title: Clinical Utility of a Comprehensive, Whole Genome CMA Testing Platform in Pediatrics: A Prospective Randomized Controlled Trial of Simulated Patients in Physician Practices.
abstract: BACKGROUND
  Developmental disorders (DD), including autism spectrum disorder (ASD) and intellectual disability (ID), are a common group of clinical manifestations caused by a variety of genetic abnormalities. Genetic testing, including chromosomal microarray (CMA), plays an important role in diagnosing these conditions, but CMA can be limited by incomplete coverage of genetic abnormalities and lack of guidance for conditions rarely seen by treating physicians.
  
  
  METHODS
  We conducted a longitudinal, randomized controlled trial investigating the impact of a higher resolution 2.8 million (MM) probe-CMA test on the quality of care delivered by practicing general pediatricians and specialists. To overcome the twin problems of finding an adequate sample size of multiple rare conditions and under/incorrect diagnoses, we used standardized simulated patients known as CPVs. Physicians, randomized into control and intervention groups, cared for the CPV pediatric patients with DD/ASD/ID. Care responses were scored against evidence-based criteria. In round one, participants could order diagnostic tests including existing CMA tests. In round two, intervention physicians could order the 2.8MM probe-CMA test. Outcome measures included overall quality of care and quality of the diagnosis and treatment plan.
  
  
  RESULTS
  Physicians ordering CMA testing had 5.43% (p<0.001) higher overall quality scores than those who did not. Intervention physicians ordering the 2.8MM probe-CMA test had 7.20% (p<0.001) higher overall quality scores. Use of the 2.8MM probe-CMA test led to a 10.9% (p<0.001) improvement in the diagnosis and treatment score. Introduction of the 2.8MM probe-CMA test led to significant improvements in condition-specific interventions including an 8.3% (p = 0.04) improvement in evaluation and therapy for gross motor delays caused by Hunter syndrome, a 27.5% (p = 0.03) increase in early cognitive intervention for FOXG1-related disorder, and an 18.2% (p<0.001) improvement in referrals to child neurology for Dravet syndrome.
  
  
  CONCLUSIONS
  Physician use of the 2.8MM probe-CMA test significantly improves overall quality as well as diagnosis and treatment quality for simulated cases of pediatric DD/ASD/ID patients, and delivers additional clinical utility over existing CMA tests.
authors.affiliation: University of California, San Francisco, CA, United States of America.|University of California, Los Angeles, CA, United States of America.|QURE Healthcare, San Francisco, CA, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Peabody
authors.affiliation: Lineagen, Salt Lake City, UT, United States of America.
authors.forename: Megan
authors.initials: M
authors.lastname: Martin
authors.affiliation: QURE Healthcare, San Francisco, CA, United States of America.
authors.forename: Lisa
authors.initials: L
authors.lastname: DeMaria
authors.affiliation: QURE Healthcare, San Francisco, CA, United States of America.
authors.forename: Jhiedon
authors.initials: J
authors.lastname: Florentino
authors.affiliation: QURE Healthcare, San Francisco, CA, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Paculdo
authors.affiliation: Lineagen, Salt Lake City, UT, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Paul
authors.affiliation: Lineagen, Salt Lake City, UT, United States of America.
authors.forename: Rena
authors.initials: R
authors.lastname: Vanzo
authors.affiliation: Lineagen, Salt Lake City, UT, United States of America.
authors.forename: E Robert
authors.initials: ER
authors.lastname: Wassman
authors.affiliation: QURE Healthcare, San Francisco, CA, United States of America.
authors.forename: Trever
authors.initials: T
authors.lastname: Burgon
mesh_terms: D000293:Adolescent; D000067877:Autism Spectrum Disorder / Q000175:diagnosis* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003198:Computer Simulation; D002658:Developmental Disabilities / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis* / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010818:Practice Patterns, Physicians'; D011446:Prospective Studies