Clinical and counseling experiences of early adopters of whole exome sequencing Shubhangi Arora1; Eden Haverfield2; Gabriele Richard2; Susanne B. Haga1; Rachel Mills1 1) Duke University Center for Applied Genomics & Precision Medicine; 2) GeneDx Corresponding author: Rachel Mills, Duke CAGPM, Box 90141, Durham, NC 27708; r.mills@duke.edu Poster # 496 BACKGROUND: Whole exome sequencing (WES) is becoming more routinely used for clinical diagnosis due to improved sequencing technologies and decreasing costs. However, the comprehensive nature of the test presents a challenge for providers to educate, counsel, and communicate results. A number of case reports have been published regarding diagnoses made by WES and clinical follow-up with improved health outcomes for those patients. However, to date, there are limited data available regarding delivery of and counseling for WES. Thus, to improve understanding and inform clinical practice, we explored the clinical and counseling experiences of early adopters of WES STUDY DESIGN: All providers who ordered WES testing from GeneDx, a CLIA-certified DNA-based diagnostic testing laboratory, were invited to participate in a survey. An invitation with the link for the online survey was appended to all WES results faxed to ordering providers. Providers were asked to complete the survey only once about their experience with WES testing associated with the report accompanying the survey invitation. PATIENT POPULATION: Eligible participants ordered WES from GeneDx between April 2013 and December 2014. Though the survey was intended for physician providers, many genetic counselors responded. A total of 49 respondents completed the survey (Table 1). 57% (n=28) of respondents first learned about WES at a professional meeting Previous experience with WES varied Respondents had ordered between 1- 51 WES tests prior to the one associated with the survey (mean 12.05; median 8.5; mode 4) There was no association between previous experience and practice setting (p=0.3827) or board certification (p=1.00) RESULTS: WES TESTING INDICATION (Table 2) Primary reason for testing was to diagnose or identify cause of disease (n=47; 96%) Other 2 ordered to inform reproductive decision-making 88% (n=43) ordered WES because all other diagnostic options had been exhausted Most had ordered 2-3 genetic tests prior to WES (n=23; 47%); 12% had ordered 12 or more tests ordered (n=6) Most tests (n=43; 88%) were ordered for children, 26 of those (60%) were 5 years or younger 80% of respondents reported testing being covered by insurers Table 2. Reasons for ordering WES for their patient n (%) Exhausted all other possibilities to diagnose patient 43 (88%) Cost-effectiveness of WES compared to numerous single gene/panel tests 36 (73%) Patient/family interest 31 (63%) Perceived utility 24 (49%) Insurance coverage 20 (41%) Other (e.g., analysis for genetic heterogeneity, due to worsening of patient’s medical status) 2 (4%) RESULTS: PRE-TEST COUNSELING All but one respondent reported that pre-test counseling was performed Pre-test counseling was typically completed in one session (n=39, 81%) Took <1 hour in 25 cases (53%), 1-2 hours in 20 cases (43%), 2-3 hours in one case, and >5 hours in one case No observable difference in number of tests previously ordered for the patient and length of pre-test counseling visit Counseling was conducted by the physician provider (n=19) or genetic counselor (n=28) No significant difference in time between physicians and genetic counselors providing counseling (p=1.097) All discussed informed consent and possibility of incidental findings with patient (Table 3) Nine respondents discussed all topics queried Table 3. Topics discussed with patient during pre-test counseling n (%) Informed consent 38 (100%) Secondary/incidental findings Possibility of not finding a diagnosis 37 (97%) Implications of findings for family members 35 (92%) What secondary/incidental findings would be reported 32 (84%) Payment/reimbursement for testing 31 (82%) Technical description of the test 29 (76%) Possibility of revealing non-paternity 28 (74%) Risk for genetic discrimination/GINA 19 (50%) Table1. Respondent demographics n (%) Board Certification Genetic Counseling 20 (41%) Medical Genetics 19 (39%) Pediatrics 13 (27%) Neurology 6 (12%) Other 4 (8%) Practice Setting Academic Medical Center 26 (53%) Hospital-based specialty care Community-based specialty care 2 (4%) Hospital-based primary care 1 (2%) Year of Graduation 1969-1980 3 (6%) 1981-1990 8 (16%) 1991-2000 2001-2010 2011-2014 5 (10%) Prefer not to answer RESULTS: POST-TESTING COUNSELING WES resulted in new definitive diagnosis for 55% (n=27) of cases, suggested a possible cause in 8 Clinical management was changed in 13 patients based on the WES findings (i.e., referral to specialists, preventative care, additional testing) All but one conducted post-test counseling (not the same respondent who did not conduct pre-test counseling) Post-testing was typically completed in one session (n=40; 87%) Took <1 hour in 15 cases (33%), 1-2 hours in 27 cases (59%), and >5 hours in one case Cases with a definitive diagnosis were significantly longer than those without (p=0.0129) Counseling was conducted by the physician (n=23) or genetic counselor (n=22) or both (n=1) No significant difference in time between physicians and genetic counselors providing counseling (p=0.7474) CONCLUSIONS: More than half reported that WES provided a definitive diagnosis Higher than 30.1% positive rate of all patients tested by GeneDx* Likely due to small population size and participant bias Overall, approximately 2-3 hours of counseling time was provided to each patient Counseling time for WES appears to be comparable to counseling time for other types of genetic testing Post-test counseling for cases without definitive diagnosis were shorter, potentially due to WES being the “last option” requiring no or minimal discussion about next steps Most ACMG recommended guidelines are being followed, particularly regarding consent, discussion of incidental findings, and appropriate use of WES testing A number of providers who are not medical geneticists or genetic counselors are ordering WES, contrary to ACMG recommendations Variability exists in the provider who provides counseling, time spent on counseling, and topics discussed during pre-test counseling Lack of consistency implies providers may benefit from more detailed guidelines (Note: Board certification total does not equal 100% as respondents could select multiple responses) *Neidich et al (2014) Annual ACMG Clinical Genetics Meeting, Abstract 567 This study was approved by the Duke University Health System Institutional Review Board (Pro00042368). It has been submitted for publication to the Journal of Genetic Counseling.