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

Parents’ Reported Likelihood of 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 of 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 opioids • (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

Demographics 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%)

Race (N=117) 4 4 109

Demographics 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%)

My child’s doctor can use this CYP2D6 research test result when providing care to him/her. Would you say you… Metabolizer Strongly Somewhat Somewhat Strongly Total type agree agree Disagree disagree Actionable 7 0 7 (5.98%) Potentially 62 7 69 actionable (58.97%) Not 29 12 41 actionable (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 Extremely Somewhat Not very Not at all N (%) type likely likely likely likely Actionable 7 0 0 7 (5.98) Potentially 59 10 0 69 (58.97) actionable Not 19 20 2 41 (35.04) actionable 117 Total [n (%)] 85 (72.65) 30 (25.64) 2 (1.71) (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 Extremely Somewhat Not very Not at all N (%) type likely likely likely likely Actionable 3 3 1 0 7 (6.03) Potentially 21 32 12 3 68 (58.62) actionable Not 7 13 13 8 41 (35.34) actionable 116 Total [n (%)] 31 (26.72) 48 (41.38) 26 (22.41) 11 (9.48) (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 of 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.