This document summarizes a presentation by Mark Barnes of Ropes & Gray LLP on biospecimen research under the proposed changes to the Common Rule. It discusses the background of the Common Rule, the 2011 ANPRM that proposed requiring consent for future research uses of biospecimens, public comments on this proposal, and the 2015 NPRM. The NPRM would expand the definition of "human subject" to include research using identifiable and non-identifiable biospecimens. It proposes allowing broad consent for future unspecified research but with additional required elements. Waivers of consent would only be granted rarely for biospecimen research under new criteria.

1. ROPES & GRAY LLP
Biospecimens and the NPRM
November 16, 2015
Mark Barnes
Ropes & Gray
mark.barnes@ropesgray.com

2. ROPES & GRAY2
Agenda
• Background
• ANPRM
• Biospecimen Research under NPRM
– Broad Consent
– Waiver of Consent
– IRB Review
– Data Security Safeguards
– Compliance & Harmonization
• Conclusion

3. ROPES & GRAY3
Examples of significant uses of banked
biospecimens
• Ascertaining the time at which HIV entered the U.S.
population, through research use of banked
biospecimens originally collected for hepatitis B
• Development of tests to predict response to therapies for
breast cancer
• Isolation of the 1918 flu virus
• Identification of helicobacter pylori as a cause of gastric
ulcers, which also has been linked to the development of
stomach cancer
• These discoveries were obtained from the use of
previously existing pathology collections for which it
arguably would have been infeasible or impossible
to obtain broad prior consent.

4. ROPES & GRAY4
Background:
Common Rule
• In 1991, the Department of Health and Human Services
(HHS) developed a set of regulations, adopted by 14
other federal departments and agencies, known as the
Common Rule
• Intended to create a uniform body of regulations to
protect human subjects involved in clinical research
• Applied Belmont Report’s three principles of:
– Respect for Persons
– Beneficence
– Justice

5. ROPES & GRAY5
Background:
Biospecimen Research under Current Common Rule
• Currently, Common Rule defines “human subject” to include individuals
about whom investigators obtain identifiable private information
• At present, OHRP does not consider research involving only coded
private information or biospecimens to involve “human subjects” if:
• The investigator(s) cannot readily ascertain the identity of the
individual(s) to whom the coded private information or biospecimens
pertain because, for example:
– The investigators and the holder of the key enter into an agreement
prohibiting the release of the key to the investigators;
– There are IRB-approved written policies for a repository that prohibit the
release of the key to the investigators; or
– There are other legal requirements prohibiting the release of the key to the
investigators
45 CFR 46.102(f); OHRP Guidance on Research Involving Coded
Private Information or Biological Specimens (Oct. 16, 2008)

6. ROPES & GRAY6
Agenda
• Background
• ANPRM
• Biospecimen Research under NPRM
– Broad Consent
– Waiver of Consent
– IRB Review
– Data Security Safeguards
– Compliance & Harmonization
• Conclusion

7. ROPES & GRAY7
ANPRM
• On July 26, 2011, HHS, in
coordination with the Executive
Office of the President’s Office of
Science and Technology Policy,
published an advanced notice of
public rulemaking (ANPRM) to
request comment on how to
modernize and improve
effectiveness of Common Rule
• ANPRM posed 74 questions to
the public

8. ROPES & GRAY8
ANPRM:
Biospecimen Proposal
Consent for future biospecimen research
– Generally require written consent for secondary
research use of biospecimens initially collected for
clinical purposes
– Consent could be obtained by use of a general
consent form agreeing to permit unspecified future
research
– Studies using biospecimens initially collected for
clinical purposes would not require IRB review but
would be subject to data security and information
protection standards

9. ROPES & GRAY9
ANPRM:
SACHRP 2011 Comments on “General Consent”
• SACHRP believed that a general consent for future use should
not be a necessary predicate for any and all future research uses
• General consent cannot act as a substitute for careful
consideration by an IRB through the existing waiver of consent
process, of specific future research uses and their risks to
subjects
• Even with general consent for future research uses, no
researcher, under current Common Rule interpretations, would
believe that such a consent would obviate the need, in the case
of future specific research uses, for that researcher to seek and
obtain from an IRB a waiver of consent
• Although the subject may have been generally notified of and
may have permitted future research uses, general consent could
not have addressed specific future studies, for which the IRB, in
considering waiver of consent, would seek to protect the welfare
and rights of the subjects

