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PROVIDER POLICIES & PROCEDURES FETAL ANEUPLOIDY DNA SEQUENCE ANALYSIS The purpose of this document is to assist providers enrolled in the Connecticut Medical Assistance Program (CMAP) with the information needed to support a medical necessity determination for cell-free fetal DNAbased prenatal screening for fetal aneuploidies. By clarifying the information needed for prior authorization of services, HUSKY Health hopes to facilitate timely review of requests so that individuals obtain the medically necessary care they need as quickly as possible. Chromosomes are the structures in our cells that carry our genetic material. Humans typically have 46 chromosomes in each cell. A change in the number of chromosomes can trigger problems with growth, development, and function of the body s systems. These changes can occur during the formation of reproductive cells, in early fetal development, or in any cell after birth. A gain or loss of chromosomes from the normal 46 is called aneuploidy. Trisomy is a type of aneuploidy in which there are three copies of a particular chromosome instead of two. The American College of Obstetricians and Gynecologists (ACOG) recommends cell-free fetal DNA-based screening using cell-free fetal DNA from maternal plasma as one option in the screening of women with an increased risk of aneuploidy (see clinical guideline below). ACOG does not recommend that cell-free fetal DNA testing be used as part of routine prenatal laboratory evaluation, but rather should be an informed choice after counseling. Additionally, cell-free fetal DNA testing should not be offered to low-risk women or women with multiple gestations as this testing has not been adequately evaluated in these groups. During pre-test counseling providers should communicate that: (1) cell-free fetal DNA testing is limited to screening for common trisomies and, currently, gives no other genetic information about a pregnancy; and (2) a negative cell-free fetal DNA test result does not ensure an unaffected pregnancy. During counseling, a family history should be obtained to determine if other forms of screening or prenatal diagnosis for familial genetic conditions are required. An individual with a positive test result should be referred for genetic counseling and offered invasive prenatal diagnosis for confirmation of test results. The results of testing can provide individuals and families with the information necessary to make fully informed health-care decisions. Cell free fetal DNA does not replace the accuracy and precision of prenatal diagnosis with chorionic villus sampling (CVS) or amniocentesis, which remain an option for women. CLINICAL GUIDELINE Coverage guidelines for cell-free fetal DNA-based prenatal screening are made in accordance with the Department of Social Services (DSS) definition of Medical Necessity. The following criteria are guidelines only. Coverage determinations are based on an assessment of the individual and their unique clinical needs. If the guidelines conflict with the definition of Medical Necessity, the definition of Medical Necessity Please note that authorization is based on medical necessity at the time the authorization is issued and is not a guarantee of payment. Payment 1is

shall prevail. The guidelines are as follows: Typical clinical circumstances when cell-free fetal DNA-based prenatal screening for fetal aneuploidy (trisomy 13, 18 and 21) may be considered medically necessary include: 1. The individual to be tested is carrying a single gestation; and 2. The individual is considered at high risk for fetal aneuploidy due to ANY of the following: A. The expectant mother will be 35 years or older at the time of delivery; or B. The fetus has ultrasonographic findings that indicate an increased risk of aneuploidy; or C. The expectant mother has a history of a prior pregnancy with trisomy; or D. The expectant mother has a positive first or second-trimester standard biomarker screening test; or E. Either parent has been identified as having a balanced Robertsonian translocation with an increased risk of fetal trisomy 13 or trisomy 21. Note: For testing panels, including but not limited to, multiple genes or multiple conditions, and in cases where a tiered approach/method is clinically available, testing would typically be covered only for the number of genes or test that are reasonable and necessary to obtain necessary information for therapeutic decision making; however, a testing panel may be considered medically necessary based on an assessment of the individual and their unique clinical needs. NOTE: EPSDT Special