Software as Medicine: Global Trial Map Reveals Where Digital Therapeutics Are Headed

Digital therapeutics, the software-based medical devices that deliver clinically validated treatment through a screen rather than a syringe or a pill, have quietly become one of the fastest-moving corners of modern medicine. Yet for all the enthusiasm surrounding prescription apps and therapeutic video games, the field has lacked something basic: a comprehensive map of where its clinical evidence actually comes from. A new analysis published in PLOS Digital Health by Paolo Rocco, Valentina Pagella, Umberto M. Musazzi, Sara Manellari, Elena Paola Lanati and Paola Minghetti offers exactly that, combing through global trial registries to reveal which diseases, which technologies and which regions dominate the clinical development of this emerging class of treatment.

The research team systematically searched ClinicalTrials.gov, the largest public registry of clinical studies, for randomised clinical trials involving digital therapeutics registered through January 2025. To keep the analysis rigorous, the authors applied a formal definition drawn from the international technical standard ISO/TR 11147:2023, which specifies what qualifies as a digital therapeutic rather than a general wellness app. That distinction matters enormously, because the market is crowded with products that claim health benefits without ever generating clinical trial evidence. By filtering the landscape through this standard, the researchers identified 254 eligible randomised trials, providing the most complete snapshot to date of how software-based medicine is actually being tested in patients.

The technological breakdown is striking in its concentration. Mobile applications account for 65 percent of all trials, making the smartphone the undisputed delivery vehicle of digital therapeutics. Web-based tools and virtual reality together represent roughly 20 percent, with the remainder distributed across other platforms. This dominance of the mobile app reflects practical realities: smartphones are ubiquitous, inexpensive for developers to target, and capable of delivering interventions ranging from cognitive behavioural therapy modules to real-time symptom tracking. Virtual reality, while a smaller slice of the pie, has carved out niches where immersion matters, such as exposure therapy for phobias and rehabilitation protocols that benefit from controlled, simulated environments.

Even more revealing is the therapeutic focus. Psychiatric disorders are the primary target of 52 percent of the identified trials, with insomnia, depression and anxiety standing out as the conditions most frequently addressed. This is not a random pattern. Mental health conditions are particularly suited to software-delivered interventions because their treatment often relies on structured behavioural change, cognitive restructuring and repeated therapeutic exercises, all of which can be standardised and delivered algorithmically. A well-designed app can guide a patient through the same evidence-based protocols a therapist might use, at a fraction of the cost and with none of the scheduling barriers that make traditional mental health care so difficult to access.

Geographically, the clinical development of digital therapeutics is heavily skewed toward wealthy regions. North America hosts 41 percent of the trials and Europe 32 percent, with Germany, Spain and Italy emerging as the most active European countries. The concentration is unsurprising given that running randomised trials requires substantial funding, established regulatory pathways and a commercial ecosystem willing to invest in software that must clear medical device hurdles. But the imbalance also signals a gap: large parts of the world, including regions where mobile phone penetration is highest and where scalable mental health interventions could have the greatest impact, are barely represented in the evidence base. The therapies being built for global smartphones are, so far, being validated mostly in American and European populations.

Beneath these headline numbers lies a deeper problem the authors emphasise: regulatory fragmentation. Digital therapeutics occupy an awkward position between consumer software and traditional medical devices, and different jurisdictions have answered the question of how to classify and approve them in different ways. There is no harmonised legal definition of a digital therapeutic across major markets, which complicates everything from trial design to market authorisation. A company seeking approval in the United States, the European Union and Asia may face distinct evidentiary expectations, classification criteria and post-market obligations in each, multiplying costs and slowing the translation of promising products into clinical practice.

Reimbursement is where fragmentation bites hardest. Even within the European Union, policies on whether and how health systems will pay for digital therapeutics vary dramatically from country to country. Germany has pioneered a dedicated fast-track pathway for digital health applications, allowing products to be prescribed and reimbursed while further evidence accumulates, while other member states have moved far more cautiously or not at all. The new analysis identifies these divergent reimbursement policies, together with differences in governments’ capacity to fund research and development, as key factors shaping whether industry is willing to invest in these devices at all. Cultural and ethical considerations, including attitudes toward data privacy and the acceptability of software as a medical treatment, add further layers of complexity that vary across markets.

The consequences of this patchwork extend beyond commercial strategy. Without harmonised standards for evidence generation, clinicians and health technology assessment bodies struggle to compare products or to know whether a trial demonstrating benefit in one context would translate to another. Patients may encounter a bewildering landscape in which an app prescribed by their physician in one country is unavailable or unsubsidised across a border a few hundred kilometres away. The authors argue that comprehensive overviews of the clinical trial landscape, like the one they have produced, are essential for informing policy, research priorities and regulatory strategy, giving regulators and funders a shared factual basis for deciding where the field is heading and where the gaps lie.

The concentration of trials in psychiatric and nervous system disorders also raises questions about the direction of the field. On one hand, it reflects genuine unmet need: depression, anxiety and insomnia affect hundreds of millions of people worldwide, and traditional care systems are chronically unable to meet demand. Digital therapeutics offer a rare prospect of scalable, evidence-based treatment that does not depend on recruiting scarce clinicians. On the other hand, the dominance of mental health applications means that other areas where software might plausibly help, from chronic pain to cardiovascular rehabilitation to diabetes management, remain comparatively underexplored in the randomised trial record, at least by the ISO-defined standard the researchers applied.

What emerges from the 254-trial map is a field at an inflection point. The technology has matured, the trial pipeline is real and growing, and the clinical focus is clear: software aimed squarely at the mind. But the infrastructure surrounding that science, the definitions, the regulations and the payment systems that determine whether a validated app ever reaches a patient, remains fragmented and uneven. The PLOS Digital Health analysis suggests that the next phase of digital therapeutics will be decided less by what the software can do in a trial than by whether governments and health systems can agree on what it is, how to judge it and who should pay for it. Until they do, the promise of medicine delivered by code will remain unevenly distributed, validated in North American and European trials while the world’s smartphones wait.

Subject of Research: Global clinical trial landscape of software-based digital therapeutics and their regulatory and reimbursement challenges

Article Title: Pathologies and technologies for digital therapeutics: An analysis of global clinical trials

Article References: Rocco, P., Pagella, V., Musazzi, U. M., Manellari, S., Lanati, E. P., & Minghetti, P. (2026). Pathologies and technologies for digital therapeutics: An analysis of global clinical trials. PLOS Digital Health, 5(10), e0001750. https://doi.org/10.1371/journal.pdig.0001750

Image Credits: AI Generated

DOI: 10.1371/journal.pdig.0001750

Keywords: digital therapeutics, clinical trials, mobile health applications, psychiatric disorders, regulatory fragmentation, reimbursement policy, ClinicalTrials.gov, insomnia, depression, anxiety, virtual reality, medical devices