From the event "Specimen Science: Ethics and Policy Implications," held at Harvard Law School on November 16, 2015. This event was a collaboration between The Center for Child Health and Policy at Case Western Reserve University and University Hospitals Rainbow Babies & Children’s Hospital; the Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics at Harvard Law School; the Multi-Regional Clinical Trials Center of Harvard and Brigham and Women's Hospital; and Harvard Catalyst | The Harvard Clinical and Translational Science Center. It was supported by funding from the National Human Genome Research Institute and the Oswald DeN. Cammann Fund at Harvard University. For more information, visit our website at http://petrieflom.law.harvard.edu/events/details/specimen-science-ethics-and-policy

1. November 16, 2015
SuzanneM.Rivera,Ph.D.,M.S.W.,AssistantProfessorofBioethics
HeideAungst,M.A.,ResearchAssociate&Narrative Medical Writer
Biospecimens: What We Know about What
Donors Think and Other Considerations that
May Sometimes Matter More

2. Specimens Are Important
• At least 300 million stored samples in the US
• Need even more to answer important
questions that affect human health
• Most valuable when connected to clinical data

3. Why Donors Give #1: Altruism
“It’s my obligation”
“To benefit future patients”
“Advancing science”
“Gift to society”

4. Why Donors Give #2: Self-interest
Personal health information through return of results
A long-term contribution to science that benefits
themselves, a relative, a particular disease, or a
population/country
Perception that treatment will be improved by (or in
exchange for) donation

5. Why Donors Give #3: Trust
“Trust of key actors”
Confidence that specimens will be used appropriately,
as well as that any personal genetic information will be
kept confidential
“Consequences for researchers who violate” an
agreement about how the specimen would be used

6. Barriers to Donation
• Study of “stigmatizing” diseases
• Results not actionable
• Specimen type
• Religious or cultural objections (or the perception of)
• Mistrust/fear of exploitation
• Lack of knowledge/understanding about safeguards
• Level of educational attainment
• Science fiction (cloning, satanic rituals, monitoring by
government though DNA)

7. What Donors Want
• Information– as specific as possible
• Protection of personal information
• Results (individual or study-level)
• Ability to specify future uses/disposition
• Re-consent for new uses
• Re-consent at 18 for minor donors
• Option to withdraw at any point

8. Why That’s Hard to Do
• We cannot know or predict all potential future uses; it’s not
possible to say today every way a specimen could be useful in
the future.
• The more specific our promises about how to handle, store,
share, dispose, the greater likelihood we will inadvertently fail
to honor donor choices.
• Donors move, die, change providers. Re-contactingover time
is notoriously difficult.

9. Should We Try?
• If we can’t follow-through on our commitments, do
we make it worse by suggesting we can?
• The promise of precision medicine requires huge
numbers of specimens and records to be shared.
This makes it even harder to comply.
• Research exceptionalism is bad for science.

10. NPRM: Proposed Changes
• Redefines “human subject” to include even “non-identified”
biospecimens
• Introduces concept of ‘‘broad’’consent form*, through which a
person could consent to storage and eventual future unspecified
research uses
• Waivers of consent for research involving biospecimens (regardless
of identifiability) to occur only in very rare circumstances
* “broad” consent form template to be promulgated by the Secretary of HHS

11. Ethical Considerations
#1 Lack of Consensus
A majority of the ANPRM commenters (including patient advocacy orgs)
opposed the ANPRM’s suggested requirement of consent for research
use of all biospecimens, regardless of identifiability.
Some commenters cited lack of convincing evidence of harm caused by
research use of non-identified clinical biospecimens without consent.
Yet, most of the comments from individual members of the public strongly
supported consent requirements for use of their biospecimens, regardless
of identifiability.
.

12. Ethical Considerations
#2 Autonomy vs. Beneficence & Justice
Requiring consent for the re-use of existing de-identified specimens gives
greater weight to the principle of autonomy than to the principles of
beneficence and justice:
-limits risks to a few but distributes benefits of science to all;
-may result in lower participation rates in research by underserved
members of society;
-may delay important advances in human health.

13. Ethical Considerations
#3 Dimensions of Nonmaleficence
While obtaining consent prior to re-use of existing specimens may be
seen as preventing a theoretical dignitary harm, to the extent consent
cannot be obtained, the destruction of existing specimens may require
new/more people to provide specimens to answer important questions
(thereby exposing them to unnecessary risks, and exposing all of us to
unnecessary delays).
Given conditions of scarce resources, the expense of collecting new
specimens also should be considered.

14. Conclusions
• Specimens are valuable and their use advances
human health.
• It’s hard to do what donors want.
• We need to honor beneficence and justice, not just
autonomy.
• It’s time for a different ethos: opt-out rather than opt-in.