10. ROPES & GRAY10
ANPRM:
SACHRP 2011 Comments on “General Consent”
• Respect for Persons - seeking a situation in which every subject
has given consent to every use, even if in general terms, or has
opted out of a use and had that opt-out respected; the ANPRM
proposes a model in which respect for persons invariably trumps
beneficence and justice
• Beneficence
– The obligation that all of us have, one to the other, to participate in activities
that benefit society at large, and that yield benefit and promise for those
who come after us
– There should be more exacting, more protective standards on the waiver of
informed consent process, and measures to penalize attempts to re-identify
subjects through their data and biospecimens
• Justice - should not advocate a state of affairs in which persons
may refuse use of their own data and biospecimens, even when
risk to them is negligible, but who nevertheless themselves
benefit from such research by depending upon the beneficence
of others

11. ROPES & GRAY11
ANPRM:
A Sampling of the 1100 Public Comments to Biospecimen Proposal
Reproduced from Cadigan, Nelson, Henderson et al., Public Comments on Proposed Regulatory Reforms that Would Impact Biospecimen Research,
IRB: Ethics and Human Research, Sept.-Oct. 2015.
re

12. ROPES & GRAY12
Agenda
• Background
• ANPRM
• Biospecimen Research under NPRM
– Broad Consent
– Waiver of Consent
– IRB Review
– Data Security Safeguards
– Compliance & Harmonization
• Conclusion

13. ROPES & GRAY13
NPRM
• On September 8, 2015, HHS issued the NPRM, joined
by 15 other federal departments and agencies
• Marks the first systematic attempt to overhaul the
Common Rule since its promulgation in 1991
• NPRM aims to “protect human subjects involved in
research, while facilitating valuable research and
reducing burden, delay, and ambiguity for investigators”
• The 90-day comment period closes on December 7,
2015

14. ROPES & GRAY14
NPRM Proposal for Biospecimen Research
• NPRM would expand “human subject” definition
(§_.102(e)(1)) to cover all research uses of
biospecimens, regardless of whether the biospecimens
are identifiable
– NPRM would require consent for future research uses of
identifiable private information and for research use of both non-
identified and identifiable biospecimens
• NPRM stated bioethical justification is respect for
persons (“special autonomy interest of a person in
controlling the research use of [] biospecimens”), and not
a necessary measure to strengthen human subject
protections (to date, research on biospecimens has not
typically presented significant risk to subjects)

15. ROPES & GRAY15
NPRM:
Alternative Options for Biospecimen Research
• In preamble, NPRM proposes alternative definitions of
“human subject”
- Whole genome sequencing data, or any part of the data generated
as a consequence of whole genome sequencing, regardless of the
individual identifiability of the biospecimens used to generate such
data; or
- Research use of information produced using a technology applied to
a biospecimen that generates information unique to an individual
such that it is foreseeable that, when used in combination with
publicly available information, the individual could be identified (“bio-
unique information”)

16. ROPES & GRAY16
NPRM Proposal for Biospecimen Research
• Storage, maintenance, and secondary research
use of stored/maintained biospecimens (and
identifiable private information) would be exempt
under new §_.104(f)
• Criteria for exemption:
– Informed consent
– Limited IRB review
– Data security protections
– However, if investigator will return individual research
results to subjects (which presumably could be done only
with identifiable biospecimens), the research will not be
exempt

17. ROPES & GRAY17
Biospecimens v. Data
• Exclusion from IRB review for all research
uses of identified data in HIPAA covered
entities
• Why does the revision treat de-identified
biospecimens more strictly than identified
data?

18. ROPES & GRAY18
Agenda
• Background
• ANPRM
• Biospecimen Research under NPRM
– Broad Consent
– Waiver of Consent
– IRB Review
– Data Security Safeguards
– Compliance & Harmonization
• Conclusion

19. ROPES & GRAY19
Informed Consent
• Consent for storage/maintenance/secondary research
use of biospecimens (and identifiable private
information) must be obtained with:
– Specific consent (§_.116(a),(b))
• Include basic and additional elements describing the particular, or a
range of potential, storage, maintenance, and secondary research use
activities, when known
• Would limit the storage/maintenance/secondary research use to those
activities specified in the consent, and would not allow for broad,
unspecified storage, maintenance, and secondary research use
– Broad consent (§_.116(c))
• Permission for biospecimens and identifiable information to be used in
future, unspecified research
• Generally describe types of research/risks/benefits
– Waiver of consent (§_.116(f)(2))
• Limited to “compelling” research needs
• Should be rarely granted according to NPRM

