Digital therapeutics (DTx) is a new concept of medical technology that has emerged abroad in recent years and has developed rapidly during the new crown pneumonia epidemic. At the heart of digital therapy is the use of highly intelligent medical software to drive the prevention, treatment and management of specific diseases.
In April 2020, the U.S. Food and Drug Administration (FDA) issued urgent approval guidelines for digital therapies for the treatment of mental illness, significantly speeding up the approval and marketing of DTx products[1].
The mainland's National Medical Products Administration (NMPA) also opened a digital therapy approval channel in 2020.
What is Digital Therapy?
The Digital Therapeutics Alliance defines DTx as evidence-based, clinically validated software for the treatment, management, and prevention of disease [2].
In terms of product form, the core of DTx is computer software, which can be used with hardware, but the core function is driven by software.
Digital therapy has applications in psychiatric, nervous system, respiratory system, endocrinology, cardiovascular, ophthalmology, skin, digestive system and other disease fields. Among them, the intervention, treatment and management of chronic diseases and psychiatric diseases are the most important application areas of digital therapy.
Two important features of digital therapy
DTx is still essentially a combination of computer technology and medical technology, but compared with the digital and smart medicine that we are familiar with, DTx also has two important characteristics [3]:
It is an intervention for a specific disease
There is evidence-based medical evidence of its efficacy
According to its technical principles and the role played in disease intervention, DTx can be divided into three categories: prevention, treatment and management, covering three important scenarios in the evolution of patients' diseases.
Preventive products, mainly for users who have not occurred but belong to high-risk groups, effectively prevent the occurrence of diseases by providing detection functions and prevention means.
In January 2016, NeuroTrack launched a product called Neurotrack Imprint, which uses eye tracking technology to identify the degree of damage to the hippocampus in the human brain, which can detect earlier whether patients are at risk of cognitive decline, and once the risk is found, Neurotrack will propose treatment options such as diet, exercise, sleep, stress management and cognitive training, which will help promote the prevention and treatment of cognitive disorders such as Alzheimer's disease.
(Image source: neurotrack official website)
(Image source: neurotrack official website)
In response to the problem of inhaled drug dose management in patients with chronic lung disease, Propeller Health in the United States has developed a respiratory health management application product. The product has a matching hardware, which is a small sensor that fits on top of the inhaler. Every time a patient with bronchial asthma or chronic obstructive pulmonary disease uses the device, the sensor collects a large amount of data, sends it to the mobile app, and then collects it into the background, where the algorithm mines big data and then accurately pushes personalized diagnosis and treatment recommendations to the user [4,5].
(Image source: Propeller Health official website)
Such products are mainly used in the fields of neurological, psychological and rehabilitation medicine, and the product itself is part of the treatment plan, and the patient can produce a clear therapeutic effect after use. Such products are usually software or hardware products loaded with DTx through algorithms to intelligently interact with patients to improve patient cognition and behavior, so as to achieve therapeutic effects.
In 2017, the U.S. FDA approved ReSET, the first DTx software for the treatment of drug addiction, to be marketed as an adjunctive treatment for drug addiction in prescription form[6], developed by Pear Therapeutics, a leader in digital therapy, and a 12-week clinical multicenter study of 399 patients enrolled before launching.
The results of the study showed that patients using the product had an alcohol and cannabis withdrawal rate of up to 40.3% (17.6% in the control group) compared with the control group (without reSET) and did not have any associated adverse reactions.
Due to the product's novelty, the FDA has adopted a "de novo premarket review" approval channel. The incident was seen as a milestone in DTx's official entry into the public eye.
(Image source: Pear Therapeutics product ReSETTM)
In June 2020, the U.S. FDA approved the release of Endeavor Rx, a video game for the treatment of ADHD in children aged 8 to 12 years. The product has been shown in several clinical studies to significantly improve children's attention scores and academic performance without serious adverse effects. EndeavorRx thus became the first video game supported by data from a randomized controlled clinical trial and officially approved for medical prescription.
