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January 6, 2016

Jerry Menikoff, MD, JD


Office for Human Research Protections
Department of Health and Human Services
1101 Wootton Parkway, Suite 200
Rockville, MD 20852
Submitted electronically at www.regulations.gov.
RE: Docket Number HHS-OPHS-2015-0008, Federal Policy for the Protection of
Human Subjects Notice of Proposed Rulemaking, published in the September
8, 2015 Federal Register (80 FR 53933)
Dear Dr. Menikoff:
I write on behalf of PersonalGenomes.org (PG.org),1 and certain of its affiliates, to comment on
Question 55 presented in the above NPRM, whether and how the provision regarding the return
of research results in the proposed exemption __.104(f)(2) should be revised. PG.org
appreciates the tremendous effort that has gone into the NPRM and we appreciate the
opportunity to comment on 104(f)(2) as well as a related proposed provision, 111(a)(8).
PG.org is a 501(c)(3) nonprofit organization working to generate, aggregate and interpret human
biological and trait data on an unprecedented scale. Our mission is to make a wide spectrum of
data about humans accessible to increase biological literacy and improve human health. PG.org
supports the Personal Genome Project global network. The first Personal Genome Project
research study was founded at Harvard Medical School in 2005, and Personal Genome Project
sites now exist at leading institutions in four countries. We also produce the annual Genomes,
Environments and Traits (GET) Labs and Conference, at which researchers collect a wide range
of additional data and biospecimens from Personal Genome Project participants, often analyze
that data in combination with participants stored genomic and other data, and return individual
results to participants. PG.orgs latest project is Open Humans, funded by the Knight Foundation
and the Robert Wood Johnson Foundation. Open Humans is a new online portal that aims to
break down data silos in human health and research by allowing members to aggregate data from
the research in which they participate, thereby connecting individuals willing to share existing
research data about themselves with other researchers who are interested in using that data. This,
of course, depends on researchers having previously returned individual research results to Open
Humans members.

1

PersonalGenomes.org is in the process of changing its name to Open Humans Foundation.

PG.orgs efforts are informed by many of the values described in the NPRM, including
encouraging greater transparency and collaboration between researchers and research
participants. It is in that spirit that we write to express our concerns about proposed exemption
__.104(f)(2)(ii).
As you know, __.104(f)(2)(i) would exempt secondary research using stored biospecimens or
identifiable private information, if IRB-approved broad consent for unspecified secondary
research was previously obtained under __.104(f)(1). The NPRM contemplates that an
investigator, by entering accurate information about her proposed secondary research study into
an HHS-created decision tool, could determine herself that it is exempt. Under __.104(f)(2)(ii),
however, if the researcher anticipates that individual research results will be provided to a
research subject, the situation is dramatically different. The research is not exempt; instead, as
we read the NPRM, it is subject to full IRB review and researchers must obtain the explicit, fully
informed consent from each research participant for each such secondary research project, per
__.116(a)-(b).
We appreciate that some individual research results are sensitive, that there are more and less
ethically appropriate ways to return such results to participants, and that an IRB (or expert panel
or OHRP guidance) can potentially play a useful role in guiding the ethical return of research
results. However, we believe that __.104(f)(2)(ii) unnecessarily sweeps far too broadly, both in
the unlimited scope of the individual research results it covers and in the level of IRB review it
requires, and provides a strong incentive for researchers to decline to share participants own
data with them. These results are inimical to the NPRMs laudable goals of making the level of
review more proportional to the seriousness of the harm or danger to be avoided (p. 53936) and
moving toward a participant-centered research model that adequately respects participants as
partners (p. 53938).
Below, we ask some clarifying questions and also offer several suggestions for revising
__.104(f)(2)(ii) so that it is more consistent with these goals while also protecting participants
from receiving carelessly or inaccurately disclosed individual research results. The net result of
these suggestions yields the following suggested revision to __.104(f)(2)(ii):
If the investigator anticipates that clinically relevant individual research results (i.e.,
those that a reasonable participant would be expected to use in making decisions about
his or her health care), not including uninterpreted, raw data, will be provided to a
research subject, or if those results are otherwise likely, in light of the available evidence,
to cause significant harm to participants, then the research may not be exempted under
this provision and the plan to return results must be reviewed by the IRB and informed
consent for the research must be obtained to the extent required by __.116(a) and (b) to
ensure that __111(a)(8) is satisfied.
1. Meaning of individual research results for purposes of __.104(f)(2)(ii) is unclear
We find the NPRMs discussion of __.104(f)(2)(ii) unclear on the pivotal issue of what
constitutes an individual research result. The NPRM refers to unexpected (i.e., not related to
the purpose of the research) genetic findings, to patient-participants whose clinical care may

