Latest Review Date: February 2024

Category: Laboratory

POLICY:

The use of maternal serum biomarker tests with or without additional algorithmic analysis for prediction of preeclampsia is considered investigational.

The use of maternal serum biomarker tests with or without additional algorithmic analysis for prediction of spontaneous preterm birth is considered investigational.

DESCRIPTION OF PROCEDURE OR SERVICE:

Improved accuracy of the identification of pregnant people at risk of preeclampsia and spontaneous preterm birth has the potential to reduce maternal and perinatal morbidity and mortality. Assessment of historical risk and clinical factors represents the traditional approach to diagnosis and planning interventions. Maternal serum biomarker testing is proposed as an adjunct to standard screening to identify pregnant people at risk of preeclampsia and spontaneous preterm birth.

Preeclampsia

Hypertensive disorders in pregnancy affected approximately 1 in 7 delivery hospitalizations between 2017 and 2019 in the US with prevalence being approximately 1 in 5 delivery hospitalizations among Black women and 1 in 3 among women aged 45–55 years. Preeclampsia is defined as new onset maternal hypertension and proteinuria or new onset hypertension and significant end-organ dysfunction (with or without proteinuria) after the 20th week of gestation.

Maternal complications of preeclampsia include progression to eclampsia, placental abruption, and a life-threatening complication known as the hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. In the fetus, preeclampsia can lead to fetal growth restriction and intrauterine fetal death. Preeclampsia can develop in nulliparous women with no known risk factors.3, Maternal factors associated with an increased risk of preeclampsia include advanced maternal age, presence of a chronic illness such as diabetes mellitus, chronic hypertension, chronic kidney disease, or systemic lupus erythematosus, obesity, multiple gestations, and a prior history of preeclampsia. Preeclampsia can also develop in the postpartum period. In women determined to be at increased risk of developing preeclampsia, the use of daily, low-dose aspirin beginning in the 12th week of gestation is associated with a reduction in risk and is recommended by the U.S. Preventive Services Task Force (USPSTF) and the American College of Obstetricians and Gynecologists (ACOG).

Despite decades of research, accurate identification of women at risk of preeclampsia, particularly prior to the 20th week of gestation, remains challenging. Standard methods for preeclampsia risk-factor assessment are based on medical and obstetric history and clinical assessment, including routine maternal blood pressure measurement at each prenatal visit. The use of maternal serum biomarker assays as an adjunct to standard preeclampsia risk assessment has been suggested as a mechanism that could improve accurate identification of at-risk individuals. More accurate identification of risk could create an opportunity for additional assessment, surveillance, and interventions that would ultimately reduce the maternal and fetal or newborn morbidity and mortality associated with preeclampsia. Individual maternal serum biomarkers, such as serum placental growth factor (PlGF), soluble Fms-like tyrosine kinase 1 (s-Flt 1), and pregnancy-associated plasma protein A (PAPP-A) have been investigated as predictors of preeclampsia. Multivariable preeclampsia risk assessment tools have been developed that incorporate maternal serum biomarkers; several of these tools have been commercially produced (see Regulatory Status) but few have been externally validated. Clinically useful risk assessment using maternal serum biomarker testing would need to show increased predictive value over standard assessment of preeclampsia risk without serum biomarker testing.

Spontaneous Preterm Birth

Preterm birth is defined as birth occurring between the 20th and 37th week of pregnancy and can be spontaneous following preterm labor and rupture of membranes or iatrogenic due to clinical interventions for maternal or fetal medical indications. The preterm birth rate was estimated by the Centers for Disease Control (CDC) to be 10.1% (about 360,000 births were preterm among 3,600,000 births) in 2020 in the United States and has consistently been approximately 10% for over a decade. Preterm birth rates vary according to race and ethnicity independent of social determinants of health, ranging from 8.5% for Asian women to 14.4% for non-Hispanic Black women. Prior preterm birth is the strongest predictor of a subsequent preterm birth, although absolute risk varies according to the gestational age of the prior preterm birth and maternal clinical factors. Characteristics in a current pregnancy that increase the risk of preterm birth include cervical changes (shortened length and/or early dilation), vaginal bleeding or infection, and maternal age under 18 years or over 35 years. Smoking, pre-pregnancy weight, interpregnancy interval, maternal stress, and lack of social support have also been associated with an increased risk of preterm birth. Despite recognition of risk factors, most preterm births occur without clearly identifiable maternal risk factors. Maternal consequences of preterm delivery include intrapartum and postpartum infection. Psychosocial adverse effects including postpartum depression have been reported. Infants born preterm have an increased risk of death up to 5 years of age relative to full-term infants. Preterm birth is also associated with morbidity extending into adulthood.