20. ROPES & GRAY20
Broad Consent Elements
– Basic elements (§_.116(a)(2), (3), (5), and (7))
• Reasonably foreseeable risks or discomforts
• Any benefits that may reasonably be expected
• A statement describing extent of confidentiality
• Whom to contact for questions about subjects’ rights and
research-related injuries
– Additional elements (NEW) (§_.116(b)(7), (8), and (9))
• Statement that biospecimens may be commercialized and
whether subject will share in profits
• Whether clinically relevant research results will be returned
and, if so, under what conditions
• An option to consent, or refuse to consent, to being re-
contacted for additional information/biospecimens or for
another research study

21. ROPES & GRAY21
Broad Consent Elements
• 8 new elements specific to research on
biospecimens or identifiable private
information (§_.116(c))
– General description of types of:
• Research that may be conducted
• Information expected to be generated from the
research
• Biospecimens/information that might be used in
research
• Institutions that might conduct research with the
biospecimens/information

22. ROPES & GRAY22
Broad Consent Elements
– Materials covered by broad consent
• Description of the types of biospecimens/information that were
or will be collected and the period of time during which
biospecimen/information collection will occur
• May include all biospecimens/information from the subject’s
medical record existing at the institution when consent is
sought
• For biospecimens/information collected for non-research
purposes, there is an expiration of broad consent for collection
– Biospecimen/information collection cannot occur after 10
years from date of consent
– For research involving children, the time period cannot
exceed 10 years after parental permission is obtained or
until the child reaches the legal age for consent, whichever
is shorter

23. ROPES & GRAY23
Broad Consent Elements
– Duration of the broad consent
• Include in broad consent form a description of the
period of time during which an investigator can
continue to conduct research on the
biospecimens/information
• Could be a definite period of time (e.g., number of
years) or could be indefinite
• Investigators likely would not self-impose a time
limitation on the duration of the consent for collected
biospecimens
• 10-year deadline is for the collection of biospecimens;
this specified timeframe is for the use of collected
biospecimens

24. ROPES & GRAY24
Broad Consent Elements
– Ability to withdraw consent, but biospecimens/information already
distributed may not be retrieved
– Statement that subject will not be informed of details of any
specific research studies
– Statement that biospecimens/information will be used by multiple
investigators and institutions
– Names of institution(s) at which subject’s biospecimens were or
will be collected
– Option for adult to consent to inclusion of de-identified data in
public database
• EMA and certain journals require that all research participant-
level de-identified data used, respectively, to support a marketing
application or as the basis of an article be posted publicly or
otherwise be made available to third-party researchers

25. ROPES & GRAY25
Broad Consent Template (§_.116(d))
• NPRM proposes that HHS Secretary will publish
in Federal Register broad consent templates
containing all required elements of consent
• Use of broad consent template would be
required for exemption under §_.104(f)
• At least two broad consent templates would be
developed:
1. For biospecimens/information originally collected in the
research context; and
2. For biospecimens/information originally collected in the
non-research context

26. ROPES & GRAY26
Obtaining Broad Research Consent in
Clinical/Educational/Administrative Settings
– Health care providers and all settings where biospecimens are
regularly collected (e.g. physician offices, school clinics, public
health clinics, mental health agencies, developmental disability
settings, nursing homes, emergency rooms, ex-US service and
demonstration projects) will be required to secure broad
consent from patients for those biospecimens to be available
for future research
– Hospitals, outpatient clinics, and educational and social service
providers would need to train clinical staff on how to obtain
research consent
– Need to ensure that patients or clients with questions about
broad consent have opportunity to ask questions and receive
answers at the point of contact, before signing broad consent

27. ROPES & GRAY27
Obtaining Broad Research Consent in
Clinical/Educational/Administrative Settings
– NPRM estimates that administrative staff in
the clinical setting will spend 10 minutes
seeking broad consent and entering the
consent information in the appropriate
tracking system (NPRM at 54020).
• Likely a severe underestimate of the amount of time
necessary to explain fully the concepts of broad
consent and biospecimen research, allow an
adequate opportunity to discuss, fully address any
research questions that the prospective subject may
have, and input the relevant responses into a
tracking database
Will broad consent be so routinized that it will be meaningless?

