DTx and the case for fit-for-purpose evidentiary standard

Digital health innovation has accelerated in recent years, particularly with the rise of digital therapeutics (DTx) and growing evidence of their clinical benefits. DTx deliver evidence-based therapeutic interventions that are driven by high-quality software programs to prevent, manage, or treat a medical disorder or disease.¹

Globally, organisations are recognising the need to develop guidelines for DTx products that are tailored to their unique characteristics, and distinguish them from both pharmaceuticals and the broader class of digital health solutions. Organisations such as the United States Food and Drug Administration (FDA), the National Institute for Health and Care Excellence (NICE) in the United Kingdom, the World Health Organization (WHO), and others are developing recommendations focused on documenting best practices in clinical evidence generation for digital health and therapeutic products. Digital therapeutics require a fit-for-purpose evidentiary standard, and this article establishes foundational principles and expectations to evaluate and implement DTx in real-world settings.

DTx require a fit-for-purpose evaluation framework

During the DTx product life cycle, a variety of evidence is collected, including formal clinical studies evidence, real-world evidence (RWE), health economic and outcomes research (HEOR), and context-specific implementation pilots. As more Healthcare Decision-Makers (HCDMs) at the local, national, and regional levels embark on evaluating DTx, it is important that evidence dossier requirements and frameworks move toward a harmonised set of expectations related to the type, timing, and quality of DTx studies sufficient to assess product safety, efficacy, and impact at the individual and population health levels of care. Developing a common understanding of what types and quality of DTx evidence comprises a sufficient evidence package will minimise delays in providing patients around the world access to DTx products that meet a broad range of unmet and under-addressed medical needs.

HCDMs are frequently perceived to evaluate DTx products using the same or similar criteria as pharmaceuticals. This expectation for DTx products to meet the same requirements, in terms of types, quality, and timing of clinical evidence as pharmaceuticals ignores digital therapeutics’ inherently safer mechanisms of action, agile development processes, ability to generate real-time outcomes, and ongoing iterative nature.

DTx therefore require a fit-for-purpose evaluation framework that incorporates aspects of existing pharmaceutical and medical device evaluation frameworks, but designed to specifically evaluate the safety, efficacy, and impact of DTx therapies. Pharmaceuticals are recognised as an “embodied technology”, for which the efficacy relates solely to the correct dose of the drug, which chemically interacts with the body’s physiological systems. DTx products, on the other hand, use software-driven technology to deliver behavioural and physical impacts on end-users, thus carrying different types and levels of risk than chemical-based products. For example, a counterfeit or low-quality DTx that relies on or disseminates incorrect, incomplete, or inconsistent therapeutic impact may be harmful to end-users by delivering inadequate or inappropriate clinical interventions² (e.g., inaccurate directions based on connected-sensor or user-input parameters, or insufficient infrastructure for mental health risk management at scale).

HCDMs should adopt a fit-for-purpose evaluation approach

Although DTx products are not risk-free, they do present different risks than pharmaceuticals, and should thus be evaluated accordingly. Because digital therapeutics are regulated as medical devices, it follows that these products be evaluated similarly, using a risk-based approach, as opposed to being required to meet pharmaceutical-specific clinical evidence criteria.

Additionally, unlike pharmaceuticals, DTx products undergo incremental product modifications during the post-marketing phase. These product changes, or iterations, may impact many things, ranging from product functionality and bug fixes to clinical and usability improvements, which may impact the therapy’s effectiveness. Thus, more traditional approaches to assessment of therapeutic intervention, relying on a single RCT and/or prospective studies prior to first market launch, often need to be paired with additional evidence generation activities during the product’s life cycle, to account for the iterative nature of technological product design.³ Where applicable, HCDMs may consider accepting study designs that account for specific DTx characteristics, such as multi-phasic optimisation strategies, sequential multiple assignment randomised trials, and micro-randomised trials developed with an adaptive design.⁴

Considering the unique nature and innovation cycles of DTx products, HCDMs should adopt a fit-for-purpose evaluation approach. Furthermore, to enable patient access to DTx therapies across the global marketplace, HCDMs and product manufacturers require unified evaluation frameworks, to ensure consistency in DTx product assessment, regulation, reimbursement, and clinical scalability. Notably, a fit-for-purpose DTx product evidence evaluation framework does not weaken evidentiary requirements, but rather provides greater evidentiary strength and robustness by reflecting how DTx products are designed, developed, and used (or managed) in real-world settings.

Developing a common expectation of what constitutes appropriate, sufficient, and optimal clinical evidence for DTx will lead to safer product use and prevent unnecessary delays in providing patients around the world with access to high-quality, clinically validated DTx products.

About the authors

Megan Coder, PharmD, MBA, is chief policy officer of the Digital Therapeutics Alliance (DTA), an international non-profit trade association of industry leaders and stakeholders dedicated to improving clinical and health economic outcomes through the use of high quality, evidence-based digital therapeutics (DTx). Coder founded the DTA in 2017 and remains instrumental in developing the foundations for this quickly evolving industry. She leads the DTA’s efforts related to thought leadership, global policy, international standard development, and the Alliance’s DTx Value Assessment & Integration Guide.

Pooja Raghani, M.S., Psy.D., is director of Industry Affairs at the Digital Therapeutics Alliance (DTA). She leads efforts related to global thought leadership, DTx policy analysis, and resource development for patients, clinicians, policymakers, and payors. Raghani has an interdisciplinary background in biochemistry, biomedical informatics, and clinical psychology. She is passionate about scaling the dissemination of digital, evidence-based clinical interventions to improve population health outcomes.

Whitney Stewart has 10 years of experience in clinical trial operations. Currently, as a director of Clinical Project Management at Curebase, she oversees the execution of numerous trials, including many for digital therapeutics.

Dario Motti is evidence lead for Regulated Digital Products at Roche. He has more than 15 years of experience in pre-clinical and clinical research, many spent in the digital and medical device space. He focuses on supporting product teams in delivering effective, beneficial, and impactful digital solutions into the hands of patients and care teams worldwide.

Simon Thomas is president of Freespira. He is a proven leader with experience developing and bringing to market new medical devices and treatments. Thomas joined at Freespira’s founding and in the years since has led product development, clinical studies, quality, biostatistics, finance, operations, and regulatory approvals, including the company’s two FDA clearances. Before Freespira, he led engineering, research and development, QA/RA, and operations for a number of medical technology companies.