Translation of genomics into medicine and drug development requires comprehensive, high-quality, genomic variant databases. To support translation, there is a movement towards sharing clinical annotations of variants (e.g., benign, unknown, pathogenic) internationally via open access. Despite the growing popularity of variant databases, ethical issues and liability risks have received scant attention. Ethical priorities for variant databases include 1) competence – ensuring that data is responsibly managed, curated, and used; 2) confidentiality – ensuring appropriate safeguards for patient data; 3) communication – clearly describing the purpose, quality standards, and data handling practices to contributing patients and potential users; and 4) continuous oversight to adapt database governance in a rapidly evolving environment. How can database managers fulfill these obligations when these responsibilities are increasingly distributed along the clinical pipeline? Legal issues include medical liability based on potential harm to patients; liability based on third-party intellectual property or privacy rights in the data; and regulatory risks as variant data is integrated into genetic tests or devices. Can these risks can be managed through appropriate governance structures – including adequate consents, access processes, contributor agreements, and disclaimers – while still facilitating sharing and clinical use?

1. genomicsandhealth.org
Bartha M. Knoppers
Director of the Centre of Genomics and Policy, McGill
Chair, GA4GH Regulatory and Ethics Working Group
Canada Research Chair in Law and Medicine
Adrian Thorogood
Academic Associate, Centre of Genomics and Policy. McGill
Coordinator, GA4GH Regulatory and Ethics Working Group
Use of open, curated variant databases:
Ethics? Liability?

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Mission
To accelerate progress in human health
by helping to establish a common framework of
harmonized approaches to enable effective and
responsible sharing of genomic and clinical data, and by
catalyzing data sharing projects that drive and
demonstrate the value of data sharing

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GA4GH Framework for Responsible
Sharing of Genomic and Health-Related
Data
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• Current frameworks are founded on the principle of protection
from harm. In contrast,
• GA4GH Framework aims to activate the right to science and
the right to recognition for scientific production by promoting
responsible data sharing.
http://genomicsandhealth.org/framework

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Human Rights Foundation
Universal Declaration of Human Rights, (1948)
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“The Right to Science”
“Everyone has the right to the
protection of the moral and
material interests resulting from
any scientific, literary or artistic
production of which he is the
author.”
“Everyone has the right freely
to participate in the cultural
life of the community, to
enjoy the arts and to share in
scientific advancement and its
benefits.”
27(1) 27(2)
“The Right to
Recognition”

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Framework for Responsible Sharing of Genomic
and Health-Related Data
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The Framework is currently available in 12 languages. Thank you to all the volunteers!
• Arabic
• Chinese
• French
• German
• Greek
• Hindi
• Italian
• Japanese
• Portuguese
• Spanish
• Russian
Πλαίσιο για την Υπεύθυνη Κοινοχρησία Γονιδιωματικών και άλλων Ιατρικών
Δεδομένων
基因组学与健康相关数据负责任的共享框架
‫بالصحة‬ ‫والمتصلة‬ ‫الجینومیة‬ ‫للمعلومات‬ ‫مسؤول‬ ‫لتبادل‬ ‫إطار‬
Cadre pour un partage responsable des données génomiques et des données de santé
ゲノム及び健康関連データの責任ある共有に関する枠組み
Marco de actuación para el uso compartido responsable de datos genómicos y relativos a la salud
Framework para Compartilhamento Responsável de Dados Genômicos e Relacionados à Saúde
Rahmenkonzept für die verantwortungsvolle Datenweitergabe genomischer und
gesundheitsbezogener Daten
Framework per la condivisione responsabile di dati genomici e relativi alla salute
Концепция ответственного обмена геномными данными и данными,
связанными со здоровьем человека

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GA4GH Regulatory and Ethics Working Group
• Consent Policy
• Consent Clauses
and Template for
International
Data Sharing
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• Privacy &
Security Policy
• Data Sharing
Lexicon
• Accountability
Policy
Framework for Responsible Sharing of
Genomic and Health-Related Data

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• Undertaken by the members
• Catalyzed and supported by GA4GH coordinators and Working
Groups
• Purpose: to drive learning, identify requirements, evaluate value
and coordinate activity
Beacon Project
Matchmaker Exchange
BRCA Challenge
Demonstration projects

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3 Tiers of the BRCA Exchange
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Variant Databases: Ethics?
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Variant Databases: Ethics?
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Negligent Laboratory and Database Curation?
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(2007) (2008)

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Negligent Laboratory and Database Curation? (cont’d)
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Alleged that Athena:
• Failed to provide an accurate genetic result
• Failed to update its variant classifications
Standard of Care for Variant Classification?
• Athena did not follow its own scheme for classification.
• Athena had specific knowledge variant was pathogenic
• 2 (Athena) publications linked the mutation to the disease
• Athena patent applications included the variant

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Negligent Communication?
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Update:

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Variant Databases: Shared Responsibility?
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GA4GH Framework
“It interprets the right of all people to share in the benefits of scientific
progress and its applications as being the duty of data producers and users
to engage in responsible scientific inquiry and to access and share genomic
and health-related data across the translation continuum, from basic
research through practical applications. It recognizes the rights of data
producers and users to be recognized for their contributions to research,
balanced by the rights of those who donate their data. In addition to being
founded on the right of all citizens in all countries to the benefits of the
advancements of science, and on the right of attribution of scientists, it also
reinforces the right of scientific freedom.”
Global Alliance for Genomics and Health, “Framework for Responsible Sharing
of Genomic and Health-Related Data”

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