Provision Early and Periodic Screening, Diagnosis, and Treatment (EPSDT) is a federal Medicaid requirement that requires the Connecticut Medical Assistance Program (CMAP) to cover services, products, or procedures for Medicaid enrollees under 21 years of age where the service or good is medically necessary health care to correct or ameliorate a defect, physical or mental illness, or a condition identified through a screening examination. The applicable definition of medical necessity is set forth in Conn. Gen. Stat. Section 17b-259b (2011) [ref. CMAP Provider Bulletin PB 2011-36]. PROCEDURE Prior authorization of cell-free fetal DNA-based prenatal screening for fetal aneuploidy (trisomy 13, 18 and 21) is required. Requests for coverage will be reviewed in accordance with procedures in place for reviewing requests for genetic testing. Coverage determinations will be based upon a review of requested and/or submitted case-specific information. The following information is needed to review requests for cell-free fetal DNA-based prenatal screening for fetal aneuploidy: 1. Fully completed Outpatient Prior Authorization Request Form; and 2. Documentation from the referring provider which substantiates the high risk nature of the pregnancy and supports the medical necessity of the testing. EFFECTIVE DATE This Policy is effective for prior authorization requests for cell-free fetal DNA-based prenatal screening for fetal aneuploidy (trisomy 13, 18 and 21) for individuals covered under the HUSKY Health Program beginning January 1, 2014. LIMITATIONS N/A Please note that authorization is based on medical necessity at the time the authorization is issued and is not a guarantee of payment. Payment 2is

CODES: Code Description 81420 Fetal chromosomal aneuploidy (e.g., trisomy 21, monosomy X) genomic sequence analysis panel, circulating cell-free fetal DNA in maternal blood, must include analysis of chromosomes 13, 18, 21 81507 Fetal aneuploidy (trisomy 21, 18 and 13) DNA sequence analysis of selected regions using maternal plasma, algorithm reported as a risk score for each trisomy. DEFINITIONS 1. HUSKY A: Connecticut children and their parents or a relative caregiver; and pregnant women may qualify for HUSKY A (also known as Medicaid). Income limits apply. 2. HUSKY B: Uninsured children under the age of 19 in higher income households may be eligible for HUSKY B (also known as the Children s Health Insurance Program) depending on their family income level. Family cost-sharing may apply. 3. HUSKY C: Connecticut residents who are age 65 or older or residents who are ages 18-64 and who are blind, or have another disability, may qualify for Medicaid coverage under HUSKY C (this includes Medicaid for Employees with Disabilities (MED-Connect), if working). Income and asset limits apply. 4. HUSKY D: Connecticut residents who are ages 19-64 without dependent children and who: (1) do not qualify for HUSKY A; (2) do not receive Medicare; and (3) are not pregnant, may qualify for HUSKY D (also known as Medicaid for the Lowest-Income populations). 5. HUSKY Health Program: The HUSKY A, HUSKY B, HUSKY C, HUSKY D and HUSKY Limited Benefit programs, collectively. 6. HUSKY Limited Benefit Program or HUSKY, LBP: Connecticut s implementation of limited health insurance coverage under Medicaid for individuals with tuberculosis or for family planning purposes and such coverage is substantially less than the full Medicaid coverage. 7. Medically Necessary or Medical Necessity: (as defined in Connecticut General Statutes 17b- 259b) Those health services required to prevent, identify, diagnose, treat, rehabilitate or ameliorate an individual's medical condition, including mental illness, or its effects, in order to attain or maintain the individual's achievable health and independent functioning provided such services are: (1) Consistent with generally-accepted standards of medical practice that are defined as standards that are based on (A) credible scientific evidence published in peer-reviewed medical literature that is generally recognized by the relevant medical community, (B)recommendations of a physicianspecialty society, (C) the views of physicians practicing in relevant clinical areas, and (D) any other relevant factors; (2) clinically appropriate in terms of type, frequency, timing, site, extent and duration and considered effective for the individual's illness, injury or disease; (3) not primarily for the convenience of the individual, the individual's health care provider or other health care providers; (4) not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the individual's illness, injury or disease; and (5) based on an assessment of the individual and his or her medical condition. 