demand prompt reporting of findings to them (in which case, the NPRM somewhat
optimistically expects that researchers will always have anticipated this possibility and have
submitted their protocol to IRB review under 104(f)(2)(ii)), and to genetics studies in which in a
significant percentage of instances investigators will be learning information, not necessarily
related to the specific purpose of their studies, that would nonetheless be significant to
participants in terms of making decisions about their health care (p. 53967).
This focus on unexpected findings fails to consider what is always expected: detailed raw data
for every individualfor instance, a variant call file (VCF). Interpretation of data might yield an
unexpected genetic (or other) finding, but data can be shared without interpretation.2
Similarly, and as discussed further below, the NPRMs discussion of clinically relevant research
results ignores the many kinds of biospecimens research results that are irrelevant to making
decisions about [participants] health care. Even when individual research results do not inform
a participants health care, returning them may constitute a valuable act of respect for
participants as partners in research. In some cases, returning results serves as a gesture of
gratitude. In other cases, it serves as an incentive to greater participation in research, itself an
important goal.
And in still other cases, returning results helps rebalance the peculiar information asymmetry that
exists between researcher and participant when the researcher learns something about the
participant that he or she herself does not know by giving them equal access3 to that
information. As Madeleine Price Ball notes, in comments submitted to you in her capacity as a
private citizen, Access to our own data balances the disempowerment that occurs when another
entity holds information about us. Participants may perceive a lack equal access, conversely, as
disempowering and paternalistic.
Equal access to ones own research results (whether interpreted or not) also enables participants
to share that data with other researchers through a platform like Open Humans, thus helping to
break down data silos and accelerate scientific progress.
We respectfully request clarification regarding what constitutes individual research results for
purposes of __.104(f)(2)(ii), and in particular whether it includes raw data and whether it is in
some way limited to clinically relevant data.
2. Applicability of __.111(a)(8) and meaning of clinically relevant are unclear
NPRM __.111(a)(8) proposes to add an additional 111 criterion for IRB approval of research:
If the investigator proposes a research plan for returning clinically relevant results to subjects,
that the plan is appropriate. At p. 54016, the NPRM explains:
[This] proposed change relates to the new exemption at __.104(f)(2) that includes a

2

Cf. FDA regulation of 23andMes return of health-related interpretations, but not raw data files, to users.
See Quantified Self Public Health Symposium (April 2014) at pp. 1820, available at
http://quantifiedself.com/symposium/Symposium-2014/QSPublicHealth2014_Report.pdf (describing presentation
by Jason Bobe at Robert Wood Johnson-supported symposium).
3

