public comment on the proposed, but not yet developed, broad
consent templates was mixed, with a majority of comments stating that
it was impossible to comment on a template that had not yet been
created. Even among those who supported the use of broad consent, some
had questions about whether broad consent provided at one institution
would be sufficient for research ultimately conducted at another
institution. Many comments further noted that the entire regulatory
schema around broad consent (e.g., exemptions dependent on broad
consent, prohibition on an IRB waiving broad consent if broad consent
had been sought and someone declined) required additional study and
discussion and recommended that the department issue another NPRM on
these issues following some form of systematic analysis and broader
public consultation. A professional investigative pathology association
and many of its members endorsed the concept of broad consent and the
development of templates by the Federal Government, writing that they
would be less burdensome but still a functional way of promoting
ethically conducted biomedical research with biospecimens.
    Several commenters suggested that institutions needed to retain the
ability to create and amend broad consent forms tailored to a variety
of situations rather than rely on a federal template. These comments
also generally stressed the importance of retaining an IRB's active
role in reviewing the broad consent process and specific secondary
research studies to ensure that interests other than autonomy and
concerns other than those related to privacy were considered in a
proposed study. A minority of commenters additionally expressed concern
with the Federal Government's ability to develop broad consent
templates that the regulated community might feel were sufficiently
informative.
    Public comments were also mixed on whether or not broad consent as
proposed in the NPRM would constitute meaningful consent. Many comments
noted that a consent form sufficiently broad to cover all potential
future secondary research uses of biospecimens or identifiable private
information might be so broad and vague as to be not meaningful or
informative to prospective research subjects. Others doubted the
meaningfulness of broad consent obtained in the clinical setting. One
academic research institution questioned whether it was really consent
at all, but rather an agreement or permission, and another commenter
questioned whether broad consent would increase subjects' autonomy.
    Many of the commenters who opposed broad consent also argued
against any requirement to obtain consent for the use of nonidentified
biospecimens. One academic research institution raised serious concerns
about obtaining meaningful broad consent, which undermines existing
privacy and other protections for subjects in research. Others noted
that requiring broad consent for all secondary use of all biospecimens
would require that there always be a link or code between the
biospecimen and the subject's identity, which ultimately would result
in an overall increase in privacy risks. Many commenters favored an
opt-out system for broad consent (especially with respect to broad
consent for use of nonidentified biospecimens). An AI/AN organization
expressed overall concern about the concept of broad consent, noting
that many AI/AN people believe that specimens and blood are considered
sacred and recommending that all secondary uses of collected specimens
and data should require an additional consent process, including tribal
consent when specimens and data are obtained from AI/AN populations.
    Few comments were received on the actual proposed elements of broad
consent. Of these, a majority expressed confusion with the proposals
related to the duration of the consent and the scope of the
biospecimens and identifiable information that could be collected.
    The NPRM also asked whether broad consent to secondary research use
of information and biospecimens collected for nonresearch purposes
should be permissible without a boundary, or whether a time limitation
or some other

type of limitation should be imposed on information and biospecimens
collected in the future that could be included in the broad consent. If
a time limit should be required, the NPRM asked whether up to 10 years
was a reasonable limitation. It also asked whether a limitation related
to an identified clinical encounter would better inform individuals of
the clinical information and biospecimens that would be covered by a
broad consent document. Approximately 65 commenters specifically
answered this question.
    Most who commented were opposed to the 10-year limitation on the
period of time that an institution could collect biospecimens and
information from an individual once broad consent had been sought and
obtained. They stated that the limitation was arbitrary, not
supportable by anything discussed in the NPRM, and presented an
administrative burden for institutions and investigators to time stamp
and track the 10-year limit for each subject. A few commenters stated
that a 10-year limit is a reasonable boundary, but were concerned about
the need to re-consent people once they reach the legal age of consent.
In large data sets, identifying such people could be very challenging
as people often move locations during such lengths of time, which would
create an administrative barrier. A few commenters suggested that 10-
year boundary was too long and one research institution commented that
in its experience individuals seem to prefer shorter time limits tied
to specific periods (e.g., a series of clinical encounters,
participation in an ongoing study).
    A few comments stated that any time limit could have a negative
effect on rare disease research as the numbers of affected people are
so small and, as discoveries are made, there is often a need to go back
to years' worth of information or stored biospecimens to search for
markers, mutations, or clinical information that is related to the new
discovery. Such commenters expressed concern that this could be
deleterious to individuals with rare disease seeking a diagnosis.
    Some commenters were confused about how the 10-year boundary
proposed in the NPRM was supposed to function. Some comments assumed
that one could only use the biospecimens or data for a 10-year period
and after that period one would be required to get consent again for
the use of those items. Others assumed that investigators would have to
re-consent people every 10 years, but the information and biospecimens
could be used indefinitely. For these reasons, many comments on the 10-
year boundary said it was unreasonable and unworkable operationally.
Some suggested that instead of 10-year boundary, patients could be
routinely reminded that they gave consent and can be reminded that they
can opt out at any time. Several large research institutions commented
that the time limit would necessitate a lot of tracking for
institutions and could lead to smaller health care institutions ceasing
their collection of biospecimens for research, which would ultimately
have a negative impact on research.
    The NPRM also asked whether all of the elements of consent proposed
at Sec.  __.116(c) should be required for the secondary use of
biospecimens or identifiable private information originally collected
as part of a research study that was conducted without consent because
either the original research study met an exclusion or exempt category
of research, or a waiver of consent was approved by an IRB.
Approximately 30 comments answered this question. Responses ranged from
those saying the elements are not as relevant as the burden of having
to seek consent every 10 years. Many stated that the elements of
consent appeared to be growing in the proposed rule at the same time
that the rule was requiring simpler and shorter consent forms. As such,
efforts should not be made to include all of the elements required in
specific consent to broad consent; otherwise the intent of broad
consent would be lost.
    The NPRM also asked whether oral consent should be permissible in
limited circumstances as proposed under the exemption for the storage
and maintenance of biospecimens and identifiable private information.
More than 60 pathologists, pathology departments, and pathology
organizations suggested that oral consent should not be allowed in this
context because it raises too many administrative challenges and may
undermine public trust. A few commenters felt oral consent should be
permitted but generally did not provide a rationale.
    Finally, some comments indicated that broad consent as a concept
should not be included in a final rule, and that the standards that
exist under the pre-2018 rule for secondary research (i.e., either that
an investigator obtains study specific consent or a waiver of informed
consent from an IRB) should be maintained in a final rule.
4. Response to Comments and Explanation of the Final Rule: Elements of
Broad Consent
    The final rule includes an option to obtain broad consent for the
storage, maintenance, and secondary research use of identifiable
private information or identifiable biospecimens, as defined at Sec.
__.102(e)(5) and (6), but several significant changes were made in
response to public comments. Although in some ways the final rule's
broad consent provision resembles the provision that was proposed in
the NPRM, it is important to recognize a very fundamental difference
between the role that this provision will play under the final rule, as
compared to the role it was intended to play under the NPRM. This key
difference relates to the fact that the provisions in the NPRM that
would have generally required consent for secondary research use of
nonidentified biospecimens, including imposing narrow stringent
criteria for IRB waiver of consent with respect to such research, are
not being implemented because the NPRM's proposal that all
biospecimens, regardless of their identifiability, be covered under the
Common Rule has not been adopted. Importantly, under the final rule,
broad consent is permissible only for secondary research and no other
types of research.
    Thus, had all of those NPRM provisions been implemented,
investigators who wanted to conduct secondary research with
biospecimens would in most instances have found themselves essentially
forced to use the new broad consent provisions as their only practical
option for conducting such research. This is because generally, under
the NPRM proposals, they would no longer have had the option to de-
identify information or biospecimens, or to use them in coded form, to
avoid application of the Common Rule's requirements. Under the NPRM's
proposals, had investigators not obtained broad consent, they would
often not practicably be able to meet the informed consent requirements
relating to such research (which would have been covered under the
Common Rule). Therefore, it would generally have been the case that
they would have had little choice but to obtain broad consent, assuming
they did not want to undertake the alternative of obtaining study-
specific consent from subjects each and every time they conducted a
study involving secondary use of biospecimens.
    Given that we did not adopt the NPRM's proposal to cover all
biospecimens regardless of their

