Secondary Findings in Genomic Research

Cover
Secondary
Findings in
Genomic Research
Copyright
Contributors
In Memoriam: Pia Erdmann
Introduction
	Unexpected findings in medicine
	Our general approach in this book
	Clarifying the issues by defining the terms—Different types of additional findings
	The chapter structure of the book—Topics and approaches
	References
1
Concept, history, and state of debate
	Introduction: “Additional” findings in medical research
	History of debate: A four-layer model
	Lessons learned from population-based imaging
		Quality of information
		To tell or not to tell?
		What to tell? Actionability and clinical utility
		How to tell?
		How to prepare participants?
		How to design an appropriate research protocol
	In search of an appropriate ethical framework
	Conclusion
	References
2
Oversight, governance, and policy for making decisions about return of individual genomic findings
	Introduction
	International legal and ethical principles
	Planning ahead: Return of results protocols
	Consent
	What to return (or not)
	How to return
	Children and adults who lack decisional capacity: Special considerations
	Return of secondary findings versus the right of access
	International data sharing and return
	Conclusion
	Acknowledgments
	References
3
Selecting secondary findings to report: Creating a list that suits your study
	Types of genomic findings
		Multifactorial disease risks
		Pharmacogenomics
		Mendelian disease
		Carrier status
	Criteria for a reportable secondary finding
		Confirmation and reporting
		Genes
		Actionability
		Participant and study factors
		Variants
		Balancing risks and benefits
	Lists
	Conclusion
	References
4
How secondary findings are made
	Secondary findings in clinical sequencing
	Chapter overview
	Current methods for large-scale DNA sequencing in clinical laboratories
	Sequence read alignment, variant calling, and annotation
	Use of variant filtration to detect or avoid secondary findings
	Potential categories of secondary findings
	Variant validation via alternative sequencing assay
	Conclusion
	References
5
Informed consent and decision-making
	Introduction
	Ethical issues
		Respect for autonomy and informed consent
		Providing information
		Offering options and eliciting preferences
		Deciding what to disclose
	Counseling challenges
		Addressing barriers to understanding
		Accounting for changing information
		Managing therapeutic and diagnostic misconceptions
	Approaches for addressing ethical issues and counseling challenges
		Genetic counseling
		Decision-making without formal counseling
	Consent models
		Staged consent
		Modular consent
		Family consent
		Broad consent
	Conclusion
	References
6
Reporting of secondary findings in genomic research: Stakeholders’ attitudes and preferences
	Introduction and background
	Why measure preferences? Normative ethical questions
		Methodological answer: It depends on the validity of the empirical research
		Epistemological answer: It depends on the intended use of the empirical data
			Gaining insights into current moral stances or into moral behavior
			Identifying ethical problems or aspects
			Solidifying or contextualizing (specifying) accepted norms or principles
			Justifying norms: Information regarding acceptability/practicality
			Justifying norms/single actions: As a component in coherentism
			Justifying norms/single actions: As (more or less) direct justification
		Relevance of background premises for guideline development
		Eliciting preferences for developing policies
	How to measure preferences? Strategies and tools for eliciting preferences on secondary findings
		Whose preferences need to be elicited?
		Factors influencing preferences: Personal and disease related
		Tools or instruments to elicit stakeholders’ preferences
		When to elicit stakeholders’ preferences?
	What has been found? Stakeholders’ attitudes and perspectives
		Professionals’ attitudes toward disclosing or not disclosing: Clinicians, researchers, and IRB members
			Preferences for secondary findings
			Impacts and implications of secondary findings and the question of understanding and literacy
			Information process before consent to genetic research and process after disclosure of secondary findings
			Rights, responsibilities, policies, and practices
		Participants’ and lay attitudes and preferences
			Preferences for secondary findings
			Impacts and implications of secondary findings
			Information process before consent to genetic research and process after disclosure of secondary findings
			Rights, responsibilities, policies, and practices
	Summary
	References
	Further reading
7
Disclosing genomic sequencing results
	Context of the research: Managing participant expectations
	Characteristics of the study participants
		Notification to participants of a sequence result
	Disclosure modality and content
		Laboratory reports of genomic findings
		Who will return results
	Summary
	References
	Further reading
8
Implications of secondary findings for clinical contexts
	Introduction
	International approaches to genomics in clinical care and translational medicine
		United States
		United Kingdom
		Australia
		Germany
		France
		Canada (Quebec)
		Singapore
		Estonia
		Japan
		Summary
	Emerging and future scenarios
		Pediatric, neonatal, and prenatal genomics
		Wellness genomics
		Storage and return of raw sequence data in the clinical and research settings
	Economic dimensions of returning secondary findings from genomics in clinical routine care
	Discussion and conclusions
	References
9
Secondary findings: Building a bridge to the future of ELSI
	Secondary findings as sentinel debate
	Secondary findings as cultural crossroads
	Secondary findings and the future of ELSI scholarship
		Reanalysis for clinical purposes
		Polygenic risk scores
	References
Index
	A
	B
	C
	D
	E
	F
	G
	H
	I
	J
	L
	M
	N
	P
	Q
	R
	S
	T
	U
	V
	W
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