Ethical Considerations for Data Use with Children

1. Ethical Considerations for Data Use with Children Kelly Edwards, PhD University of Washington

2. Talk Overview • Recent public debates about research • Where is the disconnect in expectations? • Trustworthy research practices • How can we create responsible infrastructure? • What are groups doing nationally? • Pediatric specific issues • How should we address consent, results return, data sharing, in a pediatric environment?

3. Cells taken without her permission Researchers everywhere have profited from this Her family does not even have access to healthcare Public Narrative on Research

4. Discarded Newborn Bloodspots • “The Government has Your Baby’s DNA” • Parents’ lawsuit led to destruction of 5+million samples • What can we learn from this? • Engage the public • Be transparent • Ask!

5. Public Communication Challenges • “If you go to a hospital and you don’t speak English, you’re going to get a translator. If you go to the hospital and you don’t speak science, you’re not, and in a way, that’s what people need.” • Rebecca Skloot, Interview for Amy Harmon’s NYT article “Where’d You Go with My DNA?” (4/25/10)

6. How do we make good on our public promise? “[To] advance significantly the Nation's capacity to protect and improve health,…[to] ensure a continued high return on the public investment in research, …[to] exemplify and promote the highest level of scientific integrity, public accountability, and social responsibility in the conduct of science.” http://www.nih.gov/about/index.html#mission NIH Mission

7. Argument • Thesis: Trustworthy practices in research are going to be critical to long-term success • Problem: Old practice paradigms may no longer preserve public trust • Upfront regulatory review • Heavy burden on consent procedures • Focus on individual privacy and identifiability • Proposed Solution: Transformed data management and research practices are needed

8. Argument • Usual research practices can (without intention) lead to harm for communities, including: • Samples shared widely beyond investigator group with whom relationship/trust established • HIPAA identifiers as focus for privacy protection • Focus on scientific literature for dissemination • Research reports often focus on describing the problem, or use “deficit model” language • Promise of benefits do not get back to participants • Goering et al. 2008

9. The New Research Ethics Reality Preparing for the Next Generation of Biorepository Research DNA MARKERS • ABSTRACT • Early biorepository research, which we will refer to as “first-generation” (1st-gen) biorepository research, typically involved local, small-scale research at single institutions. However, technological advances in bioinformatics, combined with increasing recognition in the biomedical research community of the benefits of research using large sample cohorts, have highlighted the desirability of data sharing among institutions. Discovering and sharing specimens and data across biorepositories, what we will refer to here as “second-generation” (2nd-gen) biorepository research, has thus become a national goal We argue that the era of first-generation biorepository research is nearing its end and the research community needs to prepare itself for this new reality. • CONFIDENTIALITY & DE-IDENTIFICATION • Confidentiality is a central issue in ethical analyses related to biorepositories, and is best achieved through de-identification of donor specimens and data • From a 1st-gen biorepository standpoint, sample de-identification allows future research on previously collected samples to be exempt from IRB review • But in 2nd-gen biorepositories, advances in genomics have enabled the possibility of re-identification • Identifiable samples are more useful anyway, and donors retain control over their use if identity is retained • 2nd-gen biorepositories will retain sample identifiers • IRB REVIEW • By de-identifying samples and claiming they were not human subjects, 1st-gen biorepository research was exempt from IRB review • Maintaining identity in 2nd-gen biorepositories will make IRB approval of research necessary • In order to legitimize the sharing of identifiable data across institutions, the process of review must be harmonized across institutions. This may be accomplished by requiring: • All investigators to obtain IRB approval at own institution: ensures community-specific challenges required for approval are met • Collaborating investigators to harmonize inter-institutional IRB needs: evaluates specific secondary use requirements distinct from initial purpose of sample collection • Collaborating investigators to sign a confidentiality agreemnent: establishes expectations of management of the research process • All investigators to sign a materials transfer agreement: defines the specimen rights of the provider and the recipient • CONSENT • Because 2nd-gen biorepositories will retain sample identifiers, initial informed consent documents will need to be more specific; 3 types: • Specific or narrow consent to research related to a specific condition, prohibited biospecimen use in other studies • Blanket consent to research, unspecified range of conditions • Consent with several options for research use, all pre-specified • For all prospective studies that informed consent was not given, investigators will have to re-contact and re-consent • Re-consent is a laborious proposition; investigators and institutions will need to think about responsibilities • EVOLVING MODELS OF STEWARDSHIP • We need to start thinking about different models that go beyond oversight of biorepositories, and are moving toward stewardship • When data sharing and access crosses institutional or even international borders, challenges for governance abound when setting research priorities • Possible models for biorepository stewardship: • BR Jeffers: The steward of the resources assumes responsibility for the donor’s intent, the manner in which the resources are used, and the outcomes that will result from their use • J Kaye and SMC Gibbons: Combination of formal regulatory bodies such as IRBs as research gatekeepers and government bodies that pass legislation, plus informal bodies such as professional organizations and funding bodies, working in tandem • OTHER EXAMPLES??? • POSSIBLE INFORMATICS CHALLENGES • Nick, I leave this to you… • POSSIBLE INFORMATICS SOLUTIONS • Same as above… • DISCUSSION • In 2nd-gen biorepositories, data sharing is desirable among researchers and donors should want to retain the identity • The bioinformatics community can address these matters by _______. • It will take interdisciplinary input to develop pragmatic responses to issues such as: • The ethical implications of de-identification vs. maintaining identifiers • How ethical and regulatory considerations are weighed against related scientific and technical concerns • The form of research governance required to ensure responsible use of widely shared clinical data • The role community consultation should play in the development of governance mechanisms • WORKS CITED 1st Generation Biobanks 2nd Generation Biobanks HUMAN SUBJECTS Anonymized or De-identified Samples Identifiable Human Subjects FUTURE RESEARCH No IRB Review IRB Review DATA SHARING Blanket Consent Re-contact, Re-consent HIPAA Laws Stewardship Fullerton, Anderson, Fryer-Edwards 2010

