Parents Reported Likelihood of Sharing Actionable Vs. Non- - - PowerPoint PPT Presentation

Parents’ Reported Likelihood

• f Sharing Actionable Vs. Non-

Actionable Genetic Results

Carrie A. Weaver, MA Melanie Myers, PhD, MS, LGC Matt Veerkamp, BA And Cynthia A. Prows, MSN, CNS, FAAN

Arguments against Returning Research Results

• 1. Rests on a mistaken interpretation of

autonomy

– Decision lies in informed consent

• 2. Poses an unsustainable burden on

research infrastructure

– Money, time

• 3. Harmful consequences

– Psychological, physical

[1, 4, 6]

Arguments for Returning Research Results

• 1. Beneficence

– Increase physical, psychological well being

• 2. Autonomy

– Choice to be given results

• 3. Reciprocity

– Results as compensation

• 4. Disclosure improves public understanding
• f genetics

[1, 4, 6]

Present Study

• Sample: 117 parents of children with extra

biological samples for future research stored at Cincinnati Children’s Hospital

– Case: participant’s child exposed to opioids

• (n= 55, 47.01%)

– Control: participant’s child without previous exposure to

• pioids
• (n= 62, 52.99%)

– Samples genotyped for CYP2D6 to determine predisposition for codeine response. Results given to parents over the phone

Methods

• Return of eMERGE research results survey

– Adapted from Haga et al. (2012)

• Similarities:

– telephone interviews concerning genomic results

• Differences:

– hypothetical testing vs. actual pharmacogenetic testing and returning of results – Adults answering questions about their own hypothetical results vs. parents answering questions about their child’s actual result

– Survey administered immediately following result disclosure

• If not possible then within 1 week of return of results
• 10 to 20 minutes to complete

Actionability Classification

• Actionable

– 1 CYP2D6 gene that does not make enzyme and 1 CYP2D6 gene that makes an enzyme that does not work as well as expected – 2 CYP2D6 genes that do not work – at least 3 CYP2D6 genes that work well

• Potentially actionable

– 1 CYP2D6 gene that makes normal amount of enzyme and one gene that makes enzyme that does not work as well as expected. – 1 CYP2D6 gene that makes normal amount of enzyme and one gene that does not. – 2 CYP2D6 genes that make enzyme that does not work as well as expected

• Not actionable

– 2 CYP2D6 genes that make normal amounts of enzyme

Hypotheses

• Child’s previous opioid exposure will influence

parents’ likelihood of sharing results with health care providers

• Parents who receive actionable results will be

more inclined to share results with health care providers

Analyses

• Data analyzed with PSPP and JMP
• Descriptive statistics

– Frequencies

• Pair-wise comparisons

– Wilcoxon Rank Sum

Demographic Frequency (%)

Education

Some High School 2 (1.71%) HS grad/GED 19 (16.24%) Some college/2year 27 (23.08%) 4 year college 48 (41.03%) 4 year + 21 (17.95%)

Income

Less than $25,000 9 (7.69%) $25,000 to $49,999 12 (10.26%) $50,000 to $74,999 24 (20.51%) $75,000 to $99,999 26 (22.22%) More than $100,000 36 (30.77%) Refused 8 (6.84%) Don’t know 1 (0.85%)

Demographics

Race (N=117)

109 4 4

Demographic Frequency (%)

Worked in Health Care

Yes 56 (47.86%) No 61 (52.14%)

Has Health Insurance

Yes 116 (99.15%) No 1 (0.85%)

Actionability

Actionable 7 (5.98%) Potentially 69 (58.97%) Not Actionable 41 (35.04%)

Demographics

My child’s doctor can use this CYP2D6 research test result when providing care to him/her. Would you say you…

Metabolizer type Strongly agree Somewhat agree Somewhat Disagree Strongly disagree Total Actionable 7 7 (5.98%) Potentially actionable 62 7 69 (58.97%) Not actionable 29 12 41 (35.04%) Total [n (%)] 98 (83.76) 19 (16.24) N=117

Potentially Actionable vs. Not Actionable: p=.0041 100.00%

How likely are you to share (your child’s) CYP2D6 research test result with his/her doctor?

Metabolizer type Extremely likely Somewhat likely Not very likely Not at all likely N (%) Actionable 7 7 (5.98) Potentially actionable 59 10 69 (58.97) Not actionable 19 20 2 41 (35.04) Total [n (%)] 85 (72.65) 30 (25.64) 2 (1.71) 117 (100.00)

Not actionable vs. Actionable: p=.0220 Potentially Actionable vs. Not Actionable: p=.0012 98.29%

How likely are you to share your child’s CYP2D6 research test result with his/her pharmacist?

Metabolizer type Extremely likely Somewhat likely Not very likely Not at all likely N (%) Actionable 3 3 1 7 (6.03) Potentially actionable 21 32 12 3 68 (58.62) Not actionable 7 13 13 8 41 (35.34) Total [n (%)] 31 (26.72) 48 (41.38) 26 (22.41) 11 (9.48) 116 (100.00)

Not significant. 68.10%

Discussion

• Actionability confers clinical utility.

– Clinical utility: a result is clinically useful when it leads to an improved health outcome [1]

• Results, regardless of category, have personal utility

– Personal utility: a result is personally useful when the outcome has value to the individual

• Replication of literature suggesting individuals want to

receive results [2,5,6]

Acknowledgments

– John B. Harley, M.D., Ph.D. – Andrea Murad, B.A. – Brooke McLaughlin, M.S. – Lisa Martin, Ph.D. – Cincinnati Children’s Research Foundation – Cincinnati Genomic Control Cohort

References

1. Bredenoord, A. L., Kroes, H. Y., Cuppen, E., Parker, M., & van Delden, J. J. M. (2011). Disclosure

• f individual genetic data to research participants: the debate reconsidered. Trends in Genetics,

27 (2): 41-47. doi: 10.1016/j.tig.2010.11.004. 2. Fullerton, S. M., Wolf, W. A., Brothers., K. B., et al. (2012). Return of individual research results from genome-wide association studies: Experience of the electronic medical records & genomics (eMERGE) network. Genetic Medicine, 14 (4): 424-431. doi: 10.1038/gim.2012.15. 3. Haga, S. B., O’Daniel, J. M., Tindall, G. M., Lipkus, I. R., Agans, R. (2012). Survey of US public attitudes toward pharmacogenetic testing. Pharmacogenomics, 12 (3): 197-204. doi: 10.1038/tpj.2011.1. 4. Hens, K., Nys, H., Cassiman, J. , Dierickx, K. (2011). The reutrn of invidiual research findings in paediatric genetic research. Journal of Medical Ethics, 37: 179-183. doi: 10.1136/jme.2010.037473. 5. Jarvik, G. P., Amendola, L. M., Berg, J. S., et al. (2014). Return of genomic results to research participants: the floor, the ceiling, and the choices in between. The American Journal of Human Genetics, 94: 818-826. doi: 10.1016./j.ajhg.2014.04.009. 6. Kleiderman, E., Knoppers, B. M., Fernandez, C. V. et al. (2014). Returning incidental findings from genetic research to chidren: views of partents of children affected by rare diseases. Journal of Medical Ethics, 40: 691-696. doi: 10.1136/medethics-2013-101648.