Coverage Policy Manual
Policy #: 2022036
Category: Medicine
Initiated: January 2023
Last Review: September 2023
  Digital Health Technologies: Diagnostic Applications

Description:
Digital health technologies is a broad term that includes categories such as mobile health, health information technology, wearable devices, telehealth and telemedicine, and personalized medicine. These technologies span a wide range of uses, from applications in general wellness to applications as a medical device, and include technologies intended for use as a medical product, in a medical product, as companion diagnostics, or as an adjunct to other medical products (devices, drugs, and biologics). The scope of this review includes only those digital technologies that are intended to be used for diagnostic application (detecting the presence or absence of a condition, the risk of developing a condition in the future, or treatment response [beneficial or adverse]) and meet the following 3 criterion- 1) Must meet the definition of "Software as a medical device" which states that software is intended to be used for a medical purpose, without being part of a hardware medical device or software that stores or transmits medical information. 2) Must have received marketing clearance or approval by the U.S. Food and Drug Administration either through the de novo premarket process or 510(k) process or pre-market approval and 3) Must be prescribed by a healthcare provider.
 
Autism Spectrum Disorder
Autism spectrum disorder (ASD) is a biologically based neurodevelopmental disorder characterized by persistent deficits in social communication and social interaction and restricted, repetitive patterns of behavior, interests, and activities. ASD can range from mild social impairment to severely impaired functioning; as many as half of individuals with autism are non-verbal and have symptoms that may include debilitating intellectual disabilities, inability to change routines, and severe sensory reactions. The American Psychiatric Association’s Diagnostic and Statistical Manual, Fifth Edition (DSM-5) provides standardized criteria to help diagnose ASD (APA, 2013).
 
Diagnosis of ASD in the United States generally occurs in two steps: developmental screening followed by comprehensive diagnostic evaluation if screened positive. American Academy of Pediatrics (AAP) recommends general developmental screening at 9, 18 and 30 months of age and ASD specific screening at 18 and 24 months of age (Lipkin, 2020; Hyman, 2020). Diagnosis and treatment in the first few years of life can have a strong impact on functioning as it allows for treatment during a key window of developmental plasticity (Dawson, 2013; Dawson, 2010). However, early diagnosis in US remains an unmet need even though studies have demonstrated a temporal trend of decreasing mean ages at diagnosis over time (Hertz, 2009; Leigh, 2016). According to a 2020 study by Autism and Developmental Disabilities Monitoring (ADDM) Network, an active surveillance system that provides estimates of ASD in the US, reported median age of earliest known ASD diagnosis ranged from 36 months in California to 63 months in Minnesota (Maenner, 2021).
 
Scope of Review
Software has become an important part of product development and is integrated widely into digital platforms that serve both medical and non-medical purposes. Three broad categories of software use in medical device are
 
    1. Software used in the manufacture or maintenance of a medical device (example software that monitors x-ray tube performance to anticipate the need for replacement),
    2. Software that is integral to a medical device or software in a medical device (example software used to "drive or control" the motors and the pumping of medication in an infusion pump)
    3. Software, which on its own is a medical device referred to as "Software as a Medical Device" (SaMD) (example, software that can track the size of a mole over time and determine the risk of melanoma)
 
The International Medical Device Regulators Forum, a consortium of medical device regulators from around the world led by the U.S. Food and Drug Administration (FDA) defines SaMD as "software that is intended to be used for one or more medical purposes that perform those purposes without being part of a hardware medical device" (IMDFR, 2013). Such software was previously referred to by industry, international regulators, and health care providers as "standalone software," "medical device software," and/or "health software," and can sometimes be confused with other types of software.
 
The scope of this review includes only those digital technologies that are intended to be used for diagnostic application (detecting presence or absence of a condition, the risk of developing a condition in the future, or treatment response [beneficial or adverse]) and meet the following 3 criterion-
 
    1. Must meet the definition of "Software as a medical device" which states that software is intended to be used for a medical purpose, without being part of a hardware medical device or software that stores or transmits medical information.
    2. Must have received marketing clearance or approval by the U.S. Food and Drug Administration either through the de novo premarket process or 510(k) process or pre-market approval and
    3. Must be prescribed by a healthcare provider.
 