8. Prior Authorization: A process for approving covered services prior to the delivery of the service or initiation of the plan of care based on a determination by CHNCT as to whether the requested service is medically necessary. 9. Trisomy 13: A chromosomal condition, also called Patau syndrome, associated with severe intellectual disability and physical abnormalities in many parts of the body. Individuals with trisomy 13 often have heart defects, brain or spinal cord abnormalities, micropthalmia, extra fingers or toes, a cleft lip and palate and hypotonia. Many infants with trisomy 13 die within their first days or weeks of life. Most cases of trisomy 13 result from having three copies of chromosome 13 in each cell of the Please note that authorization is based on medical necessity at the time the authorization is issued and is not a guarantee of payment. Payment 3is

body instead of the usual two copies. 10. Trisomy 18: A chromosomal condition, also called Edwards syndrome, associated with abnormalities in many parts of the body. Individuals with trisomy 18 often have intrauterine growth retardation and low birth weight. Individuals may have heart defects and abnormalities of other organs that develop before birth. Other features include a small, abnormally shaped head; small jaw and mouth; and clenched fists with overlapping fingers. Many infants with trisomy 18 die before birth or within their first month of life. Most cases of trisomy 18 result from having three copies of chromosome 18 in each cell of the body instead of the usual two copies. 11. Trisomy 21: A chromosomal condition, also called Down syndrome, associated with intellectual disability, a characteristic facial appearance, and hypotonia in infancy. Individuals with trisomy 21 may have a variety of birth defects. About half are born with heart defects. Most cases of trisomy 21 result from having three copies of chromosome 21 in each cell of the body instead of the usual two copies. ADDITIONAL RESOURCES AND REFERENCES: American College of Obstetricians and Gynecologists (ACOG). Committee opinion no. 545: noninvasive prenatal testing for fetal aneuploidy. Obstet Gynecol. 2012; 120(6):1532-1534. American Medical Association, Current Procedural Terminology Manual: 2016 Centers for Medicare and Medicaid Services (2014, September 1) Local Coverage Determination for Molecular Pathology Procedures (L34506) National Government Services, Inc. Retrieved from http://www.cms.gov/medicare-coverage-database/details/lcddetails.aspx?lcdid=34506&contrid=300&ver=9&contrver=1&docid=l34506&bc=aaaaaagaa AAAAA%3d%3d& National Library of Medicine (NLM). Genetics Home Reference. Trisomy 13. Reviewed January 2009. Published December 2, 2012. Available at: http://ghr.nlm.nih.gov/condition/trisomy-13 Accessed on January 8, 2014. National Library of Medicine (NLM). Genetics Home Reference. Trisomy 18. Reviewed March 2012. Published December 2, 2012. Available at: http://ghr.nlm.nih.gov/condition/trisomy-18 Accessed on January 8, 2014. National Library of Medicine (NLM). Genetics Home Reference. Trisomy 21. Reviewed June 2012. Published December 2, 2012. Available at: http://ghr.nlm.nih.gov/condition/down-syndrome Accessed on January 8, 2014 PUBLICATION HISTORY Status Date Action Taken Original publication January 1, 2014 Reviewed March 16, 2015 Clinical Quality Sub-Committee review. Reference updated. Update approved at the March 16, 2015 Clinical Quality Sub-Committee meeting. Reviewed March 20, 2015 Medical Management review. Clinical Guideline section update to address coverage of testing panels as outlined in LCD L34506. Reference added: CMS Local Coverage Determination for Molecular Pathology Procedures. Please note that authorization is based on medical necessity at the time the authorization is issued and is not a guarantee of payment. Payment 4is

Update approved by the Department of Social Services (DSS) on March 23, 2015. Updated August 2015 Updated definitions for HUSKY A, B, C and D programs at reques of DSS. Updated March 2016 Updates to language in introductory paragraph pertaining to purpose of policy. Updates to Clinical Guideline section pertaining to definition of Medical Necessity. Updates throughout policy to reflect the importance of person-centeredness when reviewing requests for this service. Changes approved at the March 21, 2016 Clinical Quality Subcommittee meeting. Changes approved by DSS on April 11, 2016. Please note that authorization is based on medical necessity at the time the authorization is issued and is not a guarantee of payment. Payment 5is