As shown in the flow diagram (Figs. 1), 1399 records were identified potentially relevant. Following screening with titles, abstracts, and methods and full-text review, 117 records which included DTx products with the primary indication of insomnia were identified. After the duplicates and the products without regulatory reviews by regulatory authorities in the records were removed, the total of 6 products were identified (Table 1).

Flow diagram of product identification

Somryst®, previously called SHUTi was cleared by FDA as 510 (k) Class II medical device in 2020 under Software Precertification Pilot program [9]. Somryst® has not been authorized in any other countries outside the US. The indication of Somryst® is limited to chronic insomnia which is different from the other 5 identified products [30]. The prescription is needed to start Somryst®. The price is $899, and the patients’ copay depends on the insurance plan [31].

Sleepio® received a CE mark I in 2018 and was recommended by the National Institute for Health and Care Excellence (NICE) in 2022 [32], but the product had been on the market much before in 2013. Sleepio® has also been distributed in the US market under the FDA enforcement excretion under the COVID-19, but has not been regulatory cleared by FDA [33]. Another unique characteristic of Sleepio® is this is not a PDTx. The price of Sleepio® is £45 (excluding VAT), and the insomnia patients who live in England, Scotland and people with or beyond cancer in some selected areas can start Sleepio® free on NHS [34, 35].

Somnio® is the only DTx product for insomnia permanently listed in DiGA directory in 2022 [36]. Somnio® has not been authorized with regulatory reviews in any other countries rather than Germany. Somnio® is a PDTx and the price is €224.99, and the patients can start the program without any out-of-pocket expenses for the products listed in DiGA directory [36, 37].

SUSMED Med CBT-I® is the PDTx product for insomnia authorized only in Japan after the regulatory review by Pharmaceuticals and Medical Devices Agency (PMDA) as Class II medical device in 2023 [38]. The price of medical devices usable in insurance-covered healthcare, is specified by Minister of health, Labor and Welfare (MHLW) in Japan and the price of SUSMED Med CBT-I® has not been determined.

Somzz® is the first DTx product approved in February 2023 by Ministry of Food and Drug Safety (MFDS) in accordance with the guidelines on review and approval of digital therapeutics issued in 2020 [17, 39]. WELT-I® was also approved by MFDS 2 months later [40, 41]. Both products were PDTx authorized only in South Korea and the prices have not been determined yet.

The features of 6 products were summarized (Table 2). The features of all the products were very similar regardless of the differences of the manufactures and of the authorized countries. Especially, all the identified products had the core components of CBT-I such as sleep restriction, stimulus control, sleep hygiene and cognitive restructuring [42,43,44,45,46,47]. Some products had additional CBT-I related features. Sleepio® and Somnio® had web applications in addition to mobile applications as platforms. Some products had the functions of muscle relaxation, relapse prevention and some unique functions. On the other hand, only Somnio® covered multiple languages and other products covered only the official language in the authorized countries.

The study design of pivotal clinical trial for each product was summarized (Table 3). In addition to the similarity of the features of the products, the study designs of the pivotal clinical trials were also similar among the identified products [45,46,47,48,49,50].

All the pivotal clinical trials were randomized, parallel-group, blind studies against insomnia patients. The patients were screened by international diagnostic criteria for insomnia such as Diagnostic Statistical Manual of Mental Disorder, Fifth Edition (DSM-5) and International Classification of Sleep Disorders - Third Edition (ICSD-3) except for Somryst® which defined chronic insomnia patients by its own criteria. In the pivotal clinical trials for SUSMED Med CBT-I®, Somzz® and WELT-I®, sham apps which excluded the clinically active components of CBT-I from the products were used as comparators. The treatment periods of the pivotal clinical trials were 6–9 weeks, but the long-term persistence of the efficacy was also investigated in the pivotal clinical trials in Somryst® and Somnio® (up to 12 months). The sample size varied in each pivotal clinical trials ranging from 56 to 303, but the size to investigate statistical significance against comparators were set in each study. The similar primary endpoints used in pharmacotherapy and cognitive therapy for insomnia such as insomnia severity index (ISI), sleep efficiency (SE), sleep onset latency (SOL) and wake after sleep onset (WASO) were adopted as the primary endpoints of the pivotal clinical trials. No MRCTs were conducted in any of the pivotal clinical trials of the identified products although some pivotal clinical trials were multi-centered trials in one country. The patients living in multi-regions in Switzerland, Austria, and Germany participated in the pivotal clinical trial of Somnio®, but this was single-center clinical trial.