October 20, 2011
Ethics and de-identified genomic plus phenotypic (health) data
Image source: Amazon
During the annual Cerner Health Conference last week, several
clients came up to discuss my previous post and associated essay on de-identified health data. In my essay, I basically agree
with Marc Lappé and others
who have asserted that medical ethics as it exists and is practiced today is
different from—and historically antagonistic toward—public health ethics (‘communitarian ethics’). This point of view is covered at some length in a paper by Eric Meslin and Ibrahim Garba in the September issue of Human Genetics.
The clients who visited with me substantially agreed with
the idea that there is presently an imbalance between individualistic ethics
and communitarian ethics. They asked what resources might be available to
correct this imbalance, particularly with respect to genomics-based research
and predictive/preventive tests or algorithms based on these that might bear
upon not only the person who was tested but also on their relatives and on
members of their community or groups of people (ones currently alive, plus
those who may be born in the future) who have similar genetic and other
One of the clients noted that Kathy Hudson’s paper in the New England Journal of Medicine last month repeats the misconception that true de-identification of biologic
specimens or genomic data is not always possible, because a small number of
genetic markers can uniquely identify a participant. “Even aggregate data (e.g., pooled data from several hundred subjects) may not be safe,” Hudson
I advised them that that statement is only true if someone
wishing to identify a participant (a) independently possesses some identified
tissue from the individual that can be or has been sequenced or tested for
markers that are in the other pooled data, or (b) independently has access to
some identified, different data from the individual where those markers or
sequences exist, such that the pooled de-identified data can be matched with
certainty against the independent identified data. Hudson’s conjectured
inferring someone’s identity with certainty from observable phenotypic
characteristics (Shurin 2008) is therefore extremely remote.
“Study participants are asked to consent to future studies
with unspecified aims, broad data sharing policies, and ongoing uncertainties
regarding confidentiality protections and the potential benefit of incidental
genomic research findings. Because more research is conducted under these new
conditions, the very nature of the researcher-subject relationship is shifting
and will require new governance mechanisms to promote the original goals of
informed consent.” Gail Henderson, 2011
Consenting for secondary-use was another topic that clients visiting with me were keen to learn more about. In that regard, you may like to look at the paper by de Vries and colleagues. They point out differences in
genomics research that affect the consenting process. Genomics and other
biomarker studies are “hypothesis-generating,” rather than “hypothesis-testing” like most conventional studies. The scope and endpoints are unknown
or only partially known at the beginning, so to do "narrow" consent
either forecloses upon pursuit of hypotheses that are generated or forces
Genomics studies are undertaken in a climate of
collaboration, with multiple secondary uses of the same information and biobanked
specimens over an indefinite period of time. In the course of multiple secondary uses, sharing may extend to
additional collaborators (both academic ones and commercial ones) who were not
party to the original process (and were therefore not mentioned in the initial
informed consent materials under which consent was obtained), whereas the
investigational center(s) and sponsors in conventional studies are known to
each study subject at the time of consenting. Conventional studies—with some
exceptions, such as the Framingham Heart Study, generally have
a crisply defined beginning and end.
“One ‘size’ [with regard to genomics study ethics and
secondary uses of data and specimens] does not fit all, and the development of
appropriate responses to these ethical issues will need to be conducted on a
case by case basis. What will link international genomics research projects,
though, are the more general principles of justice, ownership and the fair
distribution of resources.” Jantina de Vries, 2011
I will now summarize some of the recommendations I made to
the clients who met with me at CHC last week. Links are appended at the bottom so you and they can access these
resources easily and pursue your review and policy-making efforts on your own.
First of all, I strongly recommend conducting multiple pre-study workshops among the participating investigational centers that
will be involved in any genomics-based study, to flush out and address
differences in IRBs’ interpretations of ethics requirements that the genomics
study presents. This would be similar to what was famously done in the
multinational MalariaGEN project. Each time a new secondary-use study
that would re-use the materials collected in the original study is proposed,
conduct a new round of workshops among the newly expanded set of centers to
achieve transparency and consensus among the IRBs.
