Treuman Katz Center for Pediatric Bioethics - 2008 Conference Banking Biological Samples for...

Treuman Katz Center for Pediatric Bioethics - 2008 Conference

Banking Biological Samples for Pediatric Research

Banking Biological Samples for Pediatric Research

Jeffrey R. Botkin, M.D., M.P.H.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.Jeffrey R. Botkin, M.D., M.P.H.Professor of Pediatrics and Medical Ethics

Associate Vice President for Research

University of Utah

Treuman Katz Center for Pediatric Bioethics - 2008 Conference2

Stored Human TissuesStored 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


Tissue BankingTissue 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



• 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



• 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


Research with Human SubjectsResearch 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.


Research with Human TissuesResearch 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


What are the ethical issues raised by research with human

tissues?

What are the ethical issues raised by research with human

tissues?


Ethical and Regulatory IssuesEthical 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


Ethical and Regulatory IssuesEthical 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?


Case DiscussionCase Discussion

Retention and research use of residual newborn screening blood

spots

Retention and research use of residual newborn screening blood

spots


Residual Newborn Screening SpecimensResidual 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


Reasons for Specimen StorageReasons 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


Reasons for Discarding SpecimensReasons 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


NBS RetentionNBS 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 policySource: Therrell et al. Pediatrics 2006;117:S212


Research OptionsResearch 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)


Research OptionsResearch 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


Research OptionsResearch 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


Informed Permission in NBSInformed 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?


Waiver of ConsentWaiver 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


Policy QuestionsPolicy 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?

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