Editorial

Ethical, Legal, and Policy Issues: Dominating theBiospecimen Discussion

Jimmie B. Vaught,1 Nicole Lockhart,1 Karen S. Thiel,2 and Julie A. Schneider1

1Office of Biorepositories and Biospecimen Research, National Cancer Institute, NIH, Department of Health andHuman Services, Bethesda, Maryland and 2Patton Boggs LLP, Washington, District of Columbia

With over 300 million human specimens currently storedin the United States, biospecimens are invaluable to thescientific research community. In addition to technicalconsiderations related to the physical quality of a bio-specimen, multiple ethical, legal, and policy issues alsoaffect the ability of researchers to use these resources.The National Cancer Institute (NCI) Best Practices forBiospecimen Resources was developed in response tothe results of an internal NCI study that found consider-able variability in the procedures and guidelines used forbiospecimen resource management across NCI facilities.The study also revealed that some of the primary sourcesof variability were divergent approaches to ethical, legal,and policy issues. The NCI Office of Biorepositoriesand Biospecimen Research was established in 2005 toaddress these issues, resulting in publication of the First-Generation Guidelines for NCI-Supported Bioreposito-ries in April 2006. Following a public comment period,the document was revised and renamed the NCI BestPractices for Biospecimen Resources (NCI Best Practices)and is available on the NCI Office of Biorepositoriesand Biospecimen Research Web site (1). This editorialdescribes some of the key ethical, legal, and policy issuesrelated to the use of biospecimens in research. Althoughthe NCI Best Practices attempts to address some of theseissues, many remain unresolved and will require fur-ther discussion among stakeholders within the biospe-cimen research community. The Office of Biorepositoriesand Biospecimen Research has been engaged in suchdiscussions through its involvement in an AACR paneldiscussion at the 2007 annual meeting and more recentlythrough sponsorship of a workshop on biospecimencustodianship.

Biospecimens in the News

In the past year and a half, ethical issues related tobiospecimens have produced headlines in the New YorkTimes on three separate occasions (2-4). The topics ofthese stories have ranged from chronicling the status of‘‘ownership’’ of biospecimens over the last 20 years (2) to

outrage from indigenous peoples who feel their bloodsamples were not properly consented and were usedinappropriately (3). The case of Catalona v. WashingtonUniversity , relating to biospecimen ownership, wascovered in the scientific and popular press (5). In March2006, a Missouri judge ruled in favor of WashingtonUniversity, stating that the institution rather than theresearcher or the patient owned the biological samplesunder dispute, which had been contributed for researchpurposes. This decision was subsequently upheld onappeal. In a separate case, an Arizona Native Americangroup that had donated biospecimens for diabetesresearch raised concerns that the biospecimens also werebeing used for other unspecified uses, such as schizo-phrenia research (6). And there were objections to aNational Geographic Society project in which DNAmarkers collected from Native Americans were to beused to study human migration patterns (4).

These court cases and recent interest in the popularpress underscore the importance of developing newpolicies and standard practices in biospecimen-basedresearch, particularly with respect to ethical and legalareas. Five major topic areas are addressed in the NCIEthical, Legal, and Policy Best Practices: (a) principles forresponsible custodianship, (b) informed consent, (c) pri-vacy protection, (d) access to biospecimens and dataand, (e) intellectual property and resource sharing. Thepublic comments received by NCI and the media reportsand court decisions outlined above show that there areseveral unresolved issues that are not addressed in thecurrent NCI Best Practices or other guidance documents.

Custodianship and Ownership Issues

From a legal standpoint, few cases or studies directlyaddress the ownership or custodianship of biospecimens(7), and there are no laws or regulations that directlyaddress these issues. Although regulatory guidance andbest practices exist, they do not have the force of law and,therefore, are not used as the basis for court rulings.Current judicial precedent is to settle such cases usingcommon law property theories or the elements of a dona-tion under a state’s gift law. This precedent was setnearly 20 years ago in the landmark Moore v. Regents ofthe University of California case (8) in which the Californiacourts determined that the plaintiff’s specimen donationwas a ‘‘gift’’ to the institution, and therefore, he couldnot lay any claim to the financial benefit derived fromresearch using his biospecimen. This is, of course, prob-lematic as human specimens may not clearly fall under

Cancer Epidemiol Biomarkers Prev 2007;16(12). December 2007

Cancer Epidemiol Biomarkers Prev 2007;16(12):2521 – 3

Received 11/1/07; accepted 11/1/07.

