Digital therapeutics, a subset of

digital health Digital health is a discipline that includes digital care programs, technologies with health, healthcare, living, and society to enhance the efficiency of healthcare delivery and to make medicine more personalized and precise. It uses informatio ...

, are evidence-based therapeutic interventions driven by high quality software programs to prevent, manage, or treat a

medical disorder A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that ar ...

disease A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...

. Digital therapeutic companies should publish trial results inclusive of clinically meaningful outcomes in peer-reviewed journals. The treatment relies on behavioral and lifestyle changes usually spurred by a collection of digital impetuses. Because of the digital nature of the methodology, data can be collected and analyzed as both a progress report and a preventative measure. Treatments are being developed for the prevention and management of a wide variety of diseases and conditions, including

type II diabetes Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, ...

congestive heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...

Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...

dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...

asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, cou ...

substance abuse Substance abuse, also known as drug abuse, is the use of a drug in amounts or by methods which are harmful to the individual or others. It is a form of substance-related disorder. Differing definitions of drug abuse are used in public health, ...

ADHD Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inapp ...

hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...

, depression, and several others. Digital therapeutics often employ strategies rooted in

cognitive behavioral therapy Cognitive behavioral therapy (CBT) is a psycho-social intervention that aims to reduce symptoms of various mental health conditions, primarily depression and anxiety disorders. CBT focuses on challenging and changing cognitive distortions (suc ...

Definitions

Although digital therapeutics can be employed in numerous ways, the term can broadly be defined as a treatment or therapy that utilizes digital and often

Internet The Internet (or internet) is the global system of interconnected computer networks that uses the Internet protocol suite (TCP/IP) to communicate between networks and devices. It is a '' network of networks'' that consists of private, pub ...

-based health technologies to spur changes in patient behavior. The use of digital products to improve health outcomes dates as far back as 2000. The term itself has been in use since around 2012. The first mention of the term in a peer-reviewed research publication was in 2015, in which Dr. Cameron Sepah formally defined the field as: "Digital therapeutics are evidence-based behavioral treatments delivered online that can increase accessibility and effectiveness of health care." Digital therapeutics can be used as a standalone therapy or in conjunction with more conventional treatments like pharmacological or in-person therapy. As of 2018, digital therapeutics continues to be an evolving field that medical professionals, students, and patients are beginning to utilize. The Digital Therapeutics Alliance states: "Digital therapeutics (DTx) deliver evidence-based therapeutic interventions to patients that are driven by high quality software programs to prevent, manage, or treat a broad spectrum of physical, mental, and behavioral conditions." Digital therapeutics are different from wellness apps or medication reminders in that they require rigorous clinical evidence to substantiate intended use and impact on disease state. It is often used as a preventive measure for patients who are at risk of developing more serious conditions. For instance, a patient with

prediabetes Prediabetes is a component of the metabolic syndrome and is characterized by elevated blood sugar levels that fall below the threshold to diagnose diabetes mellitus. It usually does not cause symptoms but people with prediabetes often have obesit ...

may be prescribed digital therapeutics as a method to change their diet and behavior that could otherwise lead to a diabetes diagnosis. Digital therapeutics can also be used as a treatment option for existing conditions. For instance, a patient with type II diabetes can use digital therapeutics to manage the disease more effectively. The methodology uses a variety of digital implements to help manage, monitor, and prevent illnesses in at-risk patients. These include

mobile devices A mobile device (or handheld computer) is a computer small enough to hold and operate in the hand. Mobile devices typically have a flat LCD or OLED screen, a touchscreen interface, and digital or physical buttons. They may also have a physical ...

and technologies, apps, sensors,

desktop computers A desktop computer (often abbreviated desktop) is a personal computer designed for regular use at a single location on or near a desk due to its size and power requirements. The most common configuration has a case that houses the power supply ...

, and various

Internet of Things The Internet of things (IoT) describes physical objects (or groups of such objects) with sensors, processing ability, software and other technologies that connect and exchange data with other devices and systems over the Internet or other comm ...

devices. These implements can collect a wide variety of data, ranging from

big Big or BIG may refer to: * Big, of great size or degree Film and television * ''Big'' (film), a 1988 fantasy-comedy film starring Tom Hanks * ''Big!'', a Discovery Channel television show * ''Richard Hammond's Big'', a television show present ...

to small. Digital therapeutics can theoretically collect a high volume of data from a variety of sources. It also collects "smaller" data, "capturing personalized physiological parameters, behavior patterns and social and geographical patterns that can be recorded from multiple digital sources."