Cervical length is one measure available to clinicians to assess risk of preterm birth. Shortened cervical length prior to 24 weeks gestation is associated with an increased risk of preterm birth. The ACOG recommends ultrasonographic assessment of cervical length in the second trimester to identify women at an increased risk of preterm birth. In women with a prior history of preterm birth, serial measurement of cervical length using transvaginal ultrasound is recommended, although optimal timing of measurements has not been clinically established. In women without a history of preterm birth or other risk factors, universal ultrasonographic screening of cervical length in women has not been demonstrated to be an effective strategy due to the overall low incidence in this group. In women determined to have a shortened cervix and therefore an increased risk of preterm birth, the use of either vaginal or intramuscular progesterone supplementation has been associated with a reduced risk of preterm birth. There are some limitations in assessment of cervical length in predicting risk of preterm birth. These limitations include uncertainty as to what constitutes “shortened” length, with transvaginal ultrasound measurements ranging from <15 mm to <25 mm implicated in indicating increased risk and uncertainty regarding ideal timing of ultrasonographic assessment.

Given the limitations of cervical length assessment in predicting risk of preterm birth, the use of other biomarkers has been suggested as a mechanism that could improve accurate identification of women at risk of preterm birth, including maternal serum biomarkers.

KEY POINTS:

The most recent literature update was performed through January 2, 2024.

Summary of Evidence

For individuals who are pregnant without known risk factors for preeclampsia who receive maternal serum biomarker testing with or without additional algorithmic analysis, the evidence includes systematic reviews of observational clinical validity studies and an RCT that selected eligible participants based on an algorithm that included biomarker testing results. Relevant outcomes are test validity, and maternal and perinatal morbidity and mortality, symptoms, functional outcomes, quality of life, hospitalizations, resource utilization. The clinical validity studies primarily included populations from Europe and tests that are not cleared for use in the US. PlGF cutoffs for identifying high risk pregnant people were not prespecified and varied significantly. The RCT used a test not cleared for use in the US to identify people for enrollment. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who are pregnant with known risk factors for preeclampsia who receive maternal serum biomarker testing with or without additional algorithmic analysis, the evidence includes systematic reviews of observational clinical validity studies and cohort studies RCTs. Relevant outcomes are test validity, and maternal and perinatal morbidity and mortality, symptoms, functional outcomes, quality of life, hospitalizations, resource utilization. Studies evaluating the predictive ability of maternal serum biomarker testing have found measurement of sFlt-1, PlGF, and the sFlt-1/PlGF ratio can identify women at risk of developing preeclampsia. One sFlt-1/PlGF ratio test system (Kryptor) has been cleared in the US. One prospective observational study (PRAECIS) has been conducted in a second and third trimester, US population reporting clinical validity of the Kryptor test system. PRAECIS included a racially diverse population reflective of US diversity. While PRAECIS proposed a cutoff for the sFlt-1:PlGF ratio of 40, other publications have proposed various cutoffs. The clinical decision that would be informed by the test is unclear. While 5 RCTs have been conducted using various biomarker tests, the Kryptor test system has not been used in any RCTs. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who are pregnant without known risk factors for spontaneous preterm birth who receive maternal serum biomarker testing with or without additional algorithmic analysis, the evidence includes a RCT and cohort studies. Relevant outcomes are test validity, and maternal and perinatal morbidity and mortality, symptoms, functional outcomes, quality of life, hospitalizations, resource utilization. Measurement of the insulin-like growth factor binding protein-4 (IBP4) and sex hormone binding globulin (SHBG) ratio demonstrated acceptable discrimination in identifying asymptomatic women who may be at risk of preterm birth, based on evidence from 2 industry-sponsored cohort studies. However, a randomized trial did not find a difference in risk of preterm birth with use of the commercially produced PreTRM test, which includes the IBP4/SHBG ratio as part of an algorithmic analysis, versus no use. There were also no differences in neonatal outcomes in infants of women who underwent PreTRM testing versus no testing. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who are pregnant with known risk factors for spontaneous preterm birth who receive maternal serum biomarker testing with or without additional algorithmic analysis, the evidence includes a systematic review of observational studies. Relevant outcomes are test validity, and maternal and perinatal morbidity and mortality, symptoms, functional outcomes, quality of life, hospitalizations, resource utilization. The systematic review did not identify any individual biomarker that adequately identified women at risk of spontaneous preterm birth based on high sensitivity and specificity. No studies assessing maternal serum biomarkers as part of an algorithmic analysis were identified. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Practice Guidelines and Position Statements