28. ROPES & GRAY28
Posting of Consent Forms (§_.116(h))
• Under NPRM, an additional means of increasing transparency and
facilitating the development of more informative informed consent
forms would be to require that a copy of the final version of the
consent form for clinical trials conducted or supported by a
Common Rule department or agency be posted on a publicly
available Federal website
• Within 60 days after the trial closes to recruitment, the awardee or
the federal department or agency conducting the clinical trial would
be required to post the consent document, the name of the clinical
trial and information about whom to contact for additional details
about the trial
• “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”

29. ROPES & GRAY29
Agenda
• Background
• ANPRM
• Biospecimen Research under NPRM
– Broad Consent
– Waiver of Consent
– IRB Review
– Data Security Safeguards
– Compliance & Harmonization
• Conclusion

30. ROPES & GRAY30
Waiver of Consent:
New General Criterion (§_.116(f)(1))
• NPRM proposes to add a new waiver criterion:
for research involving access to or use of
identifiable biospecimens or identifiable
information, the research could not
practicably be carried out without accessing
or using identifiers
• NPRM modeled this on the similar criterion in
the HIPAA Privacy Rule, which requires that the
research could not practicably be conducted
without access to and use of the protected
health information

31. ROPES & GRAY31
Waiver of Consent:
New Biospecimen Criteria (§_.116(f)(2))
• Additional waiver criteria for biospecimen research; waiver to
be granted “rarely”
1. “Compelling scientific reasons” for the research use of the
biospecimens; and
 Under what conditions exploratory research, for example, could meet this criterion
remains unclear
2. Research could not be conducted with other biospecimens for
which informed consent was or could be obtained
 Due diligence and logistical considerations - whether a researcher would be
expected to survey all potential biobanks and determine the availability of the
banked biospecimens remains unclear
• NPRM would prohibit IRBs from waiving informed consent if
individuals were asked and refused to provide broad consent
• Implication is that broad consent or refusal to consent must be
recorded and tracked
• Prohibitive transaction costs; demographic “matching”
challenges

32. ROPES & GRAY32
Agenda
• Background
• ANPRM
• Biospecimen Research under NPRM
– Broad Consent
– Waiver of Consent
– IRB Review
– Data Security Safeguards
– Compliance & Harmonization
• Conclusion

33. ROPES & GRAY33
Limited IRB Review (§_.111(a)(9))
• IRBs must only determine that the following
requirements are satisfied:
– Procedures for obtaining broad consent for
storage/maintenance/secondary research use of biospecimens
or identifiable private information will be conducted in
accordance with the requirements of the first paragraph in
§_.116; and
– If there will be a change in the storage/maintenance, the privacy
and information protection standards must be satisfied for the
creation of any related storage database or repository
• IRBs are not required to make any other determinations
under §_.111(a)

34. ROPES & GRAY34
Agenda
• Background
• ANPRM
• Biospecimen Research under NPRM
– Broad Consent
– Waiver of Consent
– IRB Review
– Data Security Safeguards
– Compliance & Harmonization
• Conclusion

35. ROPES & GRAY35
Data Security Safeguards (§_.105)
• For biospecimen storage/maintenance/secondary research use to be
exempt under §_.104(f), in addition to consent and limited IRB review,
research must apply the standards for biospecimen protections in
accordance with §_.105
• NPRM proposes to set uniform standards that would help to assure
reasonable and appropriate privacy and confidentiality protections
• NPRM proposes to require that investigators and institutions implement
reasonable and appropriate safeguards for:
– Protecting against risks to the security or integrity of biospecimens or
identifiable private information; and
– Protecting from any intentional or unintentional use, release, or disclosure
• Uniform standards would eliminate need for IRBs to review individual
plans for safeguarding biospecimens and research so long as there is
compliance with standards because IRB often lack expertise in
evaluating privacy and confidentiality risks

36. ROPES & GRAY36
Data Security Safeguards
• NPRM would allow investigators and institutions to
implement either:
– A list published by the Secretary of HHS of specific measures
that an institution or investigator can use to meet the
requirements
• Security safeguards to limit access to physical biospecimens or
information
• Access to electronic information is only authorized for appropriate use
• Information/biospecimens posing informational risks to subjects would
be protected
– Safeguards that meet the standards in the HIPAA rules
• Institutions not subject to HIPAA could voluntarily adopt

