Coverage Policy Manual
Policy #: 2023004
Category: Medicine
Initiated: January 2023
Last Review: January 2024
  Digital Health Technologies: Therapeutic 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 therapeutic application and meet the following 3 criteria: 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 (FDA) either through the de novo premarket process or 510(k) process or pre-market approval and 3) Must be prescribed by a healthcare provider.
 
Regulatory Status
The following are examples of Practitioner-prescribed, FDA cleared or approved mobile based software applications.
 
BlueStar®Rx, WellDoc®
BlueStar is a digital health platform for type 2 diabetes that provides tailored guidance driven by artificial intelligence and is focused on six critical dimensions of chronic disease care, which apply to diabetes as well as many other conditions like blood pressure, pre-diabetes, and heart failure.
 
d-Nav Insulin Guidance System®, Hygieia
The d-Nav Insulin Guidance System was evaluated in a multicenter RCT of 181 individuals with uncontrolled type 2 diabetes. Participants were randomized to either d-Nav and healthcare professional support (intervention group; n=93) or healthcare professional support alone (control group; n=88). The primary outcome of interest was to compare average change in HbA1c from baseline to 6 months. Safety was assessed by the frequency of hypoglycemic events. The mean decrease in HbA1c from baseline to 6 months was 1.0% in the intervention group, and 0.3% in the control group (p<0.0001). The difference in frequency of hypoglycemic events between the groups was not statistically significant (Bergenstal, 2019). Current data is limited to a single study of small sample size and long-term data of net health outcomes is lacking.
 
Insulia®, Voluntis
Insulia is a Software program that recommends basal insulin doses for adults with Type 2 diabetes treated with long-acting insulin analogs as an aid in the management of diabetes based on the treatment plan created by a healthcare provider.
 
Freespira® (Canary Breathing System), Freespira
Freespira received FDA approval in 2018 It is a small breathing sensor with a tablet that is used twice a day for 17 minutes. Individuals are trained to use the Sensor with the Mobile App to measure and display their EtCO2 level and RR and how different breathing habits affect EtCO2 levels. The FDA cleared indication for Freespira is intended for use as a relaxation treatment for the reduction of stress by leading the user through guided and monitored breathing exercises. The device is indicated as an adjunctive treatment of symptoms associated with panic disorder and/or PTSD, to be used under the direction of a healthcare professional, together with other pharmacological and/or non-pharmacological interventions.
 
NightWare(TM), NightWare, Inc
NightWare received FDA approval with breakthrough device designation clearance in 2020. The NightWare is a therapeutic platform using a proprietary AppleWatch® application. The app learns the wearer’s sleep patterns and customizes treatment to the individual. The app monitors the wearer’s heart rate and movement while sleeping and arouses the wearer with a vibration alert when a stress threshold is reached so as not to awaken the individual. Users wear the watch only while sleeping and not during the day. The FDA cleared indication for NightWare is to provide vibrotactile feedback on an Apple Watch based on an analysis of heart rate and motion during sleep for the temporary reduction of sleep disturbance related to nightmares in adults 22 years or older who suffer from nightmare disorder or have nightmares from PTSD. It is intended for home use.
 
Parallel™, Mahana Therapeutics, Inc
Parallel (formerly known as Regul8) is a Digital program that uses cognitive behavioral therapy (CBT) to reduce the severity of symptoms for irritable bowel syndrome (IBS). It is intended to be used together with other IBS treatments to treat adults, 22 years or older, for up to 3 months.
 
Regulora®, metaMe Health Inc.
Regulora provides gut-directed hypnotherapy for adults 22 years of age and older who have been diagnosed with IBS. Regulora is indicated as a 3-month treatment for individuals with abdominal pain due to IBS and is intended to be used together with other IBS treatments.
 
Somryst®, Pear Therapeutics
Somryst received FDA approval in 2020. The therapy is a self-directed 9-week course of 6 core modules delivered via an app used on an individual’s mobile device. Somryst® is identical to an earlier internet-based web-based platform called SHUTi. SHUTi incorporates the primary tenets of face-to-face CBT-I except for relaxation and medication titration. SHUTi did not include the clinician dashboard feature that Somryst utilizes. The FDA cleared indication is to provide a neurobehavioral intervention (CBT-I) in individuals 22 years of age and older with chronic insomnia. Somryst treats chronic insomnia by improving a patient’s insomnia symptoms.
 
Coding
 
There are no specific CPT or HCPCS codes for this service. The following codes may be billed:
 
CPT
 
99199 Unlisted special service, procedure or report [when specified as a mobile-based health management software application]
 
HCPCS
 
A9291 Prescription digital cognitive and/or behavioral therapy, fda cleared, per course of treatment
 
E1399 Durable medical equipment, miscellaneous [when specified as a mobile-based health management software application]
 
T1505 Electronic medication compliance management device, includes all components and accessories, not otherwise classified [when specified as a mobile-based health management software application]

Policy/
Coverage:
For Digital Health Technologies: Diagnostic Applications see coverage policy 2022036.
 