criterion at (f)(2)(ii) that the exemptions do not apply if the investigator intends to return
individual research results to subjects. Thus, a new provision would be added at
__.111(a)(8) clarifying that IRBs need to review any plan in a research protocol for
returning individual research results to subjects and to determine whether it is
appropriate.
This explanation could be read as suggesting that __.111(a)(8) was intended to apply only to
research to which __.104(f)(2) applies, namely, [r]esearch using biospecimens or identifiable
private information that have been stored or maintained for secondary research use following
broad consent. But as written, __.111(a)(8) applies whenever the investigator proposes a
research plan for returning clinically relevant results to subjects; such cases are not limited to
secondary research involving biospecimens or identifiable private information.
Moreover, __.111(a)(8) is limited to the return of clinically relevant results. Clinically
relevant is not defined (itself a significant problem), but it is clearly not co-terminous with
104(f)(2) research. Some results of research on stored biospecimens or on identifiable private
information will not be clinically relevant by any plausible definition of that phrase, while some
non-104(f)(2) research (e.g., some prospective biospecimens research), will be clinically
relevant. We request that the relationship between 104(f)(2)(ii) and 111(a)(8) and the meaning of
clinically relevant results both be clarified.
3. Scope of individual research results requiring IRB review is overbroad
As written, although 111(a)(8) would require IRB review of any plans (in any kind of research
project) to return only clinically relevant individual results, 104(f)(2)(ii) requires full IRB
review of any project involving stored biospecimens or identifiable private data that proposes to
return any kind of individual research results. This disconnect is itself problematic, in ways
already discussed. Here, however, we focus on what we believe is the overly broad scope of
results to which 104(f)(2)(ii) applies.
In keeping with the NPRMs commitment to risk-based regulation of human subject research,
IRB review of plans to return individual research results should be limited to results whose
return to participants poses significant risk. The determination that returning particular research
results poses more than minimal risk should rest on a determination that it is likely, based on
evidence (not speculation or anecdote) to cause significant harm (not mild, transitory feelings of
anxiety, which are part of daily life) to many participants (not to an idiosyncratically sensitive
participant, whom it will always be possible for an IRB to imagine).
Not all individual results of biospecimens research plausibly meet this risk-based test. For
instance, through its GET Labs, PG.org has hosted biospecimens research and the return of
individual results to Personal Genome Project participants regarding their ancestry, the
composition of their armpit and gut microbes, the nature and extent of their face mites, and how
their genome might contribute to the shape, size, and pigmentation of their areolas. An additional
study, Flu Near You, collects biospecimens from participants who self-report as ill and test for 812 viruses in order to track the prevalence of virus in communities. Researchers return to
participants their individual results (whether they tested positive for any virus or not) months

later, when they are no longer clinically relevant.


It is implausible to suppose that returning any of these or similar results poses any significant
risk to participants. In particular, such results are very unlikely to implicate the NPRMs worry
about the [c]hallenges [that] can arise regarding return of individual research results when it is
not clear if the findings have clinical validity or utility, or when the knowledge imparted may
cause psychological distress or social harm (p. 53988). In our experience tracking Personal
Genome Project participants experiences receiving a wide range of results, some of which are
both clinically relevant and sensitive, returning results has resulted in exactly zero adverse
events.
While returning these results is unlikely to pose any significant risks to participants, doing so is
likely to confer benefits on both participants and society. The researchers involved in all of these
projects, and many others, believe that returning results can be educational for participants and is
one way of showing appreciation for participants contribution and indeed can help encourage
their participation and increase their interest in science and research. Permitting participants to
upload their returned results to the Open Humans portal, in turn, allows researchers an
unprecedented opportunity to study perhaps the most phenotyped participants in the world.
Section __.104(f)(2)(ii) would impose burdens of full IRB review and of individual, studyspecific consent on researchers, participants, and IRBs where otherwise no IRB review and no
further consent of any kind would be required. Those burdens are unwarranted in the context of
such low- and no-risk return of results.
Moreover, the difference, from the investigators perspective, between 104(f)(2)(i)s regulatory
path and that of 104(f)(2)(ii) constitutes an enormous incentive for researchers to eschew the
return of results, even as the NPRM elsewhere touts a move towards a participant-centered
research model that adequately respects participants as partners (p. 53938). Nor will all
investigators find IRB review equally burdensome; 104(f)(2)(ii) is likely to have a disparate
impact on junior researchers working under time pressures related to graduation, postdoctoral
fellowships, and tenure and on researchers at institutions with understaffed IRBs. This would
result in some participants being offered equal access to their results while others are not for
reasons that have nothing to do with risks to participants or expected benefits to participants or
society, a result that is in some tension with the Belmont Reports principle of justice.4 To the
extent that researchers do find 104(f)(2)(ii)s regulatory path to be prohibitively burdensome,
both society and participants would be deprived of knowledge production and education, without
any offsetting benefits in the form of protecting participants.
Suggestions for risk-based regulation of return of individual research results
We appreciate that codifying criteria for distinguishing low-risk from high-risk return of results
is difficult, as is the more general task of codifying which categories of research are sufficiently
low-risk as to merit exemption, exclusion, and expedited review. However, this difficulty is