37. ROPES & GRAY37
Data Security Standards:
Limitations on Transfer of Biospecimens Collected in Research
(§_.105(c))
• Under the NPRM, unless otherwise required by law, institutions and investigators
may release biospecimens collected for research subject to the Common Rule only
for, among other purposes: (1) any lawful purpose with the consent of the subject; or
(2) other research purposes if the institution or investigator has obtained adequate
assurances from the recipient that:
i. The recipient will implement and maintain Common Rule-prescribed data security
safeguards;
ii. Except for certain low-risk research, the research has been approved by an
institutional review board (IRB) before release of the biospecimens; and
iii. The recipient will not further release the biospecimens except for Common Rule-
regulated human subject research, or other permitted purposes.
• The proposal would mandate that “recipients” of biospecimens, even of de-identified
biological samples, be subject to the Common Rule’s requirements of data security
protections and IRB review unless the subject consents to the release of the
biospecimens to the recipient

38. ROPES & GRAY38
Agenda
• Background
• ANPRM
• Biospecimen Research under NPRM
– Broad Consent
– Waiver of Consent
– IRB Review
– Data Security Safeguards
– Compliance & Harmonization
• Conclusion

39. ROPES & GRAY39
Compliance Dates
• Effective date of final rule: one year after publication in the
Federal Register
• Compliance dates of final rule:
– Generally, 1 year from the publication of the Final Rule
– 3 years for new rules covering all biospecimen
research and the mandate of a single reviewing IRB

40. ROPES & GRAY40
Compliance Transition Period for
Biospecimen Research (§_.101(k)(2))
• Prior collections of biospecimens” are grandfathered and need not
comply with new requirements if:
1. The biospecimens were “collected for either research or
non-research purposes before the compliance date for the
additional requirements [relating to biospecimens as
‘human subjects’]”; and
2. Research use occurs after all identifiable information is
removed
• Therefore, research using biospecimens would not be subject to
revised Common Rule if:
a) Prior collections of biospecimens are not identifiable; or
b) There is a link to identifiers, but the identifiers are removed
before the researcher’s use

41. ROPES & GRAY41
Applying the same federal requirements to
identifiable and de-identified biospecimen research
– By attaching the same requirements for broad consent, data security
safeguards, and limited IRB review for identifiable and de-identified
biospecimen research, the NPRM would disincentivize
researchers from de-identifying biospecimens before
conducting research
– NPRM states that the goal of the data security safeguards is to
“create information privacy protections that would apply to research,
calibrated to the level of identifiability and sensitivity of the
information being collected.” (80 Fed. Reg. 53933, 53978 (Sept. 8,
2015)).
• However, the NPRM would establish the same regulatory
framework for both identifiable and de-identified biospecimen
research, despite de-identified biospecimen research posing
fewer privacy and informational risks
41

42. ROPES & GRAY42
FDA Harmonization (§_.101(j))
• NPRM includes a provision that would require that federal
guidance on the requirements of the Common Rule be issued
only after consultation, to the extent appropriate, with other
Common Rule departments and agencies, if feasible
• While FDA is not a Common Rule agency, the preamble
specifies that FDA intends to modify its regulations in light of
this NPRM, to the extent appropriate, considering FDA’s
unique statutory framework and regulatory mission
• NPRM preamble further states that FDA and OHRP will
continue to work together in developing guidance on their
respective regulatory requirements that are found both in FDA
regulations and in Common Rule, to the extent feasible

43. ROPES & GRAY43
Agenda
• Background
• ANPRM
• Biospecimen Research under NPRM
– Broad Consent
– Waiver of Consent
– IRB Review
– Data Security Safeguards
– Compliance & Harmonization
• Conclusion

44. ROPES & GRAY44
JURISDICTION:
Determining Whether Broad Consent Is Needed
For Future Research Uses
– Determined by the circumstances of the: (1) collection of
biospecimens and (2) secondary research use
– Recipient of biospecimens will need to identify and track whether
broad consent was needed and obtained for each batch of
biospecimens based on:
1. Collection of biospecimens:
– If biospecimens are initially collected for non-research purposes (and no
federally-funded research using the biospecimens is envisioned) –
Common Rule does not apply
– If biospecimens are initially collected for research purposes and
research is not federally-funded – Common Rule does not apply
– If biospecimens are initially collected for research purposes and the
research is federally-funded – Common Rule applies
– If biospecimens are initially collected as part of a non-FDA-regulated
“clinical trial” that itself is not federally-funded but conducted at a U.S.
institution that receives federal funding – Common Rule applies