BCBSA Evaluation Framework for Digital Health Technologies
SaMDs, as defined by FDA, are subject to the same evaluation standards as other devices; the Blue Cross and Blue Shield Association Technology Evaluation Criterion are as follows:
 
    1. The technology must have final approval from the appropriate governmental 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. [The technology must assure protection of sensitive patient health information as per the requirements of The Health Insurance Portability and Accountability Act of 1996 (HIPAA)]
    4. The technology must be as beneficial as any established alternatives.
    5. The improvement must be attainable outside the investigational settings. (The technology must demonstrate usability in a real-world setting.)
 
Other regulatory authorities such as the United Kingdom's National Institute for Health and Care Excellence (NICE) have proposed standards to evaluate SaMD (NICE, 2021).
 
Regulatory Status
Digital health technologies that meet the current scope of review:
 
Canvas DX (formerly known as Cognoa App), manufactured by Cognoa, received FDA clearance (DEN200069) in 2021 for use by healthcare providers as an aid in the diagnosis of Autism Spectrum Disorder (ASD) for patients ages 18 months through 72 months who are at risk for developmental delay based on concerns of a parent, caregiver, or healthcare provider. The device is not intended for use as a stand-alone diagnostic device but as an adjunct to the diagnostic process. The device is for prescription use only (Rx only). It is described as an artificial intelligence app for use by health care providers as an adjunct in the diagnosis of autism spectrum disorder for patients ages 18 to 72 months. Canvas DX includes 3 questionnaires: parent/caregiver, a video analyst, and a health care provider, with an algorithm that synthesizes the 3 inputs for use by the primary care provider. FDA Product Code: QPF
 
Drowzle® Pro, Resonea
Drowzle Pro is a mobile software system that records and analyzes respiratory patterns during sleep to facilitate the in-home screening of obstructive sleep apnea (OSA).
 
Halo™ AF Detection System, LIVMOR, Inc
Halo is a wearable smartwatch device for intermittently monitoring pulse rhythms to detect atrial fibrillation (AF).
 
myVisionTrack® (Home Vision Monitor) Model 0005 (K143211), manufactured by Vital Art and Science, LLC, received FDA clearance March 20, 2015. It is intended for the detection and characterization of central 3 degrees metamorphopsia (visual distortion) in patients with maculopathy, including age-related macular degeneration and diabetic retinopathy, and as an aid in monitoring progression of disease factors causing metamorphopsia. It is intended to be used by patients who have the capability to regularly perform a simple self-test at home. The myVisionTrack® Model 0005 is not intended to diagnose; diagnosis is the responsibility of the prescribing eye-care professional.
 
The myVisionTrack® (Home Vision Monitor) Model 0005 is a modification to the myVisionTrack® Model 0003 (K121738) which was cleared in February 2013. The myVisionTrack® Model 0005 has the same intended use and indications for use, principles of operation, and similar technological characteristics as the previously cleared predicate. The major elements of the technology remain unchanged. The target population and the area of vision monitored is identical between the two devices. The vision test algorithm used and the test algorithm implementation is identical between the two devices.

Policy/
Coverage:
Effective June 2023
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Digital health technologies as a diagnostic aid do not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness unless they are listed as covered in this or another coverage policy. This includes, but is not limited to, the following:
 
    • Canvas Dx™ (Cognoa)
    • myVisionTrack® (Home Vision Monitor®) (Vital Art and Science, LLC)
    • Drowzle™ (Resonea)
    • Halo™ AF Detection System (LIVMOR, Inc)
 
For members with contracts without primary coverage criteria, digital health technologies as a diagnostic aid are considered investigational unless listed as covered in this or another coverage policy. This includes, but is not limited to, the following:
 
    • Canvas Dx™ (Cognoa)
    • myVisionTrack® (Home Vision Monitor®) (HVM) (Vital Art and Science, LLC)
    • Drowzle™ (Resonea)
    • Halo™ AF Detection System (LIVMOR, Inc)
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective April 15, 2023 through May 31, 2023
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Prescription digital health technologies that have received clearance for marketing by the U.S. Food and Drug Administration as a diagnostic aid do not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness including but not limited to the following:
 
    • Canvas Dx™ (Cognoa)
    • Home Vision Monitor® (HVM) (Vital Art and Science, LLC)
 
 
For members with contracts without primary coverage criteria, prescription digital health technologies as a diagnostic aid are considered investigational, including but not limited to:  
 
