May 6, 2021 PAO-05-21-NI-01
Digital therapeutics (DTx) represents a collection of technologies, products, and services across healthcare and wellness.1 More specifically, DTx delivers evidence-based therapeutic interventions that prevent, manage, or treat medical disorders and can either supplement or supplant existing treatments for a variety of diseases and conditions.1 DTx differs from diagnostics, telehealth, and other digital health products, as DTx products must be approved by regulatory entities. Proof of concept is at the core of their models, as DTx products not only have to be driven and backed by evidence but must also be able to prevent and/or manage a disease or disorder.1
As COVID-19 proliferated across the globe, forever changing the way we interact in both physical and digital environments, combined with a growing mental health crisis and surging prevalence of chronic conditions around the world, the DTx space is now projected to reach $56 billion by 2025.2 DTx has the potential to disrupt traditional pharmaceutical markets, and big pharma and medical device companies must decide whether to embrace this technology or potentially lose market share to DTx startups in a rapidly expanding market.
The Digital Therapeutics Alliance (DTA) is the leading international organization on thought leadership in the DTx space, providing patients, clinicians, and policymakers with the necessary tools to evaluate and utilize DTx products — including ethics, best practices, and product categorization.3 According to the DTA, all products claiming to be a digital therapeutic must:
DTx products can eliminate many gaps in healthcare by delivering therapies on devices to which a large percentage of people have access — such as smartphones and tablets — and, owing to the regulatory rigor being applied to determine efficacy, patients are beginning to rely on DTx products in ways that parallel traditional care. DTx allows for increased patient access to clinically safe and effective therapies while lowering stigmas associated with traditional care, expanding patient accessibility regardless of age, language, culture, income, or geography.3
The DTA adopted four categories for classifying DTx products — suggesting they should do one of the following: 4
The regulatory requirements for each DTx category vary depending on the purpose of the product — for example, products designed to address a medical condition can go the direct-to-consumer route, whereas products developed to treat a medical disease or disorder require prescriptions.4 There are many companies developing DTx products to treat conditions including diabetes, hypertension, asthma, COPD, heart disease, cancer, stroke, insomnia, musculoskeletal disorders, stress, substance abuse, schizophrenia, cognitive impairments, and more. Many people suffering from these conditions are underserved due to limited or inconvenient access to healthcare; DTx can help narrow this gap.
More than 100 million Americans have diabetes or prediabetes and, as a result, are at greater risk of developing other serious conditions, including stroke, kidney disease, neuropathy, hypertension, and foot and eye complications.3 Diabetes is more prevalent in rural areas, and rural residents are 30% more likely to die as a result of diabetes-related conditions than their non-rural counterparts.3 To make matters worse, about 62% of non-metropolitan counties do not have diabetes self-management education and support.3 To combat this, BlueStar, developed by Welldoc, is a DTx product that provides tailored guidance driven by artificial intelligence that collects and analyzes health data to provide precise, real-time feedback and intelligent coaching to help patients better manage their diabetes. Insulia from Voluntis provides automated basal insulin dose recommendations and coaching messages for people with type 2 diabetes and allows a healthcare team to remotely monitor progress, as well as leveraging blood glucose readings and hypoglycemic symptoms to recommend insulin doses in real time while sharing data with healthcare providers for further recommendations.3
Although companies are developing DTx products across a robust array of conditions, patients suffering from chronic, debilitating diseases stemming from their own behaviors may benefit the most from DTx products.5 For these patients, DTx can offer both preventative and therapeutic value in the form of education, gamification, and real-time monitoring and feedback — supplementing traditional clinical care that can only be administered in-person and on a limited basis.5 Additionally, some DTx products can achieve the same clinical benefits as traditional drugs without toxicity and other associated side effects.5 DTx can also reduce costs associated with hospital and clinic visits, increase prescription adherence (due to the fact that patients are constantly monitored), and provide easier opportunities for clinicians to interact with and empower larger numbers of patients.5
While the potential benefits are extensive, DTx faces a number of challenges. Software bugs and glitches can negatively affect patients without mechanisms in place for immediate correction. Additionally, some patients may not be honest in their interactions with these apps — providing false information or trying to “trick” the apps — which can lead to misdiagnoses that come with a myriad of cascading, negative health outcomes.5
As such, regulatory bodies including the U.S. FDA are creating DTx approval processes and protocols, but there are inherent blind spots and unique questions for regulators to ponder. Traditional quality-control measures for drugs — such as potency, purity, and toxicity — clearly do not apply to DTx. Questions abound regarding how to effectively implement a commensurate level of scrutiny and rigor in the approval process of DTx products juxtaposed with traditional drugs. For example, what is an appropriate placebo in DTx clinical trials? What would classify a DTx product as generic? Would other usage aspects, such as operating systems, connectivity, and device types, also need regulation? Would patients whose digital treatment depends on a fast and stable internet connection also need to be issued an approved mobile hotspot and internet service provider?