(Image source: EndeavorRx page)
The core technology of EndeavorRx games is selective stimulation management engine (SSMETM) software that utilizes video game-specific sensory stimuli and motor challenges to activate the nervous system through the human senses, thereby improving the patient's cognitive function. The game adjusts the difficulty of the game in real time through artificial intelligence, that is, the "dose" is adjusted in real time, from one "dose" to the next "dose", from one patient to another patient, it is different. Dosage varies from person to person and is also an advantage of digital therapy.
Management products are mainly used for patients with clear diagnosis, by guiding patients to self-manage the conditions and factors that affect the progression of the disease, improve patient compliance, thereby improving the treatment effect, controlling the condition, reducing complications, etc.
Voluntis' digital therapy product, Oleena software, has been licensed by the U.S. FDA to manage oncology-related symptoms and remotely monitor patients. Through the analysis and judgment of the symptoms of cancer patients, patients are provided with self-management of adverse reactions in the process of tumor treatment and guidance on timely medical treatment.
(Image source: oleena official website)
(Image source: oleena official website)
In China, the small shell application (APP) developed by Zhilan Health in cooperation with Professor Hou Jinlin of Southern Medical University is a hepatitis B maternal and infant blocking management software designed on the basis of standardized clinical pathways, which can manage the pregnancy and childbirth process of the target object through the mobile app.
The small shell consists of two parts: the patient end and the doctor's end. Patient-side modules include pregnancy tracking reminders, hepatitis B knowledge base, online communication, and electronic medical records. The modules on the doctor's side include diagnosis and treatment advice, key focus, patient management, online communication, and data statistics. Through the collection, management and analysis of detection indicators, clinical manifestations and pregnancy information in pregnant women with hepatitis B virus infection, the product provides clinicians with auxiliary diagnosis and treatment recommendations and improves patient compliance.
Studies have shown that the use of this software can increase the success rate of blocking mother-to-child transmission of hepatitis B to 99.7%. As a result, in 2019 and 2020, The Little Shell APP was approved as a medical device registration certificate and production license by the State Drug Administration of China, becoming the first DTx product approved for marketing in the field of liver disease [8,9].
In November 2020, the Shukang APP independently developed by the mainland was approved for listing by the State Drug Administration of China, and was directly prescribed by doctors for patients as a prescription, unveiling the prelude to China's digital therapy.
(Image source: Shukang official website)
With cardiopulmonary endurance improvement as the core, shukang APP conducts exercise assessment and treatment of chronic diseases, mainly for the treatment and prevention of chronic diseases related to decreased cardiopulmonary endurance, including at least 26 kinds of chronic diseases such as common endocrine metabolic diseases, cardiovascular diseases, tumors, and some respiratory diseases, as well as intervention after discharge of patients including hypertension, diabetes, hyperuricemia, metabolic syndrome, chronic heart failure, coronary heart disease, atrial fibrillation, colorectal cancer, breast cancer, chronic obstructive pulmonary disease and intervention after discharge of new coronary pneumonia patients.
In the past few years, innovation in China's digital health field is mainly in its infancy, dominated by "connected" functions. 2021 is known as the first year of Digital Therapy in China, and digital therapy has begun to truly enter the medical field and provide auxiliary interventions for diseases.
The development prospects of domestic digital therapy are very broad, but at the same time they are facing challenges, compared with the United States and other countries with relatively mature development of digital therapy, china has not yet given a clear definition of the definition, scope, application scenarios, etc. of digital therapy. As the concept becomes widespread and confidence grows, it is believed that digital therapies can play a key role in reducing the prevalence of chronic diseases and leading to more preventive holistic care.
Review expert: Bo Shining
Deputy Chief Physician of the Department of Critical Care Medicine, Peking University Third Hospital
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[8] China Hepatitis Prevention and Control Foundation, Infectious Diseases Branch of Chinese Medical Association, Hepatology Branch of Chinese Medical Association. Clinical management process of maternal and infant blockade of hepatitis B[J]. Chinese Journal of Hepatology,2017,25(4):254-256. DOI:10.3760/cma.j.issn.1007-3418.2017.04.004.
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Author: Yu Jia
Editors: Ye Yichu, Wu Jiaxiang, Ye Zhengxing
Proofreading: Wu Yihe | Typesetting: Li Yongmin
Operation: Han Ningning | Coordinator: Ye Yichu