Effective January 2024
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Digital health technologies as a therapeutic aid do not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness unless listed as covered in this or another coverage policy. This includes, but is not limited to, the following:
 
· BlueStar Rx™ (WellDoc®)
· d-Nav Insulin Guidance System® (Hygieia)
· Embrace2™ Watch technology (Empatica Inc.)
· Freespira® (PaloAlto Health Sciences, Inc)
· Insulia® (Voluntis)
· leva® Pelvic Digital Health System (Renovia, Inc.)
· Luminopia (Luminopia, Inc) (eff. 10/01/2023)
· MindMotion™ GO (MindMaze)
· My Dose Coach™ (Sanofi, Inc.)
· Natural Cycles Birth Control (NC Birth Control)
· Natural Cycles Plan Pregnancy (NC Plan Pregnancy)
· NightWare™ (Apple Watch®)
· Nerivio™ (Theranica)
· Parallel™ (Mahana Therapeutics, Inc)
· RelieVRx™ (AppliedVR, Inc.)
· Regulora® (metaMe Health Inc.)
· Somryst® (Pear Therapeutics, Inc) (Note: Effective 04/07/2023, Pear Therapeutics is no longer accepting new prescriptions or dispensing refills.)
 
For members with contracts without primary coverage criteria, digital health technologies as a therapeutic aid are considered investigational unless listed as covered in this or another coverage policy. This includes, but is not limited to, the following:
 
· BlueStar Rx™ (WellDoc®)
· d-Nav Insulin Guidance System® (Hygieia)
· Embrace2™ Watch technology (Empatica Inc.)
· Freespira® (PaloAlto Health Sciences, Inc)
· Insulia® (Voluntis)
· leva® Pelvic Digital Health System (Renovia, Inc.)
· Luminopia (Luminopia, Inc) (eff. 10/01/2023)
· 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) (Note: Effective 04/07/2023, Pear Therapeutics is no longer accepting new prescriptions or dispensing refills.)
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective June 2023 through September 2023
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Digital health technologies as a therapeutic aid do not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness unless listed as covered in this or another coverage policy. This includes, but is not limited to, the following:
 
    • BlueStar Rx™ (WellDoc®)
    • d-Nav Insulin Guidance System® (Hygieia)
    • Embrace2™ Watch technology (Empatica Inc.)
    • Freespira® (PaloAlto Health Sciences, Inc)
    • Insulia® (Voluntis)
    • leva® Pelvic Digital Health System (Renovia, Inc.)
    • MindMotion™ GO (MindMaze)
    • My Dose Coach™ (Sanofi, Inc.)
    • Natural Cycles Birth Control (NC Birth Control)
    • Natural Cycles Plan Pregnancy (NC Plan Pregnancy)
    • NightWare™ (Apple Watch®)
    • Nerivio™ (Theranica)
    • Parallel™ (Mahana Therapeutics, Inc)
    • RelieVRx™ (AppliedVR, Inc.)
    • Regulora® (metaMe Health Inc.)
    • Somryst® (Pear Therapeutics, Inc) (Note: Effective 04/07/2023, Pear Therapeutics is no longer accepting new prescriptions or dispensing refills.)
 
For members with contracts without primary coverage criteria, digital health technologies as a therapeutic aid are considered investigational unless listed as covered in this or another coverage policy. This includes, but is not limited to, the following:
 
    • BlueStar Rx™ (WellDoc®)
    • d-Nav Insulin Guidance System® (Hygieia)
    • Embrace2™ Watch technology (Empatica Inc.)
    • Freespira® (PaloAlto Health Sciences, Inc)
    • 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) (Note: Effective 04/07/2023, Pear Therapeutics is no longer accepting new prescriptions or dispensing refills.)
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective April 15, 2023- 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 therapeutic 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®)
    • d-Nav Insulin Guidance System® (Hygieia)
    • Drowzle™ (Resonea)
    • Embrace2™ Watch technology (Empatica Inc.)
    • Freespira® (PaloAlto Health Sciences, Inc)
    • Halo™ AF Detection System (LIVMOR, Inc)
    • 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) (Note: Effective 04/07/2023, Pear Therapeutics is no longer accepting new prescriptions or dispensing refills.)
 
For members with contracts without primary coverage criteria, prescription digital health technologies as a therapeutic aid that have received clearance for marketing by the U.S. Food and Drug Administration 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 coverage policy with literature search through October 2022.
 
