When IBM's IBM Waston (Watson) project, which was partnered with the world's top cancer research institution MD Anderson Center (MD Anderson), entered the field of cancer care in 2013, the imagination of medical AI was opened.
From Microsoft, Google and GE to countless start-ups, AI is spread across image recognition, assisted diagnosis, drug research and development, health management and other fields. Although Waston's final development was not satisfactory, Anderson' attempt to promote new technologies in the medical field as the world's top cancer medical institution is commendable. All kinds of new technologies and new technologies also need to prove their value through clinical trials in front-line hospitals.
The United States has many top hospitals that value the transformation of research results, such as the Mayo Clinic (formerly known as the Mayo Clinic), which has been at the top of the U.S. News and World Report rankings for many years, with more than $1 billion in research expenditure in 2021, 2,889 active clinical trials, and 13,697 articles published in peer-reviewed publications. The Cleveland Clinic, which has received thousands of patents each year and witnessed many major breakthroughs in human medicine, has nearly 100 scientific research transformation products in 2019.
It can be said that it is precisely because of the exploration of new technologies and new technologies in the clinical aspects of these top hospitals that the medical level has developed rapidly. Today, in the context of the era of the Internet of Everything, various digital information technologies are a fiery outlet for medically empowered digital therapy. So what are the clinical attempts of these three top hospitals in the United States in this regard? Arterial Network mined their information on this from the U.S. Clinical Trials Database in an attempt to find answers.
ClinicalTrials is a clinical trial database run by the National Library of Medicine (NLM) and the U.S. FDA under the Institutes of Health (NIH) and is currently the world's largest clinical trial registry. All clinical trial items in this article are selected from them. It is important to note that because the FDA does not define a phase in trials that intervene in devices or behaviors, there are no phase markers for such clinical trials.
Sleep interventions
The core element of digital therapy is software. The treatment process can be carried out using software alone or with instruments (including monitoring devices and therapeutic devices), drugs. Software-driven drug or device therapy is more effective and less costly than using drugs or devices alone. Arguably, software is the greatest value of digital therapy.
The software itself is based on cognitive behavioral therapy (CBT), which is simply a short-term treatment method that improves psychological problems by changing irrational thinking and behavior patterns to reduce the generation of bad emotions and behaviors.
CBT-i, the cognitive behavioral therapy for insomnia for sleep disorders, coincides perfectly with the design logic of digital therapy software, and CBT-i therapy is recommended by the American College of Physicians and the European Sleep Research Association as the first choice for the treatment of insomnia, and is the most effective non-drug treatment for insomnia.
It improves sleep by correcting inappropriate attitudes and attitudes toward sleep and bad behavior habits, including sleep hygiene education, relaxation therapy, cognitive therapy, stimulation control methods, and sleep restriction methods.
Compared with drug treatment, CBT-i therapy has the advantage, but due to the long treatment cycle, limited doctor resources, psychological counseling caused by patient resistance and distance problems, patient compliance is low and the experience is poor. However, these shortcomings can be improved by digital therapy empowerment. To that end, Cleveland developed a suite of GoToSleep software to help people with moderate to severe insomnia avoid thoughts and behaviors that affect deep sleep.
GoToSleep is a 6-week treatment plan consisting of a series of graphics, animations, audio and video tutorials. It covers sleep hygiene, sleep restriction, stimulus control, cognitive reassembly, and relaxation training. In addition, given the prevalence of insomnia in patients with epilepsy and the known association between seizures and sleep disturbances, the trial will also be used to study improving insomnia symptoms and seizure control in patients with epilepsy.
Of course, for some symptoms such as sleep apnea syndrome, the use of software alone is not enough, and instrumental treatment is required. Such patients will repeatedly intermittently lack oxygen during sleep, which greatly increases the risk of hypertension, cardiovascular and cerebrovascular diseases, diabetes, etc., and is related to Alzheimer's disease, arrhythmias and other chronic diseases of the respiratory system. This will bring a huge social and health economic burden.
Cleveland targeted people at high risk of sleep apnea syndrome with a BMI of 30 or more, using philips Respironics or ResMed ventilator solutions to track the effects of Using Auto-CPAP devices in a home environment over a long period of time. Participants will receive medical follow-up to improve compliance and to assess effectiveness. The study used patient readmission rates after 6 months to evaluate the effectiveness of software interventional instrumentation.