Methodologies

Digital therapeutics can be used for a variety of conditions. There is no single methodology used in the practice of digital therapeutics. Many approaches use methods based upon

to spur patients to make lifestyle changes, reinforced with

gamification Gamification is the strategic attempt to enhance systems, services, organizations, and activities by creating similar experiences to those experienced when playing games in order to motivate and engage users. This is generally accomplished thro ...

peer support Peer support occurs when people provide knowledge, experience, emotional, social or practical help to each other. It commonly refers to an initiative consisting of trained supporters (although it can be provided by peers without training), and can ...

, and in some cases

telehealth Telehealth is the distribution of health-related services and information via electronic information and telecommunication technologies. It allows long-distance patient and clinician contact, care, advice, reminders, education, intervention, mon ...

such as coaching or

psychotherapy Psychotherapy (also psychological therapy, talk therapy, or talking therapy) is the use of psychological methods, particularly when based on regular personal interaction, to help a person change behavior, increase happiness, and overcome pro ...

. The method can be used to manage and improve outcomes in numerous conditions, including type II diabetes, Alzheimer's disease, dementia, congestive heart failure,

chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by long-term respiratory symptoms and airflow limitation. The main symptoms include shortness of breath and a cough, which may or may not produce ...

, asthma,

lung disease The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...

, obesity, substance abuse, ADHD,

insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...

, anxiety, depression, and others. Methodologies can be as simple as

psychoeducation Psychoeducation (a portmanteau of psychological education) is an evidence-based therapeutic intervention for patients and their loved ones that provides information and support to better understand and cope with illness. Psychoeducation is most oft ...

or sending notifications designed to alter behavior to patients who are at risk of obesity or diabetes and as complex as administering an ingestible radio tag that communicates with an external sensor to monitor the efficacy of a given medication. Diabetes and obesity prevention and management is a major focus in the field of digital therapeutics. Connected devices like

insulin pump An insulin pump is a medical device used for the administration of insulin in the treatment of diabetes mellitus, also known as continuous subcutaneous insulin therapy. The device configuration may vary depending on design. A traditional pump ...

s, blood glucose meters, and wearable devices can all send data to a unified system. The therapy also uses self-reported data like diet or other lifestyle factors. It is also often used to monitor the potential for heart and lung conditions and change behaviors like smoking, poor diet, or a lack of exercise. Digital therapeutics can also be used to treat patients with psychological and neurological symptoms. For example, patients with disorders like ADHD, depression, and anxiety can receive cognitive behavioral therapy via their mobile devices. One study looked at the efficacy of

avatar Avatar (, ; ), is a concept within Hinduism that in Sanskrit literally means "descent". It signifies the material appearance or incarnation of a powerful deity, goddess or spirit on Earth. The relative verb to "alight, to make one's appearanc ...

-based therapeutic interventions to reduce depressive symptoms. Another study analyzed seven clinical trials to demonstrate the efficacy of a digital therapeutic in significantly reducing blood pressure. A preliminary study suggested that a mobile mindfulness app may be able to decrease acute stress while improving mood.

Outcomes

The general consensus among researchers in the field of digital therapeutics is that the discipline requires more clinical data and investigation to be fully evaluated. A variety of studies have been conducted to evaluate the efficacy and impact of behavior change techniques that utilize a digital platform, however. In a meta-analysis of 85 such studies comprising a total sample size of over 43,000 participants, researchers discovered that digital therapeutics have a "statistically small but significant effect on health-related behavior." The study also showed that a broader use of theory, behavior change techniques, and modes of delivery (especially regular notifications) improved the efficacy of a given program. Individual studies have also showed some benefits for patients. For instance, a diabetes prevention program using digital therapeutics saw participants lose an average of 4.7% of baseline body weight after 1 year (4.2% after 2 years) and undergo a 0.38% reduction in A1c levels after 1 year (0.43% after 2 years). Another weight loss pilot program using digital therapeutics reported a mean weight loss of 13.5 pounds (or 7.3% of baseline) with a significant average drop in both systolic and diastolic blood pressure (18.6 mmHg and 6.4 mmHg respectively). The study also saw a slight but statistically insignificant drop in total cholesterol,

LDL Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall densit ...

triglycerides A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids (from ''tri-'' and ''glyceride''). Triglycerides are the main constituents of body fat in humans and other vertebrates, as we ...

, and A1c.

Regulation of digital therapeutics

While a broad range of unregulated health apps have historically been available in the

App Store (iOS/iPadOS) The App Store is an app store platform, developed and maintained by Apple Inc., for mobile apps on its iOS and iPadOS operating systems. The store allows users to browse and download approved apps developed within Apple's iOS Software Deve ...