identifiability under the Common Rule, the final rule also does not
adopt proposed consent requirements for secondary research with
nonidentified biospecimens. For this reason, the final rule's
provisions relating to broad consent now play a very different role
from those proposed in the NPRM. In most instances, these provisions
will be providing new options--that is, new flexibility--to an
investigator, in addition to those options that an investigator would
have had under the pre-2018 rule. An investigator wishing to do
secondary research with biospecimens will continue to have the option
of doing secondary research with nonidentifiable biospecimens, as was
the case in the pre-2018 rule. An investigator also could continue to
use biospecimens that are coded, thus allowing the collection of
additional information about the subjects over time.\47\ In both of
those instances, no additional consent would be required because the
research would not involve human subjects as defined by the final rule.
Furthermore, even if the investigator wanted to use the biospecimens
with identifiers attached, he or she would still have the option of
asking an IRB to waive the requirement to obtain informed consent: the
waiver criteria are in most respects unchanged under the final rule.
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    \47\ HHS. Office for Human Research Protections. Coded Private
Information or Specimens Use in Research, Guidance. October 16,
2008. Retrieved from https://www.hhs.gov/ohrp/regulations-and-policy/guidance/research-involving-coded-private-information/index.html.
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    For these reasons, the broad consent provisions at Sec.  __.116(d)
afford investigators wishing to conduct secondary research on
identifiable private information or identifiable biospecimens an
additional alternative to obtaining an IRB waiver of consent or to
obtaining study-specific consent. Given that these new broad consent
provisions are essentially a new alternative to other options that are
very similar to those that existed under the pre-2018 rule, these
provisions are not increasing any regulatory burden or making it more
difficult to do research. Indeed, just the opposite is the case. The
changes made in the final rule are responsive to the significant
criticisms expressed by many of the commenters about what the NPRM
proposed, under which obtaining broad consent would have imposed
substantial new burdens on a vast amount of secondary research with
biospecimens. In contrast, when investigators choose to use the broad
consent provisions under the final rule, they will presumably be doing
so because this new option is less burdensome to them than their other
(largely unchanged) options for conducting such research.
    Although we recognize public commenters' concern that broad consent
might not be as meaningful or informative as study-specific consent, it
is also important to note that when an investigator chooses to use this
new option, doing so will generally provide increased protection to the
autonomy of research subjects. It will give 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. In
addition, in response to the public's concerns that broad consent would
not be meaningful, some of the elements of broad consent have changed
from what was proposed in the NPRM to require more specific information
about the research that may be conducted. As discussed in the NPRM, one
of the main purposes of the final rule is to facilitate the conduct of
minimal risk research, while enhancing subjects' autonomy. We believe
that the option to obtain broad consent furthers this goal.
    It is important to recognize that broad consent is a permissible
option only for secondary research. Secondary research is limited to
research using identifiable private information or identifiable
biospecimens that are collected for either research studies other than
the proposed research or nonresearch purposes. It is not permissible to
obtain broad consent for any other type of research (e.g., research
involving the collection of information or biospecimens through a
research interaction or intervention with a subject). The informed
consent requirements in Sec.  __.116(b) and (c) will be applicable to
all human subjects research for which broad consent is not an option.
However, it is envisioned that research requiring study-specific
consent, such as research involving the collection of information or
biospecimens through a research interaction or intervention with a
subject, will sometimes also involve seeking subjects' broad consent
for the secondary research use of identifiable private information or
identifiable biospecimens obtained as part of the original research
study.
    When broad consent is obtained, the general requirements for
informed consent in Sec.  __.116(a) apply, except that the requirements
at Sec.  __.116(a)(5) (imposing certain requirements concerning the
presentation of information for informed consent and prescribing the
order in which consent information is presented) do not apply to broad
consent.
    We expect that, given the different requirements set forth for
study-specific consent and broad consent, some institutions and
investigators may elect to pursue study-specific consents for the
storage, maintenance, and secondary research uses of identifiable
private information and identifiable biospecimens (or for some subset
of such research) whereas other institutions and investigators may
elect to pursue broad consent for the same types of research (or for
some subset of such research). For instance, with regard to the public
comments raising concern about broad consent being sought from AI/AN
peoples, it is expected that institutions, investigators, and IRBs will
consider these concerns when determining when it might be appropriate
to seek study-specific consent for the secondary research use of
identifiable biospecimens, as well as the need for tribal consent, when
appropriate.
    Perhaps even more commonly, however, given that the NPRM proposal
regarding generally requiring consent for research use of
nonidentifiable biospecimens has not been adopted, many investigators
may choose to use the routes that previously existed under the pre-2018
rule, and will continue to exist, for conducting such research without
informed consent under the Common Rule. Those options include using
nonidentifiable biospecimens, including perhaps having a code
maintained that will allow the investigator to obtain additional
information about the subjects, or obtaining a waiver from an IRB of
the need to obtain informed consent.
    The broad consent provision in the final rule is different in three
main ways from what was proposed in the NPRM. First, consistent with
the decision not to revise the definition of human subject to include
biospecimens regardless of identifiability, the broad consent provision
in Sec.  __.116(d) only applies to secondary research using
identifiable private information and identifiable biospecimens.
    Second, the elements of broad consent have been strengthened and
simplified in response to public comments. The final rule strengthens
the element of broad consent proposed in the NPRM regarding the need to
provide a general description of the types of research that may be
conducted with identifiable private information and identifiable

biospecimens. It does this by requiring that this description must
include sufficient information to allow a reasonable person to expect
that the broad consent would permit the types of research conducted.
This ``reasonable person'' standard is consistent with the
interpretation that the Office for Civil Rights provided for
authorization obtained from an individual for the use or disclosure of
protected health information for future research purposes. In addition,
the final rule has been strengthened to require 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
of those specific research studies. It is envisioned that for certain
types of research, such as research for which there is reason to
believe some subjects will find the research controversial or
objectionable, a more robust description of the research will be
required in order to meet this ``reasonable person'' standard. This
requirement has been included in the final rule in recognition of the
concerns raised by some public commenters that broad consent would not
be meaningful because it will not provide detailed information about
specific research studies that might be conducted with the individual's
identifiable private information or identifiable biospecimens.
    As proposed in the NPRM, the final rule permits broad consent to be
sought for either a narrow type of research to be conducted in the
future (e.g., cancer research), or a broader scope of research. Given
this flexibility, while the final rule includes an exemption for
secondary research for which broad consent is required, the exemption
is contingent on several criteria being satisfied, including that an
IRB determines that the research to be conducted is within the scope of
the broad consent (Sec.  __.104(d)(8)). This exemption is further
discussed in Section V. For research that is not exempt, the IRB is
expected to assess whether the description of the research included in
the broad consent form is adequate to permit a reasonable person to
expect that they were providing consent for the currently proposed
secondary research study.
    While strengthening the broad consent requirements, the final rule
also adopts simplified and more flexible elements of broad consent than
what was proposed in the NPRM. For example, the final rule requires
that the broad consent include a description of the identifiable
private information or identifiable biospecimens that might be used in
research, whether sharing of such information or biospecimens might
occur, and the types of institutions or investigators that might
conduct research with such information or biospecimens. However, 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: (1)
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. We were persuaded by the public comments that raised
concerns about the complexity and tracking burden that such limitations
would impose, without clearly offering individuals a more meaningful
way to control the use of their information or biospecimens.
    In addition, the broad consent requirements have been simplified to
avoid creating redundant requirements with the basic elements of
informed consent under Sec.  __.116(b) that must also be included in
broad consent obtained under Sec.  __.116(d). For example, in the final
rule, it is required that broad consent include 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 loss
of benefits to which the subject is otherwise entitled ((Sec.
__.116(d)(1), incorporating Sec.  __.116(b)(8) for broad consent).
Therefore, the comparable element of broad consent that was proposed in
the NPRM is not included in the final rule.
    As discussed in the NPRM, we expect that, when appropriate, this
element of broad consent will inform subjects that information that has
been stripped of identifiers might not be traceable, and thus it might
not be feasible to withdraw consent for future use or distribution in
this case. However, if an investigator commits to permitting a subject
to discontinue use of the subject's identifiable private information or
identifiable biospecimens, it is expected that the investigator will
honor this commitment by not removing identifiers.
    Similarly, the final rule also does not include the element of
broad consent proposed in the NPRM that, when relevant, would have
required the broad consent to include an option for an adult subject or
the representative to consent, or refuse to consent, to the inclusion
of the subject's data, with removal of the identifiers listed in 45 CFR
164.514(b)(2)(i)(A) through (Q), in a database that is publicly and
openly accessible to anyone, and that this option be prominently noted
and include a description of the risks of public access to the data. We
believe this proposed requirement is unnecessary because it overlaps
with the broad consent elements included in the final rule requiring a
statement describing the extent, if any, to which confidentiality of
records identifying the subject will be maintained (Sec.  __.116(d)(1),
incorporating Sec.  __.116(b)(5) for broad consent), and a description
of any reasonably foreseeable risks or discomforts to the subject
(Sec.  __.116(d)(1), incorporating Sec.  __.116(b)(2) for broad
consent).
    The final rule includes a slightly different provision relating to
the return of research results than that proposed in the NPRM. As set
forth in Sec.  __.116(d)(6) of the final rule, 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 must be
included in the broad consent. This element of broad consent differs
from the related requirement in Sec.  __.116(c)(8) that pertains when
an investigator is seeking consent for a specific study, since unlike
the circumstances under which broad consent is likely to be sought,
investigators seeking consent for a specific study will know if the
study includes a plan to return research results to subjects. The NPRM
proposed that a general element of informed consent be included as part
of a broad consent, namely that the consent include a statement
regarding whether clinically relevant research results, including
individual research results, would be disclosed to subjects, and if so,
under what conditions. The language adopted in the final rule is
intended to provide transparency, but is tailored to the broad consent
context as those seeking broad consent may not know whether clinically
relevant research results, including individual research results, will
always be disclosed to subjects, and if so, under what conditions.
Nonetheless, unless investigators know that such results will

be disclosed to subjects in all circumstances, subjects will be
informed through a broad consent of the possibility that such results
will not be disclosed to them. This provision is intended to pertain to
all clinically relevant research results, including general or
aggregate research findings and individual research results. This
element of broad consent will affect the applicability of the exemption
set forth at Sec.  __.104(d)(8), for secondary research for which broad
consent is required. This exemption applies only if the investigator
does not include returning individual research results to subjects as
part of the study plan (noting, however, that this provision does not
prevent an investigator from abiding by any legal requirements to
return individual research results). Although it is envisioned that
broad consent will often be sought with the expectation that specific
secondary research studies using identifiable private information or
identifiable biospecimens will be exempt under Sec.  __.104(d)(8), this
will not always be the case. Broad consent can also be obtained for
secondary research that will not qualify for this exemption, such as
secondary research that will involve returning clinically relevant
research results to subjects. In these cases, the specific secondary
research study will need to undergo IRB review and approval under Sec.
__.111, and we expect that the IRB would consider what subjects were
told in the broad consent regarding the return of research results. The
only exception to the requirement for IRB review of such research, if
covered by this policy, is if the research qualifies for another
exemption or the research is carried out under a Secretarial waiver at
Sec.  __.101(i).
    Finally, the third main difference between the NPRM and final rule
provision on broad consent is that the final rule does not include
broad consent templates to be established by the Secretary of HHS. 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 (Sec.
__.104(d)(7)). This exemption is further discussed in Section V. At a
later time, the Secretary of HHS expects to develop guidance on broad
consent, which could include broad consent templates.
    In addition, we are also including in the final rule an element
that for research involving biospecimens, when appropriate, the broad
consent must state whether the research will (if known) or might
include whole genome sequencing (WGS) (Sec.  __.116(d)(1),
incorporating Sec.  __.116(c)(9)). The reasons for requiring this
element in the broad consent are similar to those discussed above
regarding the addition of this requirement in the additional elements
of consent at Sec.  __.116(c)(9). WGS generates an extremely large
amount of data, which when analyzed can yield information about an
individual, including factors that could contribute to their future
medical conditions. Therefore, given the implications of WGS
information for an individual and his or her biological family, if it
is known that the broad consent will or might permit the use of
individuals' biospecimens for WGS, we believe that this aspect of the
research must be disclosed to prospective subjects as part of the broad
consent process. The broad consent must include a general description
of the types of research that may be conducted with the identifiable
private information or identifiable biospecimens, with sufficient
information to allow a reasonable person to expect that the broad
consent would permit the types of research conducted (Sec.
__.116(d)(2)). Including an additional element of broad consent that
specifically addresses WGS makes it clear that such information must be
disclosed to prospective subjects.
    Under the final rule, if the subject or the subject's legally
authorized representative is asked to provide broad consent, the broad
consent must satisfy the general informed consent requirements at Sec.
__.116(a)(1)-(4), and (a)(6), and must include all of the following 12
elements that are applicable:
     A description of any reasonably foreseeable risks or
discomforts to the subjects (Sec.  __.116(d)(1), incorporating basic
elements of informed consent in Sec.  __.116(b)(2));
     A description of any benefits to the subject or to others
that may reasonably be expected from the research ((Sec.  __.116(d)(1),
incorporating basic elements of informed consent in Sec.  __.116(b)(3);
     A statement describing the extent, if any, to which
confidentiality of records identifying the subject will be maintained
((Sec.  __.116(d)(1), incorporating basic elements of informed consent
in Sec.  __.116(b)(5));
     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 ((Sec.  __.116(d)(1), incorporating
basic elements of informed consent in Sec.  __.116(b)(8));
     If applicable, 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
((Sec.  __.116(d)(1), incorporating additional elements of consent in
Sec.  __.116(c)(7));
     When appropriate, for research involving biospecimens,
whether the research will (if known) or might include WGS (i.e.,
sequencing of a human germline or somatic specimen with the intent to
generate the genome or exome sequence of that specimen.) ((Sec.
__.116(d)(1), incorporating the additional element of consent in Sec.
__.116(c)(9));
     A general description of the types of research that may be
conducted with identifiable private information or identifiable
biospecimens. This description must include sufficient information to
permit a reasonable person to expect that the broad consent would
permit the types of research conducted (Sec.  __.116(d)(2));
     A description of the identifiable private information or
identifiable biospecimens that might be used in research, whether
sharing of such information or biospecimens might occur, and the types
of institutions or investigators that might conduct research with such
information or biospecimens (Sec.  __.116(d)(3));
     A description of the period of time allowed 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 such information or biospecimens
may be used for research purposes (which period of time could be
indefinite (Sec.  __.116(d)(4));
     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 (Sec.  __.116(d)(5));
     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; (Sec.  __.116(d)(6)); and
     An explanation of whom to contact for answers to questions
about the subject's rights 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 (Sec.
__.116(d)(7)).
    The elements of broad consent described in the first six bullet
points above are not unique to broad consent, while the elements
described in the last six bullet points are specific to the
requirements of broad consent.

