Finding a Better Way:

Transcription

1 Finding a Better Way: Genomic Distinctiveness Kyle B. Brothers Genomics and Ethics in Research and Medical Decision-Making Cincinnati, OH March 13, 2015

2 Debates over genomic exceptionalism Overview Clinical analogies Genomic Distinctiveness

3 Genomic Exceptionalism

4 Definitions -ome = noun suffix indicating all of the specified constituents of a cell, considered collectively or in total -omic = adjective suffix with same meaning

5 Genomic Exceptionalism Large number of findings generated simultaneously High likelihood of secondary finding

6 Genomic Exceptionalism Results may need filtering due to: Genomics Overwhelming number of secondary findings Genetics Right not to know Right to an open future

7 Debate Over ACMG Recommendations

8 ACMG Recommendations [W]e felt that clinicians and laboratory personnel have a fiduciary duty to prevent harm by warning patients and their families about certain incidental findings and that this principle supersedes concerns about autonomy, just as it does in the reporting of incidental findings elsewhere in medical practice.

9 Critique of Recommendations Rejecting the need for the patient s informed consent to look for mutations in a predetermined list of 57 genes is a profound departure from prevailing law and norms.

10 Response to Critique To date, the traditions of genetic testing and reporting have exceptionalized all genetic risk information as potentially dangerous to the wellbeing of patients. This tradition, in the era of genome sequencing, must be reconsidered.

11 Clinical Analogies

12 Imaging

13 Imaging CT and MRI capture whole part of the body High likelihood of incidental findings Confirmation potentially risky Genomics WGS captures whole genome High likelihood of secondary findings Confirmation potentially risky

14 Imaging Images display incidental findings by default Filtering requires sophisticated image processing Incidental Genomics Secondary findings are hidden by default Filtering can be achieved by narrowing analysis Secondary

15 Imaging Incidental findings infrequent Narrow scope of possible findings Genomics Almost every patient has secondary findings Potential for secondary findings related to every organ system

16 Imaging vs. Genomics Similar in some ways, different in others These differences could justify differences in practice

17 Newborn Screening

18 NBS New technology (tandem mass spec) provides cheap, easy alternative to multiple existing technologies Also generates large number of results that were not previously obtained Genomics New technology (WGS) provides cheap, easy alternative to multiple existing technologies Also generates large number of results that were not previously obtained

19 NBS Many secondary findings reflect circumstances that are ambiguous not clearcut pathology Confirmatory testing can take time, cause stress Genomics Many secondary findings reflect circumstances that are ambiguous not clearcut pathology Confirmatory testing can take time, cause stress

20 NBS Genomics Results: Reflect current metabolic state Are proximal to clinical signs and symptoms Reflect potential current disease state Results: Reflect genetic composition Are distal from clinical signs and symptoms Typically reflect disease risk

21 NBS Typically performed: In public health setting On healthy patients In infants Genomics Typically performed: In research or clinical setting On patients with clinical indication In adults or children

22 NBS vs. Genomics Similar in some ways, different in others These differences could justify differences in practice

23 Routine Laboratory Panels

24 Typical Laboratory Panels Complete Blood Count: Parameters for variety of cells in the blood Basic Metabolic Panel: 7-8 parameters reflecting fluid and electrolyte status Complete Metabolic Panel: BMP + liver and nutritional parameters

25 Routine Lab Panels Genomics Laboratory devices generate package of findings Not practical to account for individual preferences in components of package Generates unexpected findings that may need to be addressed Secondary findings could be considered part of the package Concerns about practicality of accounting for preferences Can generate unexpected findings that may need to be addressed

26 Routine Lab Panels Genomics Limitations and implications well understood Package is routinely filtered, since laboratory devices can generate more parameters than requested Limitations and implications still poorly understood Concern that failure to analyze for important incidental findings would be unethical

27 Imaging vs. Genomics Similar in some ways, different in others These differences could justify differences in practice

28 Antibiotic Sensitivities

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30 Antibiotic Sensitivity Reports Genomics Potential to generate large number of findings Total number determined by analytical decisions Potential to generate large number of findings Total number determined by analytical decisions

31 Antibiotic Sensitivity Reports Genomics Filtering is common practice; sensitivities to expensive or restricted antibiotics are suppressed to influence provider practice Concerns about filtering include: Liability for not reporting potentially useful information Paternalistic laboratory practices

32 Antibiotic Sensitivities vs. Genomics Similar in some ways, different in others These differences could justify differences in practice

33 Genomic Distinctiveness

34 Dualist Perspectives Genomics is different, should be treated differently. Genomics is the same, should be treated the same.

35 Exceptionalism in Practice In many debates, both sides accuse the other of exceptionalism Most deny accusations of exceptionalism Not useful for clarifying the issues

36 Distinctiveness Every domains of medicine reflects distinctive traits Each trait is shared with other domains Unique combination of traits defines each domain

37 Genomic Distinctiveness Identify Partial Analogy Claim Practice Should Be The Same

38 Genomic Distinctiveness Identify Relevant Traits Determine Implications of Traits Decide on Practices

39 Thanks! Aaron Goldenberg Nanibaa Garrison Rich Sharp Jen McCormick