Panic Disorder and Post-Traumatic Stress Disorder
Two pivotal single-arm studies have been reported on the Freespira app for panic disorder, and PTSD (Tolin, 2017; Ostacher, 2021). No limitations in study relevance were noted. Both studies have significant dropout rate and consequently data is missing for more than 30% of study participants in both studies. For example, study dropout rate was 33%, 39%, and 52% at 2, 6, and 12 months of follow-up in Tolin et al and 24% and 31% at 2 and 6 months of follow-up in Ostacher et al. No clear description of reasons for missingness, characteristics of missing observations, or sensitivity analyses of missing data assumptions were provided. In addition to the 2 pivotal studies, one single-arm study published by Kaplan et al funded by a payer (Highmark Health) reported findings in 52 individuals with a diagnosis of panic disorder (Kaplan, 2020). The primary goal of this study was to determine if treatment with Freespira in individuals with panic disorder would significantly reduce the cost of care in the 12 months following treatment. This single-arm study suffers from similar drawbacks as the first 2 pivotal studies.
 
Nightmare Disorder and Post-Traumatic Stress Disorder-Associated Nightmares
One pivotal double-blind sham-controlled RCT conducted in a Veterans Administration Center has been reported in the manufacturers "Instructions for Use".12, This trial has not been published in a peer reviewed journal.
 
The trial was designed to enroll 240 participants with PTSD and nightmares, however, only 70 were enrolled. Data from 63 trial participants were included on the primary and secondary outcome measures. The primary outcome was the difference in the Pittsburg Sleep Quality Index (PSQI). The change from baseline was numerically higher for the NightWare group compared to sham, but the difference did not achieve statistical significance. There was no statistical difference observed in multiple other secondary endpoints such as change from baseline to day 30 in the active treated arm versus sham in the following outcome measures: PTSD Checklist for DSM-5 (PCL-5), Patient Health Questionnaire 9-item depression scale (PHQ-9), Trauma-Related Nightmare Survey (TRNS), Functional Outcomes of Sleep Questionnaire (FOSQ-10), and Veterans RAND 12 Item Health Survey (VR-12). The 2 primary safety measures of Nightmare device were to assess worsening of daytime sleepiness as assessed by the Epworth Sleepiness Scale (ESS) and increase in suicidality as assessed by the Columbia Suicide Severity Rating Scale (CSSRS).
 
This trial failed to achieve recruitment goals and was likely underpowered.
 
Chronic Insomnia
The Somryst is a mobile adaptation (with identical therapeutic content) of Sleep Healthy Using the Internet (SHUTi) – a web-based CBT-I intervention that has been evaluated in numerous RCTs with several thousand participants. Trials that have evaluated efficacy of CBT-I are not within the scope of this review. The manufacturer submitted data from 2 pivotal trials for FDA clearance for Somryst for chronic insomnia. These include The University of Virginia (UVA) study by Ritterband et al and the GoodNight study by Christensen et al (Ritterband, 2017; Christensen, 2016). The Chirstensen study is not included in this review for 2 reasons; one, the study participants did not meet the DSM-5 criteria (see Appendix) for chronic insomnia and second, the primary objective was to evaluate the efficacy of SHUTi as a depression prevention program among individuals with chronic insomnia. Further, secondary analyses of these trials have also been excluded (Batterham, 2017; Chow, 2018; Shaffer, 2020; Shaffer, 2021). In addition, other studies were excluded because they enrolled participants that did not meet the DSM-5 criteria (see Appendix) for chronic insomnia, or enrolled participants who primary complaint was not chronic insomnia such as individuals with breast cancer experiencing clinically significant sleep disturbances, or individuals with depression with insomnia, or the study evaluated a culturally tailored SHUTi version for insomnia symptoms (but not chronic insomnia defined by DSM-5) (Vedaa, 2020; Hagatun, 2019; Zachariae, 2018; Amidi, 2022; Glozier, 2019; Zhou, 2022).
 