Secondly, the 2010 paper by Malin and coworkers at
Vanderbilt is a wonderful survey of the issues and contains valuable
suggestions. You will want to take a look at that paper. Other ideas, such as
Contreras’s notion of “latency” or several months or years “embargoing” of information sharing may also be applicable
where the privacy or sensitivity of certain information has a time-scope that
is shorter than the person’s lifetime.
Narrow consent documents describe the benefits and risks of
a specific study, whereas a broad consent may ask participants to agree to any
number of future studies that will use their samples or data. In the case of
NIH’s dbGaP, because no patient identifiers are to be submitted (although they
will be retained at the institutions where primary data collection occurred),
the HHS Office of Human Research Protections (OHRP) opined that investigators
who access dbGaP data must be secondary users who are not conducting ‘human
subjects research’ as defined by federal regulations. OHRP does not require
that secondary users obtain IRB consent in order to access the data, nor do
secondary users have to re-seek informed consent from the original subjects,
who are de-identified in dbGaP.
However, because some data sets may contain information
that is conjecturally (re-) identifiable (and would be re-identifiable if the
secondary users were to obtain tissue or identified genomic information in some
other way, from a set of people that happened to include subjects from the
primary study), the primary study investigators may require that secondary
users obtain approval from their own IRBs. That’s what the Framingham SHARe
did, for example. SHARe includes data
from the Framingham Heart Study, which was based in a medium-sized community in
Massachusetts. Each NIH Institute with data in dbGaP is creating a Data Access
Committee to review applications and a Data Use Certification that secondary
investigators must sign to gain access to a dataset. In fact, the NIH has
established ongoing policies and procedures to oversee GWAS policy
implementation across the agency and to monitor whole genome association
data-use practices. Cerner’s own data-use policies and procedures emulate those
promulgated by NIH.
Finally, I suggested to the clients that the ethics of
uncertainty has in the past been one-sidedly addressed (e.g., Loewy 1987) from
the vantage point of the paternalistic clinician/expert—the possessor of facts
or prognostic information—with regard to the provider’s/researcher’s duties to
inform her passive, child-like patient/recipient and how to convey to that
recipient the imprecision with which the diagnosis or prognosis is known or,
alternatively, with regard to complying with the patient's request not to be
Instead, in the future the ethics of uncertainty should, I
believe, explicitly address things from the vantage points of other
stakeholders, including the person (the one whose [genomic] information has
been measured) and the person's family and community. In other words, these
other stakeholders are bearers of rights and duties as well, and, so long as
they are members of a family and community, they do not have the right to treat
the group with contempt and unilaterally breach their duty of care.
In other words, the act that opter-outers “commit” by their
opting-out is not a crime but a tort—those who capriciously withhold their
consent for secondary uses of their de-identified information for public health
and family and other valuable purposes. Heinz Kohut refers to such acts (or non-acts, or failures to act) as ‘breaches in empathy’. By far, the best account to-date of these ideas is in
Peter Gerhart's book Tort Law and Social Morality. Future policy-making regarding human research
subjects protections and genomics-based study ethics would do well to consider
the ideas set forth by Gerhart, as a means of reconciling individualistic
ethics and ‘other-regarding’ communitarian/public health ethics.
Please feel free to
add comments or contact me if you have criticisms, suggestions or
would like to discuss further. Thank you!
Douglas McNair, MD, PhD, is president of Cerner Math, Inc., and one of three Cerner Engineering Fellows and is responsible for innovations in decision support and very-large-scale datamining. McNair joined Cerner in 1986, first as VP of Cerner’s Knowledge Systems engineering department; then as VP of Regulatory Affairs; then as General Manager for Cerner’s Detroit and Kansas City branches. Subsequently, he was Chief Research Officer, responsible for Cerner’s clinical research operations. In 1987, McNair was co-inventor and co-developer of Discern Expert®, a decision-support engine that today is used in more than 2,000 health care facilities around the world. Between 1977 and 1986, McNair was a faculty member of Baylor College of Medicine in the Departments of Medicine and Pathology. He is a diplomate of the American Board of Pathology and the American Board of Internal Medicine.
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