1. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Banking Biological Samples for Pediatric Research Jeffrey R. Botkin, M.D., M.P.H. Professor of Pediatrics and Medical Ethics Associate Vice President for Research University of Utah Jeffrey R. Botkin, M.D., M.P.H. Professor of Pediatrics and Medical Ethics Associate Vice President for Research University of Utah

2. Treuman Katz Center for Pediatric Bioethics - 2008 Conference 2 Stored Human Tissues “The most serious and intractable issues in health law and ethics today are raised by the collection, storage, and future use of tissue samples. Imagine the vast amount of personal information contained in stored tissue samples …” Professor Lawrence O. Gostin, Georgetown University “The most serious and intractable issues in health law and ethics today are raised by the collection, storage, and future use of tissue samples. Imagine the vast amount of personal information contained in stored tissue samples …” Professor Lawrence O. Gostin, Georgetown University

3. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Tissue Banking Increasingly common element of clinical research protocols – –Genotype – phenotype correlations – –Environmental – phenotype correlations – –Pharmacogenomic research – –Toxicogenomic research Increasingly common element of clinical research protocols – –Genotype – phenotype correlations – –Environmental – phenotype correlations – –Pharmacogenomic research – –Toxicogenomic research

4. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Tissue Banking Storage of tissue permits easy access to “human subjects” – –Tissues acquired for clinical or research purposes – –Research can be conducted that is remote in time and place Storage of tissue permits easy access to “human subjects” – –Tissues acquired for clinical or research purposes – –Research can be conducted that is remote in time and place

5. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Tissue Banking Linkage of results of biological assays with informational databases – –Medical records – –Family history records – –Cancer registries – –Public health records Linkage of results of biological assays with informational databases – –Medical records – –Family history records – –Cancer registries – –Public health records

6. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Research with Human Subjects 45CFR46: Human subject means a living individual about whom an investigator (whether professional or student) conducting research obtains (1) Data through intervention or interaction with the individual, or (2) Identifiable private information. 45CFR46: Human subject means a living individual about whom an investigator (whether professional or student) conducting research obtains (1) Data through intervention or interaction with the individual, or (2) Identifiable private information.

7. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Research with Human Tissues Use in research is human subjects research if tissue source can be identified – –What constitutes “de-identification?” 45CFR46 the identity of the subject may readily be ascertained by investigator HIPAA: removal of 18 identifiers or expert opinion Use in research is human subjects research if tissue source can be identified – –What constitutes “de-identification?” 45CFR46 the identity of the subject may readily be ascertained by investigator HIPAA: removal of 18 identifiers or expert opinion

8. Treuman Katz Center for Pediatric Bioethics - 2008 Conference What are the ethical issues raised by research with human tissues?

9. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Ethical and Regulatory Issues Who “owns” tissue samples? Defining the risks to individuals from research with tissue samples Defining the risks to racial or ethnic groups from research with tissues Who “owns” tissue samples? Defining the risks to individuals from research with tissue samples Defining the risks to racial or ethnic groups from research with tissues

10. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Ethical and Regulatory Issues What sort of consent should be obtained for research with tissue samples? – –Is consent for unrestricted future use acceptable? – –What is the role of child assent? – –Should consent be obtained when subjects become adults? What sort of consent should be obtained for research with tissue samples? – –Is consent for unrestricted future use acceptable? – –What is the role of child assent? – –Should consent be obtained when subjects become adults?

11. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Case Discussion Retention and research use of residual newborn screening blood spots

12. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Residual Newborn Screening Specimens Virtually all newborns are screened for multiple conditions using dried blood spots State-based public health programs Residual dried blood spots are available for almost all infants Virtually all newborns are screened for multiple conditions using dried blood spots State-based public health programs Residual dried blood spots are available for almost all infants

13. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Reasons for Specimen Storage Confirmation of test results Quality assessment of current test modalities Forensic uses – – Post-mortem disease identification – – Identification of remains Research – – Related to newborn screening – – Unrelated to newborn screening Confirmation of test results Quality assessment of current test modalities Forensic uses – – Post-mortem disease identification – – Identification of remains Research – – Related to newborn screening – – Unrelated to newborn screening

14. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Reasons for Discarding Specimens Uncertainty over stability of sample – – DNA appears stable Storage costs and space No clearly defined justification for storage Lack of informed consent for retention Potential legal liabilities Uncertainty over stability of sample – – DNA appears stable Storage costs and space No clearly defined justification for storage Lack of informed consent for retention Potential legal liabilities

15. Treuman Katz Center for Pediatric Bioethics - 2008 Conference NBS Retention < 6 months 24 programs 1 year 6 programs 2 - 7 years 7 programs 21 - 23 years 6 programs indefinitely 8 programs 37 states have policies governing use of residual samples 23 programs have written usage policy < 6 months 24 programs 1 year 6 programs 2 - 7 years 7 programs 21 - 23 years 6 programs indefinitely 8 programs 37 states have policies governing use of residual samples 23 programs have written usage policy Source: Therrell et al. Pediatrics 2006;117:S212

16. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Research Options “Anonymized” specimens Pros – – Valuable for epidemiologic research – – Research does not involve “human subjects” under US regulations – – Minimal IRB review IRB defines exempt research IRB may review de-identification process – – No consent usually necessary for anonymous use (consent may be appropriate for collection and storage) “Anonymized” specimens Pros – – Valuable for epidemiologic research – – Research does not involve “human subjects” under US regulations – – Minimal IRB review IRB defines exempt research IRB may review de-identification process – – No consent usually necessary for anonymous use (consent may be appropriate for collection and storage)

17. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Research Options “Anonymized” specimens Cons – – Unable to link with health outcome of child Cannot detect false positives and false negatives – – Unable to contact family with beneficial health information “Anonymized” specimens Cons – – Unable to link with health outcome of child Cannot detect false positives and false negatives – – Unable to contact family with beneficial health information

18. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Research Options Linked samples (identifiable) Pros – – Health tracking possible – – Return of health information possible Cons – – IRB review and oversight necessary – – Informed permission may be necessary Undermines value of having a specimen already – – Return of information may pose risk to child and/or family Linked samples (identifiable) Pros – – Health tracking possible – – Return of health information possible Cons – – IRB review and oversight necessary – – Informed permission may be necessary Undermines value of having a specimen already – – Return of information may pose risk to child and/or family

19. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Informed Permission in NBS Permission usually not sought for NBS – – Only 2 states and DC have permission process for NBS – – No infrastructure for obtaining permission Acquire permission for retention of sample for research purposes? Acquire permission for research use? – – Research specific to newborn screening conditions? – – Broad authorization for other research uses? Permission usually not sought for NBS – – Only 2 states and DC have permission process for NBS – – No infrastructure for obtaining permission Acquire permission for retention of sample for research purposes? Acquire permission for research use? – – Research specific to newborn screening conditions? – – Broad authorization for other research uses?

20. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Waiver of Consent Permitted under 45 CFR 46.116d if all criteria are met: 1) research involves no more than minimal risk 2) waiver would not adversely affect rights and welfare of the subject 3) research could not be practicably carried out without waiver 4) when appropriate, subjects can be provided with pertinent information after participation

21. Treuman Katz Center for Pediatric Bioethics - 2008 Conference Policy Questions Should state health departments be able to retain NBS specimens without parental permission? Is biomedical research permissible with retained specimens without parental permission? – –Anonymous specimens only? – –Identifiable specimens? Should state health departments be able to retain NBS specimens without parental permission? Is biomedical research permissible with retained specimens without parental permission? – –Anonymous specimens only? – –Identifiable specimens?

22. Treuman Katz Center for Pediatric Bioethics - 2008 Conference