The UVA study showed a clinically meaningful difference in favor of SHUTi compared to a digital placebo control based on the average reduction in mean scores of self-reported insomnia severity (such as ISI) and sleep diary-derived values for outcomes related to sleep latency (such as sleep onset latency [SOL] and Wake after sleep onset [WASO]). The proportion of participants achieving a clinically meaningful insomnia treatment response or remission of insomnia (as defined above by ISI scores) was also significantly greater in favor of the SHUTi treatment group at all time points (9 weeks, 6 months and 12 months) (Ritterband, 2017). In the UVA study, 12% and 7% of participants randomized to active and control arms did not complete the Somryst program after being randomized. The proportion of participants who did not complete follow-up at 6 months was 25% and 15% in the active versus control arm respectively. At 12 months, 19% and 16% participants missed the follow-up in the active versus control arm respectively. The authors expected a 35% attrition rate and the observed rate was 17% at 12 months. The authors used a mixed model repeated measures ANOVA to account for missing data and to include all available data for participants analyzed in the trial and reported that this approach yields unbiased estimates of intervention effects in the assumption that data were missing at random. However, no clear description of reasons for missingness, characteristics of missing observations, or sensitivity analyses of missing data assumptions were provided. A systematic review conducted by American Academy of Sleep Medicine for behavioral and psychological treatments for chronic insomnia disorder in adults identified 66 RCTs of which 49 were included in the meta-analyses (Edinger, 2021). The authors concluded that the overall benefits of CBT-I versus control were moderate based on improvements in WASO, remission rates, and responder rates that met the clinical significance thresholds established by the task force. Overall quality of evidence was rated as moderate because of imprecision and a risk of bias. There was insufficient evidence to make recommendations for specific delivery methods (eg, individual, group, internet, self-help, video). Authors also noted that it was not yet clear which patients can benefit from self-directed approaches and which patients require the support of a skilled provider for CBT-I. While a non-inferiority trial between in-person CBT-I versus alternate method of delivery of CBT-I such as Somryst has not been conducted, the observed magnitude of treatment effect in the UVA study along with the body of evidence that supports efficacy of CBT-I are persuasive of overall benefit with Somryst.
 
Observational Studies
Ritterband et al, 2022 published the findings of a retrospective study comprising of 7303 adults who purchased access to the digital CBT-I therapeutic between December 2015 and February 2019 from the manufacturer (Ritterband, 2022). The study was not registered at clinicaltrial.gov and its unclear if the protocol of the study and outcome analysis was specified a priori. The study included individuals who purchased SHUTi and learned about it through word-of-mouth, news stories, online postings, and/or their healthcare provider. A prescription was not required for the purchase. Providers who were interested in SHUTi could obtain a clinician code that an individual could use when signing up for SHUTi enabling their provider to be able to monitor their progress if desired. Just over 30% used a clinician code when registering. At the start of each core, users were prompted to complete the ISI. Although a formal diagnosis of chronic insomnia was not required to purchase the app, users reported experiencing a median of 60 months of sleep difficulties (with a range of 18-120 months), and nearly all (97.6%) reported experiencing sleep difficulties at least three or more nights per week. In addition, 75.6% reported “poor” or “very poor” sleep quality, and most indicated that their poor sleep had reduced their daytime energy (92.8%), required more effort to get tasks completed (86.9%), made it more difficult to function during the day (90.3%); caused problems with concentration and/or attention (87.8%), and affected their mood (86.8%) in that they felt more irritable, tense, depressed, and/or confused. Of the 7303 participants, completion rates for core 1 through 6 were 99%, 88%, 77%. 66%, 56% and 45% respectively. The proportion of responders (defined as a reduction of >7 points on the ISI) increased from 4.8% at core 2 completion timepoint to 61.4% at the start of core 6. The proportion of individuals achieving remission (<8 on ISI) increased from 1.7% at the start of core 2 to 40.3% at the start of core 6. While these data provide reassurance that SHUTi was effective in a large real-world population of individuals with insomnia, a major challenge for interpreting this dataset is the number of participants with missing data.
 
BlueStar was evaluated in a randomized controlled trial (RCT) which enrolled 163 individuals with type 2 diabetes whose HbA1c levels were poorly controlled or abnormal at the time of enrollment. Enrolled primary care practices (PCP) were randomized to one of four study groups: control-usual care (n=56), coach-only (n=23), coach PCP portal (n=22), and coach PCP portal with decision support (n=62). Participants who were randomized to use an MSA to help manage their diabetes in addition to usual care, improved HbA1c by an average 1.9%, compared with a 0.7% improvement in those randomized to usual care alone, a difference of 1.2% (p<0.001) over the 12-month study period (Quinn, 2011). The study’s limitations include a small sample size in the study arms and due to randomization at the clinical level, potential confounding association cannot be ruled out.
 