    • Canvas Dx™ (Cognoa)
    • Home Vision Monitor® (HVM) (Vital Art and Science, LLC)
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
  
Effective January 2023 through April 14, 2023
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Prescription digital health technologies that have received clearance for marketing by the U.S. Food and Drug Administration as a diagnostic aid do not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness including but not limited to the following:
 
    • BlueStar Rx™ (WellDoc®)
    • Canvas Dx™ (Cognoa)
    • d-Nav Insulin Guidance System® (Hygieia)
    • Drowzle™ (Resonea)
    • Embrace2™ Watch technology (Empatica Inc.)
    • Freespira® (PaloAlto Health Sciences, Inc)
    • Halo™ AF Detection System (LIVMOR, Inc)
    • Home Vision Monitor® (HVM) (Vital Art and Science, LLC)
    • Insulia® (Voluntis)
    • leva® Pelvic Digital Health System (Renovia, Inc.)
    • MindMotion™ GO (MindMaze)
    • My Dose Coach™ (Sanofi, Inc.)
    • NightWare™ (Apple Watch®)
    • Nerivio™ (Theranica)
    • Parallel™ (Mahana Therapeutics, Inc)
    • RelieVRx™ (AppliedVR, Inc.)
    • Regulora® (metaMe Health Inc.)
    • Somryst® (Pear Therapeutics, Inc)
 
For members with contracts without primary coverage criteria, prescription digital health technologies as a diagnostic aid that have received clearance for marketing by the U.S. Food and Drug Administration as a diagnostic aid including but not limited to those listed above are considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Prescription digital health technologies that are not addressed in a specific coverage policy as meeting member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness are not covered. For members with contracts without primary coverage criteria, prescription digital health technologies that are not addressed in a specific coverage policy are considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Rationale:
New policy created September 2022 with a search of literature performed through April 25, 2022.
 
This evidence review was created in April 2022 with a search of the PubMed database. The most recent literature update was performed through April 25, 2022.
 
Autism Spectrum Disorder
The American Academy of Pediatrics provides details on the screening and diagnosis for autism spectrum disorder (ASD) (Likin, 2020; Hyman, 2020). Children with ASD can be identified as toddlers, and early intervention can and does influence outcomes (Zwaigenbaum, 2015). The Academy recommends screening all children for symptoms of ASD through a combination of developmental surveillance at 9, 18, and 30 months of age and standardized autism-specific screening tests at 18 and 24 months of age.
 
Screening tools typically use questionnaires that are answered by a parent, teacher, or clinician and are designed to help caregivers identify and report symptoms observed in children at high risk for ASD. While they are generally easy and inexpensive to administer, they have limited sensitivity (ability to identify young children with ASD) and specificity (ability to discriminate ASD from other developmental disorders, such as language disorders and global developmental delay) (Zwaigenbaum, 2009). Results of a screening test are not diagnostic. Due to the variability in the natural course of early social and language development, some children who have initial positive screens (suggesting that they are at risk for ASD) ultimately will not meet diagnostic criteria for ASD (Kleinman, 2008). Other children who pass early screens for ASD may present with atypical concerns later in the second year of life and eventually be diagnosed with ASD. In the context of early identification and diagnosis of ASD, sensitivity is more important than specificity for a screening test as the potential over-referral of children with positive screens is preferable to missing children at risk for ASD. Once a child is determined to be at risk for a diagnosis of ASD, either by screening or surveillance, a timely referral for a comprehensive clinical diagnostic evaluation is warranted. Structured observation of symptoms of ASD during clinical evaluation is helpful to inform the diagnostic application of the DSM-5 criteria. These tools require long and expensive interactions with highly trained clinicians. To meet diagnostic criteria, the symptoms must impair function.
 
Cognoa, the manufacturer of Canvas Dx, has stated on its website that the test “is intended for use by healthcare providers as an aid in the diagnosis of ASD for patients ages 18 months through 72 months who are at risk for developmental delay based on concerns of a parent, caregiver, or healthcare provider (Canvas Dx, 2022). The device is not intended for use as a stand-alone diagnostic device but as an adjunct to the diagnostic process. Further the manufacturer states, "Canvas Dx can aid primary care physician in diagnosing ASD in children starting at 18 months of age during a critical period when interventions are shown to provide/lead to optimal long-term outcomes". The manufacturer also makes indirect and direct assertions that the use of Canvas Dx may allow children with ASD to be diagnosed earlier than the current average age of diagnosis and that the use of this test fulfills an unmet need for a delayed formal diagnosis of ASD after parenteral concern (Canvas Dx, 2022). Some of the reasons cited for the unmet need of a delayed diagnosis is shortage of specialists, time-intensive evaluations, lack of access to care for children from ethnic/racial minorities and/or disadvantaged socioeconomic backgrounds and in rural areas, lack of standard diagnostic process for ASD and use of multiple types of specialists for referral with no clear pathway for primary care physicians.
 