American College of Obstetricians and Gynecologists and The Society for Maternal-Fetal Medicine

The American College of Obstetricians and Gynecologists (ACOG) issued practice bulletins in 2020 on preeclampsia and 2021 on preterm birth. Maternal serum biomarker screening is described as investigational and is not recommended by ACOG as a factor included in risk assessment for either preeclampsia or spontaneous preterm birth.

The 2021 joint ACOG-Society for Maternal-Fetal Medicine (SMFM) guidance on the use of aspirin for prevention of preeclampsia does not include results of maternal serum biomarker testing among the risk factors to be used to identify women at risk of preeclampsia. The guidance was reaffirmed in October 2022.

International Federation of Gynecology and Obstetrics

The International Federation of Gynecology and Obstetrics (FIGO) Initiative on Preeclampsia (PE) published a guide for first trimester screening and prevention of preeclampsia in 2019. The writing committee included representation from the National Institutes of Health (US Department of Health and Human Services) and the Society for Maternal-Fetal Medicine (Washington, DC). The guideline states that 'All pregnant women should be screened for preterm PE during early pregnancy by the first-trimester combined test with maternal risk factors and biomarkers as a one-step procedure.' The guidance further states that 'The best combined test is one that includes maternal risk factors, measurements of mean arterial pressure (MAP), serum placental growth factor (PLGF) and uterine artery pulsatility index (UTPI).' The combined test referred to in the guidance is the Fetal Medicine Foundation (FMF) risk calculator.

International Society for the Study of Hypertension in Pregnancy

The International Society for the Study of Hypertension in Pregnancy (ISSHP) issued practice guidelines in 2021 on classification, diagnosis and management of hypertension in pregnancy. The ISSHP committee included US representation. The guidelines make the following recommendation: 'To the assessment of women suspected of having pre-eclampsia (<37 weeks), we recommend adding evaluation of angiogenic imbalance, when available, as a marker of uteroplacental dysfunction to be used in conjunction with other clinical tests.' The quality of the evidence for the recommendation was rated as 'Moderate' and the strength of recommendation was rated as 'Strong'. Angiogenic imbalance was defined as reduced PlGF (<5th centile for gestational age) or increased sFlt/PlGF ratio.

National Institute for Health and Care Excellence

The National Institute for Health and Care Excellence (NICE) published guidance in 2022 on PLGF-based testing to help diagnose suspected preterm pre-eclampsia. The guidance recommends use of four tests to help decide on care (to help rule in or rule out pre-eclampsia) for people with suspected preterm (between 20 weeks and 36 weeks and 6 days of pregnancy) pre‑eclampsia. The tests are: DELFIA Xpress PLGF 1‑2‑3, DELFIA Xpress sFlt‑1/PLGF 1‑2‑3 ratio, Elecsys immunoassay sFlt‑1/PLGF ratio, Triage PLGF Test. The guidance states that "BRAHMS sFlt‑1 Kryptor/BRAHMS PLGF plus Kryptor PE ratio is not recommended for routine use in the NHS. Further research is needed to show the accuracy of this test when using specified thresholds."

