This document summarizes the complex issues around regulating biospecimen research under the revised Common Rule. It notes that while the final rule did not require consent for research using unidentified biospecimens as the proposed rule had, the definition of "identifiable" is still weak and leaves much unclear. It discusses the public comments opposing the proposed rule's expansion and the agencies' decision to not adopt that proposal. Going forward, the agencies will reexamine what is considered identifiable and potentially issue guidance on new technologies like whole genome sequencing. The pathways for conducting research with specimens and data under the revised rule are outlined.

1. Common
Rule
HHS
Defense
NSF
Education
Agriculture
EPA
DOE
NASA
Commerce
USAID
DOJ
CIA
DHS
SSA
DOT
VA HUD
CPSC
(Still) Waiting to Exhale:
Why the Future of Biospecimens Research
Remains Unclear after the Final Rule
Michelle N. Meyer, PhD JD
Assistant Professor
Associate Director, Research Ethics
Center for Translational Bioethics
& Health Care Policy

2. Applicability of
2016 Common Rule
Identifiable Non-identifiable
BiospecimeData
Identifiable Non-identifiable
BiospecimensData
?!
• For secondary research, a lot hinges
on identifiability
• Weak definition of “identifiable”:
readily ascertainable (re-ID concerns)
• Separate autonomy concerns
Applicability of
NPRM
• Broad consent for all biospecimens
• Alternative A: WGS/WES data
• Alternative B: “Bio-unique” data

3. Public Comments: COGR Analysis

4. 0
20
40
60
80
100
120
Pre-Skloot
(N=121 over
16 wks)
Post-Skloot
(N=570 in 10
days)
Category 3 Category 4
Chart Title
Pro Con Series 3
Non-Patient General Public Comments
“Based on the timing and content
of the submissions, support
appears to have been largely in
response to the opinion piece by
Rebecca Skloot.” —COGR

5. Public Comments: COGR Analysis
0% 20% 40% 60% 80% 100% 120%
Public (N=692)
Researchers (N=276)
Patients (N=230)
Unis/Med Centers/IRBs (N=145)
Prof Assoc (N=58)
Advocacy Grps (N=44)
Industry (N=27)
Health Depts (N=14)
Biorepositories (N=12)
Tribal Nations (N=10)
Advisory Grps (N=5)
Indep IRBs (N=3)
Opposition
30%
48%
55%

6. “Most notably, the new rule does not adopt the proposal to cover researchers’ use of
unidentified biospecimens…and to require informed consent for such research. This
proposal generated far more comments than any other, and by a substantial margin those
comments opposed the proposal. Commenters in every category — institutions,
researchers, people working in programs that protect research participants, and people
with no employment connection to the research world — expressed concern that
implementing this proposal could significantly harm the ability to do important research,
without producing any substantial off-setting benefits. The public response was
particularly noteworthy, given that the premise behind the proposal was specifically tied
to public sentiment: the NPRM had stated that continuing to allow research on
unidentified biospecimens without consent would place ‘the publicly-funded research
establishment in an increasingly untenable position because it is not consistent with the
majority of the public’s wishes.’ That premise now seems questionable.”

7. Applicability of
2018 Common Rule
Identifiable Non-identifiable
BiospecimeData
Agencies, in consultation
w/experts, shall w/in 1
year & at least every 4
years thereafter…
If permitted by
law, agencies
may alter
interpretation of
“identifiable,”
including
through
guidance
1) Reexamine
meaning of
“identifiable”
2) Assess if
technologies/techniques
(e.g., WGS) create per se
identifiable data
Any such tech
placed on list
published in Fed
Reg for public
notice & comment
“recommendations
might accordingly be
made” to require
consent

8. Some Reasons Why Agencies Issues
Guidance Instead of Rules
(All of Which Could Be at Play Here)
• Need to fulfill policy mandate within time
constraint (e.g., DHS post 9/11, TSA, DOE & No
Child Left Behind)
• Avoidance of Executive control via OIRA (e.g., FDA)
• Technical/fast-moving changes not amenable to
rulemaking process

9. NPRM Final Rule
Net cost of proposed rule:
$10b
• Biospecimens cost: $19.67b
• Among rules House
Freedom Caucus sought to
overturn in Trump’s first
100 days
Net savings of final rule: $1b
• Biospecimens: $0
OIRA review: >6 months OIRA review: 12 days
• Jan. 4: submitted
• Jan. 16: approved
• Jan. 18: public inspection
• Jan. 19: published Fed Reg
• Jan. 20: Trump inaugurated

10. Would Forcing the NPRM via
Guidance Survive Judicial Review?
Potentially relevant factors that generally weigh against:
• Has practical effect of imposing a standard (e.g., regulated
entities believe compliance necessary to avoid adverse
determination)
• Agencies base enforcement on guidance (may be ok if notice &
prospective application only, see U.S. v. Chrysler Corp., 158 F.3d 1350 (D.C. Cir.
1998))
• Guidance-based norm can’t be discerned from reg (e.g., chemical
components reduced to level protective of human health –> 4 ppm; see
General Electric Co. v. EPA, 290 F.3d 377, 382-85 (D.C. Cir. 2002))
• Guidance significantly increases cost of compliance
• Guidance reverses course on policy on which regulated entities
had relied
• Agency proposed but didn’t finalize policy now issued through
guidance (Appalachian Power Co. v. EPA, 208 F.3d 1015, 1022-23 (D.C. Cir. 2000))

11. And Keep In Mind…
Long understanding, reaffirmed in 2009 Orszag
Memorandum, that OIRA may review “significant”
free-standing guidance documents even if they
would be exempt from public notice and comment
under the APA)
See Guidance for Regulatory Review, Memorandum from Peter R. Orszag to the
Heads and Acting Heads of Executive Departments and Agencies (Mar. 4, 2009)

12. The
Future of
“Identifiability”
???

13. 2018 Common Rule: Regulatory Pathways for
Conducting Research w/Specimens or Data
Study-
specific
consent
Limited IRB review &
broad consent
If research doesn’t meet no-
consent exemption criteria (—>),
this is an alternative to stripping
identifiers
No consent required
• Publicly available
• Data recorded so can’t readily ascertain ID,
no reID, no recontact
• HIPAA-regulated research, OR
• Federally-conducted research
Newly collected
for a study
Previously collected for another study or
for non-research (secondary research)
IRB
review/consent
Identified or
identifiable
Nonidentifiable
No human
subjects (no IRB
review/consent)
IRB review
Meet exemption
criteria
Waived
consent

14. May-June 2017