Agarwal and colleagues conducted a multicenter, pragmatic RCT to determine if BlueStar application usage leads to improved HbA1c levels among diverse participants across diverse clinical scenarios (Agarwal, 2020). In total, 223 study participants were randomized to either the ‘immediate treatment group’ (ITG; n=110 [received the BlueStar intervention for 6 months]) or the wait-list control group (WLC; n=113 [received usual care for the first 3 months and then received the intervention for 3 months]). The primary outcome was HbA1c levels at 3-month follow-up. Secondary outcomes assessed disease self-management, experience of care, and self-reported health utilization. At 3 months, the mean difference in HbA1c levels between the ITG and WLC groups was not statistically significant (mean difference = -0.42; 95% confidence interval [CI], -1.05 to 0.21; p=0.19). Similarly, there was no effect on secondary outcomes and BlueStar usage was found to vary significantly across clinical sites (median of 9 versus 36 log-ins over 14 weeks at the lowest, versus highest usage sites, respectively). Evidence of BlueStar’s clinical efficacy remains to be established in addition to defining factors that may affect individual and site-specific variations that impact the application’s usage as recommended.
 
d-Nav Insulin Guidance System®, Hygieia
The d-Nav Insulin Guidance System was evaluated in a multicenter RCT of 181 individuals with uncontrolled type 2 diabetes. Participants were randomized to either d-Nav and healthcare professional support (intervention group; n=93) or healthcare professional support alone (control group; n=88). The primary outcome of interest was to compare average change in HbA1c from baseline to 6 months. Safety was assessed by the frequency of hypoglycemic events. The mean decrease in HbA1c from baseline to 6 months was 1.0% in the intervention group, and 0.3% in the control group (p<0.0001). The difference in frequency of hypoglycemic events between the groups was not statistically significant (Bergenstal, 2019). Current data is limited to a single study of small sample size and long-term data of net health outcomes is lacking.
 
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). Drowzle was evaluated in a longitudinal cohort study of 59 individuals who were administered a clinically indicated polysomnography (PSG) in a sleep lab where investigators compared the DROWZLE algorithm to PSG results. Investigators found the algorithm provided a sensitivity of 93.7%, specificity of 63.0%, negative predictive value of 89.5%, and positive predictive value of 75.0%, in the detection of moderate and severe OSA among individuals compared to PSG scores (Narayan, 2019). Studies evaluating real-world application are lacking, as is data describing how screening results impact diagnosis and management of OSA as compared to generally accepted standards of medical practice.
 
Halo™ AF Detection System, LIVMOR, Inc
Halo is a wearable smartwatch device for intermittently monitoring pulse rhythms to detect atrial fibrillation (AF). While there is no published peer-reviewed evidence at this time evaluating the Halo device, a retrospective propensity-matched cohort study was published in 2021 (Wang) which included 125 individuals with AF using wearables to monitor heart rate and rhythm and 500 with AF who did not use wearables. Study participants were followed for 90 days to compare pulse rate and healthcare use between individuals who wore wearables and those who did not. The study found that prior to propensity matching, those who use wearables were, on average, significantly younger (p<0.001) and healthier (composite score of congestive heart failure, hypertension, diabetes, prior ischemic event, vascular disease, age, and gender; p<0.001). After matching, study participants using wearables were found to have similar pulse rates, to those who did not, but utilized significantly more healthcare. In particular, there was a significant difference in receipt of a cardiac ablation, with 17.6% (n=22) in the wearables group compared to 7.4% (n=37; p=0.001) having received an ablation. The study authors conclude, “Given the increasing use of wearables by patients with AF, prospective, randomized, long-term evaluation of the associations of wearable technology with health outcomes and health care use is needed.”
 
ome Vision Monitor® (HVM), Vital Art and Science, LLC
Home Vision Monitor is intended for the detection and characterization of central 3 degrees metamorphopsia (visual distortion) in individuals with maculopathy, including age-related macular degeneration and diabetic retinopathy, and as an aid in monitoring progression of disease factors causing metamorphopsia.
 
Korot and colleagues studied the Home Vision Monitor in a cohort study of 417 individuals to evaluate uptake and engagement of the application but no published studies have evaluated clinically meaningful outcomes related to use of the software (Karot, 2021).
 
Insulia®, Voluntis
Insulia is a Software program that recommends basal insulin doses for adults with Type 2 diabetes treated with long-acting insulin analogs as an aid in the management of diabetes based on the treatment plan created by a healthcare provider.
Insulia was evaluated in a 13-month RCT which enrolled a total of 191 participants with inadequately controlled type 2 diabetes who were randomized into three groups: group 1 (standard care, n=63), group 2 (interactive voice response system, n=64) and group 3 (Diabeo-BI app software, n=64). At 4 months follow-up, HbA1c reduction was significantly higher in the telemonitoring groups (p<0.002). Fasting blood glucose was reached by twice as many subjects in the telemonitoring groups as in the control group, and insulin doses were also titrated to higher levels. No severe hypoglycaemia was observed in the telemonitoring groups and mild hypoglycaemia frequency was similar in all groups (Franc, 2019). Current data is limited to a short period of evaluation, and the comparison arms sample sizes were limited.
 