10. Ethics Issues and Questions • Consent: • What information management systems will best enhance or extend traditional consent mechanisms? • Communications: • In what ways might technical systems enhance on-going engagement with participants and/or the public? • Auditability: • What are the benefits and risks of rich audit trails and data use tracking systems? How should we respond to errors or lapses? • Governance: • How do we incorporate, and track, participant preferences into research governance decision-making? • Sustainability: • What are the best ways to engage the public about the open-ended nature of translational research?

11. Transforming Research Ethics Rethinking our core principles: • Respect for Persons: • Is consent or anonymization really the only way to demonstrate “respect”? Is it all about control? • Beneficence: • What are the benefits of biobanking, according to whom? • Justice: • Who will benefit, at who’s expense?

12. Key Issues in Governance • Engaging the Public • Realistic assessment of benefits and risks • Expect a continued diversity of preferences • Rethinking the Regulations • Strive for excellence within system (consent is an opportunity for relationship-building) • Consider benefits of identifiability • Accountability and Stewardship • Must have real recourse when things go awry • Must have audit trails and oversight Dynamic systems need dynamic governance. February 5, 2010 Seattle

13. Pediatric Biobanks: Consent • Do you need to re-consent at 18? • Informal poll of 14-17 year-olds: YES! • Telephone interviews were conducted with 1186 patients from 5 academic medical centers by using a hypothetical scenario about future use of data. • 67% would not be concerned about use • 46% believed their consent should be obtained • Of these, 75% would be at least moderately willing to give consent, when asked. • Of the 1186 respondents, 26% would not want researchers to use their sample/data when they could not be located. • Goldenberg et.al. 2009

14. Pediatric Biobanks: Data Sharing • Proposal: Do not share data until children become adults and can give consent • Pros: Protects genetic identity • Cons: Slows research, ties up investment • How can we think creatively about solutions that promote ethical and effective research? • Gurwitz et.al.2009; Levenson 2010

15. Lessons in Leadership from Health Care Reform in Bimodal House • You might not be able to achieve consensus • You might not be able to accommodate everyone’s preferences and values • You sometimes just need to make a policy decision that will based on core values, best evidence, and best available options. • Your solution for today may not be your solution tomorrow.

16. Transformed Research Practices • Develop review, oversight, and accountability processes (long term investments) • Cultivate ethical and effective research collaborations (in and out of the research institutions) • Configure processes for transparency and traceability (set up communication channels) • Take seriously the need to aim research toward community benefit (and think creatively about benefits) • Consider interdisciplinary team configurations to meet short-term needs, or other processes that would build capacity (consider benefits from participant perspective) • Caulfield et al. 2008; Goering et al. 2008

17. Select References • Fullerton, SM, Anderson, NR, Guzauskas, G, Freeman, D, & Fryer-Edwards K. Meeting the governance challenges of next generation biorepository research. Science Translational Medicine, 2, 15cm3, 2010. • Yarborough M, Fryer-Edwards K, Geller G, Sharp R. Transforming the Culture of Biomedical Research from Compliance to Trustworthiness: Insights from Non-Medical Sectors. Acad Medicine. 2009 Apr;84(4):472-7. • Goering S, Holland S, Fryer-Edwards K. Transforming genetic research practices with marginalized communities: a case for responsive justice. Hastings Center Report. 2008 Mar-Apr; 38(2):43-53. • Fryer-Edwards K, Fullerton SM. Relationships with test-tubes: where's the reciprocity? Am J Bioeth. 2006 Nov-Dec;6(6):36-8. • Gurwitz D, Fortier I, Lunshof JE, Knoppers BM. Research ethics. Children and population biobanks. Science. 2009 Aug 14;325(5942):818-9. • Goldenberg AJ, Hull SC, Botkin JR, Wilfond BS. Pediatric biobanks: approaching informed consent for continuing research after children grow up. J Pediatr. 2009 Oct;155(4):578-83.

18. Acknowledgments • Institute for Translational Health Sciences (NCRR) • Nick Anderson, Malia Fullerton, Holly Tabor, Ben Wilfond • Center for Genomics & Healthcare Equality (NHGRI) • Wylie Burke, Helene Starks, Rose James (UW) • Bert Boyer & Scarlett Hopkins (University of Alaska, Fairbanks) • Janice Brendible and Adib Jamshedi (NWIC and Lummi Ventures) • Testing Justice Project (Greenwall Foundation) • Sara Goering and Suzanne Holland • TIES Project (UCD and Office of Research Integrity) • Gail Geller (Hopkins), Rich Sharp (Cleveland), Mark Yarborough (Colorado), and several community health leaders