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Ethical issues in genomics research

Bernard Lo, M.D.

March 3, 2009

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Study of predisposition to prostate cancer

Carry out genome-wide analyses

Use as controls men who were

subjects of study on diabetes

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Additional research questions

Do controls develop disease?

Do those with SNPs have higher risk of

developing disease?

What genes predict better prognosis or

response to treatment?

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Ethical concerns

1. Can you share genome-wide data

with other researchers?

2. Are de-identified samples and

sequences rendered identifiable by

whole genome sequencing?

3. Can you use existing data for

additional research without consent?

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Ethical concerns

4. Can you follow participants as prospective

cohort using medical records without

consent? Need identifiers Link to cancer regsitry, Medicare claims

databases

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Review of ethical issues

1. Risk/ benefit balance must be

acceptable Risks must be minimized Confidentiality is main concern

2. Informed consent Exception for de-identified data or waiver

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Confidentiality

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Special concerns about genetic confidentiality

Information considered particularly

sensitive About relatives and groups Highly predictive of future illness

• “Future diaries”

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Special concerns about genetic confidentiality

Sensitive research projects Genetics of antisocial behavior Human evolution Beliefs about group ancestry Some participants may object

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Breaches of confidentiality

Stolen or lost laptops with identifiable

data

Bankruptcy

Although low probability, large impact

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Genetic Information Nondiscrimination Act (2008)

Remove barriers to genetic testing

Health insurers may not Use genetic information to set eligibility or

premiums Require or request genetic testing

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Genetic Information Nondiscrimination Act (2008)

Employers may not Use genetic information in employment or

promotion decisions Require or request genetic testing

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Limitations of GINA

After job offer, employer may request

medical records Impractical to delete genetic information

Not apply to disability, life, long-term

care insurance Adverse selection if individual rating

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HIPAA and research

Must get authorization to use

identifiable health information For each specific research study

• No future authorization May waive authorization Limited data set

De-identified data exempt

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What are de-identified data?

18 specific identifiers Overt identifiers Geographic data more precise than first 3

digits of zip code Dates except for year Biometric identifiers Any other unique identifying characteristic

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Impact of HIPAA on research

More difficult to recruit participants

Increased selection bias

Made use of existing specimens more

difficult

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HIPAA fails to protect privacy

Poor oversight of research Weak security protections

Applies only to covered entities

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HIPAA fails to protect privacy

Protection does not follow information

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Privacy concerns about sharing sequencing data

Identify individual from pooled specimens

Re-identification of de-identified specimens

Use in objectionable studies Cannot withdraw from research once data

are released

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Re-identification of genome-wide association subjects

Reference samples in forensic

databases DOJ has 6.2 million profiles STRs at 13 locations Full genome sequence can be matched Although low probability, high impact

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Re-identification of genome-wide association subjects

What additional protections might

make risk of re-identification minimal? Explicit ban Strengthen protections for databases that

contain identifiers

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Sharing genomic sequence data

Data use agreement Restrict future uses

Restrict access to whole-genome data Access only at certain sites Not download data from site NIH biostatistician to do analyses

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Sharing of genomic sequence data

Tradeoffs between research efficiency

and privacy

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Use of existing samples in research

Value for research

No consent required if anonymized (de-

identified)

General consent for unspecified future

research or genetic research suffices

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Ethical rationale for waiver or general consent

Very low risk

No participant would object

May not be appropriate for sensitive

genomic studies

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Problems with general consentif not understand

Whole genome sequencing

Dissemination of data

Not feasible to withdraw from research

Possibility of re-identification

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Problems with general consentif not understand

Intention to patent discoveries

Income from licensing and royalties

Future studies that might be

considered objectionable

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Recommendations for consent

Explicit consent for Whole genomic sequencing Dissemination of sequencing data

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Recommendations for consent

Explicit consent for Patents arising from discoveries

• Specify financial arrangements

• Sharing with individual donors not feasible

• May need to negotiate with advocacy groups who recruited donors

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Recommendations for consent

Explicit consent for Future studies

• Consent for all studies approved by IRB or oversight committee

• Require specific consent for highly sensitive studies

• Permission to recontact for sensitive studies

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Recommendations for consent

Tradeoff between research efficiency

and respect for donors

Researchers may exclude those who

do not accept these conditions

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Reforming HIPAA

IOM report “Beyond the HIPAA Privacy

Rule: Enhancing Privacy, Improving

Health through Research

http://www.iom.edu/CMS/3740/43729/61796.aspx

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Conclusion

Privacy Rule does not protect privacy

and impedes important research

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New Framework

Congress should authorize new

approach to ensuring privacy that

would apply to all health research

Enhance privacy through improved

security, transparency, accountability

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Recommendations

Revise provisions of Privacy Rule that

hinder research but do not provide

meaningful protections

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Recommendations

Encourage use of limited data sets Make data use agreements more efficient

and effective

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Recommendations

Facilitate use of existing data Allow future research with IRB oversight Allow linking data from multiple sources

• Certify trusted intermediaries, who then give researchers de-identified data sets

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Recommendations

Clarify if DNA sequences are

considered identifiable

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Recommendations

Stronger security protections Encryption IRB to include security expert Penalties for attempted re-identification Notify participants of breaches

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Recommendations

Inform participants and public of

research results and their importance

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Take home points

Resolving ethical issues is crucial for

genomics research to proceed

Scientists need to be involved in

addressing ethical issues

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