Parallel™, Mahana Therapeutics, Inc
Parallel (formerly known as Regul8) is a Digital program that uses cognitive behavioral therapy (CBT) to reduce the severity of symptoms for irritable bowel syndrome (IBS). It is intended to be used together with other IBS treatments to treat adults, 22 years or older, for up to 3 months.
 
The premise behind Parallel (web-based CBT) was evaluated in the Assessing Cognitive behavioural Therapy for IBS (ACTIB) trial, a three-arm, RCT in which 558 participants were enrolled into either a telephone-delivered CBT (TCBT; n=186) group, web-based CBT (WCBT; n=185) group with minimal therapist support, or treatment as usual (TAU, n=187) (Everitt 2019a). Both intervention groups continued to also receive treatment as usual. The primary outcomes of interest were IBS Symptom Severity Score (IBS-SSS) and Work and Social Adjustment Scale (WSAS) at 12 months. At study end, 27% of the TCBT arm, 73% of the WCBT arm, and 30% of the TAU group were lost to follow-up. Of the remaining study participants, compared with TAU, IBS-SSS and WSAS scores were significantly lower in the TCBT group (both scores p<0.001) and the WCBT group (p=0.002 and p=0.001, respectively) at 12 months. There were no serious adverse reactions to any interventions. The study was limited by a substantial loss to follow-up and the dissimilarities between the interventions in the study and the Parallel application. Also, comparison to in-person CBT is lacking.
 
Everitt and colleagues (2019b) conducted a 24-month follow-up to the ACTIB trial, at which time, 58% (n=323 of the original 558 participants remained). At 24 months the IBS-SSS score was significantly lower in the TCBT group (p=0.002) relative to TAU but the differences in the WCBT group were not sustained (p=0.33). Similarly, the mean WSAS score was lower in the TCBT group (p<0.001) but differences in the WCBT group fell to marginal significance (p=0.036) relative to the TAU group. Given the continued substantial loss to follow-up and loss in significance in the WCBT group (more comparable to the Parallel application software design than TCBT), the efficacy of the application as an intervention for refractory
IBS, remains to be established.
 
Regulora®, metaMe Health Inc.
Regulora provides gut-directed hypnotherapy for adults 22 years of age and older who have been diagnosed with IBS. Regulora is indicated as a 3-month treatment for individuals with abdominal pain due to IBS and is intended to be used together with other IBS treatments. There is no published peer-reviewed evidence evaluating the efficacy of Regulora.
 
reSET® and reSET-O®, Pear Therapeutics, Inc
reSET® and reSET-O are mobile device software applications intended to increase retention of individuals with opioid use disorder (OUD) and substance use disorder in outpatient treatment by providing cognitive behavioral therapy, as an adjunct to outpatient treatment, for individuals 18 years or older who are currently under the supervision of a clinician.
 
ReSET-O was evaluated in a randomized, unblinded, parallel trial conducted in 170 opioid-dependent adults who received supervised buprenorphine treatment paired with a behavior therapy program, with or without the addition of a desktop-based version of reSET-O, which was accessed at the clinic 3 times a week for 30 minutes per visit. At study-end (12 weeks), participants who used the desktop computer version of reSET-O had an overall retention rate of 80 percent compared with 64 percent overall retention rate for those who did not. Use of reSET-O was not shown to decrease illicit drug use or improve abstinence compared to the control group (Christensen, 2014). A secondary analysis of the pivotal study data reported outcomes of treatment retention and abstinence relative to ‘treatment as usual’ but was hampered by the same study limitations (Maricich, 2020a).
 
In 2020, Velez and colleagues reviewed retrospective pharmacy and medical claims data from commercial, Medicare and Medicaid databases (2018-2019). Ultimately, 334 study participants were included who activated reSET-O and were continuously enrolled in their medical plan for at least 4 weeks of the 6-month pre-activation and post-activation periods. Despite the abundance of clinically significant pre- and post-activation measures reported (including but not limited to, inpatient encounters [45 less; p=0.03], emergency department visits [27 less; p=0.25] psychiatry encounters [349 less; p<0.04], case management encounters [176 additional; p=0.59], behavioral health services [111 additional; p=0.12], alcohol and substance abuse services [96 less; p=0.35], and mental health services [61 additional; p=0.10]), some were only marginally statistically significant while most were not significant (i.e., p-value > 0.05), with the exception of 638 less drug test events recorded post reSET-O activation (p<0.001) an outcome that may not be desirable in this clinical scenario. Claims data also revealed of the 240 participants who had pharmacy claims data, pre-/post- activation medication possession ratios increased from 0.73 to 0.82, respectively (p=0.004); however, possession of buprenorphine is unlikely to be a valid surrogate measure for medication adherence. In this real-world clinical scenario, generalizability is lacking (> 80% Medicaid enrollees), mortality data (a crucial outcome in this setting) is not reported and reSET-O’s ability to impact health behaviors or clinically relevant outcomes was not demonstrated.
In another pragmatic, retrospective evaluation, Maricich and colleagues (2020b) enrolled 3144 individuals upon their downloading the reSET-O application to their personal device. Engagement and therapeutic use data were collected and analyzed on a population, versus individual, level. Substance use was evaluated using a composite measure of self-reported data collected by reSET-O and urine drug screens which were nonuniformly administered by different clinic sites. When excluding participants with missing data from analysis, the abstinent rate (defined as abstinent in the last 4 weeks of treatment) was observed to be 91%, when missing data was considered ‘positive’ the abstinence rate was 66%. Just 29% of the study population used reSET-O appropriately and consistently for the first 4 weeks (completed 4 or more modules per week), thus adherence to reSET-O’s proper use was low in this very large, real-world cohort. The study outcomes relied on self-report, lacking clinically meaningful measures beyond urine drug screens which were not routinely measured across study sites.
 