45. ROPES & GRAY45
JURISDICTION:
Determining Whether Broad Consent Is Needed
For Future Research Uses
2. Secondary research use:
– If secondary research use of biospecimens is federally-
funded – Common Rule applies
– If secondary research use is not federally funded but
specimens were received from Common Rule-regulated
research – certain Common Rule provisions apply (data
security protections and IRB review)
– If secondary research use is not federally funded but is a
non-FDA-regulated “clinical trial” conducted at a U.S.
institution that receives federal funding – Common Rule
applies

46. ROPES & GRAY46
THE DAY AFTER

47. ROPES & GRAY47
Mercy University and Hospital
Mercy University has a massive tertiary care
hospital, staffed by SOM faculty and with a
large residency teaching program.
Mercy Hospital, a separately incorporated
entity fully owned by the University, is part of
a large health network of clinics and
community hospitals, that send patients to
Mercy and that use Mercy labs and facilities
for multiple specialized tests

48. ROPES & GRAY48
THE DAY AFTER …
IRB is part of the University.
Grants are received by the University,
through SOM.
SOM faculty are the PIs.
SOM provides the clinical research
coordinators and other research staff who
work inside and outside the Hospital and
associated network facilities.

49. ROPES & GRAY49
THE DAY AFTER …
• You are the Mercy Hospital CEO.
• What do you do on DAY ONE? How do
operations change?

50. ROPES & GRAY50
THE DAY AFTER …
• You must assure that general consents for
future use of biospecimens are obtained
• Otherwise, Mercy biospecimen collections
are useless for federal research funding
• Hire additional clerical staff for inpatient
and outpatient admitting, to secure
consents – this is cheapest option
• SOM research coordinators and IRB staff
train the clerical staff in obtaining general
consents

51. ROPES & GRAY51
THE DAY AFTER …
• Set time limits for admissions staff on each
informed consent, so that admissions is
not clogged by this new function
• Patients who refuse consent are
encouraged to go to “consent specialists”
who are hired for this purpose
• How much counseling/how many requests
are abusive?
• EMR captures who has consented and
who has not

52. ROPES & GRAY52
THE DAY AFTER …
• Patients whose biospecimens are received
from network facilities must be consented
there, because Mercy never sees them
• Ask network facilities to obtain consent;
they balk unless they are paid to do this
• Grants and training for additional
consent/admissions staff at network
facilities
• Anti-kickback law problems

53. ROPES & GRAY53
THE DAY AFTER …
• How to track general consents obtained
from network facilities?
• EMRs may not be interoperable
• Quality assurance to assure that consents
are appropriately obtained?
• Do you need to reconsent the same
patient when he/she shows up at Mercy as
a new patient, or can the network-obtained
consent cover all Mercy future collections
from that same patient?

54. ROPES & GRAY54
THE DAY AFTER …
• For Mercy patients and for network
patients, set up 10 year reminders
• At that time, each patient will be flagged
upon his/her appearance at Mercy or a
network facility, to be asked to re-consent

55. ROPES & GRAY55
THE DAY AFTER …
• Selection bias leads to identifiable patient
population groups not consenting in representative
numbers
• Researchers with unrepresentative biospecimens
who want to do research ask you for funds to
purchase supplemental samples from for-profit
firms or other hospitals
• Biospecimens collected from MSPH and Hospital
programs abroad have no general consent and so
cannot be used for federally funded research

56. ROPES & GRAY56
THE DAY AFTER …
• Because non-federally funded research can use
biospecimens lacking the general consent, shift
Hospital’s own research funds into this area
• Make master collaboration deals with industry so that
they receive de-identified biospecimens and can conduct
biospecimen research with SOM faculty: off-shoring this
research avoids these prohibitions
• Consider setting up spin-off corp solely owned by
Hospital or University and transfer all de-identified
biospecimens to it, to avoid these rules limiting
biospecimen research