E. Waiver or Alteration of Informed Consent Involving Public Benefit
and Service Programs (Sec.  __.116(e))

1. Background and Pre-2018 Requirements
    The pre-2018 rule permitted an IRB to waive the requirements for
obtaining informed consent, or to alter such requirements, under two
sets of circumstances described at Sec.  __.116(c) or (d) of the pre-
2018 rule. The first set of circumstances, described at Sec.  __.116(c)
of the pre-2018 rule was more narrow and was limited to certain
research or demonstration projects conducted by or subject to the
approval of state or local government officials. These projects are
similar in some ways to the projects identified in the exemption at
Sec.  __.104(d)(5) of this final rule. The broader provisions
concerning waivers or alterations of the requirements of informed
consent that apply beyond the circumstances described in Sec.
__.116(c) of the pre-2018 rule are discussed below in the section
concerning Sec.  __.116(f).
2. NPRM Proposal
    The NPRM proposed retaining the waiver and alteration of informed
consent provisions included in the pre-2018 rule with respect to
research involving public benefit and service programs conducted by or
subject to the approval of state or local officials, with two
exceptions. First, the NPRM proposed (for proposed Sec.  __.116(e)(2)),
additional criteria for waiver or alteration of consent for
biospecimens. This was tied to the NPRM's proposal that all
biospecimens, regardless of their identifiability, be covered under the
Common Rule. Under these proposed criteria, IRBs would be able to
approve waivers or alterations of the required informed consent
elements only if an IRB found and documented both that there were
compelling scientific reasons to conduct the research and that the
research could not be conducted with other biospecimens for which
informed consent was obtained or could be obtained. Second, the NPRM
proposed new language (for proposed Sec.  __.116(e)(3)), providing that
if an individual was asked to consent to the storage or maintenance for
secondary research use of biospecimens or identifiable private
information in accordance with the proposed broad consent provisions
and that individual refused to consent, the IRB would be prohibited
from waiving consent for the storage, maintenance, or the secondary
research use of the biospecimens or information.
3. Response to Comments and Explanation of the Final Rule: Waiver or
Alteration of Informed Consent Involving Public Benefit and Service
Programs
    Public comments on this proposal are described in section F below
because the comments submitted generally addressed the waiver and
alteration criteria under both proposed Sec.  __.116(e) and Sec.
__.116(f).
    The final rule adopts one of the two proposals made in the NPRM for
proposed Sec.  __.116(e). The final rule adopts (in Sec.  __.116(e)(1))
the language proposed in the NPRM providing that if an individual was
asked to consent to the storage or maintenance for secondary research
use of identifiable private information or identifiable biospecimens in
accordance with the proposed broad consent provisions and such
individual refused to consent, the IRB would be prohibited from waiving
consent for the storage, maintenance, or the secondary research use of
such biospecimens or information. The references in this provision to
biospecimens are changed to refer specifically to identifiable
biospecimens as the final rule does not apply to the research use of
nonidentifiable biospecimens. This change is intended to honor the
autonomy of individuals and to further the Belmont Report principle of
respect for persons, in that this provision will prevent an
individual's refusal to consent to additional research use of
information or biospecimens from being overridden.
    The final rule does not incorporate the NPRM's proposed additional
waiver criterion to apply to research involving the use of
biospecimens. This change is not necessary given that the proposal in
the NPRM that the Common Rule extend to all biospecimens has not been
adopted in the final rule. We determined that the waiver and alteration
criteria included in the final rule are appropriately protective of
identifiable biospecimens, as defined at Sec.  __.102(e)(6) and that an
additional waiver criterion for such biospecimens is not warranted. For
example, Sec.  __.116(e)(3)(ii) mandates that an IRB may not waive or
alter the requirements of informed consent with respect to research
under this category unless the research could not practicably be
carried out without the waiver or alteration.
    The format and organization of Sec.  __.116(e) in the final rule is
different from that included in the pre-2018 rule or proposed in the
NPRM. These changes were implemented to be clearer about the effect of
each requirement. Most significantly, Sec.  __.116(e) in the final rule
provides separate paragraphs concerning the applicable criteria for
waiver and the applicable criteria for alteration of the requirements
for informed consent. This differs from the approach proposed in the
NPRM, and the approach included in the pre-2018 rule, that did not
separate those discussions. We concluded that separating the discussion
of waiver and the discussion of alteration would help clarify the
applicable criteria, particularly given that the final rule addresses
broad consent.
    Section __.116(e)(1) describes the general framework for an IRB to
waive the requirements for informed consent. This paragraph explains
that an IRB may waive the requirement to obtain informed consent under
Sec.  __.116(a) (general requirements for informed consent), Sec.
__.116(b) (basic elements of informed consent), or Sec.  __.116(c)
(additional elements of informed consent that apply to certain
research) if the IRB satisfies the criteria set forth at Sec.
__.116(e)(3) (discussed below). As explained above, the ability to
satisfy the requirement to obtain informed consent of a subject or a
subject's legally authorized representative through use of a broad
consent in particular circumstances is a flexibility offered to
institutions, but institutions are never required to obtain informed
consent through a broad consent process. For this reason, Sec.
__.116(e)(1) does not provide that an IRB may waive the requirement to
obtain informed consent under Sec.  __.116(d) (broad consent) because
use of broad consent is not a requirement. As noted above, and to honor
the autonomy of individuals, Sec.  __.116(e)(1) prohibits an IRB from

waiving consent for the storage, maintenance, or secondary research
uses of identifiable private biospecimens or identifiable private
information if an individual was asked to provide broad consent for
such purposes and refused to provide such consent.
    Section __.116(e)(2) describes the general framework for an IRB to
alter the requirements for informed consent. An IRB may omit or alter
some or all of the elements of informed consent under Sec.  __.116(b)
(basic elements of informed consent) or Sec.  __.116(c) (additional
elements of informed consent that apply to certain research) if the IRB
satisfies the criteria set forth at Sec.  __.116(e)(3) (discussed
below). This is consistent with the proposal made in the NPRM. This
paragraph further explains that an IRB may not omit or alter any of the
requirements described in Sec.  __.116(a) (general requirements for
informed consent). This is also consistent with the proposal made in
the NPRM (which proposed permitting an IRB to omit or alter elements of
informed consent, but did not propose permitting omissions or
alterations of the general requirements of informed consent that were
included in the unnumbered introductory paragraph in the pre-2018 rule
at Sec.  __.116). This paragraph also specifies that if a broad consent
is used, an IRB may not omit or alter any of the elements required
under Sec.  __.116(d). We determined that it would not be appropriate
to permit the omission or alteration of any of the broad consent
elements given the fact that the required elements of broad consent are
limited and given our view that each of these elements (described at
Sec.  __.116(d)) is critical for the purpose of soliciting broad
consent that is both informed and ethically appropriate. This approach
is different from what was proposed in the NPRM because of the NPRM's
different approach to broad consent than that adopted in the final
rule.
    Section __.116(e)(3) sets forth the specific criteria that an IRB
must find and document to waive or alter the requirements for informed
consent, consistent with the limitations set forth in Sec.
__.116(e)(1) and Sec.  __.116(e)(2). These criteria are the same as
those proposed in the NPRM. First, the IRB must find and document that
the research or demonstration project is to be conducted by or subject
to the approval of state or local government officials and is designed
to study, evaluate, or otherwise examine public benefit or service
programs; procedures for obtaining benefits or services under those
programs; possible changes in or alternatives to those programs or
procedures; or possible changes in methods or levels of payment for
benefits or services under those programs. Second, the IRB must find
and document that the research could not practicably be carried out
without the waiver or alteration.