In 2020, the Institute for Clinical and Economic Review (ICER) published an evidence report which included published data, to date, evaluating the reSET-O. ICER concluded, “We found no randomized trials, cohort studies or case series that evaluated the DHTs [digital health technologies] reviewed in this report until after the draft report was released. Recently, two uncontrolled studies suggested potential benefits with reSET-O, but there was a high risk of bias for both studies.”
 
Current data is limited to short-term follow-up, and impact on net health outcomes has not been demonstrated. Few of the published studies assess the use of the reSET-O when used outside of a clinic (for example, when downloaded directly to a personal device such as a mobile phone or tablet).
 
Practice Guidelines and Position Statements
 
American Academy of Sleep Medicine
In 2021, the American Academy of Sleep Medicine (AASM) published an evidence-based clinical practice guideline on behavioral and psychological treatments for chronic insomnia disorder in adults (Edinger, 2021). The AASM provides a strong recommendation for multicomponent cognitive behavioral therapy for insomnia (CBT-I) for the treatment of chronic insomnia disorder in adults. Multicomponent CBT-I includes cognitive therapy strategies, education about sleep regulation plus stimulus control, and sleep restriction. Multicomponent CBT-I may also include sleep hygiene, relaxation training, and other methods to counter arousal. Conditional recommendations included brief therapies (1 to 4 sessions of CBT-I), and single component treatment consisting of stimulus control, sleep restriction, or relaxation therapy alone. AASM gave a conditional recommendation to not use sleep hygiene as a single-component therapy for insomnia disorder. The systematic review identified 3 studies that compared in-person delivery with internet delivery (by any method) and found no clinically significant difference between in-person over internet delivery of CBT-I (Edinger, 2021). The guideline concluded that there was insufficient evidence to make recommendations for specific delivery methods (eg, individual, group, internet, self-help, video) for any of the treatments (Edinger, 2021).
 
In 2018, the AASM published a position paper on the treatment of nightmare disorder in adults (Morgenthaler, 2018). The following non-medication treatments were recommended for post-traumatic stress disorder-associated nightmares: image rehearsal therapy; cognitive behavioral therapy (CBT); CBT-I; eye movement desensitization and reprocessing; exposure, relaxation, and rescripting therapy, and medications. For the treatment of nightmare disorder, AASM recommended the following non-medication treatments: image rehearsal therapy; CBT; exposure, relaxation, and rescripting therapy; hypnosis; lucid dreaming therapy; progressive deep muscle relaxation; sleep dynamic therapy; self-exposure therapy; systematic desensitization; testimony method.
 
American College of Physicians
In 2016, the American College of Physicians published a clinical practice guideline on the management of chronic insomnia (Oaseem, 2016). The college recommends that "all adult individuals receive cognitive behavioral therapy for insomnia (CBT-I) as the initial treatment for chronic insomnia disorder." (Grade: strong recommendation, moderate-quality evidence)
 
Ongoing and Unpublished Clinical Trials
Some currently unpublished trials that might influence this review are listed below.
 
