Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Anatomic and cognitive abnormalities
Treatment: Chromosomal Microarray Analysis 
The insurer denied the Chromosomal Microarray Analysis.
The denial is overturned. 

This boy has developmental delays, clotting abnormalities and multiple congenital anomalies. His attending physician (AP) geneticist has requested chromosomal Microarray to determine whether a chromosomal deletion or duplication is at the origin of his anatomic and cognitive abnormalities. The findings do not suggest a specific single gene disorder for which molecular genetic testing is available.

Yes, the proposed chromosomal Microarray analysis is medically necessary.

Chromosomal Microarray represents a first-line standard of care in genetic testing for individuals with this patient's medical and cognitive problems that is well supported by authoritative, published, medical literature and guidelines, examples of which are cited and discussed in the paragraphs below.

The requested service, Chromosomal Microarray/Comparative Genomic Hybridization, is not experimental, investigational, or unproven in this boy with developmental delays, birth defects, and clotting abnormalities. The entire medical genetic and pediatric neurology communities support the use of chromosomal Microarray in individuals with this patient's developmental delays, congenital anomalies and clinical problems. Use of chromosomal Microarray in this clinical context is clearly of utility, will refine the prognosis, is safe, will improve the medical outcome and is supported by reliable, authoritative, peer-reviewed, published medical literature. The research regarding and supporting chromosomal Microarray testing in this clinical context is extensive and demonstrates safety, utility, efficacy and accuracy of this technology. Chromosomal Microarray is not regarded as experimental or investigational by the Food and Drug Administration (FDA). Chromosomal Microarray testing constitutes accepted medical practice under the standards of the case and under the standards of the medical genetic and pediatric neurology community, it is lawfully marketed for its use and does not require Food and Drug Administration (FDA) approval, is not currently under study in a phase I/II/III clinical trial and is not under and does not require any other study to determine its safety and efficacy. Furthermore, the available authoritative, peer-reviewed, published medical literature and the professional society recommendations cited below do not support the presence of major or minor malformations as being necessary criteria for the performance of chromosomal Microarray/comparative genomic hybridization in a given individual with developmental delay, intellectual disability, or an autism spectrum disorder. 

Chromosomal Microarray/Array Comparative Genomic Hybridization (CMA/CGH) in this patient: is medically necessary, and clinically appropriate in this clinical context. It is consistent with the diagnosis of this patient's medical problems, is in accordance with recognized reliable standards of care for individuals with developmental delays and congenital anomalies, as discussed below. It is appropriate and in accordance with the generally accepted Reliable "best practices" in medical genetics and pediatric neurology and meets the generally accepted Reliable standards of medical practice and the most up-to-date recommendations of the major professional medical genetic and pediatric neurology organizations in the United States; is clinically appropriate for individuals with intellectual disability, autism spectrum disorders, birth defects, and developmental delays; the available authoritative, peer-reviewed, published scientific evidence clearly demonstrates identification of specific chromosomal duplication deletion syndromes to be effective in improving health outcomes; its use is not for the convenience of the member, physician, or other health care practitioner. In addition, this testing is lawfully marketed for the proposed use and is performed in Clinical Laboratory Improvement Amendments (CLIA) approved laboratories. Its use is not solely for the convenience of the affected individual, his or her physician, plan provider, hospital, or other health care provider and is the most appropriate level of diagnostic service for this patient. This testing is well supported by reliable, authoritative, peer-reviewed, published medical literature and is considered a standard of care in medical genetics, developmental pediatrics, and pediatric neurology.

The results for chromosomal Microarrays have the potential to impact the clinical management of the patient. The extensive scientific evidence, reviews and meta-analyses quoted below overwhelmingly support the conclusions that identifying a specific chromosomal duplication deletion clearly improves health outcomes. Many chromosome abnormalities detectable by Chromosomal Microarray/Array Comparative Genomic Hybridization (CGH/CMA) have varying clinical manifestations that require quite distinct medical assessments, prognosis and therapeutic interventions. To cite a few examples, the major chromosomal trisomies involving chromosomes 13, 18 and 21; Velocardiofacial syndrome (22q11 deletion syndrome); Williams syndrome (elastin gene deletions); Turner syndrome (XO); and the many disorders involving duplication or deletion of chromosomes 1 and 16 have identifiable patterns of medical problems, birth defects, developmental and psychiatric abnormalities and organ malformation and dysfunction (see GeneReviews.org for the individual disease entries).  Identifying a specific chromosomal deletion or duplication syndrome in this individual will refine prognosis, direct medical care, identify previously unknown problems, avoid unnecessary additional testing and improve outcomes. It is contrary to the published, peer-reviewed medical literature to conclude that identifying a specific chromosomal duplication deletion syndrome does not improve the outcome, prognosis and care of the affected individual.

This chromosomal Microarray testing is more beneficial than any established alternatives, i.e. routine chromosomal karyotyping, in identifying chromosomal duplication deletion syndromes. In fact, it has been amply demonstrated that Chromosomal Microarray/Array Comparative Genomic Hybridization (CMA/CGH) is clearly and statistically significantly more sensitive in identifying such chromosomal duplication deletion syndromes than is classic chromosomal karyotyping. This conclusion is amply justified in the references cited below and has recently been strongly supported by a review article in the prestigious New England Journal of Medicine. Genomics, Intellectual Disability, and Autism.
 
Chromosomal Microarray/Array Comparative Genomic Hybridization (CMA/CGH) is now considered a first-line/first-tier test in individuals with developmental delays, intellectual disability or congenital anomalies. This assessment is now supported by consensus statements and practice guidelines from the two largest human and medical genetic professional organizations, The American Society of Human Genetics and the American College of Medical Genetics: Consensus Statement: Chromosomal Microarray Is a First-Tier Clinical Diagnostic Test for Individuals with Developmental Disabilities or Congenital Anomalies, D. T. Miller et al., American Journal of Human Genetics; American College of Medical Genetics Practice Guidelines: Array-based Technology and Recommendations for Utilization in Medical Genetics Practice for Detection of Chromos. 

The requested service, Chromosomal Microarray/Comparative Genomic Hybridization, is not experimental, investigational, or unproven. The entire medical genetic and pediatric neurology communities support the use of chromosomal Microarray in individuals with this patient's developmental delays and clinical problems. Use of chromosomal Microarray in this clinical context is clearly of utility, will refine the prognosis, is safe, will improve the medical outcome and is supported by reliable, authoritative, peer-reviewed, published medical literature. The research regarding and supporting chromosomal Microarray testing in this clinical context is extensive and demonstrates safety, utility, efficacy and accuracy of this technology. Chromosomal Microarray is not regarded as experimental or investigational by the Food and Drug Administration (FDA). Chromosomal Microarray testing constitutes accepted medical practice under the standards of the case and under the standards of the medical genetic and pediatric neurology community, it is lawfully marketed for its use and does not require Food and Drug Admiration (FDA) approval, is not currently under study in a phase I/II/III clinical trial and is not under and does not require any other study to determine its safety and efficacy. Furthermore, the available authoritative, peer-reviewed, published medical literature and the professional society recommendations cited below do not support the presence of major or minor malformations as being necessary criteria for the performance of chromosomal Microarray/comparative genomic hybridization in a given individual with developmental delay, intellectual disability, or an autism spectrum disorder. 

Furthermore, a recent comprehensive study of interlaboratory reproducibility for Chromosomal Microarray (CMA) has demonstrated a high concordance rate (almost 96%) of results between different laboratories.