Adults have strong adherence, their sleep disorders can only be regarded as ordinary problems, and the real trouble is the sleep disorders of autistic children, which is definitely a hellish problem. Sleep problems in children with autism are mainly manifested in sleep anxiety, drowsiness, and chaotic circadian rhythms. For example, children with autism have difficulty falling asleep, often feel irritable before going to bed, and must be accompanied by adults to calm down. In this case, the doctor is not the first choice, and whether the parents respond properly is the key factor.
Cleveland's subjects were the parents of children with autism sleep disorders (ages 2 to 7). The study offers a tested parent training program that is specifically targeted at bedtime and sleep disorders to be used before children go to bed, with real-time instructions for parents through an app presentation.
The trials were divided into two groups, both conducted through apps, but one set of content was only standardized content education, while the other group provided comprehensive intervention, training in basic concepts and practical skills, in addition to three HIPAA-compliant video home visits to learn about treatment, solve specific problems and flexibly adjust treatment plans in a one-on-one manner. The main indicator of the trial was the child's sleep after a 10-week course; the secondary indicator was the parents' stress index.
Sleep medicine was included in the list of training directories in the "Catalogue of Standardized Training Specialties for Specialist Physicians (2019 Edition)" issued by the Chinese Medical Doctor Association in 2019, becoming a second-level independent discipline, alongside the well-known neurology, cardiology, gastroenterology, etc.
Domestic enterprises such as quick sleep, through the promotion of lifestyle medicine to solve the sleep problem, they have developed the use of pulse magnetic targeting technology pulse magnetic therapy system, is can achieve real-time monitoring and treatment integration and through the NMPA certification of sleep aid "black technology". There are also digital therapy products based on CBT-i. Sleep enjoyment is to analyze the sleep status through intelligent healthy sleep products, monitor heart rate variation, breathing, turning over and other indicators, and propose improvement plans.
Addiction intervention
From the perspective of medical classification, sleep disorders are a psychiatric disease, and mental illness is also the largest application object of digital therapy at home and abroad. Therefore, mental illnesses such as addiction and depression are also popular in digital therapy clinics. All three top hospitals have corresponding addiction tests, but the focus of the three is significantly different.
Take the most common nicotine addiction as an example, it includes both "physical addiction" and "mental addiction". While smoking cessation drugs are effective in treating physical addiction and associated withdrawal symptoms, coping with mental addiction remains difficult, especially when patients are far from hospital.
The distance between doctors and patients is a must consider for addiction treatment, and Miaoyou deliberately recruited participants from remote areas to conduct a 12-week, evidence-based behavioral health cessation program. The main way is to intervene in life through apps, coupled with remote coaching, and use motivational interviews to increase engagement and help them learn to use digital devices.
Relatively speaking, Anderson's trials are more traditional, with app interventions for the average smoker and smoking cessation programs for specific groups of pregnant women. Both are basic life interventions through apps for positive psychology training and breathing relaxation training. For pregnant women, Anderson offers a dedicated Baby Steps for Health remote coaching program.
The application of digital therapy in the field of smoking cessation is not a new topic, and previously Clickotine in the United States and CureApp SC in Japan were both digital therapy applications for this scenario.
However, the focus of the Miaoyou clinical trial is on the consistency and stability of the effect of digital therapy on residents in remote areas, the clinical objects recruited this time are all remote rural residents, and the content of the trial also deliberately adds a tutorial on the use of digital devices, and the evaluation indicators also increase digital access, digital literacy and patient experience. This is also relevant for a vast continent, and is the same digital therapy universal for people with significant differences in educational attainment in economically developed and economically underdeveloped regions?
In addition to addiction, there is also opioid dependence. Opioids are derivatives extracted from the poppy, or synthetic substances with similar effects, which can play an analgesic role in medical treatment, but long-term overdose can easily cause drug dependence, addiction, and even death. According to the U.S. Centers for Disease Control and Prevention, between 1999 and 2019, as many as 500,000 Americans died from opioid overdose, and more than 2 million Americans developed a severe dependence on opioids.
For patients with tumor surgery, postoperative analgesia is inseparable from opioids, but how to avoid addiction is what Anderson wants to study. Anderson used Lucid Lane's program to adjust mood and maintain mental health through CBT, combining the use of psychosomatic therapies MBTs that reduce pain and demand for painkillers to achieve the purpose of the Opioid Reduction Program.
The researchers hope to understand how these techniques improve a patient's ability to reduce or avoid opioid dependence after surgery, and whether behavioral therapy can improve quality of life, emotional health, and functional status around surgery.