4

Cf. NPRM at p. 53967 ([I]t is likely that many IRBs do not have any particular unique expertise in making these
determinations about returning results, which again could lead to inappropriate variability in disclosure from study
to study, and would seem to be in conflict with the ethical goal of justice.).

inherent and inescapable in the risk-based approach to regulation to which the NPRM is
(commendably) committed.
Below, we suggest three different options for limiting the scope of individual results to which
104(f)(2)(ii) applies. All, in our view, would be significantly preferable to __.104(f)(2)(ii), as
currently drafted. In all three cases, we imagine that our proposed criterion for triggering
__.104(f)(2)(ii) could be incorporated into the decision tool, so that researchers themselves
could determine whether their secondary research is exempt under __.104(f)(2)(i) or not.
A. One possibilityperhaps the cleanest, given 111(a)(8)would be for __.104(f)(2)(ii) to
mirror the NPRMs proposed new criterion for IRB approval of research, __.111(a)(8), which,
as discussed above, requires IRBs to determine that any plan for returning clinically relevant
results to subjects is appropriate (emphasis added). That is, __.104(f)(2)(ii) might provide:
If the investigator anticipates that clinically relevant individual research results will be
provided to a research subject . . . .
Section 104(f)(2) research involving the return of results that are not clinically relevant would
therefore be exempt under __.104(f)(2)(i). However, we think it would be important for either
final rule to define, or OHRP to issue guidance regarding, the meaning of clinically relevant.
We do not favor borrowing from NPRM __.102(b)s definition of clinical trial and defining
as clinically relevant any result that relates to biomedical or behavioral health, as this is
entirely too broad and captures many results whose return would pose little or no risk to
participants.
B. A variation on this first option, then, would be to further specify the meaning of clinically
relevant by limiting the scope of __.104(f)(2)(ii) to individual research results that are
expected to be used to guide clinical care or, in the NPRMs own words, that would . . . be
significant to participants in terms of making decisions about their health care. To help keep
IRBs from being distracted by thoughts of what some imagined participant might hypothetically
do, an even better qualifier might be something like those results that a reasonable participant
would be expected to use in making decisions about his or her health care. Any of these
alternative wordings would help clarify that something like Flu Near You results, which are
received well after an illness has ended, do not trigger __.104(f)(2)(ii).
C. It may be that clinically relevant and its cognates are in the end too crude a proxy for risk,
being both underinclusive and overinclusive. For instance, non-paternity results do not have
direct clinical relevance, but they are certainly sensitive. Conversely, it is not obvious that
returning results to participants about their gut microbiome, which may have clinical relevance
for overweight or obesity, is especially risky.
One way of addressing this concern would be to limit the scope of 104(f)(2)(ii) to clinically
relevant results or to some specified version of the same, as just discussed, but to include an
additional prong under which IRB review might be triggered, such that 104(f)(2)(ii) would apply
to clinically relevant results or results that are otherwise likely, in light of the available
evidence, to cause significant harm to participants.

D. A different solution would be to limit __.104(f)(2)(ii) to results that meet criteria that are
published (and regularly updated) in the Federal Register (similar to the list of categories of
research eligible for expedited review under Common Rule 46.110). That list could be created
either by HHS or by an expert federal panel similar to the one that the NPRM contemplates (but
used for a somewhat different purpose5). Returning results that fall outside of this list would not
be subject to __.104(f)(2)(ii) and the research would be exempt under __.104(f)(2)(i).
There are advantages to having HHS or a standing expert panel identify the criteria for
determining which individual research results may and may not be returned without IRB review,
compared to codifying such criteria in the Common Rule itself. Relying on an expert panel
whose determinations evolve would allow flexibility as the research community learns more both
about the range of biospecimens research results that investigators may wish to return and
participants wish to receive and the outcomes for participants who receive such results. (On the
latter point, we strongly urge OHRP to track, or encourage others to track, participant outcomes
of receiving a wide range of individual research results so that policy regarding return of results
is evidence-based.)