Comparators
The comparator would depend on exactly how the test fits into the diagnostic pathway. Possible comparators could be validated tools used for developmental surveillance, ASD specific-screening tools, and comprehensive diagnostic evaluation tests for confirmatory diagnosis of ASD that are commonly used in the United States.
 
Multiple validated screening tools are available, and tools commonly used in the U.S are summarized in below. The choice of screening test depends upon the age of the child and whether they are being screened for the first time or have been identified through developmental surveillance or screening to be at risk for developmental problems. The AAP recommends developmental and behavioral screening for all children during regular well-child visits at the age of 9, 18, and 30 months. In addition, the AAP also recommends that all children be screened specifically for ASD during regular well-child visits at age of 18 and 24 months.3, At present, there are no validated screening tools available for children older than 30 months and the Academy does not recommend universal screening for ASD in that age group.
 
Commonly Used Screening Instruments and Tools for Autism Spectrum Disorder in the United States:
  • M-CHAT-R/F (16 to 30 months)
    • Description:
      • Parent/caregiver completed questionnaire designed to identify children at risk for autism from the general population
      • 20 items (Dumont, 2005); 5-10 minutes administration time (Robins, 2014)
      • Available in multiple languages (DuBay, 2021)
      • Available for free
    • Sensitivity/Specificity
      • Sensitivity: 91%
      • Specificity: 95% (Robins, 2014)
    • Validation
      • >15,000 children in primary care practices (Robins, 2014)
    • Comments:
      • Validated as first tier screen (First-tier screening tools are used to identify children at risk for ASD from a general population; second-tier screening tools are used to discriminate ASD from other developmental disorders in children with developmental concerns.)
      • This is the most frequently-used test for “screening aged” children in the United States (AAP Toolkits, 2022).
      • Assesses risk of ASD as low, medium, or high. Children at medium risk require structured follow-up questions for additional information before referral for diagnostic evaluation. Follow-up interview takes approximately 5 to 10 minutes (Robins, 2014).
  • STAT (24 to 36 months) (Stone, 2000; Stone, 2004)
    • Description:
      • Clinician-directed, interactive, and observation measure; requires training of clinician for standardized administration; not for population screening (Robins, 2006)
      • 12 observed activities during 20-minute play session (Stone, 2004)
    • Sensitivity/Specificity
      • Sensitivity: 83 to 95% (Stone, 2004)
      • Specificity: 73 to 86% (Stone, 2008)
    • Validation
      • 52 children with ASD and other developmental disorders and 71 high-risk children (Stone, 2004; Stone, 2008)
    • Comments:
      • Not validated as a first tier screen (First-tier screening tools are used to identify children at risk for ASD from a general population; second-tier screening tools are used to discriminate ASD from other developmental disorders in children with developmental concerns.)
      • Primarily a second-stage screen for children already suspected to have high ASD risk, to rule out ASD (AAP Toolkits, 2022).
      • Language comprehension is not required (Robins, 2006).
  • SCQ (4+ years) (Berument, 1999)
    • Description
      • Parent/caregiver completed questionnaire; designed to identify children at risk for ASD from the general population; based on items in the ADI-R
      • 40 items (yes/no); <10 minutes administration time and <5 minutes to score
    • Sensitivity/Specificity
      • Sensitivity: 85%
      • Specificity: 75% (Berument, 1999)
      • 90% of children who failed (SCQ score 15) had a neurodevelopmental disorder (Chandler, 2007)
    • Validation
      • 200 high-risk patients (Berument, 1999)
      • 247 low-risk children from school or general population (Chandler, 2007)
    • Comments
      • Additional studies are necessary before the SCQ can be used as a first-tier screen. (First-tier screening tools are used to identify children at risk for ASD from a general population; second-tier screening tools are used to discriminate ASD from other developmental disorders in children with developmental concerns.)
      • This tool is for older children.
      • Nonverbal children may require different cut-off scores (Eaves, 2006).
  • ITC (6 to 24 months) (Wetherby, 2008)
    • Description
      • Parent/caregiver questionnaire: screens for language delay
      • 24-item (component of CSBS-DP); 15 mins administration time (Wetherby, 2008)
    • Sensitivity/Specificity
      • Sensitivity and specificity of 88.9 for identifying ASD or other developmental delays
      • PPV: 71 to 79 and NPV: 88 to 99 for 9- to 24-month-old children (Wetherby, 2008).
    • Validation
      • 5385 children from a general population (Wetherby, 2008)
      • Digital screening (n=57,603) as part of community-screen-evaluate-treat model (Pierce, 2021)
    • Comments:
      • Studies support the validity for children 9 to 24 months of age but not 6 to 8 months. (Wetherby, 2008)
  • POSI (16 to 35 months)
    • Description
      • Parent/caregiver questionnaire used to assess autism risk developed as part of a comprehensive primary care screening instrument, the Survey of Wellbeing of Young Children
      • 7-item parent/caregiver reported items; 5 minutes to complete
    • Sensitivity/Specificity
      • Age 16 to 36 months
        • Sensitivity: 83% and Specificity: 74%
      • Age 18 to 48 months
        • Sensitivity: 89% and Specificity: 54%
      • Age 16 to 48 months (Salisbury, 2018)
        • Sensitivity: 94% and Specificity: 41%
      • Age 16 to 30 months (Salisbury, 2018)
        • Sensitivity: 75% and Specificity: 48%
    • Validation
      • 232 children (16 to 36 months) from primary care and specialty clinics
      • 217 children (18 to 48 months) from specialty clinic
      • 524 children (16 to 48 months) referred to a developmental-behavioral clinic
    • Comments
      • Additional studies in community samples are necessary before the POSI can be recommended as a first-tier screen. (First-tier screening tools are used to identify children at risk for ASD from a general population; second-tier screening tools are used to discriminate ASD from other developmental disorders in children with developmental concerns.)
      • This is a good choice for practices that seek integrated autism and developmental screening.
 