The continuously evolving nature of technology also requires consideration, as DTx products will inevitably become obsolete relative to broader technological advances. Furthermore, as digital therapies get “smarter” through artificial intelligence and machine learning, app developers must make changes that impact user interfaces (UIs) and the user experience (UX), making it nearly impossible for regulatory bodies to fastidiously review each software update. As such, regulators face unprecedented challenges in implementing policies that ensure that these products remain efficacious.
Although much of the DTx landscape is uncharted territory, the FDA has begun addressing some of these questions and challenges. In April 2019, the FDA released a discussion paper describing a possible regulatory approach to premarket review for machine learning–driven modifications.5 The document introduces a “predetermined change control plan” to anticipate potential future software updates and a total product life cycle regulatory approach that aims to facilitate a seamless review of product performance improvements and subsequent deployment without compromising consumer safeguards.6 In addition, it offers a framework based on the International Medical Device Regulators Forum risk categorization principles, outlining when a manufacturer would need to submit a new 510(k) for a machine learning–driven software change to an existing device.6
The FDA also introduced its Digital Health Software Precertification Program, a pilot for approving software-based medical devices.6 Given how unrealistic it would be for regulators to approve every software release for a digital product, this program instead approves developers, allowing for product development to occur efficiently in rapid iterations without delays from perpetual approval cycles.
Due to the nature of cloud-connected apps, DTx products are at risk for compromised patient privacy. Implementation of rigid cybersecurity standards is necessary for mass adoption of DTx. Like all other forms of data transferred over the internet, risks of unauthorized access and manipulation of DTx data remain a constant threat, and failure to protect the underlying data could potentially threaten both trust in DTx products and wider perceptions of digital patient care. The FDA released draft guidance regarding cybersecurity in DTx apps and networked medical devices in October 2018, and medical device manufacturers must comply with federal quality system regulations to address cybersecurity risks of their products both before and after FDA review.7
While the FDA has issued guidance regarding cybersecurity device design, labeling, and documentation for premarket submissions, the agency does not currently mandate the completion of premarket security audits for medical devices.7 The current review model relies on device manufacturers to determine the level of cybersecurity risk associated with their product and include a set of cybersecurity design controls to minimize that risk.7 The FDA then evaluates the manufacturer’s design and risk-management documentation for reasonable assurance of safety and effectiveness.7
As more networked medical devices and DTx apps are developed and commercialized, and new cybersecurity threats continue to emerge, inclusion of a standardized, public cybersecurity set of protocols in premarket applications may help to resolve the information gap between manufacturers and users of DTx products.7 Ensuring that manufacturers remain vigilant in making design decisions that minimize security risk may reduce the number of security breaches and increase patient confidence. However, the ability for DTx companies to continually update their security protocols to stay ahead of emerging threats is of paramount importance, as achieving nearly infallible cybersecurity infrastructure is a constantly moving target and next to impossible.
DTx presents the potential to provide patients with access to care with efficacious results in ways that mitigate challenges that span access and affordability. There are no shortage of companies developing DTx products, and with organizations like the DTA setting standards and providing guidance and thought leadership, and regulatory bodies like the FDA creating new protocols for review and approval, we are likely to see the DTx space continue to grow at exponential rates. As the world around us becomes even more digital, it stands to reason that someday in the not-too-distant future, the use of digital therapeutics could become as common as picking up traditional prescriptions at your local pharmacy.
David is a writer, content creator, and marketing strategist with experience that spans various industries. He is adept at research and seamlessly crafting stories from disparate sources to bring clarity to complex topics, as well as skillfully articulating company and product value propositions. Beyond content and writing, David also spent nearly a decade working in various capacities in education, and leverages all of these skillsets to deliver engaging pieces for Nice Insight.
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