5

Because it is likely that many IRBs do not have any particular unique expertise in making these determinations
about returning results, the NPRM contemplates the creation of an expert panel to make determinations about
which unexpected findings should be disclosed to human subjects in research, and what information should be given
to subjects about themselves (p. 53967, emphasis added). In that case, 104(f)(2) research would be exempt even if
it involves the return of individual results, so long as disclosures were made consistent with the rules announced by
the federal panel. It is unclear whether the second clause, what information should be given to subjects about
themselves, refers to what expected results should be returned to participants or to what information should be
disclosed to them regarding particular kinds of results (i.e., how results should be returned).
As for the first clause, it would seem to have the NPRM contemplating a role for a federal panel in determining
whether, not how, unexpected findings should be disclosed. Yet in its discussion of the primary alternative to such a
panel, the NPRM explicitly limits __.111(a)(8) to IRB review of the appropriateness of any plan the researcher
may happen to propose and not to a determination of whether there should be a plan for returning individual
research results (p. 53988). If, in that brief paragraph at p. 53967, the NPRM is indeed proposing an expert panel to
decide whether there should be a plan for returning results (either unexpected and/or expected)a task that is in fact
different from, and so not a substitute for, the IRBs proposed task under 111(a)(8)we suggest that the NPRM has
provided insufficient notice to the public that HHS intends to regulate the threshold question of whether results
should be returned. As a result, HHS should take no further action on that matter at this time.
Should HHS nevertheless proceed to contemplate such a role for a panel, however, we acknowledge that,
relative to individual IRBs, many of whom lack relevant expertise, either a standing expert panel or OHRP guidance
(perhaps developed in consultation with such a panel) could helpfully summarize the current (but quickly evolving)
empirical literature about the effects of different methods of returning results to participants, the extent to which a
finding that seems valid today is likely to remain so in the near future, and so on. We note, however, that one
advantage of individual IRBs is that, using expert guidance, they could ensure an appropriate plan for returning
results that is study- and participant cohort-specific. For instance, in the case of the Harvard Personal Genome
Project (a pioneer in returning individual research results), the Harvard IRB initially approved enrolment and return
of results to participants who held the equivalent of a Masters degree in genetics, and later, after tracking outcomes,
expanded the inclusion criteria to any participants who pass a comprehension test. Other relatively sophisticated
populations have been shown to comprehend complex, sensitive results quite well. See, e.g., JE Osterren et al. How
well do customers of direct-to-consumer personal genomic testing services comprehend genetic test results?
Findings from the impact of Personal Genomics Study. Public Health Genomics June 16, 2015, DOI:
10.1159/000431250. IRBs could also attend to other local factors such as researcher resources. We would find it
extremely problematic from the perspective of beneficence, respect for persons, and justice if a federal panel
produced universally-applicable rules that failed to recognize and accommodate heterogeneity among participants,
researchers, and results.

With respect to the composition of any such panel, we think that it would be important to include
members beyond the clinical genomics community, including social scientists, as clinical
genomics does not begin to exhaust the category of biospecimens research potentially subject to
__.104(f)(2)(ii), as currently written. We also recommend that the panel include some members
who themselves have been through the process of receiving a range of individual research
results, and some patient advocates. The comments submitted to you by Steven Keating in his
capacity as a private citizen struggling to obtain equal access to the data he has donated to
scientific research in the wake of a cancer diagnosis are indicative of the kinds of important
perspectives that are omitted when decision-makers are insufficiently diverse.
4. Scope of IRB review required under 104(f)(2)(ii) is overbroad
The NPRM remarks that [i]f this alternative proposal [for an expert panel] were adopted, then it
would not be necessary to have full IRB review of these protocols. Actually, full IRB review of
protocols that contemplate the return of results is not necessary under any circumstance, not even
as regards risky results (however determined). In all cases, IRB review of plans to return
individual research results should be limited to a review of the plan to return results.
Absent a researchers anticipation that she will return results, under __.104(f)(2)(i), the
secondary research would be exempt and subject to no additional IRB review (beyond the
limited IRB review involved in ensuring adequate broad consent for storing the biospecimens or
identifiable private information under 104(f)(1)(i) in the first place). Because the only
difference between a secondary research protocol in which the researcher anticipates returning
results and the identical protocol in which she does not is the plan to return results, any IRB
review logically should be limited to review of that plan. A researchers laudable willingness to
offer to return individual research results to participants should not operate as an open invitation
to the IRB to second-guess the importance of the knowledge that may reasonably be expected to
result from the secondary research or otherwise to relitigate the risk-benefit compromise the
NPRM has already struck in permitting secondary research to be conducted on biospecimens and
identifiable private information with broad consent, to question whether subject selection is
equitable, or to evaluate the underlying secondary research proposal under any of the other
elements of __.111(a)(1)(7).
Instead, to whatever extent the final rule requires IRB review under __.104(f)(2), that review
should be explicitly limited to __.111(a)(8), ensuring that, [i]f the investigator proposes a
research plan for returning clinically relevant results to subjects, that the plan is appropriate.
(We have retained the limiting clause, clinically relevant, that appears in NPRM
__.111(a)(8). Obviously, the wording there should match whatever criteria is used to separate
low-risk from higher-risk return of results at __.104(f)(2), discussed in section 2 of these
comments.)
The NPRM itself explains that protocols that contemplate returning individual research results
would undergo full IRB review primarily for the purpose of determining what information
participants should be provided regarding such . . . findings. We think that the word primarily
is unnecessary, and in any case is unexplained and unjustified in the NPRM. There is already