Ongoing Trials   
 
NCT04909229a Prescription Digital Therapeutic for the Treatment of Insomnia (SLEEP-I)
Planned Enrollment: 100 Completion Date: June 2023
 
NCT04325464a Open-label, 9-week Treatment, De-centralized Trial to Collect Real World Evidence for a Digital Therapeutic (DT) Delivering Cognitive Behavioral Therapy for Insomnia (CBT-I) for Participants With Chronic Insomnia (DREAM)
Planned Enrollment: 1500 Completion Date: Jul 2024
 
NCT04040387a TNT/NW: Traumatic Nightmares Treated by NightWare (To Arouse Not Awaken)
Planned Enrollment: 270 Completion Date: Aug 2023
 
NCT05365607a NightWare and Cardiovascular Health in Adults With PTSD
Planned Enrollment: 50 Completion Date: Apr 2024
 
NCT03633305 Optimization of Insomnia Treatment in Primary Care
Planned Enrollment: 300 Completion Date: Dec 2023
 
NCT04721067 HIV-related Insomnia and Inflammation
Planned Enrollment: 50  Completion Date: Aug 2023
 
NCT03327519 Solving Insomnia Electronically: Sleep Treatment for Asthma (SIESTA)
Planned Enrollment: 210 Completion Date: Dec 2022
 
NCT04700098 Internet-based Cognitive-behavioral Treatment for Insomnia in COPD Patients Undergoing Pulmonary Rehabilitation
Planned Enrollment: 125 Completion Date: Mar 2025
 
NCT03493958 RCT of Web-Based Behavioral Sleep Intervention for Individuals With Alcohol Use Disorder
Planned Enrollment: 79 Completion Date: Dec 2024
 
NCT04317742 eHealth Insomnia Intervention for Adult Survivors of Childhood Cancer
Planned Enrollment: 352 Completion Date: Jun 2026
 
NCT04377009 Internet-guided Cognitive Behavioral Therapy for Insomnia in Military Service Members With History of Traumatic Brain Injury
Planned Enrollment: 125 Completion Date: Jun 2023
 
NCT04621643 Digital Cognitive Behavior Therapy for Insomnia Compared With Digital Patient Education About Insomnia in Individuals Referred to Public Mental Health Services in Norway (Norse4)
Planned Enrollment: 800 Completion Date: Jan 2023
 
NCT05226585 Mechanisms of Change in Cognitive Behavioral Therapy for Insomnia (CBTi)
Planned Enrollment: 100 Completion Date: Oct 2023
 
NCT04468776 CBT-I or Zolpidem/Trazodone for Insomnia (COZI)
Planned Enrollment: 1200 Completion Date: May 2025
 
NCT04986904 Optimizing Efficiency and Impact of Digital Health Interventions for Caregivers
Planned Enrollment: 100 Completion Date: Jan 2023
 
NCT04564807 Testing an Online Insomnia Intervention
Planned Enrollment: 50  Completion Date: Dec 2022
 
NCT04986007 Addressing Nocturnal Sleep/Wake Effects on Risk of Suicide in Older Adults (ANSWERS-OA)
Planned Enrollment: 70  Completion Date: Sep 2024
 
NCT04909229 Prescription Digital Therapeutic for the Treatment of Insomnia (SLEEP-I)
Planned Enrollment: 100 Completion Date: June 2023
 
NCT05353296 Digital Cognitive-Behavioral Therapy for Insomnia in Spanish Speaking Latinas/os (Dormir Mejor Study)
Planned Enrollment: 200 Completion Date: Feb 2024
 
Unpublished
NCT03828656a NightWare Open Enrollment Study
Planned Enrollment: 400 Completion Date: Feb 2022
 
NCT03934658a A Remote Randomized Double-Blind Sham-Controlled Clinical Trial of NightWare in Adults With Post-Traumatic Stress Disorder and Co-Morbid Nightmare Disorder
Planned Enrollment: 400 Completion Date: Dec 2021
 
NCT03064321 Diabetes Sleep Treatment Trial for Insomnia (DSTT-I)
Planned Enrollment: 18  Completion Date: Mar 2020
 
NCT03390114 Cognitive Behavioral Therapy to Treat Insomnia in Persons With HIV Infection
Planned Enrollment: 20  Completion Date: Dec 2019
 
NCT03922867 Web-based CBT for Insomnia Patients With Fibromyalgia
Planned Enrollment: 18  Completion Date: Mar 2021
 
NCT03366870 Efficacy of a Computerized Cognitive Behavioral Treatment for Insomnia: Increasing Access to Insomnia Treatment to Decrease Suicide Risk (Vets Sleep)
Planned Enrollment: 250 Completion Date: Jun 2020
 
NCT: national clinical trial.
a Denotes industry-sponsored or cosponsored trial.
 
2024 Update
Annual policy review completed with a literature search using the MEDLINE database through December 2023. No new literature was identified that would prompt a change in the coverage statement.

CPT/HCPCS:
99199Unlisted special service, procedure or report
A9291Prescription digital cognitive and/or behavioral therapy, fda cleared, per course of treatment
A9292Prescription digital visual therapy, software-only, fda cleared, per course of treatment
E1399Durable medical equipment, miscellaneous
E1905Virtual reality cognitive behavioral therapy device (cbt), including pre-programmed therapy software
T1505Electronic medication compliance management device, includes all components and accessories, not otherwise classified

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