F. General Waiver or Alteration of Informed Consent (Sec.  __.116(f))

1. Background and Pre-2018 Requirements
    Beyond the circumstances addressed in Sec.  __.116(c) of the pre-
2018 rule (which is limited to certain research conducted by or subject
to the approval of state or local government officials), the pre-2018
rule includes a more general provision that is not limited to any
particular type of research and that permits an IRB to either waive the
requirements for obtaining informed consent, or to alter such
requirements. Waiver or alteration of the requirements of informed
consent under this general provision requires that the following four
criteria be satisfied: (1) the research involves no more than minimal
risk to the subjects; (2) the waiver or alteration will not adversely
affect the rights and welfare of the subjects; (3) the research could
not practicably be carried out without the waiver or alteration; and
(4) whenever appropriate, the subjects will be provided with additional
pertinent information after participation.
    Concerns have been expressed that requirements for obtaining
waivers of informed consent or waivers of documentation of informed
consent were confusing and inflexible, resulting in inconsistent
application and a lack of uniformity in interpretation, which led to
the proposals in the NPRM.
2. NPRM Proposals
    The NPRM offered three substantive proposals related to the general
waiver or alteration of informed consent provisions. First, the NPRM
proposed to add a new waiver criterion that would require that for
research involving access to or use of identifiable biospecimens or
identifiable private information, the requirements of informed consent
could only be waived or altered if the research could not practicably
be carried out without accessing or using identifiers. This criterion
was modeled on the comparable criterion in the HIPAA Privacy Rule,
which requires as a condition of waiver of the requirement to obtain an
individual's authorization that the research could not practicably be
conducted without access to and use of protected health information.
The principle embodied in this additional proposed criterion was that
nonidentified information should be used whenever possible in order to
respect subjects' interests in protecting the confidentiality of their
data and biospecimens.
    Second, the NPRM proposed two additional waiver criteria for
research involving the use of biospecimens. For such research, the NPRM
proposed that the requirements of informed consent could only be waived
or altered if an IRB found and documented that: (1) there were
compelling scientific reasons for the research use of the biospecimens;
and (2) the research could not be conducted with other biospecimens for
which informed consent was or could be obtained.
    Third, the NPRM proposed that the Common Rule prohibit IRBs from
waiving informed consent if individuals were asked and refused to
provide broad consent to the storage and maintenance for secondary
research use of biospecimens and identifiable private information. If a
subject refused to provide broad consent, it was proposed that this
refusal would need to be recorded by the investigator to better ensure
that the subject's wishes would be honored.
3. Public Comments
    Approximately 975 public comments discussed the NPRM proposals
found at Sec.  __.116(f) either directly, or as related to linked
provisions related to the definition of human subject, the broad
consent proposal, or proposed exemptions. A majority of these discussed
the NPRM proposals related to the more stringent waiver criteria for
research involving biospecimens. A majority of these comments were from
patients (including family members of patients) and other individuals
who commented anonymously. Patients tended to oppose these proposals
because they believed they would severely restrict access to
biospecimens, which would slow research. Some commenters were opposed
to waiver of consent under any conditions, whether specific or broad
consent.
    Approximately 40 comments were received on the NPRM's proposal to
prohibit an IRB from waiving consent for the storage, maintenance, or
secondary research uses of identifiable biospecimens or identifiable
private information if an individual was asked to provide broad consent
for such purposes and refused to provide such consent. Public comment
was mixed. Those who supported it indicated that this requirement made
sense in order to respect subject autonomy. Those who

opposed the proposal indicated that it would be impossible for an IRB
to know the reasons why an individual refused to sign a broad consent
form. Thus, these individuals argued, the prohibition on waiver of
consent did not seem appropriate given the difficulty in understanding
why someone refused to sign a broad consent form. Several commenters
noted that it would be reasonable to prohibit an IRB from waiving a
subject's refusal to provide consent to a specific study, but that such
a prohibition in the context of broad consent seemed unduly burdensome.
    The NPRM sought comments concerning language in the pre-2018 rule
(that the NPRM proposed retaining) that waiver or alteration of
informed consent only occur if the IRB finds that the research could
not practicably be carried out without the requested waiver or
alteration. Several commenters recommended further defining or
clarifying the meaning of ``practicably.'' Some members of the public
felt that this criterion was too open-ended and that greater emphasis
should be placed on respect for persons over other ethical concerns and
scientific validity. Several commenters favored SACHRP's
recommendations on this topic, including that this requirement be
interpreted to mean that it would be impracticable to perform the
research, not impracticable to obtain consent due to financial or
administrative burdens, without the waiver or alteration. Another
commenter argued that because of a lack of clarity as to the meaning of
terms including ``minimal risk,'' ``practicably,'' and ``the rights and
welfare of subjects,'' as well as the potential that IRBs may not apply
the criteria uniformly, IRBs should not be able to waive or alter
consent. The following suggestions were offered as replacement
language: ``reasonably done without excessive time or financial
constraints to the researcher that would delay the project so
significantly as to make it impossible to conduct the research,''
``capable of being done or accomplished with available means or
resources,'' ``reasonably feasible,'' ``capable of being effective,''
and ``could practicably be obtained.'' Several commenters favored
retaining the term ``practicably'' and were satisfied that it was
clear.
    Other comments raised different issues about waiver or alteration.
Many commenters who opposed all classified research conducted without
consent recommended that waivers be prohibited with respect to
classified research involving humans. One commenter recommended a
reorganization of the waiver and alteration provisions to clarify the
different standards that apply to waivers and alterations. Another
commenter expressed concern that the NPRM's proposed waiver provision
would unreasonably limit the flexibility of IRBs. One commenter
believed that the Sec.  __.116(f) alteration criteria were too rigid
and that the final rule should incorporate a notion of risk adjustment.
Another commenter (a professional medical organization) supported
SACHRP's proposed revisions to the waiver criteria at Sec.  __.116(f)
to allow an IRB to approve the storage, maintenance, and secondary
research use of identified data.
    The NPRM sought public comment on the proposed differences between
the criteria for waiving informed consent for the research use of
biospecimens versus identifiable information. Approximately 60 comments
stated that no justification exists for treating biospecimens and
information differently. Some also noted that the proposed criteria for
waiver of consent for use of biospecimens is so high as to be virtually
impossible to meet and asked why biospecimens should have a higher
standard than information (which theoretically could be more easily
identifiable). One commenter noted that the proposed waiver criteria
promotes ``biospecimen exceptionalism'' and that data and biospecimens
should be treated the same.
    A request in the NPRM for public comment on whether the proposal to
permit an IRB to waive consent for research involving the use of
biospecimens should be included in the regulations received few
comments. One commenter noted that it seemed incongruous to include
biospecimens in the definition of ``human subject,'' but then allow
waiver based on different criteria. Others stated that IRBs should
continue to have the ability to waive consent.
    The NPRM sought public comment regarding how likely investigators
are to seek broad consent for the use of identifiable private
information (as contrasted with biospecimens), given that the NPRM
contains provisions that would make it easier to do such research
without consent (such as the new exemption proposed for Sec.
__.104(e)(2)). Approximately 30 commenters responded to this question.
A majority said they would not use the broad consent mechanism for
secondary use of information if other options were available. Some said
that they suspected that investigators would continue to seek consent
waivers for secondary use of identifiable private information instead
of seeking broad consent.
    The NPRM also sought public comment on several aspects of the
proposed prohibition on waiving consent when an individual has been
asked to provide broad consent and refused, including the following
questions: In particular, how would this prohibition on waiving consent
affect the secondary research use of identifiable private information?
If an individual was asked to provide such consent, should the absence
of a signed secondary use consent be considered a refusal? Does this
prohibition on waiving consent for the secondary use of identifiable
private information create a disincentive for institutions to seek
broad consent for secondary use and instead seek a waiver of consent
from an IRB? Under what circumstances, if any, would it be justified to
permit an IRB to waive consent even if an individual declined or
refused to consent?
    Approximately 35 comments were received on this set of questions.
Approximately half of these stated that ``no means no.'' If someone was
asked to give broad consent and the person specifically said no,
researchers should not be allowed to obtain a waiver of consent. Those
who opposed the idea of a prohibition on waiver argued that it would be
very difficult for institutions to understand why someone said no to
providing broad consent. In other words, a blanket prohibition does not
accurately address all the issues that can occur in this situation.
    A majority of the responses did not address the questions of how a
broad consent form with no indication either way should be treated. The
responses we received to this question suggested that absence of a
signed form should not be treated as if the individual explicitly said
no to broad consent (i.e., that in those situations, waiver should be
permitted).
    A majority of the responses that we received on the question of
whether the prohibition on waiver in the broad consent context created
a disincentive for the use of broad consent with identifiable private
information answered in the affirmative.
4. Response to Comments and Explanation of the Final Rule: General
Waiver of Alteration of Consent
    Overall, two of the three proposals made in the NPRM for proposed
Sec.  __.116(f) have been retained. The final rule adopts (in Sec.
__.116(f)(3)(iii)) a new waiver criterion very similar to that proposed
in the NPRM, which now mandates that for research involving access to
or use of identifiable private