The AAP does not approve/endorse any specific tool for screening purposes (AAP Toolkits, 2022). This list is not exhaustive, and other tests are available such as the Autism Spectrum Screening Questionnaire (ASSQ), Developmental Behavior Checklist-Autism Screening Algorithm (DBC-ASA), Developmental Behavior Checklist-Early Screen (DBC-ES), Developmental Behavior Checklist for Pediatrics (DBC-P), Intelligence Quotient (IQ), and Rapid Interactive Screening Test for Autism in Toddlers (RITA-T).
 
First-tier screening tools are used to identify children at risk for ASD from a general population; second-tier screening tools are used to discriminate ASD from other developmental disorders in children with developmental concerns.
 
Diagnostic tools commonly used in the US are summarized below. The accuracy of many of these tools has not been well studied (Randall, 2018). Tools that are recommended in national guidelines and used in the U.S. include Autism Diagnostic Interview-Revised (ADI-R), Autism Diagnostic Observation Schedule-2nd edition (ADOS-2), and Childhood Autism Rating Scale 2nd edition (CARS-2). According to a 2018 Cochrane systematic review and meta-analyses, authors observed substantial variation in sensitivity and specificity of all tests. According to summary statistics for ADOS, CARS, and ADI-R, ADOS was found to be the most sensitive. All tools performed similarly for specificity (Randall, 2018).
 
Commonly Used Diagnostic Instruments and Tools for Autism Spectrum Disorder in the United States
  • ADI-R (Mental age 18 months)
    • Description
      • 2- to 3-hour 93-point semi-structured clinical interview that probes for ASD symptoms
    • Comments
      • Not practical for clinical settings
      • Usually used in research settings, often combined with the ADOS-2
  • ADOS-2nd edition (Age 12 months through adulthood)
    • Description
      • Semi-structured assessment by trained clinician of social interaction, play/imaginative use of materials, communication and atypical behaviors
      • 5 modules based on child's expressive language abilities (including one for toddlers)
      • Takes 40 to 60 minutes to administer
    • Comments:
      • Reference standard for diagnosis of ASD in research studies and clinical settings
      • The information obtained from the ADOS-2 is used by the clinician in conjunction with the history of peer interactions, social relationships, and functional impairment from symptoms to determine if the DSM-5 criteria are met
  • CARS-2 (Children 2 years of age)
    • Description
      • 15 items directly observed by a trained clinician and a parent unscored questionnaire
      • Takes 20 to 30 minutes to administer
    • Comments:
      • 15 items are correlated with DSM-5
 