The "Twelve Steps" Rehabilitation Program is a very popular and effective group therapy for spiritual healing support in Western countries. For patients, continuous participation is the biggest difficulty, and the Cleveland trial used apps to urge and encourage patient participation, and to assess the patient's status after each participation, positively encouraging patients to continue to participate.
In addition, the effects of postoperative analgesia and opioid consumption are targeted. Cleveland also introduced VR technology to relieve pain in patients and reduce opioid consumption. Finally, the participants were counted on the frequency of pain occurrence and the assessment of the availability of the VR system. Of course, VR technology is really being used a lot.
Analgesic/anxiety interventions
If it is only software, it is not yet possible to maximize the advantages of digital therapy, and there are a large number of digital therapies based on software + devices in the clinical trials of the three top hospitals. For example, the introduction of virtual reality technology (VR), whether it is the aforementioned postoperative opioid dependence or anesthesia assistance during surgery and anxiety relief, has done a lot of exploration.
Anesthesia is a necessary part of surgery, anesthesia not only to solve the patient's perioperative pain, but also to ensure the safety of the patient's perioperative period, regional anesthesia can provide analgesic effect of the surgical site, but regional anesthesia alone can not solve the patient's nervousness and fear, often need to assist in the use of sleep aids or through non-drug ways to distract attention.
In the past, for such area anesthesia patients, the method used by medical staff was "talk therapy", that is, chatting with the patient during the operation to distract the patient. "Talk therapy" requires good communication skills among medical staff, and medical staff will also be incompetent. Therefore, the introduction of VR technology is to allow patients to have an immersive experience to achieve the purpose of distracting patients and eliminating tension.
In orthopedic surgery, electrophysiological examination and radiofrequency ablation surgery, the Clinic tests whether VR technology can be used as an adjunct to anesthesia during surgery. Key tests included assessing patient satisfaction with the use of VR to reduce anxiety during surgery, the effect of VR on analgesic and anxiolytic dosing, and the positive effect of VR on intraoperative and postoperative hypothermia in patients.
In addition to this short-term use during surgery, Myoyo also experimented with long-term use. For example, a set of true and false VR control trials was designed for patients with stomach cramps. The True VR group featured interactive games, meditation, and deep breathing exercises specifically designed to treat acute and chronic pain. Fake VR groups just use VR devices to play some natural landscape videos. Both groups were required to use 15 minutes before meals and bedtime for 4 weeks, and participants were required to report adverse events through questionnaires every day.
Gait intervention
VR technology is also being used by Cleveland to reproduce conditions that cause the gait of People with Parkinson's disease to freeze. Individuals who undergo deep brain stimulation (DBS) surgery for Parkinson's disease use VR devices with omnidirectional treadmills to walk in a virtual reality environment and record brain signals from DBS devices to understand the brain during gait freezing.
In addition to VR, Cleveland's experiment also involved augmented reality technology AR. Also aimed at Patients with Parkinson's disease, the experimental group used the traditional physical therapy of multimodal training as a reference, and the experimental group performed it by using the Microsoft HoloLens 2 augmented reality headset. The device allows users to see the real world and insert holograms into the environment.
For example, users can see boxes on the ground that they need to avoid when walking. These boxes are not real, but holograms that only the user can see. Augmented reality devices will guide participants on motor and cognitive tasks. At the end of the experiment, the gait speed and the frequency of falls when completing the design task are the main reference indicators.
Here we have to mention that as a technology platform company, Microsoft, in the face of such a cross-field industry as digital therapy, Microsoft can combine its own IoT, MR technology and other advanced technologies into the digital therapy scenario, empower enterprises from different angles, help cooperative enterprises break the barriers of technical capabilities from 0 to 1, and then focus on broadening the boundaries of digital therapy. For digital therapy startups, Microsoft's complete ecosystem is an attractive development environment.
VR-based digital therapy can work not only on patients, but also for medical personnel. Cleveland conducted clinical trials for nurses. Caregivers learn to manage patients at risk of falls during induction, which is usually achieved on an educational module on an online platform.
Cleveland introduces VR technology, and caregivers will see many scenarios full of fall risk from VR, and caregivers will move around in a virtual environment to identify all the fall risks in the scene. The duration of the trial was 3 months, after which a competency assessment was conducted against a control group using only general education modules.
Digital therapy using VR technology, domestic virtual reality, heartscape and other enterprises are also following up. Digital therapies like Virtual Reality focus on psychopsychological VR+AI for the treatment of mild cognitive dysfunction (MCI) and Alzheimer's disease (AD). In addition to applying VR+AI digital therapy to the rehabilitation treatment of mental illness, Heartscape Technology also extends the scope of treatment to children's attention training, brain cognitive rehabilitation, drug and alcohol rehabilitation assessment and rehabilitation.