U.S. Preventive Services Task Force Recommendations

The U.S. Preventive Services Task Force (USPSTF) issued updated recommendations in 2023 on screening for hypertensive disorders of pregnancy. The recommendation states: "Several models have been developed with the aim of identifying pregnant individuals who are at risk of developing preeclampsia. Many of these models include variables for medical history, patient characteristics, blood serum biomarkers (e.g., serum placental growth factor), mean arterial pressure (MAP), and ultrasound readings (e.g., Doppler uterine artery pulsatility index). The most extensively researched of these are various iterations of the Fetal Medicine Foundation (FMF) model. Currently, risk assessment and risk prediction tools are being used to inform the use of aspirin for prevention of preeclampsia; however, no randomized controlled trials (RCTs) have incorporated the use of a risk prediction model to evaluate the optimal frequencies or intervals of screening for hypertensive disorders of pregnancy. In the absence of clinical implementation studies, it is not yet clear whether screening informed by risk prediction models would necessarily be superior to risk evaluations based on clinical history taking. Moreover, it remains to be seen whether risk-based screening protocols, regardless of the risk-assessment approach used, could improve outcomes relative to usual care screening."

The USPSTF issued updated recommendations in 2021 on the use of aspirin for the prevention of preeclampsia. The USPSTF recommendation notes "predictive models that combine risk factors to identify pregnant persons at risk for preeclampsia, such as serum biomarkers, uterine artery Doppler ultrasonography, and clinical history and measures, have been developed. However, there is limited evidence from external validation and implementation studies to demonstrate sufficient accuracy of predictive models for clinical use."

KEY WORDS:

Maternal serum biomarker, Preeclampsia, PreTRM, PlGF Preeclampsia Screen, Spontaneous Preterm Birth, Triage PlGF™ (Quidel), Elecsys sFlt-1/PlGF™ (Roche Diagnostics), DELFIA Xpress PIGF 1-2-3™, Kryptor test system (Thermo Fisher Scientific)

APPROVED BY GOVERNING BODIES:

Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory-developed tests must meet the general regulatory standards of the Clinical Laboratory Improvement Amendments (CLIA). Laboratories that offer laboratory-developed tests must be licensed by the CLIA for high-complexity testing. To date, the U.S. Food and Drug Administration (FDA) has chosen not to require any regulatory review of these tests. Therefore, maternal serum biomarker tests would be provided by CLIA licensed laboratories.

The B·R·A·H·M·S sFlt-1/ PlGF KRYPTOR Test System (Thermo Fisher Scientific) was cleared for marketing by the FDA as a prognostic test through the De Novo process (DEN220027) in May 2023. The Test System includes quantitative determination of Placental Growth Factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) in human serum and plasma. The clearance letter states that the Test System is to be used 'along with other laboratory tests and clinical assessments to aid in the risk assessment of pregnant women (singleton pregnancies between gestational age 23+0 to 34+6/7 weeks) hospitalized for hypertensive disorders of pregnancy (preeclampsia, chronic hypertension with or without superimposed preeclampsia, or gestational hypertension) for progression to preeclampsia with severe features (as defined by the American College of Obstetricians and Gynecologists (ACOG) guidelines) within 2 weeks of presentation.'

Commercially produced, maternal serum biomarker tests for preeclampsia include the Triage PlGF™ (Quidel), Elecsys sFlt-1/PlGF™ (Roche Diagnostics), and DELFIA Xpress PIGF 1-2-3™ (PerkinElmer). These commercially produced tests are not currently available in the United States.

The PreTRM™ test (Sera Prognostics) uses maternal serum biomarkers (insulin-like growth factor binding protein-4 [IBP4] and sex hormone binding globulin [SHBG]) in combination with biometric measures to assess the risk of spontaneous preterm birth. According to the manufacturer, the PreTRM test is only intended to be used in women aged 18 years or older, who are asymptomatic (that is, with no signs or symptoms of preterm labor, with intact membranes, and with no first trimester progesterone use) with a singleton pregnancy. The PreTRM test is performed via a single blood draw during the nineteenth week of gestation.

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits. Group-specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply.

FEP contracts: Special benefit consideration may apply. Refer to member’s benefit plan.

