1. 2016
Office of Information & Regulatory
Affairs, OMB: Guidance on
Informed Consent for In Vitro
Diagnostic Device Studies Using
Leftover Human Specimens
ATTN: FDA DESK OFFICER
WILLIAMSON, KIRK BASCOM

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Control No. 0910-0582
Docket No. FDA-2012-N-0560
Author of “The Immortal Life of Henrietta Lacks,” Rebecca Skloot, in a recent New York
Times article, recounted the story of a Des Moines University Medical School Professor who
recently instructed his medical students to unlock their cellphones and pass their unlocked
phones to the student sitting behind them. The students fired back a litany of questions, such as,
“Why? What will they look at? How will they use that information?1
” This social experiment
illustrates that people want to be informed, and they want to give their consent. It would come as
a surprise if one found out their cells, which contain all of the genetic sequencing that makes
them entirely unique, are being passed around by researchers without one’s consent.
U.S. informed consent law takes its roots in the Nuremburg Code2
, explicitly spelling out
the need to proactively secure voluntary consent of any human research subject, but one of the
law’s grounding foundations is the case of Moore v. Regents of University of California Los
Angeles. Over the course of several years, Moore’s doctor removed blood and other bodily fluids
which eventually became a “cell line” that was patented and sold for commercial use, without
Moore’s knowledge of the physician’s research interest. Although rejecting the theory of
conversion allegation, The Court noted, “that the breach of fiduciary duty and the lack of
informed consent theory were better suited to protect the rights of patients3
.” I argue that the
devolution of informed consent into a nationalized “broad consent” standard would be a
detriment to public trust in the study of human subjects because deference given towards
researchers prioritizes the advancement of medical discovery over the protection of patients’
rights. The authorization requirements set forth by the regulations should bolster public trust by
protecting an individual’s right to privacy, not make it easier to perform research involving the
use of de-identified biospecimens4
.
In a Level One document entitled “Guidance on Informed Consent for In Vitro
Diagnostic Device Studies Using Leftover Human Specimens That Are Not Individually
Identifiable5
,” the Food and Drug Administration (FDA) outlines its intended use of enforcement
discretion as to the informed consent regulations for clinical investigators, sponsors, and IRBs.
Current FDA regulations regarding investigational device (IVD) studies that are exempt from
most provisions of part 812, “Investigational Device Exemptions” (21 CFR 812.2(c)(3)), do not
contain exceptions from the requirements of informed consent “on the grounds that the
specimens are not identifiable or that they are remnants of human specimens… that would
1
Skloot, R. (2015, December 30). Your Cells. Their Research. Your Permission? The New York Times. Retrieved
from http://www.nytimes.com/2015/12/30/opinion/your-cells-their-research-your-permission.html?_r=0
2
Teitelbaum, J. B., & Wilensky, S. E. (2013). Individual Rights and the Health Care System. Essentials of Health
Policy and Law (pp. 111–112). Burlington, MA: Jones & Bartlett Learning.
3
Rosenbaum, S. (2001). Part Three. Health Care Quality and Law: Defining Standards and Structuring Enforcement
and Accountability. Law and the American Health System (pp. 98–101).
4
Hudson, K., & Collins, F. (2015). Bringing the Common Rule into the 21st Century. The New England Journal of
Medicine, 373(24), 2293–2296. Retrieved from http://www.nejm.org/doi/pdf/10.1056/NEJMp1512205
5
Guidance for Sponsors, Institutional Review Boards, Clinical Investigators and FDA Staff; Guidance on Informed
Consent for In Vitro Diagnostic Device Studies Using Leftover Human Specimens that are Not Individually
Identifiable. (2006). Retrieved from
www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm078384.htm

