Pathologies and technologies for digital therapeutics: An analysis of global clinical trials
- 1Department of Pharmaceutical Sciences, University of Milan, Milan, Italy
- 2INDICON S.r.l. Società Benefit, Milan, Italy
Abstract
CDigital therapeutics (DTx) are software-based medical devices that deliver evidence-based therapeutic interventions directly to patients. While the clinical use of DTx is expanding rapidly, regulatory fragmentation and the absence of harmonized legal definitions hinder their assessment and reimbursement policies, as well as their integration into healthcare systems. There is currently a lack of comprehensive overviews of DTx clinical development, which are essential for informing policy, research and regulatory priorities. This paper provides an updated overview of randomised clinical trials involving DTx. 254 eligible trials on DTx, (defined according to ISO/TR 11147:2023) registered through January 2025 were identified through a search on ClinicalTrials.gov. Mobile applications represent the most prevalent technology (65%), followed by web-based tools and virtual reality (20%). Psychiatric disorders are the primary therapeutic target (52% of the studies) with insomnia, depression, and anxiety being the most addressed conditions. Trials were primarily conducted in North America (41%) and Europe (32%), where Germany, Spain, and Italy represent the most active countries. The analysis of clinical trials registrations on ClinicalTrials.gov reveals a heterogenous geographical distribution of DTx development but also a clear direction in the type of conditions for which they are mostly indicated, namely psychiatric and nervous system disorders. The fragmented policies on DTx reimbursement, even among EU countries, and the different capacity of governments to fund DTx research and development emerge as key factors, along with cultural and ethical issues, in determining the willingness of the industry to invest in these devices. Author summary: When a software is intended by its manufacturer to treat, prevent, diagnose or monitor a pathologic condition, it cannot be considered as a general use product. Indeed, in most legislative framework, it is a Medical Device and, as such, it is subject to strict legislation which is in place to guarantee its safety and efficacy. Nomenclature, market access and reimbursement policies for such products vary worldwide, but there is wide acceptance of the term “Digital Therapeutics” (DTx) to mean software with a therapeutic function, as formalized by the ISO. In the paper we investigate, through the analysis of DTx clinical trials registrations in ClinicalTrials.gov, the regional distribution of active studies, the type of technology most actively researched (mobile app, web-based app, virtual reality or other) and the therapeutic indications. Our analysis highlighted on the one hand a heterogenous worldwide distribution of DTx, which reflects a fragmented landscape of reimbursement policies and funding capacity. On the other hand, a clear direction in both the type of technology employed (mobile apps) and in the prevalent therapeutic indications (psychiatric and nervous system disorders) clearly emerged.
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BibTeX
@article{rocco2026pathologies,
title = {{Pathologies and technologies for digital therapeutics: An analysis of global clinical trials}},
author = {Paolo Rocco and Valentina Pagella and Umberto M. Musazzi and Sara Manellari and Elena Paola Lanati and Paola Minghetti},
journal = {PLOS Digital Health},
year = {2026},
month = oct,
doi = {10.1371/journal.pdig.0001750},
url = {https://journals.plos.org/digitalhealth/article?id=10.1371/journal.pdig.0001750},
note = {CC BY},
}
RIS
TY - JOUR
TI - Pathologies and technologies for digital therapeutics: An analysis of global clinical trials
AU - Paolo Rocco
AU - Valentina Pagella
AU - Umberto M. Musazzi
AU - Sara Manellari
AU - Elena Paola Lanati
AU - Paola Minghetti
PY - 2026
DA - 2026/10/01
JO - PLOS Digital Health
DO - 10.1371/journal.pdig.0001750
UR - https://journals.plos.org/digitalhealth/article?id=10.1371/journal.pdig.0001750
AB - CDigital therapeutics (DTx) are software-based medical devices that deliver evidence-based therapeutic interventions directly to patients. While the clinical use of DTx is expanding rapidly, regulatory fragmentation and the absence of harmonized legal definitions hinder their assessment and reimbursement policies, as well as their integration into healthcare systems. There is currently a lack of comprehensive overviews of DTx clinical development, which are essential for informing policy, research and regulatory priorities. This paper provides an updated overview of randomised clinical trials involving DTx. 254 eligible trials on DTx, (defined according to ISO/TR 11147:2023) registered through January 2025 were identified through a search on ClinicalTrials.gov. Mobile applications represent the most prevalent technology (65%), followed by web-based tools and virtual reality (20%). Psychiatric disorders are the primary therapeutic target (52% of the studies) with insomnia, depression, and anxiety being the most addressed conditions. Trials were primarily conducted in North America (41%) and Europe (32%), where Germany, Spain, and Italy represent the most active countries. The analysis of clinical trials registrations on ClinicalTrials.gov reveals a heterogenous geographical distribution of DTx development but also a clear direction in the type of conditions for which they are mostly indicated, namely psychiatric and nervous system disorders. The fragmented policies on DTx reimbursement, even among EU countries, and the different capacity of governments to fund DTx research and development emerge as key factors, along with cultural and ethical issues, in determining the willingness of the industry to invest in these devices. Author summary: When a software is intended by its manufacturer to treat, prevent, diagnose or monitor a pathologic condition, it cannot be considered as a general use product. Indeed, in most legislative framework, it is a Medical Device and, as such, it is subject to strict legislation which is in place to guarantee its safety and efficacy. Nomenclature, market access and reimbursement policies for such products vary worldwide, but there is wide acceptance of the term “Digital Therapeutics” (DTx) to mean software with a therapeutic function, as formalized by the ISO. In the paper we investigate, through the analysis of DTx clinical trials registrations in ClinicalTrials.gov, the regional distribution of active studies, the type of technology most actively researched (mobile app, web-based app, virtual reality or other) and the therapeutic indications. Our analysis highlighted on the one hand a heterogenous worldwide distribution of DTx, which reflects a fragmented landscape of reimbursement policies and funding capacity. On the other hand, a clear direction in both the type of technology employed (mobile apps) and in the prevalent therapeutic indications (psychiatric and nervous system disorders) clearly emerged.
SN - 2767-3170
ER -