Arterial Network retrieved from the China Clinical Trial Registry the projects that have used virtual reality technology for clinical trials in china in the past two years. It can be seen that clinical trials based on VR technology are basically the same at home and abroad, focusing on pain suppression, gait training and sports rehabilitation.
In addition, the domestic condensed medical treatment has also made a breakthrough in the application boundary of VR technology, and it announced that the "Specific Fear Psychological Rehabilitation Training Software" translated from the Shanghai Mental Health Center in cooperation with the Shanghai Intelligent Psychological Assessment and Intervention Engineering Technology Research Center has been officially approved as an independent software medical device in Wuhan, Hubei Province in 2022, becoming the first specific fear psychological rehabilitation training software approved for use in professional psychotherapy institutions and medical institutions and based on virtual reality equipment in China. The product is also the world's first Class II medical device for specific phobias (fear of heights).
Remote life monitoring intervention for wearable devices
In addition to VR, wearable smart devices are also instruments often used in digital therapy, and the daily use of such devices represented by smart watches will not cause discomfort to patients, while monitoring their own exercise levels and certain physiological indicators, providing important reference data for APP intervention.
For example, the Fitbits Sense smartwatch, which has been approved by the FDA, can use the ELECTROCardiogram application in the United States. Therefore, the Cleveland study intervened in 8- to 18-year-olds whose body mass index BMI is about to exceed the standard. Access data on their activities by using Fitbits smartwatches to provide relevant nutritional knowledge and exercise advice to help them live healthy lives.
Anderson applied Fitbits to guide the lifestyle of cancer patients after surgery. In the case of breast cancer, current research concludes that patients can recover better with a healthy diet, regular exercise, and good stress management, but a paper life guide is not enough to constrain and drive patients.
Trials monitor patient body data through Fitbits, offering recommendations including healthy eating, physical activity, stress management and sleep hygiene, mindfulness training, and remote counseling. The trial expected to assess the feasibility of a life intervention through a 26-week life intervention.
Some patients who are discharged after surgery are readmitted within 30 days for various reasons. In addition to the economic and quality-of-life impact on patients themselves, patients returning to the hospital unexpectedly further divert medical resources. Therefore, reducing the number of readmissions in the 30 days after surgery is important not only for patients but also for hospitals. The risk of associated complications after readmission of surgical patients complicates the course of treatment compared to hospitalization of the average patient.
For example, for people with heart disease, preventing myocardial infarction is an eternal topic. Although symptoms of chest discomfort, shortness of breath, and upper body discomfort are usually present at the onset of the disease, as well as manifestations of nausea, vomiting, and dizziness, it is difficult for patients to accurately judge.
Miaoyou's trial uses a smartHeart's portable 12-lead hospital-grade ECG device, allowing patients to perform complete ECG tests anytime, anywhere, maintaining high-quality standards of medical care. The ECG data obtained by the device complies with HIPAA standards and can be viewed and synchronized to a telemedicine monitoring center that works 24 hours a day for 7 ×, which evaluates and warns based on current data. The results of the trial were finally assessed by measures of emergency visits, readmissions, mortality, and adverse cardiovascular events within 90 days of discharge.
In addition, there are telethocarage trials for patients with moderate and highly complex surgical procedures such as abdominal wall reconstruction, weight loss, hepatic resection, pancreaticectomy, aortic surgery, lower extremity bypass, esophageal resection and colectomy. Participants will use a remote patient monitoring kit containing tablets, blood pressure cuffs, thermometers, pulse oximeters, and scales to feed back physiological data back to the hospital as required, allowing the hospital to adjust the care plan based on physiological indicators.
CGM empowers chronic disease management
Chronic disease management is an area that digital therapy cannot avoid. Diabetes is the largest group in the management of chronic diseases. For patients with type II diabetes, Cleveland introduces Twin Health's WHOLE Body Digital Twin platform, powered by AI and IoT technologies, which uses smart scales, continuous blood glucose monitors (CGMs), sphygmomanometers, ketone body measuring instruments, and fitness bracelets to capture body metrics and provide patients with precise guidance on activity and sleep.
Cleveland uses the platform for anything but the fact that it can capture data on 174 health markers, up to 3,000 data points per day. It's also about the company's digital therapy that introduces the concept of "digital twins." Based on the measurement data, the platform generates a virtual model of the patient and predicts the health direction of the virtual character.