information or identifiable biospecimens, the requirements of informed
consent can be waived or altered only if the research could not
practicably be carried out without using such information or
biospecimens in an identifiable format. The minor wording change made
in the language of this provision, as compared with that proposed in
the NPRM, is intended for clarity. This change is intended to protect
the privacy of individuals, while not unduly inhibiting research. After
considering the diversity of opinions expressed in the public comments
on this issue, including many comments seeking further guidance
concerning the proper interpretation of the ``practicably'' language,
the final rule does not define this language (which was also included
in the pre-2018 rule). We have concluded that the requirements for
waiver and alteration in Sec.  __.116(e) and (f) appropriately honor
respect for persons and balances this with other ethical principles.
    The final rule also adopts (in Sec.  __.116(f)(1)) the language
proposed in the NPRM (for Sec.  __.116(f)(3)) prohibiting IRBs from
waiving informed consent if individuals were asked and declined to
provide broad consent to the storage and maintenance for secondary
research use of identifiable private information or identifiable
biospecimens (except that the final rule's formulation is limited to
identifiable biospecimens, consistent with changes made in the final
rule). We considered public comments that opposed this prohibition and
understand that IRBs may not always understand the reason that
individuals refused to sign a consent form and that the effects of this
broad prohibition could be significant in the context of broad consent
(given the broad scope of research that such a broad consent could
potentially extend to). Nonetheless, we determined that it is important
to prevent an individual's refusal to consent to additional research
use of such information or biospecimens from being overridden. This
change to the Common Rule is intended to honor the autonomy of
individuals and to further the Belmont Report principle of respect for
persons.
    The final rule does not incorporate the NPRM's proposed additional
waiver criteria (proposed for Sec.  __.116(f)(2)) to apply to research
involving the use of biospecimens. This change is not necessary given
that the proposal in the NPRM that the Common Rule extend to all
biospecimens regardless of their identifiability has not been adopted
in the final rule. We determined that the waiver and alteration
criteria included in the final rule are appropriately protective of
identifiable biospecimens and that an additional waiver criterion for
such biospecimens is not warranted. For example, Sec.
__.116(f)(3)(iii) in the final rule is a research criterion specific to
research that involves using identifiable private information or
identifiable biospecimens. Under this criterion, an IRB may not waive
or alter requirements of informed consent with respect to such research
unless the IRB finds and documents that the research could not
practicably be carried out without using such information or
biospecimens in an identifiable format.
    The format and organization of Sec.  __.116(f) in the final rule
are different from the proposed Sec.  __.116(f) described in the NPRM.
We made these changes in an effort to be clear about the effect of each
requirement. Most significantly, Sec.  __.116(f) in the final rule
provides separate paragraphs concerning the applicable criteria for
waiver and the applicable criteria for alteration of the requirements
for informed consent. This differs from the approach proposed in the
NPRM, and the approach included in the pre-2018 rule that did not
separate those discussions. We conclude that separating the discussion
of waiver and alteration will help clarify the applicable criteria,
particularly given that the final rule addresses the application of the
waiver and alteration provisions in the context of broad consent.
    Section __.116(f)(1) describes the general framework for an IRB to
waive the requirements for informed consent. This paragraph explains
that an IRB may waive the requirement to obtain informed consent under
Sec.  __.116(a) (general requirements for informed consent), Sec.
__.116(b) (basic elements of informed consent), or Sec.  __.116(c)
(additional elements of informed consent that apply to certain
research) if the research satisfies the criteria set forth at Sec.
__.116(f)(3) (discussed below). As explained above, the ability to
satisfy the requirement to obtain informed consent of a subject or a
subject's legally authorized representative through use of a broad
consent in particular circumstances is a flexibility offered to
institutions, but institutions are never required to obtain informed
consent through a broad consent process. For this reason, Sec.
__.116(f)(1) does not provide that an IRB may waive the requirement to
obtain informed consent under Sec.  __.116(d) (broad consent) because
use of broad consent is a regulatory flexibility, and not a
requirement. Consistent with the proposal made in the NPRM (proposed
Sec.  __.116(f)(3)), Sec.  __.116(f)(1) provides that if an individual
was asked to provide broad consent for the storage, maintenance, and
secondary research use of identifiable private information or
identifiable biospecimens and refused to consent, an IRB cannot waive
consent for either the storage, maintenance, or secondary research use
of such biospecimens or information.
    Section__.116(f)(2) describes the general framework for an IRB to
alter the requirements for informed consent. This paragraph explains
that an IRB may omit or alter some or all of the elements of informed
consent under Sec.  __.116(b) (basic elements of informed consent) or
Sec.  __.116(c) (additional elements of informed consent that apply to
certain research) if the IRB satisfies the criteria set forth at Sec.
__.116(f)(3) (discussed below). This is consistent with the proposal
made in the NPRM. This paragraph further explains that an IRB may not
omit or alter any of the requirements described in Sec.  __.116(a)
(general requirements for informed consent). This is also consistent
with the proposal made in the NPRM (which proposed permitting an IRB to
omit or alter elements of informed consent, but did not propose
permitting omissions or alterations of the general requirements of
informed consent that were included in the unnumbered introductory
paragraph in the pre-2018 rule at Sec.  __.116). This paragraph also
specifies that when reviewing a broad consent, an IRB may not omit or
alter any of the elements required under Sec.  __.116(d). As with Sec.
__.116(e)(2), we determined that it would not be appropriate to permit
the omission or alteration of any of the broad consent elements in
Sec.  __.116(f). The elements of broad consent reflected in this NPRM
are limited. We have concluded that each of these elements (which are
included at Sec.  __.116(d)) is critical to the solicitation of an
informed and ethically appropriate broad consent. For that reason, none
of the elements of broad consent may be omitted or altered if broad
consent is solicited. This prohibition is different than the NPRM's
proposal given the different formulation of broad consent represented
in this final rule.
    Section 116(f)(3) sets forth the specific criteria that an IRB must
find and document in order to waive or alter the requirements for
informed consent. These criteria are the same as those proposed in the
NPRM, except that the third criterion includes minor wording changes
that were made for clarity: (1) the research involves no more than
minimal risk to the subjects; (2) the

research could not practicably be carried out without the requested
waiver or alteration; (3) if the research involves using identifiable
private information or identifiable biospecimens, the research could
not practicably be carried out without using such information or
biospecimens in an identifiable format; (4) the waiver or alteration
will not adversely affect the rights and welfare of the subjects; and
(5) whenever appropriate, the subjects will be provided with additional
pertinent information after participation.

G. IRB Approval of Research Involving Screening, Recruiting, or
Determining Eligibility of Prospective Subjects (Sec.  __.116(g))

1. Background and Pre-2018 Requirements
    The pre-2018 rule required an IRB to determine that informed
consent can be waived under Sec.  __.116(d) before investigators could
record identifiable private information for the purpose of identifying
and contacting prospective subjects for a research study. This
requirement to waive informed consent has been viewed as burdensome and
unnecessary for protecting subjects, and is not consistent with FDA's
regulations, which do not require informed consent or a waiver of
informed consent for such activities.
2. NPRM Proposal
    The NPRM proposed a new provision at Sec.  __.116(g) that would
authorize an IRB to approve a research proposal in which investigators
obtain identifiable private information without individuals' informed
consent for the purpose of screening, recruiting, or determining the
eligibility of prospective human subjects of research. The IRB would be
permitted to approve a research proposal only in such circumstances if
the proposal included an assurance that the investigator would
implement standards for protecting the information obtained, in
accordance with and to the extent required by proposed Sec.  __.105.
This proposal was intended to address concerns that the pre-2018 rule
required an IRB to determine that informed consent can be waived before
investigators could record identifiable private information for the
purpose of identifying and contacting prospective subjects for a
research study.
3. Public Comments
    Few comments were received regarding this proposal. All were
generally supportive. One academic institution noted that ``This review
is unnecessary considering the low potential risk to subjects and will
expedite research endeavors and ensure harmonization between FDA`s
expectations and the Common Rule.'' However, one commenter thought that
prospective subjects should be notified that this might be a
possibility. Another commenter said that it should be clear that this
is not an IRB waiver of consent, but rather it is an exception to the
consent requirement.
4. Response to Comments and Explanation of the Final Rule: Approval of
Research Involving Screening, Recruiting, or Determining Eligibility of
Prospective Subjects
    The final rule adopts the NPRM proposal at Sec.  __.116(g), with
minor changes made for clarity, and without a requirement that
investigators adhere to the proposed privacy safeguards at Sec.
__.105, since this provision is not included in the final rule. The
provision at Sec.  __.116(g) addresses concerns that the pre-2018
regulations required an IRB to determine that informed consent can be
waived before investigators may record identifiable private information
for the purpose of identifying and contacting prospective subjects for
a research study. This change is intended to address these concerns by
eliminating the requirement for the IRB to waive informed consent for
these activities. In response to public comments, we are clarifying
that this is not a waiver of the consent requirement but rather an
exception to the requirement. This change is also responsive to
SACHRP's recommendation regarding how the Common Rule should apply to
activities that are conducted before subjects provide consent to
participate in research, such as identifying potential subjects,
contacting subjects, and recruiting subjects.\48\
---------------------------------------------------------------------------

    \48\ See Secretary's Advisory Committee on Human Research
Protections (SACHRP). Attachment C: Approved by SACHRP July 20,
2011. SACHRP Recommendation regarding application of 45 CFR 46 and
21 CFR 56 to early processes in research, such as identifying
potential subjects, contacting subjects and recruiting subjects.
(July 20, 2011). Retrieved from http://www.hhs.gov/ohrp/sachrp-committee/recommendations/2011-october-13-letter-attachment-c/index.html.
---------------------------------------------------------------------------

    The final rule includes some minor changes from the NPRM proposal,
to clarify the circumstances in which the IRB may approve the
investigator's proposal to obtain information directly from a
prospective subject, or to obtain already collected identifiable
private information or identifiable biospecimens by accessing records
or stored biospecimens, for purposes of screening, recruiting, or
eligibility assessment, without the informed consent of the prospective
subject or the subject's legally authorized representative. The final
rule also adds a reference to the subject's legally authorized
representative at Sec.  __.116(g)(1) to clarify that this exception to
informed consent will also apply in circumstances in which the
prospective subject has a legally authorized representative who will
provide information about the prospective subject through oral or
written communication with the investigator.
    We note that in approving this exception to informed consent for
the purpose of screening, recruiting, or determining the eligibility of
prospective subjects, the IRB will be reviewing and approving the
entire research proposal. Therefore, all of the IRB approval criteria
at Sec.  __.111 will need to be satisfied, including that when
appropriate, there are adequate provisions to protect the privacy of
subjects and to maintain the confidentiality of data (Sec.
__.111(a)(7)). Thus, as part of its review and approval of the
research, the IRB must determine that there are adequate privacy and
confidentiality safeguards for information obtained by investigators
for these preparatory-to-research activities.
    We believe that these preparatory-to-research activities are
critical means by which to identify subjects that do not involve
additional risks, given their limited nature. If prospective subjects
are identified through these ``screening'' activities, then all other
relevant requirements of this rule must be met if they are subsequently
recruited to participate in the research.

H. Posting of Consent Forms (Sec.  __.116(h))

1. Background and Pre-2018 Requirements
    The pre-2018 rule did not have a requirement to post consent forms
from clinical trials.
2. NPRM Proposal
    The NPRM proposed a new provision that would require that a copy of
the final version of the consent form (absent any signatures) for each
clinical trial conducted or supported by a Common Rule department or
agency be posted on a publicly available federal Web site that will be
established as a repository for such consent forms. The name of the
protocol and contact information would be required to be included with
the submission of the consent form. Under the NPRM proposal, the
consent form would have to be published on the Web