CURRENT CODING:

CPT codes:

REFERENCES:

1. Agrawal S, Cerdeira AS, Redman C, et al. Meta-Analysis and Systematic Review to Assess the Role of Soluble FMS-Like Tyrosine Kinase-1 and Placenta Growth Factor Ratio in Prediction of Preeclampsia: The SaPPPhirE Study. Hypertension. Feb 2018; 71(2): 306-316.
2. Agrawal S, Shinar S, Cerdeira AS, et al. Predictive Performance of PlGF (Placental Growth Factor) for Screening Preeclampsia in Asymptomatic Women: A Systematic Review and Meta-Analysis. Hypertension. Nov 2019; 74(5): 1124-1135.
3. American College of Obstetrics and Gynecology and The Society for Maternal-Fetal Medicine. Practice Advisory: Low-Dose Aspirin Use for the Prevention of Preeclampsia and Related Morbidity and Mortality. December 2021.
4. Branch DW, VanBuren JM, Porter TF, et al. Prediction and Prevention of Preterm Birth: A Prospective, Randomized Intervention Trial. Am J Perinatol. Aug 16 2021.
5. Chaemsaithong P, Sahota DS, Poon LC. First trimester preeclampsia screening and prediction. Am J Obstet Gynecol. Feb2022; 226(2S): S1071-S1097.e2.
6. Cobo T, Kacerovsky M, Jacobsson B. Risk factors for spontaneous preterm delivery. Int J Gynaecol Obstet. Jul 2020; 150(1): 17-23.
7. Conde-Agudelo A, Papageorghiou AT, Kennedy SH, et al. Novel biomarkers for the prediction of the spontaneous preterm birth phenotype: a systematic review and meta-analysis. BJOG. Aug 2011; 118(9): 1042-54.
8. Davidson KW, Barry MJ, Mangione CM, et al. Aspirin Use to Prevent Preeclampsia and Related Morbidity and Mortality: US Preventive Services Task Force Recommendation Statement. JAMA. Sep 28 2021; 326(12): 1186-1191.
9. De Oliveira L, Roberts JM, Jeyabalan A, et al. PREPARE: A Stepped-Wedge Cluster-Randomized Trial to Evaluate Whether Risk Stratification Can Reduce Preterm Deliveries Among Patients With Suspected or Confirmed Preterm Preeclampsia. Hypertension. Oct 2023; 80(10): 2017-2028.
10. Gestational Hypertension and Preeclampsia: ACOG Practice Bulletin, Number 222. Obstet Gynecol. Jun 2020; 135(6): e237-e260.
11. Hamilton BE, Martin JA, Osterman MJK. Births: Provisional Data for 2020. National Center for Health Statistics.
12. Hamilton BE, Martin JA, Osterman MJK. Births: Provisional Data for 2020. National Center for Health Statistics. Accessed January 12, 2024. www.cdc.gov/nchs/data/vsrr/vsrr012-508.pdf
13. Henderson JT, Vesco KK, Senger CA, et al. Aspirin Use to Prevent Preeclampsia and Related Morbidity and Mortality [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2021 Sep. (Evidence Synthesis, No. 205.) Available from: www.ncbi.nlm.nih.gov/books/NBK574449/
14. Henderson JT, Webber EM, Thomas RG, et al. Screening for Hypertensive Disorders of Pregnancy: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. Sep 19 2023; 330(11): 1083-1091
15. Honest H, Forbes CA, Duree KH, et al. Screening to prevent spontaneous preterm birth: systematic reviews of accuracy and effectiveness literature with economic modelling. Health Technol Assess. Sep 2009; 13(43): 1-627.
16. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
17. Jackson M, Simhan HN. Prediction and Prevention of Spontaneous Preterm Birth: ACOG Practice Bulletin, Number 234. Obstet Gynecol. Aug 01 2021; 138(2): e65-e90.
18. Lim S, Li W, Kemper J, et al. Biomarkers and the Prediction of Adverse Outcomes in Preeclampsia: A Systematic Review and Meta-analysis. Obstet Gynecol. Jan 01 2021; 137(1): 72-81.
19. Lucaroni F, Morciano L, Rizzo G, et al. Biomarkers for predicting spontaneous preterm birth: an umbrella systematic review. J Matern Fetal Neonatal Med. Mar 2018; 31(6): 726-734.
