Digital health technology tools (DHTTs) present real opportunities for accelerating innovation, improving patient care, reducing clinical trial duration and minimising risk in medicines development. This review is comprised of four case studies of DHTTs used throughout the lifecycle of medicinal products, starting from their development. These cases illustrate how the regulatory requirements of DHTTs used in medicines development are based on two European regulatory frameworks (medical device and the medicinal product regulations) and highlight the need for increased collaboration between various stakeholders, including regulators (medicines regulators and device bodies), pharmaceutical sponsors, manufacturers of devices and software, and academia. As illustrated in the examples, the complexity of the interactions is further increased by unique challenges related to DHTTs. These case studies are the main examples of DHTTs with a regulatory assessment thus far, providing an insight into the applicable current regulatory approach; they were selected by a group of authors, including regulatory specialists from pharmaceutical sponsors, technology experts, academic researchers and employees of the European Medicines Agency. For each case study, the challenges faced by sponsors and proposed potential solutions are discussed, and the benefit of a structured interaction among the different stakeholders is also highlighted.
UNSTRUCTURED Digital therapeutics (DTx) are software-based products that prevent, manage, or treat a medical condition, and are delivered through a smartphone app, web application or wearable. Clinical trials assessing DTx pose challenges, foremost amongst which is designing appropriate ‘digital shams’ (or ‘digital placebos’), which should ideally mimic the DTx (in terms of design, components and duration of treatment) while omitting the active principle/component. To understand how digital shams are being used in clinical research on DTx, we conducted a systematic literature review (SLR) of DTx in neuroscience (including neurodevelopmental, neurodegenerative, and psychiatric disorders) with a focus on controlled clinical trials involving digital shams. Our search criteria identified 461 neuroscience studies involving 213 unique DTx. Most DTx were extended reality-based (40.4%) or mobile device-based (26.3%); 313 were comparative, of which 68 used shams. The most common therapeutic areas assessed in these studies were stroke (19.7%), depression (15%) and anxiety (11.3%); and the most common treatments were cognitive behavioral therapy/behavioral therapy (32.4%), physical rehabilitation (28.2%), and cognitive training (19.2%). Results: We identified the following important issues related to the use of digital shams: shams were not validated prior to use in studies; they varied widely in design; (from being near-identical to the DTx to using different software programs altogether); the level of patient engagement/satisfaction with the sham and the impact of the sham on study outcomes was infrequently reported. Conclusions: Digital shams are critical to the clinical development of DTx. Given the importance of sham controls in evaluating DTx efficacy, we provide recommendations on the key information that should be reported in a well-designed DTx trial and propose an algorithm to allow correct interpretation of DTx study results. Sham-controlled studies should be routinely used in DTx trials – in early phase studies, to help identify DTx active components, and in late-phase studies, to confirm the efficacy of DTx. Use of shams early in development will ensure that the appropriate sham control is used in later confirmatory trials.
Background Digital therapeutics (DTx) are software-based products that prevent, manage, or treat a medical condition and are delivered through a smartphone app, web application, or wearable device. Clinical trials assessing DTx pose challenges, foremost among which is designing appropriate digital shams (or digital placebos), which should ideally mimic DTx (in terms of design, components, and duration of treatment) while omitting the active principle or component. Objective The objective of our review was to understand how digital shams are being used in clinical research on DTx in neuroscience, which is the most common therapy area for DTx. Methods We conducted a systematic literature review of DTx in neuroscience (including neurodevelopmental, neurodegenerative, and psychiatric disorders) with a focus on controlled clinical trials involving digital shams. Studies were identified from trial registries (ClinicalTrials.gov, the European Union Clinical Trials Register, and Trial Trove) and through structured searches in MEDLINE and Embase (both via the Embase website) and were limited to articles in English published from 2010 onward. These were supplemented by keyword-based searches in PubMed, Google, and Google Scholar and bibliographic searches. Studies assessing DTx in neuroscience (including neurodevelopmental, neurodegenerative, and psychiatric disorders) were included. Details related to the publication, DTx, comparator, patient population, and outcomes were extracted and analyzed. Results Our search criteria identified 461 neuroscience studies involving 213 unique DTx. Most DTx were extended reality based (86/213, 40.4%) or mobile device based (56/213, 26.3%); 313 were comparative, of which 68 (21.7%) used shams. The most common therapeutic areas assessed in these studies were stroke (42/213, 19.7%), depression (32/213, 15%), and anxiety (24/213, 11.3%). The most common treatments were cognitive behavioral therapy or behavioral therapy (67/213, 32.4%), physical rehabilitation (60/213, 28.2%), and cognitive training (41/213, 19.2%). We identified the following important issues related to the use of digital shams in neuroscience: shams were not validated before use in studies, they varied widely in design (from being nearly identical to the DTx to using different software programs altogether), and the level of patient engagement or satisfaction with the sham and the impact of the sham on study outcomes were infrequently reported. Conclusions Digital shams are critical for the clinical development of DTx in neuroscience. Given the importance of sham controls in evaluating DTx efficacy, we provide recommendations on the key information that should be reported in a well-designed DTx trial and propose an algorithm to allow the correct interpretation of DTx study results. Sham-controlled studies should be routinely used in DTx trials—in early-phase studies—to help identify DTx active components and—in late-phase studies—to confirm the efficacy of DTx. The use of shams early in development will ensure that the appropriate sham control is used in later confirmatory trials.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.