site within 60 days after the trial is closed for recruitment.
3. Public Comments
    The NPRM proposal received approximately 130 comments, most of
which opposed the proposal in whole or in part. Many commenters
expressed concern that the proposal represented administrative burden
without a corresponding increase in protections to human subjects or
benefit to the research community. Some commenters felt that the
proposal represented a waste of resources that would not increase
compliance with the regulations, and might result in longer consent
forms if researchers felt the need to include an abundance of
additional information to protect against perceived regulatory
noncompliance or legal challenge. These commenters expressed concern
that the repository of posted consent forms might be used to seek out
instances of noncompliance. For example, one large medical school
indicated that the posting requirement creates a rich environment for
litigation and represents an effort to publicly shame investigators to
improve quality of documents that will not work.
    Other commenters, including some private research firms, were
concerned that the proposal as drafted would not allow for the
redaction of proprietary or institutionally sensitive information from
consent forms before they would be posted to the Web site, and allow
competing research entities access to detailed information about
investigational drug or research programs beyond what is publicly
available already. Additional concern was expressed about the proposed
timeframe in which consent forms needed to be posted. Some felt that
more time was needed. Other commenters felt it would be more beneficial
to research participants if consent forms were posted before or during
recruitment. In addition, some commenters felt that researchers should
be allowed or encouraged to update posted consent forms if they are
updated for the study. Others felt that requiring that consent forms be
posted once (even if the forms were updated after being posted) would
lead to potential confusion among research participants. For example,
several commenters noted that should a subject participating in a trial
see a consent form for a particular study that differed from the form
that he or she originally signed, that discrepancy could cause
unnecessary concern and confusion.
    Still other commenters expressed concern that the high volume of
consent forms that would be posted as a result of this requirement
would make the collection cumbersome and difficult to use, negating any
potential benefit gained by increased transparency. Others expressed a
concern that requiring all studies to post consent forms might lead to
the perpetuation of poorly written forms, as researchers might use poor
examples from the database to write their own informed consent
documents in addition to excellent ones. A few major research
universities suggested that guidance, best practices, or exemplary
informed consent forms should be selected and shared publicly, rather
than all informed consent forms. Some commenters suggested limiting the
posting requirement to a subset of research studies, for example, to
only high risk or large multi-institution studies.
    Those who supported the proposal agreed that it would help increase
accountability and promote transparency in informed consent forms. To
that end, a minority of commenters said that this proposal should be
extended to all research that is subject to the Common Rule, not just
to studies meeting the definition of a clinical trial. Some commenters
supported the idea of publicly sharing informed consent documents but
felt it would be best accomplished through guidance or optional
posting. One federal level advisory committee supported the proposal
and recommended the creation of robust guidance with the goal of
minimizing confusion and misuse of the posted documents, and
facilitating the use of the posted forms to educate investigators,
institutions, and regulators to improve future informed consent
documents and the informed consent process generally. Others felt it
would be helpful to post additional information and documents along
with consent forms. For example, one investigator suggested that copies
of IRB proposals and decisions be made public along with approved
informed consent documents to provide additional transparency and
accountability. Another commenter suggested that investigators be given
the option to post assessment tools for evaluating prospective
subjects' understanding of important study information.
    Both those who supported and opposed the proposal indicated that in
terms of implementing this proposal, consent forms should be posted to
ClinicalTrials.gov as opposed to creating a new federal Web site in
order to limit the additional administrative burden that this proposal
would impose.
4. Response to Comments and Explanation of the Final Rule: Posting of
Consent Forms
    The final rule adopts the NPRM proposal with some modifications and
clarifications. The primary purpose of this provision is to improve the
quality of consent forms in federally funded research by assuring
that--contrary to current practices, under which it is often very
difficult to ever obtain a copy of these documents--they eventually
would become subject to public scrutiny and that they will provide
useful models for others. The consent form plays a key role in making
sure that someone asked to enter a clinical trial receives the
information they need to be making an informed decision about whether
to enroll in that trial. Accordingly, it also plays a key role in
supporting and justifying the public's trust in the integrity of our
clinical trial enterprise.
    We are not persuaded by the arguments of those commenters who
suggest that potential negative consequences of this proposal outweigh
its benefits. Fundamentally, this proposal is about increasing the
transparency of one of the most important aspects of our human subjects
protection system. Increased transparency is in general a good thing,
and in this instance, as in many others, it offers multiple benefits--
including increased trust--at very low cost. This provision is not a
form of shaming, but rather an effort to ask people to work together to
create a system that will improve the quality of informed consent.
Moreover, the new standards for determining the acceptable content of a
consent form--including Sec.  __.116(a)(5), which will require a
concise presentation of key information at the beginning of the consent
form--should counter any consequences of attempts to pad consent forms
with additional information as a response to the posting requirement.
    We agree with the conclusions of SACHRP that implementing this
proposal will indeed result in better consent forms. Having a
repository of such forms freely available for analysis and public
discussion will create multiple opportunities for improving these
forms. In an era in which we have previously unheard of capabilities
for analyzing textual material and processing large amounts of data,
the fact that there will be a high volume of consent forms posted
should be a minor impediment, if any, to the ability to learn from the
content of this database.
    With regard to those who suggested that it would indeed be
desirable to

make consent forms more public, but that posting should be optional, we
note that nothing in the pre-2018 rule prevents the people in charge of
research from making their consent forms public, yet that is rarely
done. In order to significantly increase the transparency of this
portion of our system for protecting subjects, we are finalizing this
proposal.
    With regard to the commenters who were concerned that posting
consent forms would create a rich environment for litigation, it is
noteworthy that the existing evidence fails to suggest that there has
been much of a problem with regard to inappropriate litigation over
clinical trials. Whatever disincentives currently exist for such
litigation, it seems unlikely that the mere fact that consent forms
would now be more available will dramatically alter such disincentives.
With regard to the commenters who were concerned about the added
regulatory burden, we note that this change, compared to the
traditional costs of clinical trials, will add a relatively small
amount of additional burden, one that is well justified in comparison
to the likely increase in transparency. This new provision has
specifically been designed to minimize that burden. And the final rule
has been modified in a number of respects from the NPRM proposal in
response to public comments. As discussed below in detail, the time by
which a consent form must be posted has been greatly extended. That
change would also address the concerns of some commenters that the
posted consent forms might create confusion among research subjects.
Furthermore, provisions have been added that allow for redaction, as
necessary, of portions of consent forms.
    As a means of increasing transparency and facilitating the
development of more informative consent forms, the final rule
accordingly requires at Sec.  __.116(h)(1) that for clinical trials
conducted or supported by a Common Rule department or agency, a copy of
an IRB-approved version of a consent form that was used to enroll
subjects would need to be posted by the awardee or the federal
department or agency conducting the trial on a publicly available
federal Web site that will be established as a repository for such
forms. Unlike the NPRM, which required that the ``final version'' of
the consent form be posted, the final rule adds flexibility in merely
requiring that it be an IRB-approved consent form that was used for
enrollment purposes. There is accordingly no further restriction as to
which version of a consent form (which might have been subject to many
modifications over the course of time) must be posted. The final rule
also gives greater flexibility than the NPRM proposal in terms of when
that posting needs to be done. It can take place 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 (as required by the
protocol). If the federal department or agency supporting or conducting
the clinical trial determines that certain information should not be
made publicly available on a federal Web site (e.g., confidential
commercial information), the department or agency may permit
appropriate redactions to the information posted. In rare instances, it
could be the case that the federal department or agency would determine
that the very existence of a particular clinical trial should not be
publicly disclosed, in which case no posting relating to such a trial
would be required.
    The final rule differs from the NPRM proposal in that it no longer
specifies that certain information needs to be posted in addition to
the consent form. This change eliminates the need for mandatory posting
of information that might not be justified by the purposes of this
provision.
    Only one posting would be required for each multi-institution
study. There is accordingly no expectation that a version would need to
be posted for each class of subjects in the study (for example, a
posting both for adults and for minors), nor for each study site.
    We also note that this provision applies only to those clinical
trials that are conducted or supported by a federal department or
agency.
    A Web site will be developed by HHS, which could be used by other
federal departments or agencies, or the other federal departments or
agencies could create their own Web sites for the posting of these
consent forms. Public posting of consent forms is intended to increase
transparency, enhance confidence in the research enterprise, increase
accountability, and inform the development of future consent forms. It
is anticipated that the Web site will be searchable. With regard to the
comments suggesting that ClinicalTrials.gov might be an appropriate
choice as the Web site, we agree that such a choice has the possibility
of minimizing administrative burdens. Using ClinicalTrials.gov has
another advantage, in addition to what some of the commenters said.
Many clinical trials funded by HHS have records in ClincialTrials.gov
due to requirements that certain clinical trials register and submit
results information to that database (section 402(j) of the Public
Health Service Act and 42 CFR part 11, and other policies that
incentivize trial registration and results submission, such as the NIH
Policy on Dissemination of NIH-Funded Clinical Trial Information). The
fact that these trials already have a record in the database will mean
that the burden of submission of the informed consent document will be
substantially lower. Accordingly, we will take these points into
consideration as we determine what federal Web site will be used to
implement this provision.

XV. Documentation of Informed Consent (Sec.  __.117)

A. Background and Pre-2018 Requirements

    The pre-2018 rule at Sec.  __.117 described the requirements for
documenting informed consent and when the waiver for obtaining a
written and signed consent form was allowable.

B. NPRM Proposals

    The NPRM proposed to alter the language at Sec.  __.117(b)(1) to
specify that the consent document should include only the language
required by Sec.  __.116, with appendices included to cover any
additional information.
    In addition, the NPRM would make it explicit in the regulatory
language at proposed Sec.  __.117(c)(1)(iii) that if the subjects are
members of a distinct cultural group or community for whom signing
documents is not the norm, so long as the research presents no more
than minimal risk of harm to subjects and provided there is an
appropriate alternative mechanism for documenting that informed consent
was obtained, the requirement to obtain a signed consent form may be
waived. Documentation must include a description as to why signing
forms is not the norm for the distinct cultural group or community.
    Additionally, to facilitate the tracking of broad consent to
storage or maintenance for secondary research use of biospecimens or
identifiable private information, and to provide information to IRBs
should IRB review be required, the NPRM proposed that waiver of
documentation of consent for the research use of such biospecimens
would not be allowed based upon a new provision at Sec.  __.117(c)(3).
    The NPRM also introduced the term ``oral consent'' in the context
of the various provisions related to the broad consent for the storage,
maintenance, and secondary use of biospecimens and identifiable private
information. As a general matter, under the pre-2018 rule, individuals
wanting to obtain oral

consent from subjects in a nonexempt research activity needed to seek a
waiver of documentation of informed consent under Sec.  __.117(c).
Therefore, the NPRM proposed to permit investigators to obtain oral
broad consent for the storage, maintenance, and secondary research use
in limited circumstances. Specifically, the NPRM proposals would allow
an investigator to obtain oral broad consent if:
     An investigator used the proposed broad consent template;
     Investigators only sought oral broad consent only for the
storage, maintenance, and secondary research use context for the use of
identifiable private information, not for biospecimens;
     If broad consent for the storage, maintenance, and
secondary research use was obtained only as part of a separate, primary
research study; and
     The oral broad consent was sought as part of the consent
process in a study eligible for one specific exclusion or three
specific exemptions related to the collection of identifiable
information.
    Finally, the regulatory language proposed at Sec.  __.117(c)(4) was
intended to clarify that waivers of documentation may not be permitted
for research subject to regulation by FDA.