20. Markenson GR, Saade GR, Laurent LC, et al. Performance of a proteomic preterm delivery predictor in a large independent prospective cohort. Am J Obstet Gynecol MFM. Aug 2020; 2(3): 100140.
21. Mazaki-Tovi S, Romero R, Kusanovic JP, et al. Recurrent preterm birth. Semin Perinatol. Jun 2007; 31(3): 142-58.
22. Mazer Zumaeta A, Wright A, Syngelaki A, et al. Screening for pre-eclampsia at 11-13 weeks' gestation: use of pregnancy-associated plasma protein-A, placental growth factor or both. Ultrasound Obstet Gynecol. Sep 2020; 56(3): 400-407.
23. McCarthy FP, Gill C, Seed PT, et al. Comparison of three commercially available placental growth factor-based tests in women with suspected preterm pre-eclampsia: the COMPARE study. Ultrasound Obstet Gynecol. Jan 2019; 53(1): 62-67.
24. National Institute For Health and Care Excellence (NICE). Diagnostics consultation document PLGF-based testing to help diagnose suspected preterm preeclampsia (update of DG23). www.nice.org.uk/guidance/indevelopment/gid-dg10040/documents.
25. Parry S, Carper BA, Grobman WA, et al. Placental protein levels in maternal serum are associated with adverse pregnancy outcomes in nulliparous patients. Am J Obestet Gynecol. Sep 2022, 227(3): 497.e1-497.e13
26. Poon LC, Shennan A, Hyett JA, et al. The International Federation of Gynecology and Obstetrics (FIGO) initiative on pre-eclampsia: A pragmatic guide for first-trimester screening and prevention. Int J Gynaecol Obstet. May 2019; 145 Suppl 1: 1-33.
27. Saade GR, Boggess KA, Sullivan SA, et al. Development and validation of a spontaneous preterm delivery predictor in asymptomatic women. Am J Obstet Gynecol. May 2016; 214(5): 633.e1-633.e24.
28. Sera Prognostics. PreTRM Test for Risk Management. www.pretrm.com/
29. Society for Maternal-Fetal Medicine (SMFM). Electronic address: pubs@smfm.org. Executive summary: Workshop on Preeclampsia, January 25-26, 2021, cosponsored by the Society for Maternal-Fetal Medicine and the Preeclampsia Foundation. Am J Obstet Gynecol. Sep 2021; 225(3): B2-B7.
30. Thermo Scientific. Product Specifications: BRAHMS sFlt-1 KRYPTOR. www.brahms.de/images/00_downloads/prenatal-screening/product-sheet-sflt1-kryptor-en.pdf.
31. Townsend R, Khalil A, Premakumar Y, et al. Prediction of pre-eclampsia: review of reviews. Ultrasound Obstet Gynecol. Jul 2019; 54(1): 16-27.
32. Veisani Y, Jenabi E, Delpisheh A, et al. Angiogenic factors and the risk of preeclampsia: A systematic review and meta-analysis. Int J Reprod Biomed. Jan 2019; 17(1): 1-10.

POLICY HISTORY:

Medical Policy Panel, February 2022

Medical Policy Group, February 2022 (9): “The use of maternal serum biomarkers for the prediction of adverse obstetric outcomes was previously investigational for dates of service prior to 03/01/2022 per MP#495: Investigational Criteria.”

Medical Policy Administration Committee, February 2022

Available for comment 03/01/2022 through 04/15/2022.

Medical Policy Panel, February 2023

Medical Policy Group, February 2023 (9): Updates to Description, Key Points, Practice Guidelines and Position Statements, Benefit Application and References; no change to policy statement.

Medical Policy Group, May 2023 (5): 2023 Quarterly Coding Update: Added CPT code 0390U to Current Coding Section.

Medical Policy Panel, February 2023

Medical Policy Group, February 2023 (5): Updates to Description, Key Points; Practice Guidelines and Position Statements, U.S. Preventive Services Task Force Recommendations, Key Words, Approved by Governing Bodies, and References. No change to Policy Statement.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

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 that patient’s illness, injury or disease.