precedent in the NPRM, at __.104(f)(1), for requiring a form of limited IRB review. And
requiring only limited review would reduce the disparity in burdens between the 104(f)(2)(i) and
104(f)(2)(ii) regulatory pathways that we discussed in section 3 of these comments.
5. Scope of informed consent required under 104(f)(2)(ii) is overbroad
Similarly, we can perceive no justification, simply because the researcher wishes to offer
participants the opportunity to receive their results, for converting a protocol that, under
__.104(f)(2)(i), would require no further consent to one in which researchers are required to
obtain fully informed consent under __.116(a) and (b) from each participant, not only to receive
results, but also to the use of their stored biospecimens or identifiable private data in this
particular research study (something to which they have already given broad consent).
Participants should of course be permitted to choose whether or not to receive individual results
(except, perhaps, in relatively rare circumstances in which warning a participant of a research
result is expected to prevent death or serious injury to themsomething that is beyond the scope
of these comments and, we believe, the NPRM). And in making that decision, participants
should be provided with sound information about the risks and potential benefits of receiving
such results. But we presume that this is precisely the purpose of __.111(a)(8)s requirement
that the IRB determine that the plan for returning results is appropriate. Any requirement of
additional disclosure and consent about the study is unwarranted and would only serve to burden
researchers, IRBs, and participants (who would be asked to read and comprehend the informed
consent for an entire protocol despite having already given broad consent for research).
Conversely, requiring participants to consent only to receiving individual results would reduce
the disparity in burdens between the 104(f)(2)(i) and 104(f)(2)(ii) regulatory pathways that we
discussed in section 3 of these comments.
6. What constitutes appropriate plans for returning results is unclear
If the final rule requires IRBs to review the appropriateness of plans to return individual
research results under __111(a)(8), we strongly urge OHRP to issue guidance regarding when a
plan is appropriate (and, as applicable, regarding when results are clinically relevant), or
otherwise facilitate appropriate IRB review of the appropriateness of plans to return results.
As Misha Angrist notes in comments submitted to you in his capacity as a private citizen, not
only does the NPRM create a strong disincentive to return results; even those researchers who
might nevertheless assume the regulatory burden of returning results are likely, according to the
NPRM itself, to face review by an IRB that do[es] not have any particular unique expertise in
making these determinations about returning results (p. 53967). Under these circumstances, any
mandate that IRBs review plans to return individual results that is unaccompanied by a
commitment to facilitate appropriate IRB review is likely to result in wide variation among IRBs
and in IRB decisions based on speculation rather than data. We are concerned that IRBs that are
explicitly required for the first time, upon pain of violating federal regulations, to ensure that the
return of results is appropriate, and who do so in a guidance vacuum, are likely to be highly
risk-averse relative to existing data about the outcomes of receiving various kinds of results.