Google Play Google Play, also known as the Google Play Store and formerly the Android Market, is a digital distribution service operated and developed by Google. It serves as the official app store for certified devices running on the Android (operating sys ...

since their launch, many of these have been found to produce inconsistent, misleading, or dangerous results. In response, regulators in the United States such as the

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

have developed regulatory frameworks such as software as a medical device which require manufacturers to prove that their apps are safe, effective, and that rigorous

quality management system A quality management system (QMS) is a collection of business processes focused on consistently meeting customer requirements and enhancing their satisfaction. It is aligned with an organization's purpose and strategic direction (ISO 9001:2015). I ...

processes are in place to ensure that remains the case as software updates occur. In the

European Union The European Union (EU) is a supranational political and economic union of member states that are located primarily in Europe. The union has a total area of and an estimated total population of about 447million. The EU has often been des ...

, regulation (EU) 2017/745, commonly known as "EU MDR" classifies potential digital therapeutics in terms of their intended use, application, and potential to cause harm. Because digital therapeutics are increasingly operating within a regulated environment, the degree of documentation and regulatory compliance (such as

ISO 13485 ISO 13485 ''Medical devices -- Quality management systems -- Requirements for regulatory purposes'' is a voluntary standard, published by International Organization for Standardization (ISO) for the first time in 1996, and contains a comprehensive ...

or the

CE mark On commercial products, the letters CE (as the logo ) mean that the manufacturer or importer affirms the good's conformity with European health, safety, and environmental protection standards. It is not a quality indicator or a certification ...

) has increased too.

Reimbursement and commercialization

Unlike

medication A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and re ...

or the billable hours of healthcare professionals, there are not currently clear pathways to reimbursement in most health systems. While many manufacturers seek FDA clearance or approval, this is only the first step on the path to being reimbursed for the use of a DTX. Accordingly, digital therapeutics companies pursue a range of business models: *

Direct-to-consumer Direct-to-consumer (DTC) or business-to-consumer (B2C) is the business model of selling products directly to customers and thereby bypassing any third-party retailers, wholesalers, or any other middlemen. Direct-to-consumer sales are usually tr ...

(DTC) - A digital therapeutic available directly through a smartphone's app store. Business models available include

Freemium Freemium, a portmanteau of the words "free" and "premium," is a pricing strategy by which a basic product or service is provided free of charge, but money (a premium) is charged for additional features, services, or virtual (online) or physical (o ...

, subscriptions, advertising, and selling the anonymized data to third parties *

Business-to-business Business-to-business (B2B or, in some countries, BtoB) is a situation where one business makes a commercial transaction with another. This typically occurs when: * A business is sourcing materials for their production process for output (e.g., a ...

(B2B) - Employers may wish to make digital therapeutics available for their workforce, either directly as a benefit or via a benefits administration company *

Pharmaceutical industry The pharmaceutical industry discovers, develops, produces, and markets drugs or pharmaceutical drugs for use as medications to be administered to patients (or self-administered), with the aim to cure them, vaccinate them, or alleviate symptoms. ...

partnership - Jointly developing solutions either to directly treat patients or to be used adjunctively i.e. in tandem with a drug, where the DTx may serve to enhance the effectiveness of the drug by promoting medication adherence or having its own effect. While such partnerships can bring in multi-million dollar revenues, ultimately the pharmaceutical company itself will seek reimbursement and is potentially not the ultimate customer. * Payer reimbursement - Being paid directly by a health system or health insurance company. While still in a nascent state in most countries, lobbying efforts are underway in the US for there to be specific reimbursement codes for DTx.

Germany Germany,, officially the Federal Republic of Germany, is a country in Central Europe. It is the second most populous country in Europe after Russia, and the most populous member state of the European Union. Germany is situated betwe ...

is the first country with specific processes for reimbursement (known as DiGa), with France, Italy, and the UK currently considering new pathways to reimbursement. Although German physicians and insurers can prescribe digital therapeutics and be reimbursed at a national level for around 300 Euro per course of treatment, adoption to date has been slow. To help build the

business case A business case captures the reasoning for initiating a project or task. It is often presented in a well-structured written document, but may also come in the form of a short verbal agreement or presentation. The logic of the business case is that, ...

for their usage, DTx companies often commission

health economics Health economics is a branch of economics concerned with issues related to efficiency, effectiveness, value and behavior in the production and consumption of health and healthcare. Health economics is important in determining how to improv ...

evaluations of their interventions to show that their use ultimately lowers healthcare costs in the medium-long term, such as by reducing the need for hospital admissions or expensive surgeries.

References