57. ROPES & GRAY57
Research on Fetal Material
– The biospecimen storage, maintenance, and secondary research use
exemptions at §_.104(f) apply to Subpart B (research involving
neonates, fetuses, and fetal material)
– NPRM does not modify Subpart B
– Common Rule applies to research involving after delivery, the
placenta; the dead fetus; macerated fetal material; or cells, tissue, or
organs excised from a dead fetus, if information associated with the
material is recorded to allow for identification of living individuals
(45 CFR 46.206)
– Thus, applicability of the Common Rule to research involving fetal
material hinges on identifiability; whereas the NPRM would apply the
Common Rule to all biospecimens, irrespective of identifiability
– Seeming inconsistency, likely that more specific Subpart B provisions
would govern
57

58. ROPES & GRAY58
Single IRB Mandate for
Cooperative Research (§_.114)
• The NPRM would mandate that all institutions located in the United States
engaged in cooperative research covered by the Common Rule rely on a single
IRB as the reviewing IRB for that study
• Cooperative research subject to the Common Rule would include federally
funded “research” and “clinical trials,” as that term is defined in the NPRM, that
are conducted at a US institution that receives federal funding and are not
subject to FDA’s regulations
• The NPRM requirement would not apply to cooperative research for which more
than single IRB review is required by law (e.g., FDA-regulated device studies)
• The NPRM clarifies that this proposal would not relieve any site of its other
obligations under the regulations to protect human subjects
• Although a local IRB may conduct its own additional internal review, such a
review would not be binding on the local site if not adopted by the single IRB,
and its terms would not be enforced by OHRP

59. ROPES & GRAY59
A more attainable approach in lieu of
“general consent”
• Would rely on public education about the process and
value of these future research uses of data and
biospecimens
• Provide more rigorous IRB analysis of potential
individual and group harms from the waiver of informed
consent for research
• Include specific measures that would penalize, even
criminally, researchers and others who would attempt to
re-identify subjects through use of their personal data
and biospecimens.
• SACHRP prefers this targeted approach to these issues
over the approach suggested in the ANPRM, which, by
comparison, seems less targeted, less workable, and
less protective of subjects.

60. ROPES & GRAY60
IRB Waivers More Protective
• Mechanism of IRBs analyzing waiver applications for use
of banked biospecimens, which can result either in
waiver or in a direction to researchers to seek new,
specific informed consent for new studies, is more
reliable protection for subjects than acquiring from them
a general consent of unknown and unknowable breadth
• General consent for unlimited future uses does not give
persons real information that would constitute true
“informed consent”
• Industry may collect biospecimens in primary clinical
trials, and then use them for unlimited internal research;
this proposal, which will essentially remove IRB waivers
of consent,will advantage industry researchers over
academic researchers

61. ROPES & GRAY61
Logistical and Ethical Problems with
Obtaining and Tracking General Consent
• In daily clinical care, social services, drug treatment,
criminal justice, employment screenings, blood donation,
and school clinics, biospecimens are collected all the
time, but these settings are not oriented toward
consenting these persons to “unlimited future use”
• Would shift consent process from research staff to
clerical staff – not good for “informed consent”
• How to track these general consents over time, and
assure that there are accurate demographic matches
between consented persons and persons who are
sources of biospecimens to be used in research
• Prohibitive transaction costs for consenting and tracking

62. ROPES & GRAY62
Risks of Use of Data vs Biospecimens
The proposal would treat de-identification of biospecimens as
impossible because, it is conjectured, the source of any human tissue
can now be identified if a third party is able to obtain and analyze other
tissue from the same human, making all biospecimens inherently and
presumptively identifiable.
Yet this is true of data as well, in that a third party with ill-intent could
also seek to match de-identified data with data points derived from
other data sets, thus ascertaining the identity of the person from whom
the data were collected.
The issues and risks are largely the same, although, given the plethora
of publicly available data and the relative paucity of publicly available
biospecimens, it is more likely that harm to subjects could be done
through re-identification via data matches than through matches
of biospecimens.

63. ROPES & GRAY63
Equity and “FREE RIDERS”
[It is] contrary to the principles of
beneficence and justice as put forth in
the Belmont Report to advocate a state of
affairs in which persons may refuse use
of their own data and biospecimens, even
when risk to them is negligible, but who
nevertheless themselves benefit from
such research by depending upon the
beneficence of others.