C. Public Comments

    Approximately 15 comments were received on the proposals found in
the NPRM at Sec.  __.117. Several commenters discussing the proposed
requirement at Sec.  __.117(b)(1) indicated that even if consent forms
are split into a primary document and appendices, there should be an
expectation that the content included in the appendices are discussed
with prospective subjects as part of the informed consent process.
Although very few comments discussed the requirements of proposed Sec.
__.117(b)(1) specifically, many of the comments discussing the NPRM
proposal found in the introductory paragraph of Sec.  __.116 discussed
the concept of including only the required information in the main body
of a consent form, and all additional information in appendices.
    Few comments were received on the proposal found in Sec.
__.117(c)(1)(iii) that documentation of informed consent may be waived
if consent is being sought amongst subjects who are members of a
distinct cultural group or community in which signing forms is not the
norm. Comments received on this proposal were generally favorable.
    Those who commented on the proposals related to oral broad consent
indicated that the provisions were confusing and difficult to
understand. We note that these proposals were found in the NPRM through
a series of interrelated cross references in Sec. Sec.  __.116(d),
__.117(c), and __.104(f)(1)-(2).
    Several commenters discussed the statement found in Sec.
__.117(c)(4) that waiver of documentation of consent is generally not
permitted for research subject to regulation by the FDA. These
commenters noted that this would be true regardless of whether this was
included in the Common Rule. Additionally, commenters noted that if the
FDA regulations ever permitted waiver of documentation of consent, the
existence of this provision in the Common Rule might result in
confusion and contradictory requirements for dually regulated research.

D. Response to Comments and Explanation of the Final Rule:
Documentation of Informed Consent

    The language at Sec.  __.117(b)(1) and (2) are altered in the final
rule to conform to the requirements included at Sec.  __.116, which are
discussed above. The goal in Sec. Sec.  __.116 and __.117 of the final
rule is to facilitate a prospective subject's or legally authorized
representative's understanding of the reasons why one might or might
not want to participate in the research, in part by requiring that only
the key information essential to decision making receive priority by
appearing at the beginning of the consent document. In the final rule,
these requirements also apply when a short form written informed
consent process is used, or the requirement for written informed
consent is waived.
    We agree with the majority of public comments that favored adding a
new provision allowing a waiver of the requirement for a signed consent
form if the subjects are members of a distinct cultural group or
community for whom signing documents is not the norm, provided that the
research presents no more than minimal risk of harm to subjects and
there is an appropriate alternative method for documenting that
informed consent was obtained. Therefore, this new provision is added
at Sec.  __.117(c)(1)(iii). The final rule includes a reference to the
subject's legally authorized representative to clarify that this
provision applies when a subject has a legally authorized
representative who is a member of a distinct cultural group or
community in which signing forms is not the norm.
    The final rule does not include the NPRM's proposal at Sec.
__.117(c)(3) to prohibit a waiver of documentation of broad consent for
the storage, maintenance, or secondary research use of biospecimens.
    Some of those who commented on the NPRM proposals related to oral
broad consent found it to be unnecessarily confusing. In response to
these comments, the final rule permits waiver of documentation of
informed consent under Sec.  __.117(c) when a broad consent procedure
is used. No additional criteria or special restrictions apply.
Additionally, the final rule removes all NPRM references to ``oral
consent'' to reduce confusion.
    However, we expect that it will rarely be permissible to waive
documentation of broad consent for the secondary research use of
medical records or stored biospecimens because there will likely be a
need to track which individuals have provided broad consent and which
have not, so the informed consent would not be the only record linking
the subject and the research as required for a waiver under Sec.
__.117(c)(1)(i). Additionally, when identifiable information and
identifiable biospecimens are shared for a nonresearch purposes, the
person's consent is usually required, so we expect that documentation
of consent often could not be waived under Sec.  __.117(c)(1)(ii),
which requires that the research involves only procedures for which
written consent is not normally required outside of the research
context.
    One instance when we believe it may be appropriate for the IRB to
waive the requirement for a signed broad consent form is when the
initial activity involved obtaining information from a person through
oral communication, such as a phone survey, because there might not be
an opportunity to obtain written broad consent from such individuals
for the secondary research use of their information. In this scenario,
documentation of broad consent could be waived under Sec.
__.117(c)(1)(ii) if the research presents no more than minimal risk of
harm to subjects and involves no procedures for which written consent
is normally required outside of the research context. In addition, it
might be appropriate for an IRB to waive the requirement for a signed
broad consent document under the provision included in the final rule
related to when the subjects or their legally authorized
representatives are members of a distinct cultural group or community
for whom signing documents is not the norm, provided that the research
presents no more than minimal risk of harm to subjects and an
appropriate alternative method is available for

documenting that informed consent was obtained (Sec.
__.117(c)(1)(iii)).
    The final rule also does not include the NPRM's proposed
clarification that waivers of documentation may not be permitted for
research subject to regulation by FDA. Because this is not the only
difference between what is permitted under the Common Rule and the FDA
regulations, we determined that clarifying only this specific
difference in the final rule is likely to create more confusion rather
than provide clarification.

XVI. Applications and Proposals Lacking Definite Plans for Involvement
of Human Subjects (Sec.  __.118)

A. Background and Pre-2018 Requirements

    This provision of the pre-2018 rule stated that while an award or
grant may be made for a project with indefinite plans to involve human
subjects, that project must be reviewed by an IRB before human subjects
may be involved.

B. NPRM Proposals

    The NPRM language clarified that IRB review and approval was
required before human subjects could be involved in a study unless the
study was excluded under Sec.  __.101(b), waived under Sec.  __.101(i),
or exempted under Sec.  __.104(d), (e) or (f)(2).

C. Public Comments

    No comments were received.

D. Explanation of the Final Rule

    The final rule adopts the language of the NPRM, with updated
citations. This provision makes explicit that it applies only to
nonexempt human subjects research.

XVII. Research Undertaken Without the Intention of Involving Human
Subjects (Sec.  __.119)

A. Background and Pre-2018 Requirements

    This provision of the regulations outlines the process that an
institution must undergo when a federally funded research project that
was designed without the intention of involving human subjects later
involves human subjects as defined by this policy.

B. NPRM Proposals

    The NPRM proposed to add language to make clear that this provision
applies only to nonexempt human subjects research. It also clarifies
its reference to department or agency to mean a federal department or
agency component supporting the research.

C. Public Comments

    No comments were received.

D. Explanation of the Final Rule

    The final rule adopts the language of the NPRM, with updated
citations. This provision makes explicit that it applies only to
nonexempt human subjects research, and clarifies the reference to
department or agency to be a federal department or agency component
supporting the research.

XVIII. Conditions (Sec.  __.124)

A. Background and Pre-2018 Requirements

    This provision of the regulations allows departments and agencies
to impose additional requirements on human subjects research when such
requirements are deemed necessary for the protection of human subjects.

B. NPRM Proposals

    The NPRM provided more specific language at Sec.  __.124, stating
that with respect to any research project or any class of research
projects the department or agency head of either the conducting or the
supporting federal department or agency may impose additional
conditions prior to or at the time of approval when in the judgment of
the department or agency additional conditions are necessary for the
protection of human subjects.

C. Public Comments

    One commenter discussed this NPRM proposal, arguing that this would
increase variance in implementation of the Common Rule, rather than
promote harmonization as the NPRM suggested.

D. Explanation of the Final Rule

    The final rule adopts the NPRM language, which clarifies the pre-
2018 rule by stating that the head of either the conducting or the
supporting federal department or agency may impose additional
conditions on research, when necessary for the protection of human
subjects.

XIX. Regulatory Impact Analyses

A. Introduction

    HHS has examined the impacts of this final rule under Executive
Order 12866 on Regulatory Planning and Review (September 30, 1993);
Executive Order 13563 on Improving Regulation and Regulatory Review
(January 18, 2011); the Regulatory Flexibility Act of 1980, Pub. L. 96-
354 (September 19, 1980); the Unfunded Mandates Reform Act of 1995,
Pub. L. 104-4 (March 22, 1995); and Executive Order 13132 on Federalism
(August 4, 1999).
    Executive Order 12866 directs agencies to assess all costs and
benefits of available regulatory alternatives and, if regulation is
necessary, to select regulatory approaches that maximize net benefits
(including potential economic, environmental, public health and safety
effects; distributive impacts; and equity). Executive Order 13563 is
supplemental to and reaffirms the principles, structures, and
definitions governing regulatory review as established in Executive
Order 12866. HHS expects that this rule will have an annual effect on
the economy of $100 million or more in any one year and therefore is a
significant regulatory action as defined by Executive Order 12866.
    The Regulatory Flexibility Act (RFA) requires agencies that issue a
regulation to analyze options for regulatory relief for small
businesses if a rule has a significant impact on a substantial number
of small entities.\49\ The RFA generally defines a ``small entity'' as
(1) a proprietary firm meeting the size standards of the Small Business
Administration (SBA); (2) a nonprofit organization that is not dominant
in its field; or (3) a small government jurisdiction with a population
of less than 50,000 (states and individuals are not included in the
definition of ``small entity'').\50\ HHS considers a rule to have a
significant economic impact on a substantial number of small entities
if at least 5 percent of small entities experience an impact of more
than 3 percent of revenue. HHS anticipates that the rule will not have
a significant economic impact on a substantial number of small
entities. Supporting analysis is provided in Section XIX.F below.
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    \49\ 5 U.S.C. 603.
    \50\ 5 U.S.C. 601.
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    Section 202(a) of the Unfunded Mandates Reform Act of 1995 \51\
requires that agencies prepare a written statement, including an
assessment of anticipated costs and benefits, before proposing ``any
rule that includes any Federal mandate that may result in the
expenditure by State, local, and tribal governments, in the aggregate,
or by the private sector, of $100,000,000 or more (adjusted annually
for inflation) in any one year.'' The current threshold after
adjustment for inflation is $146 million, using the most current (2015)
implicit price deflator for the gross domestic product. HHS expects
this rule to result in expenditures that will exceed this amount.
---------------------------------------------------------------------------

    \51\ 2 U.S.C. 1532.
---------------------------------------------------------------------------

    Executive Order 13132 establishes certain requirements that an
agency

must meet when it promulgates a rule that imposes substantial direct
requirement costs on state and local governments or has federalism
implications. HHS has determined that the rule will not contain
policies that would have substantial direct effects on the States, on
the relationship between the Federal Government and the States, or on
the distribution of power and responsibilities among the various levels
of government. The changes in the rule represent the Federal Government
regulating its own program. Accordingly, HHS concludes that the rule
does not contain policies that have federalism implications as defined
in Executive Order 13132 and, consequently, a federalism summary impact
statement is not required.