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otherwise have been discarded. Nor do FDA regulations allow IRBs to decide whether or not to
waive informed consent for research involving leftover or unidentifiable specimens6
.”
The revisions to the Federal Policy for Protection of Human Subjects, colloquially known
as the Common Rule, would require scientists to obtain consent on all biospecimens; however,
nothing prohibits the re-identification of anonymous samples using DNA and publicly available
data. Furthermore, the revised rule doesn’t require informed consent on research utilizing the
genetic information inside the biospecimen7
. If one of the National Proposed Rule Making’s
(NPRM) primary rationales for these regulations is to address governmental concern that data
can no longer be “unidentifiable,” it would seem self-defeating that the language used to describe
the broad consent form perpetuates the idea of “nonidentifiable data8
.”
To further illustrate the deleterious effects of the NPRM’s broad consent form, in order to
avoid the burdens of IRB review, investigators must plan to not return research results to
individual donors, even if the results are medically actionable9
. It is then plausible to believe
such perverse incentives to withhold medically actionable results will only fuel the already
vehement debate concerning what to return, how, and when such action should take place.
Certainly, the difficulty of obtaining informed consent by the donor of a de-identified
specimen is no easy feat; however, it should be emphasized that informed consent is a process,
not a form. A researcher’s intentions regarding biological samples a decade from now are simply
not foreseeable, and adding one more piece of paper on top of a stack of already confusing
informed consent documents is bad governance and poor regulation10
. Retroactively seeking
“broad consent” from patients who already have specimens that are being investigated poses an
implied breach of confidentiality that may cause the patient to question the multifarious ways in
which the medical community has been using his or her genetic information over the past years,
even decades.
In fact, creation of a broad consent form is legally restricted pursuant to 45 CFR
§164.508(b)(3)(i) “Compound Authorizations” where “any compound authorization created
under this paragraph must clearly differentiate between the conditioned and unconditioned
components and provide the individual with an opportunity to opt in to the research activities
described in the unconditioned authorization.” Clearly, delineating between the “conditioned”
and “unconditioned” components of an authorization would be confusing to the patient and has
the potential to be misconstrued if the physician fails to distinguish between the two components.
The National Bioethics Advisory Commission stated during the 2002 debate over new HIPAA
regulations, “Federal policy should be developed and mechanisms should be provided to enable
6
Agency Information Collection Activities; Submission for Office of Management and Budget Review; Comment
Request; Guidance on Informed Consent for In Vitro Diagnostic Device Studies Usi. (2016).Federal
Register,81(70), 21558–21559. Retrieved from https://www.gpo.gov/fdsys/pkg/FR-2016-04-12/pdf/2016-08329.pdf
7
Skloot, R. (2015, December 30). Your Cells. Their Research. Your Permission?
8
Robertson, C., & Rogers, J. (2016). Federal Government’s Proposed Expansion of Regulation of Biospecimen
Research Should Be Reconsidered. BIOPRESERVATION AND BIOBANKING, 00(00), 1–3.
9
Robertson, C., & Rogers, J. (2016). Federal Government’s Proposed Expansion of Regulation of Biospecimen
Research Should Be Reconsidered.
10
Robertson, C., & Rogers, J. (2016). Federal Government’s Proposed Expansion of Regulation of Biospecimen
Research Should Be Reconsidered.

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investigators and institutions to reduce threats to privacy and breaches of confidentiality. The
feasibility of additional mechanisms should be examined to strengthen confidentiality protections
in research studies.11
”
The use of bio-banked specimens in research is particularly questionable where
advancement in genetic testing currently has the ability to re-identify these specimens12
; briefly,
there are no safeguards in the law to prevent such re-identification. The new regulation also fails
to ensure that this new ideology of “broad consent” prevents human subjects from once again
being objects of specimen procurement in the name of “medical science.”
A revision of the security provision regarding the re-identification of de-identified
specimens is then sin qua non for the “additional mechanism” of waiving the requirement for
informed consent on research regarding the genetic information inside a de-identified specimen.
For example, the current statutory text for the protection of de-identified private health
information reads, “The covered entity does not use [sic] or disclose the code or other means of
record identification for any other purpose, and does not disclose [sic] the mechanism for re-
identification,” (45 CFR 164.514(c)(2)- Security). The statute provides only a duty not to
disclose on behalf of the covered entity. This vague, one sentence “safeguard” should be
amended to include the circumstances under which a covered entity is allowed to re-identify a
specimen, and whether or not this requires prior authorization in written form in compliance with
45 CFR part 46.
Willfully and clearly separating “informed consent” and “broad consent to be used in
research,” allows the patient to proceed with a given procedure without an implied stipulation
that their specimen will be taken out of their body to be used in downstream research for any
given purpose. Today’s research is moving towards a more participatory model, where
volunteers increasingly expect to be partners in research13
, with the trend to include multiple
sites and large numbers of participants. This trend rides on the heels of the 2013 publication of
the HeLa cell line (named for Henrietta Lacks), which underscored the need for greater inclusion
and respect of study participants. The experience of the Lacks family helps direct the future of
research, arguing for heightened awareness and robust knowledge to be given to participants.
Thus, there is an ethical obligation to seek permission and inform participants of risks to their
privacy14
. Empowering the public to have a choice through the use of a well-structured,
prospective broad consent form that respects well established ethics for research conducted on
human subjects from the Belmont Report and the Nuremberg Code will accordingly lead to
increased participation in the medical research community.
11
Annas, J.D., M.P.H., G. J. (2002). Medical Privacy and Medical Research- Judging the New Federal
Regulations.
12
Skloot, R. (2015, December 30). Your Cells. Their Research. Your Permission?
13
Robertson, C., & Rogers, J. (2016). Federal Government’s Proposed Expansion of Regulation of Biospecimen
Research Should Be Reconsidered.
14
Robertson, C., & Rogers, J. (2016). Federal Government’s Proposed Expansion of Regulation of Biospecimen
Research Should Be Reconsidered.