We note, first, an ambiguity in 111(a)(8)s requirement that IRBs determine that the plan [to
return results] is appropriate. This might call on IRBs to determine whether or not researchers
will be permitted to offer results to participants under any circumstances, or it may call on IRBs
to ensure that the way in which the researcher proposes to return results is appropriate, or both.
In theory, returning some research results might be so risky that there is no appropriate way to
return them. Yet the available data do not appear to bear out this worry even in the context of
APoE genotyping.6 Where participants are competent adults, review should almost always focus
on how, not whether, results may be offered. With respect to results that could reasonably be
expected to cause significant harm if misunderstood, the how might, if necessary, involve
making return of results contingent on participants passing a comprehension test, similar to the
one that the Personal Genome Project pioneered in returning an analysis of whole genome
sequence results to participants. If a willing researcher wishes to return results to a willing
participant who demonstrates his or her ability to comprehend the nature of those results (their
risks, uncertainty, and so on), we can perceive little justification for IRB veto.
We echo our remarks from section 3 that, in keeping with the NPRMs commitment to riskbased regulation of human subject research, IRB review of plans to return individual research
results, including often cost-prohibitive IRB-imposed requirements such as the availability of 24hour, in-person counseling, should focus on research results that are likely, based on evidence
(not speculation or anecdote) to cause significant harm (not mild, transitory feelings of anxiety,
which are part of daily life) to many participants (not to an idiosyncratically sensitive participant,
whom only the least imaginative IRB member will be unable to conjure).
More likely, the possibility of harm arises not from the bare act of returning results but from a
combination of a sensitive result and misinterpretation or poor communication of that result (e.g.,
carrier status marked by significant false negative or positive rates that could unduly influence
reproductive decisions). There are clearly better and worse ways of communicating probabilistic
and other complex information to laypersons, and IRBs in theory have an important role to play
in that respect.
7. Interaction of HIPAA and __.104(f)(2)(ii) is unclear
The NPRM states:
It is understood that the prospective IRB review provision set forth here does not override
existing law, such as the HIPAA Privacy Rule or the Federal Privacy Act, which give
individuals the right to access certain information about themselves in specified
circumstances.
We request that OHRP clarify how the proposed rule and these others laws would interact. For
instance, we assume that if a participant requests her research data from a HIPAA lab as part of
her designated record set, this request by a participant would not trigger IRB review and
informed consent under __.104(f)(2)(ii), since the lab, and not the researcher, would be

6

See, e.g., RC Green et al. Disclosure of APOE genotype for risk of Alzheimers Disease. NEJM 2009; 361(3):
24554.

10

returning individual results. Similarly, we assume that if a researcher alerted participants to


their HIPAA rights or enabled them to avail themselves of those rights (say, by creating a
standard), that these, too, would not trigger __.104(f)(2)(ii). However, we would appreciate
clarification on these points.
Respectfully submitted,

Michelle N. Meyer, PhD, JD


Board of Directors, PersonalGenomes.org
On behalf of
George Church, PhD
Founder and Chair, PersonalGenomes.org
Principal Investigator, Harvard Personal Genome Project
Jason Bobe, MS
Executive Director, PersonalGenomes.org
Co-Founder, Open Humans
Misha Angrist, PhD, MFA
Board of Directors, PersonalGenomes.org
Madeleine Price Ball, PhD
Director of Research, PersonalGenomes.org and Harvard Personal Genome Project
Co-Founder, Open Humans
John H. Cammack, MBA (Columbia Graduate School of Business)
Board of Directors, PersonalGenomes.org
Michael F. Chou, PhD
Director of Human Subjects Research, Harvard Personal Genome Project
Esther Dyson, BA in Economics (Harvard)
Board of Directors, PersonalGenomes.org
Juan Enriquez, MBA
Board of Directors, PersonalGenomes.org
Steven Keating, PhD Candidate (MIT)
Board of Directors, PersonalGenomes.org
Jeantine E. Lunshof, PhD
Ethics Consultant to the Harvard Personal Genome Project

11

Ryan Phelan, BA (University of California at Berkeley)


Board of Directors, PersonalGenomes.org
Alexander Wait Zaranek, PhD
Director of Informatics, Harvard Personal Genome Project

12

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