Requests for reprints: Jimmie B. Vaught, Office of Biorepositories and BiospecimenResearch, National Cancer Institute, Building 31, MSC 2580, Bethesda, MD.Phone: 301-451-7314; Fax: 301-402-3256. E-mail: vaughtj@mail.nih.gov

Copyright D 2007 American Association for Cancer Research.

doi:10.1158/1055-9965.EPI-07-2758

2521

on April 22, 2018. © 2007 American Association for Cancer Research.cebp.aacrjournals.org Downloaded from

the same category as other gifts. Nevertheless, courtscontinue to rely on this precedent for rulings today.Specific issues relevant to biospecimen donation thathave not been addressed by common law include thefollowing: What conditions are appropriate to place onthe contribution of biospecimens to research, for exam-ple, does gift law allow a gift with conditions? How doesthe decision of a research participant to discontinue theirparticipation in the study, often offered in informed con-sent forms, affect the status of the gift? What if it is thepractice of an ethnic or cultural group to have their speci-mens returned? What if a patient needs their specimenback for a purpose that may be beneficial to their healthor the health of their family?

In addition to these legal issues, patients arebecoming increasingly aware of the importance of theirbiospecimens to research, and some patients andadvocacy groups have developed biobanks to supportresearch into their disease of interest (9, 10). However,there currently are no formal systems in place forinteracting with patients about biospecimen research,and misinformation abounds. For instance, patients maybelieve that their biospecimens are freely shared withinthe research community when this is not always thecase. Based on informal discussions with patientgroups, advocates are particularly concerned aboutprivacy issues (11), biospecimen sharing, the use ofbiospecimens for commercial purposes, and the returnof research results.

Future and Secondary Uses of Biospecimens

Do investigators have an ethical obligation to patientsbeyond the time at which they donate their biospecimens(12), even though the courts have decided that thepatient relinquishes their rights to the biospecimens oncethey are donated (5, 8)? Studies suggest that patients arewilling to contribute their biospecimens to research aslong as the specimens are used appropriately and newinformation is being gathered from investigations (13).Investigators often collect and store biospecimens forfuture use awaiting the development of new techniquesor for further investigation of interesting findings. Manywould say that investigators have an obligation toinform patients if studies using their biospecimens aredependent on funding and their biospecimens are beingstored for potential future research.

Because some patients may object to their specimensbeing stored indefinitely for unknown future research,informed consent may be needed for both a particularuse as well as for banking of the biospecimens for futureresearch. There is also the question of whether specimensshould be shared with, for example, pharmaceuticalcompanies for unspecified research. Some institutionshave chosen to make the distinction that future unspec-ified use by profit-making institutions would not be inthe best interests of the patient or the biospecimenresource. However, preventing patients from enrolling ina clinical trial because they have not consented to future,unspecified use of their biospecimens could be consid-ered coercion. Given the distinction between obtainingbiospecimens for a research study and saving materialfor future, unspecified use, separate Institutional ReviewBoard approval may be required. Research groups are

struggling to develop an acceptable informed consentdocument that covers broader aspects of disease andresearch. One option is for the patient to give line-itemconsent that allows access to their biospecimens forparticular diseases. Surveys have found that a largeproportion of patients surveyed would agree to havingtheir biospecimens stored for future studies of unspec-ified medical conditions (13). The tension remainsbetween being transparent with patients and preservingbiospecimens for future unspecified research purposes.

The Informed Consent section in the NCI BestPractices includes a recommendation to consider tieredconsent to allow participants to give permission forcertain uses of specimens and not others. However, theBest Practices document also states that allowing suchoptions requires the ability to track the specific researchconsented to by each patient. Another consideration fortiered consent is that researchers also must adhere to therequirements of states’ genetic privacy statutes, whichmay require specific procedures that go beyond thoseused in obtaining informed consent for other types ofbiospecimen research. The National Conference of StateLegislatures Web site (14) has compiled each state’sprivacy laws.