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References:
Agency Information Collection Activities; Submission for Office of Management and Budget
Review; Comment Request; Guidance on Informed Consent for In-Vitro Diagnostic
Device Studies Usi. (2016). Federal Register,81(70), 21558–21559. Retrieved from
https://www.gpo.gov/fdsys/pkg/FR-2016-04-12/pdf/2016-08329.pdf
Agency Information Collection Activities; Submission for Office of Management and Budget
Review; Comment Request; Guidance on Informed Consent for In-Vitro Diagnostic
Device Studies Usi. (2015). Federal Register,80(205), 64422–64423. Retrieved from
https://www.gpo.gov/fdsys/pkg/FR-2015-10-23/pdf/2015-26985.pdf
Annas, J.D., M.P.H., G. J. (2002). Medical Privacy and Medical Research- Judging the New
Federal Regulations. The New England Journal of Medicine,346(3), 216–220.
Beskow, L. (2012). Informed Consent for Biobanking. Duke Institute for Genome Sciences &
Policy, 1–50. Retrieved from
https://www.niehs.nih.gov/news/assets/docs_f_o/informed_consent_for_biobanking_508.
pdf
Federal Policy for the Protection of Human Subjects (’Common Rule'). (2015). Retrieved from
http://www.hhs.gov/ohrp/humansubjects/commonrule/index.html
Guidance for Sponsors, Institutional Review Boards, Clinical Investigators and FDA Staff;
Guidance on Informed Consent for In-Vitro Diagnostic Device Studies Using Leftover
Human Specimens that are Not Individually Identifiable. (2006). Retrieved from
www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm
078384.htm
Hudson, K., & Collins, F. (2015). Bringing the Common Rule into the 21st Century. The New
England Journal of Medicine, 373(24), 2293–2296. Retrieved from
http://www.nejm.org/doi/pdf/10.1056/NEJMp1512205
Korenman, S. (n.d.). Respect for Persons. Teaching the Responsible Conduct of Research in
Humans. Office of Research Integrity. Retrieved from
https://ori.hhs.gov/education/products/ucla/chapter2/page02.htm

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NPRM 2015- Summary. (2015). Retrieved from
http://www.hhs.gov/ohrp/humansubjects/regulations/nprm2015summary.html
Rosenbaum, S. (2001). Part Three. Health Care Quality and Law: Defining Standards and
Structuring Enforcement and Accountability. Law and the American Health System (pp.
98–101).
Skloot, R. (2015, December 30). Your Cells. Their Research. Your Permission? The New York
Times. Retrieved from http://www.nytimes.com/2015/12/30/opinion/your-cells-their-
research-your-permission.html?_r=0
Teitelbaum, J. B., & Wilensky, S. E. (2013). Individual Rights and the Health Care
System. Essentials of Health Policy and Law (pp. 111–112). Burlington, MA: Jones &
Bartlett Learning.