Patients can intuitively see the development trend of their own health, if you want to change the health status of virtual twins, you can only follow the recommendations of the platform, from nutrition, drug treatment, sleep, activity and breathing five aspects. This set of digital therapies has successfully changed the treatment process from adjusting living habits based on test results to a game-like mode that improves user compliance.
From other clinical trials, it can be found that the devices used in digital therapies for diabetes have been replaced by BGM devices that used to require patients to take multiple times of blood measurement with fingertip blood on their own initiative to CGM. Compared with BGM measured four times a day, CGM can be easily monitored continuously for 7 to 14 days after one use. Not only is the user experience better, but the results are more comprehensive.
Although the main application scenario of CGM before was the use of patients in the home environment, two top hospitals in Myoyou and Cleveland have invariably applied CGM to the ICU and other environments in the hospital to test whether CGM can completely replace the bedside capillary blood glucose meter. Cleveland has also conducted clinical trials for specific settings, such as the utility of CGM after heart surgery and in screening for cystic fibrosis-related diabetes. CGM equipment for research mainly includes the Dekang G6 PRO and Abbott FreeStyle Libre Pro.
The domestic CGM market share is mainly occupied by Abbott and Medtronic, but the CGM products of domestic enterprises have been approved in the past six months, and there are currently 7 listed products, including San Medino, Kailite, Qianyu Technology, Princeton, Meiqi, Silicon Bionic, Weitai and Jiunuo. At present, domestic brands are actively expanding in-hospital and out-of-hospital channels.
The biggest feature of the Medtronic insulin pen used in the Miaoyou experiment is that it can be linked with Medtronic's own CGM products on the mobile app, and the patient is advised to adjust the insulin dose according to the real-time blood glucose reading, without having to switch between applications to help patients make reasonable dose decisions. CGM and insulin pump linkage is a trend of future development, the current domestic Weitai Medical and Qianyu Technology is working in this direction.
Artistic intervention
Of course, in addition to these relatively hard therapies mentioned above, there are also some experiments to regulate the state of mind and body. For example, Cleveland has done an experiment to improve the physical and mental health of individuals based on artistic appreciation; Myoyo hopes to promote health education for African Americans from a cultural perspective; and for multiple sclerosis, it helps patients improve their ability to walk by providing rhythmic auditory cues.
Art therapy represented by music is currently a popular direction in the field of digital therapy, and the domestic Shandong Heze Maternal and Child Health Hospital will use visual music therapy for rehabilitation training for autistic children. To put it simply, art therapy is a music therapy method that uses digital signal processing technology to change the adverse physiological and psychological state of the therapist and special children in the interaction between the therapist and the special child through multi-sensory stimulation such as sight, animation, and lighting. It is suitable for special groups such as autism, hyperactivity, intellectual disability, cerebral palsy, behavioral disorders, language delays, and hearing impairments.
A guide to life outside the hospital after surgery
Life guidance for patients after discharge is also an important part of the treatment process. In the past, hospitals also issued manuals such as life guides, but patients' compliance with them was extremely low. Now both Myo-woo and Anderson are trying to use this type of postoperative out-of-hospital intervention through an app and evaluate the effects.
Shukang is the first batch of digital therapy products approved by NMPA in China, with the remote intelligent assessment of heart and lungs, muscle and bone, and nutrition as the core, combined with the scientific combination of wearable devices and prepackaged medical foods, prescribed by doctors, and patients can perform remote sports rehabilitation and nutritional intervention at home, effectively reducing morbidity, admission rate, and readmission rate.
summary
Digital therapy has developed rapidly in recent years, in recent years, there have been 7 DE Novo digital therapies approved by the FDA, and how to creatively use digital technologies is a problem for every company engaged in digital therapy research to think about.
Through the clinical trials of digital therapy in 3 top hospitals in the United States, we can see that digital therapy does not necessarily create new scenes, but through technology, the pain points and patient suffering in existing scenarios are solved, which is a supplement to the unmet needs of traditional treatment. In clinical trials like these 8 digital therapies, the number and importance of research based on VR technology, CGM and wearable devices in the three top hospitals in the United States are significantly higher. What all three have in common is that they can effectively compensate for the links that have not been achieved in the traditional medical process.
Of course, this not only requires support from policy and technology, but also the participation and help of front-line clinical experts, which is also the reason for the rapid development of the digital therapy industry in the United States. If domestic digital therapy companies can work with first-line medical institution experts and technology platform companies like Microsoft to build solutions, it will definitely greatly improve the efficiency of digital therapy landing and promote the development of the digital therapy industry.
*Cover image source: 123rf