Consenting patients for future use of biospecimens isfurther complicated by the discrepancies betweenrelevant federal regulations. Although 45 CFR 46Subpart A (the Common Rule) allows consent of patientsto future unspecified research, the Health InsurancePortability and Accountability Act Privacy Rule requiresthat each authorization by the patient for release ofprotected health information includes a specific researchpurpose. In addition, under the Health InsurancePortability and Accountability Act Privacy Rule, thecreation of a biospecimen resource or database withprotected health information and subsequent disclosuresfor research purposes are considered separate activities.Each activity requires authorization from the researchparticipant unless a waiver or alteration of authorizationis obtained from a Privacy Board or Institutional ReviewBoard. Because support of future research is a majorpurpose of biospecimen resources, this lack of harmonyamong federal regulations has had a significant effect on,and created a great deal of confusion within, thebiospecimen community. Some experts have evenargued that many of the Privacy Rule provisions provideadditional burdens on researchers that do not necessarilytranslate into greater protection of privacy for researchparticipants (15, 16).

Cultural Issues Relevant to Informed Consent

Aside from the NCI Best Practices, there are severalother guidance documents that have been published(17). The documents have different goals andapproaches to ethical, legal, and policy issues thatmay create confusion in the research community aswell as among different populations of study partic-ipants. Several issues, as noted among the list of high-profile news accounts, relate to the disposition oftissues from Native American populations. A 2005study (18) addressed issues related to Native Ameri-cans and biospecimens. Native Americans have beenmade aware of the Moore case and generally disagree

Biospecimen Ethical, Legal, and Policy Issues

Cancer Epidemiol Biomarkers Prev 2007;16(12). December 2007

2522

on April 22, 2018. © 2007 American Association for Cancer Research.cebp.aacrjournals.org Downloaded from

with the California court’s conclusion that donatedtissues no longer belong to the study participant. Thisview is supported by the recent 8th Circuit opinion inthe appeal of the Catalona case (19), which rests on arigorous examination of the informed consent form andsupporting documentation to determine the donor’sintent at the time the gift was made. Investigators whoplan to work with Native American populations tocollect specimens for research need to be aware ofbeliefs and practices and to develop a relationship oftrust with potential study participants. Study partic-ipants may want their unused specimens returned forburial or other religious ceremonies, and the informedconsent must make clear whether this will be possible.State and federal biosafety regulations must also beconsidered when determining whether specimens maybe returned to the participant. Native populations maybe unwilling to consent to future unspecified researchfor fear that research may be done that would stigmatizetheir community. Recent perceived abuses, in whichspecimens from native populations were used withoutspecific consent, have only heightened this fear. Inaddition, native populations are sensitive to the use oftheir specimens for the development of treatments bycommercial entities. The perception is that such treat-ments are often too expensive and less available to nativepopulations.

Next Steps

The purpose of the Ethical, Legal, and Policy section ofthe NCI Best Practices was to clarify how key regulationspertain to biospecimens and to suggest additional bestpractices for consideration that may go beyond expect-ations of existing regulations. The NCI’s experience indeveloping and modifying the Best Practices shows that,although there are concerns in the research communityabout adoption of biospecimen technical and operationalstandards, the ethical, legal, and policy issues requireconsiderably more discussion. Several domestic andinternational efforts are under way to address informedconsent, privacy, ownership, and access issues withrespect to biospecimen collection and use. However, stateand local laws, differences in local Institutional ReviewBoard approaches, and cultural practices can varysignificantly. All of these factors must be taken intoaccount in designing and implementing research studiesinvolving biospecimens. The NCI is currently engaged in

efforts to bring together diverse groups in a series ofworkshops and public forums. In concert with othersimilar efforts, it is hoped that a series of new recom-mendations will emerge.

References1. NCI Office of Biorepositories and Biospecimen Research [homepage

on the Internet]. Bethesda (MD): National Cancer Institute, NIH,Department of Health and Human Services; 2007 [cited 2007 Oct 12].Available from: http://biospecimens.cancer.gov.

2. Skloot R. Taking the least of you. The New York Times, 2006 Apr 12;Sect 6 (The New York Times Magazine): 38.

3. Rohter L. In the Amazon, giving blood but getting nothing. The NewYork Times, 2007 June 20. Available from: http://www.nytimes.com/2007/06/20/world/americas/20blood.html?n=Top/Reference/Times%20Topics/People/R/Rohter,%20Larry.