This list is not exhaustive, and other tests are available such as Developmental Dimensional and Diagnostic Interview (3di), Diagnostic Interview for Social and Communication Disorder (DISCO), Gilliam Autism Rating Scale (GARS) and Social Responsiveness Scale, Second edition (SRS). According to AAP, validated observation tools include the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) and the Childhood Autism Rating Scale, Second Edition (CARS-2). No single observation tool is appropriate for all clinical settings (Hyman, 2020).
 
Diagnostic Performance
A study by Abbas et al evaluated the performance of the Canvas Dx (formerly known as Cognoa App) for diagnosing ASD (Abbas, 2020). The study included at-risk children 18 to 72 months of age, with English speaking parents who were referred to specialized centers in the U.S. for a comprehensive evaluation and diagnosis of ASD. All children received an Autism Diagnostic Observation Schedule (ADOS) as well as standard screening tool like Modified Checklist for Autism in Toddlers, Revised (M-CHAT-R), and Child Behavior Checklist (CBCL). Prior to the children receiving the comprehensive clinical assessment, parents of the children completed the Canvas Dx app. The app consisted of 3 modules (parent questionnaire, video, and clinician questionnaire). Much of the publication outlines the details of machine learning methods in training datasets. These details were not reviewed. Results of the study showed that Canvas Dx outperformed baseline screeners administered to children by 0.35 (90% CI: 0.26 to 0.43) in AUC and although the thresholds used for categorization were not specified, there was an improvement of 0.69 (90% CI: 0.58 to 0.81) in specificity when operating at 90% sensitivity. Compared to the baseline screeners evaluated on children less than 48 months of age, Canvas Dx outperforms baseline screeners by 0.18 (90% CI: 0.08 to 0.29 at 90%) in AUC and 0.30 (90% CI: 0.11 to 0.50) in specificity when operating at 90% sensitivity.
 
The major limitation is the lack of clarity on how the test fits into the current pathway (i.e, whether it's a screening test or a diagnostic test). As per the FDA-cleared indication, Canvas Dx is intended for use as an aid in the diagnosis of ASD. This cleared indication is not explicit about whether Canvas Dx is intended to be used as a screening test in the community setting or if it is to be used as an adjunct with other standard diagnostic tools at a specialist office for diagnosis of ASD or possibly a third scenario- as a diagnostic tool in a community setting used by primary care physicians. Each of the 3 scenarios will require a unique PICO formulation and unless there is clarity on intended use, it is difficult to interpret currently available evidence. Second, the manufacturer asserts that Canvas Dx is intended to be used by a primary care physician to aid in the diagnosis of ASD, but the only published study on clinical validity used a specialist rather than a primary care physician to complete the clinical questionnaire module. This is likely to result in higher sensitivity and specificity and thus confounds the interpretation of published data on clinical validity. Further testing in primary care clinics is needed to validate accuracy of the clinician module. In addition, all published studies were conducted on children who had been preselected as having a high risk of autism. No studies on children from the general population have been published. Other limitations include differences that may occur between the testing environments of a structured clinical setting versus the home setting.
 
American Academy of Pediatrics
The American Academy of Pediatrics (AAP) guidelines recommend ASD-specific universal screening in all children at ages 18 and 24 months in addition to developmental surveillance and monitoring (Lipkin, 2020). Toddlers and children should be referred for diagnostic evaluation when increased risk for developmental disorders (including ASD) is identified through screening and/or surveillance. Children should be referred for intervention for all identified developmental delays at the time of identification and not wait for an ASD diagnostic evaluation to take place. The AAP does not approve nor endorse any specific tool for screening purposes. The AAP has published a toolkit that provides a list of links to tools for developmental surveillance and screening for use at the discretion of the health care professional (AAP Toolkits, 2022).
 
The American Academy of Child and Adolescent Psychiatry
The American Academy of Child and Adolescent Psychiatry recommends that the developmental assessment of young children and the psychiatric assessment of all children should routinely include questions about ASD symptomatology (Volkmar, 2014).
 