B. Need for the Final Rule and Summary

    This final rule is being issued to modernize, strengthen, and make
more effective the regulations for protecting human subjects in
research. Although professional organizations have codes of conduct and
guidelines for members conducting research, only the Federal Government
has the authority to regulate the activities of institutions using
public funds for human subjects research. Since the Common Rule was
developed, the volume of research has increased, evolved, and
diversified.
    Thus, the final rule includes a number of measures to address the
issues described above. Provisions that strengthen the requirements for
informed consent and promote transparency in the informed consent
process include: (1) Requiring that the informed consent form be
designed and presented in such a way that facilitates a prospective
subject's understanding of why one would want to participate in a
research study or not; (2) revising and adding to the required elements
of consent; (3) requiring for certain clinical trials the posting of a
copy of at least one version of a consent form on a publicly available
federal Web site; and (4) clarifying the conditions and requirements
for waiver or alteration of consent to remove ambiguity, including a
new provision that, under specific conditions, an IRB may approve a
research proposal in which investigators obtain information without
individuals' informed consent for the purpose of screening, recruiting,
or determining eligibility of prospective human subjects of research.
    Provisions that strengthen the extent to which regulations promotes
the principle of respect for persons include: (1) Requiring that
informed consent forms present the key information to potential
subjects at the beginning of a consent process; (2) allowing
investigators the option of obtaining broad consent from a potential
subject for future, unspecified research use of identifiable private
information and identifiable biospecimens; and (3) adding a provision
that would prohibit a waiver of consent if someone has been asked to
provide their broad consent for the storage, maintenance, and secondary
research use of identifiable biospecimens or identifiable private
information and refused to do so.
    New provisions that would allow IRBs greater flexibility to focus
resources on higher-risk research include: (1) Distinguishing
categories of activities that are deemed not to be research; and (2)
expanding and clarifying categories of exempt research.
    Provisions that streamline or reduce burden for IRBs or
institutions include: (1) Requiring consultation among the Common Rule
agencies for the purpose of harmonizing guidance (to the extent
appropriate); (2) eliminating an administrative requirement for
reporting IRB membership; (3) removing the requirement that IRBs must
review and approve grant applications; (4) eliminating, under certain
circumstances, continuing review; (5) mandating the use of a single IRB
for multi-institutional studies; and (6) holding IRBs not operated by
an FWA-holding institution directly responsible for compliance when
appropriate.
1. Accounting Table
    Table 1 summarizes the quantified and nonquantified benefits and
costs of all changes to the Common Rule. Over the 2017-2026 period,
present value benefits of $1,904 million and annualized benefits of
$223 million are estimated using a 3 percent discount rate; present
value benefits of $1,494 million and annualized benefits of $213
million are estimated using a 7 percent discount rate. Present value
costs of $528 million and annualized costs of $62.0 million are
estimated using a 3 percent discount rate; present value costs of $474
million and annualized costs of $67.0 million are estimated using a 7
percent discount rate. Nonquantified benefits include improved human
subjects protections in research; enhanced oversight of research
reviewed by IRBs not operated by an FWA-holding institution; and
increased uniformity in regulatory requirements among Common Rule
departments and agencies. Nonquantified costs include the time needed
for consultation among Common Rule agencies before federal guidance is
issued.

                         Table 1--Accounting Table of Benefits and Costs of All Changes
----------------------------------------------------------------------------------------------------------------
                                                   Present value of 10 years by   Annualized value over 10 years
                                                    discount rate (millions of    by discount rate  (millions of
                                                           2015 dollars)                   2015 dollars)
                                                 ---------------------------------------------------------------
                                                     3 percent       7 percent       3 percent       7 percent
----------------------------------------------------------------------------------------------------------------
Benefits:
    Quantified Benefits.........................           1,904           1,494             223             213
----------------------------------------------------------------------------------------------------------------
Nonquantified Benefits:
    Improved human subjects protections in research; enhanced oversight in research reviewed by IRBs not
     operated by an FWA-holding institution; and increased uniformity in regulatory requirements among Common
     Rule departments and agencies..............................................................................
----------------------------------------------------------------------------------------------------------------
Costs:
    Quantified Costs:...........................             528             474            62.0            67.0
----------------------------------------------------------------------------------------------------------------
Nonquantified Costs:
    Time for consultation among Common Rule agencies before federal guidance is issued..........................
----------------------------------------------------------------------------------------------------------------

    Table 2 summarizes the quantified present value benefits and costs
of each change to the Common Rule using a 3 percent discount rate.

   Table 2--Accounting Table of Quantified Benefits and Costs of Each
                                 Change
------------------------------------------------------------------------
                                          Present value of 10 years at a
                                              3 percent discount rate
                 Change                     (millions of 2015 dollars)
                                         -------------------------------
                                             Benefits          Costs
------------------------------------------------------------------------
Costs to Learn New Requirements and       ..............             213
 Develop Training Materials; OHRP Costs
 to Develop Training and Guidance
 Materials, and to Implement the Rule...
Extending Oversight to IRBs Unaffiliated  ..............            85.6
 with an Institution Holding an FWA
 (impact to IRBs not operated by an FWA-
 holding institution)...................
Excluding Activities from the                       36.2  ..............
 Requirements of the Common Rule because
 They are not Research..................
Clarifying and Harmonizing Regulatory     ..............  ..............
 Requirements and Agency Guidance.......
Modifying the Assurance Requirements....            5.93  ..............
Requirement for Written Procedures and    ..............            11.4
 Agreements for Reliance on IRBs Not
 Operated by the Engaged Institution
 (impact to FWA-holding institutions)...
Eliminating the Requirement that the                 326  ..............
 Grant Application Undergo IRB Review
 and Approval...........................
Expansion of Research Activities Exempt              798            0.37
 from Full IRB Review...................
Elimination of Continuing Review of                  148            41.0
 Research Under Specific Conditions.....
Amending the Expedited Review Procedures            51.0  ..............
Cooperative Research (single IRB mandate             538             157
 in multi-institutional research).......
Changes in the Basic Elements of          ..............            4.62
 Consent, Including Documentation.......
Obtaining Consent to Secondary Use of     ..............  ..............
 Identifiable biospecimens and
 Identifiable private information.......
Elimination of Pre-2018 Rule Requirement            1.25  ..............
 to Waive Consent in Certain Subject
 Recruitment Activities.................
Requirement for Posting of Consent Forms  ..............            15.4
 for Clinical Trials Conducted or
 supported by Common Rule Department or
 Agencies...............................
Alteration in Waiver for Documentation    ..............  ..............
 of Informed Consent in Certain
 Circumstances..........................
------------------------------------------------------------------------

C. Public Comments and Response to Public Comments

1. General Comments
    Approximately 50 comments discussed the specific cost estimates
provided in the NPRM's Regulatory Impact Analyses (RIA). Several
commenters strongly suggested that the final rule eliminate the
proposals related to biospecimens, cooperative research, and expanding
coverage to nonfederally funded clinical research because the NPRM
failed to appreciate the cost and burden that would result from
implementing these proposals. Although a majority of the comments
received on the RIA suggested that several of the cost estimates were
significantly underestimated, few commenters described specific changes
to the cost and benefit estimates included in the NPRM RIA.
    One commenter noted that the NPRM cost estimates are derived from a
1998 NIH-sponsored evaluation of the implementation of Section 491 of
the Public Health Service Act and ``because of the lack of available
data about IRB effectiveness and how IRBs function operationally, many
of the estimations in this analysis are based on anecdotal evidence.''
This commenter stated that reliance on outdated and anecdotal
``evidence'' means that the NPRM assumptions seriously underestimate
predictable costs, such as those derived from current salary data for
health care workers who would have at least some background sufficient
to explain consent, and the time needed to obtain consent. They also
claimed that the NPRM analysis also seriously overestimates cost
savings because excluding an activity from the Common Rule does not
necessarily remove it from the purview of the IRB pursuant to other
laws, such as the HIPAA regulations, and may simply shift the economic
burden of responsible oversight to personnel elsewhere within the
organization. This commenter also noted that the initial transition
costs estimated in the NPRM are staggering, mostly due to costs related
to biospecimen provisions.
    One commenter stated that a review of the tables indicates that the
costs used for hourly wages of individuals affected by the proposed
changes may be underestimated by as much as 12 to 139 percent.
Similarly, the hours associated with the proposed changes are
substantially underestimated.
    One commenter stated that an institutional official must be
administratively high enough to insist on any necessary institutional
changes, most likely a Vice President or higher, and felt that such an
official would make at least $250 per hour. This commenter stated that
the $48.20 estimate in the proposed rules may apply to liberal arts
colleges, but the proportion of medical research conducted at such
institutions is small and strongly recommends that salary data from
medical institutions (published for public institutions) be used to
generate a revised cost estimate. One commenter stated that the
estimates of the salary rates presented in the NPRM for institutional
officials, IRB members and staff, and investigators are far below the
national average for these roles. Likewise, they state that the
anticipated benefits of the new proposed rule appear to be grossly
overstated.
    One commenter stated that the rule as proposed was officially
estimated to add $1.4 billion a year to the cost of the current system,
but the true cost increase will be at least triple that due to
egregious underestimates of wage costs, substantial underestimates of
time spent on red tape by investigators, and many underestimated or
omitted costs, as well as some estimates that misrepresent the effects
of the rule. They claim that the rule is likely to impose about $5
billion a year in needless costs, while reducing rather than improving
protection of human subjects. One commenter stated that, at their
institution, analysts average far greater pay levels than $15 per hour,
and many of the tasks will have to be borne by faculty whose salaries
exceed what is identified in the current cost analyses.
    One commenter proposed to mandate instead that institutions
sufficiently resource their IRBs so as to protect 10 percent of their
IRBs' and IRB administrators' time (about 1 meeting/year for an IRB
that meets monthly; about 200 hours/year for a full-time equivalent IRB
administrator with 2 weeks' vacation and 40-hour work weeks) to devote
to finding efficiencies and innovations in the IRB review process.

a. Response to General Comments
    We note that the NPRM discussed the fact that data about IRB
effectiveness and how IRBs function operationally \52\ is generally
unavailable. The NPRM further noted that many of the NPRM RIA
assumptions were based on anecdotal evidence; the NPRM requested
comment on the accuracy of the assumptions presented and on whether
better data sources might be available to support the analyses. RIA
comments did not provide the evidence necessary to improve our
estimates, and thus, limited changes have been made.
---------------------------------------------------------------------------

    \52\ See, e.g., Abbott L, Grady C. A Systematic Review of the
Empirical Literature Evaluating IRBs: What We Know and What We Still
Need to Learn. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235475/.
---------------------------------------------------------------------------

    We note that the NPRM RIA used a national average for the salary
estimates. We received no compelling evidence to change cost estimates
because we must account for the fact that personnel and salaries in
affected categories vary widely.
2. Extension of the Common Rule to Certain Nonfederally Funded Clinical
Trials
    One commenter stated that coverage of this subset of projects will
extend requirements, such as the single IRB requirement, without any
consideration or mechanism for how to implement or fund this
requirement and they do not believe that they should be required to
accept added cost and burdens without any meaningful or measureable