4. Harmon A. DNA gatherers hit a snag: the tribes don’t trust them. TheNew York Times 2006;1(col. 1).

5. Kaiser J. Court decides tissue samples belong to university, notpatients. Science 2006;312:346.

6. Dalton R. When two tribes go to war. Nature 2004;430:500 – 2.7. Hakimian R, Korn D. Ownership and use of tissue specimens for

research. JAMA 2004;292:2500 – 5.8. Barnes M, Heffernan KG. The ‘future uses’ dilemma: secondary uses

of data and materials by researchers and commercial researchsponsors. Med Res Law Policy Rep 2004;3:1 – 11.

9. Multiple myeloma research consortium [cited 2007 Oct 18]. Availablefrom: http://www.themmrc.org/.

10. Genetic Alliance BioBank [cited 2007 Oct 18]. Available from: http://www.biobank.org/english/.

11. McGuire AL, Gibbs RA. No longer de-identified. Science 2006;312:370 – 1.

12. Knoppers BM, Joly Y, Simard J, Durocher F. The emergence of anethical duty to disclose genetic research results: internationalperspectives. Eur J Hum Genet 2006;14:1170 – 8.

13. Report of the Public Responsibility in Medicine and Research(PRIM&R) Human Tissue/Specimen Banking Working Group [cited2007 Oct 15]. Available from: http://www.primr.org/AboutUs.aspx?id=208&terms=Human+Tissue%2fSpecimen+Banking+Working+Group.

14. The National Conference of State Legislatures [cited 2007 Oct 15].Available from: http://www.ncsl.org/.

15. Bankhead C. Privacy regulations have mixed impact on cancerresearch community. J Natl Cancer Inst 2004;96:1738 – 40.

16. Nosowsky R, Giordano T. The HIPAA privacy rule: implications forclinical research. Annu Rev Med 2006;57:575 – 90.

17. Common minimum technical standards and protocols for biologicalresource centres dedicated to cancer research [cited 2007 Oct 15].Available from: http://www.iarc.fr/IARCPress/pdfs/standardsBRC/index.php.

18. Burhansstipanov L, Bemis L, Kaur JS, Bemis G. Sample genetic policylanguage for research conducted with native communities. J CancerEduc 2005;20:52 – 7.

19. United States Court of Appeals for the Eighth Circuit. No. 06-2286.Washington University, Appellee v. William J. Catalona, Appellee[cited 2007 Oct 22]. Available from: http://www.ca8.uscourts.gov/opndir/07/06/062286P.pdf.

Cancer Epidemiology, Biomarkers & Prevention

Cancer Epidemiol Biomarkers Prev 2007;16(12). December 2007

2523

on April 22, 2018. © 2007 American Association for Cancer Research.cebp.aacrjournals.org Downloaded from

2007;16:2521-2523. Cancer Epidemiol Biomarkers Prev   Jimmie B. Vaught, Nicole Lockhart, Karen S. Thiel, et al.   Biospecimen DiscussionEthical, Legal, and Policy Issues: Dominating the

  Updated version

  http://cebp.aacrjournals.org/content/16/12/2521

Access the most recent version of this article at:

   

   

  Cited articles

  http://cebp.aacrjournals.org/content/16/12/2521.full#ref-list-1

This article cites 9 articles, 2 of which you can access for free at:

  Citing articles

  http://cebp.aacrjournals.org/content/16/12/2521.full#related-urls

This article has been cited by 3 HighWire-hosted articles. Access the articles at:

   

  E-mail alerts related to this article or journal.Sign up to receive free email-alerts

  Subscriptions

Reprints and

  .pubs@aacr.orgDepartment at

To order reprints of this article or to subscribe to the journal, contact the AACR Publications

  Permissions

  Rightslink site. (CCC)Click on "Request Permissions" which will take you to the Copyright Clearance Center's

.http://cebp.aacrjournals.org/content/16/12/2521To request permission to re-use all or part of this article, use this link

on April 22, 2018. © 2007 American Association for Cancer Research.cebp.aacrjournals.org Downloaded from