The UK National Screening Committee
The UK National Screening Committee does not recommend systematic population screening for ASD because
    • There is not currently a test that is good enough for screening the general population
    • It is not known if screening would improve long term outcomes for children with autism
    • There is not an established approach to screening which is acceptable to parents (UK National Screening Committee, 2022)
 
These recommendations were based on a summary of evidence published in 2012. The next review is estimated to be completed in 2022.
 
U.S. Preventive Services Task Force Recommendations
The U.S. Preventive Services Task Force (USPSTF) published recommendations for ASD in young children in 2016 (Siu, 2016). The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for ASD in young children (children 18 to 30 months of age) for whom no concerns of ASD have been raised by their parents or a clinician.
 
Ongoing and Unpublished Clinical Trials
Ongoing Clinical Trials
  • NCT05223374 Extension for Community Healthcare Outcomes (ECHO) Autism Diagnostic Study in Primary Care Setting with a planned enrollment of 100 and a completion date of June 30, 2023
 
Unpublished Clinical Trials
  • NCT04326231a Cognoa ASD Digital Therapeutic Engagement and Usability Study with a planned enrollment of 30 and completion date of July 2020
  • NCT04151290a Cognoa ASD Diagnosis Aid Validation Study with a planned enrollment of 711 and a completion date of August 31, 2020
 
2023 Update
Annual policy review completed with a literature search using the MEDLINE database through August 2023. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
A study on diagnostic performance of Canvas Dx was published by Megerian et al. It was a double-blind, multicenter, prospective, comparator cohort study testing the diagnostic accuracy of Canvas Dx in a primary care setting (Megerian, 2022). The study compared Canvas Dx output to diagnostic agreement by 2 or more independent specialists in a cohort of 18 to 72-month-olds with developmental delay concerns. A total of 711 participants were enrolled and 425 completed both the device input and specialist evaluation component of the study between August 2019 and June 2020. The majority of study participants (68% or 290/425) were classified as “indeterminates” by Canvas DX. For the 32% of participants who received a determinate output (ASD positive or negative), sensitivity was 98.4% (95% CI, 91.6% to 100%), specificity was 78.9% (95% CI, 67.6% to 87.7%), PPV was 80.8% (95% CI, 70.3% to 88.8%) and NPV was 98.3% (95% CI, 90.6% to 100%).

CPT/HCPCS:
99199Unlisted special service, procedure or report
A9291Prescription digital cognitive and/or behavioral therapy, fda cleared, per course of treatment
E1399Durable medical equipment, miscellaneous
T1505Electronic medication compliance management device, includes all components and accessories, not otherwise classified

References: Abbas H, Garberson F, Liu-Mayo S, et al.(2020) Multi-modular AI Approach to Streamline Autism Diagnosis in Young Children. Sci Rep. Mar 19 2020; 10(1): 5014. PMID 32193406

American Psychiatric Association (APA).(2013) Diagnostic and Statistical Manual of Mental Disorders (DSM-5), 5th ed. Washington, DC: American Psychiatric Association; 2013

Autism Spectrum Disorder: Links to Commonly Used Screening Instruments and Tools (AAP Toolkits).(2022) American Academy of Pediatrics. Accessed on April 27, 2022. Available at https://publications.aap.org/toolkits/pages/asd-screening-tools

Berument SK, Rutter M, Lord C, et al.(1999) Autism screening questionnaire: diagnostic validity. Br J Psychiatry. Nov 1999; 175: 444-51. PMID 10789276

Canvas Dx Website.(2022) Accessed on April 25, 2022. Available at https://canvasdx.com/

Chandler S, Charman T, Baird G, et al.(2007) Validation of the social communication questionnaire in a population cohort of children with autism spectrum disorders. J Am Acad Child Adolesc Psychiatry. Oct 2007; 46(10): 1324-1332. PMID 17885574

Dawson G, Bernier R.(2013) A quarter century of progress on the early detection and treatment of autism spectrum disorder. Dev Psychopathol. Nov 2013; 25(4 Pt 2): 1455-72. PMID 24342850

Dawson G, Rogers S, Munson J, et al.(2010) Randomized, controlled trial of an intervention for toddlers with autism: the Early Start Denver Model. Pediatrics. Jan 2010; 125(1): e17-23. PMID 19948568

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