Designing a digital therapeutics (DTx) study in a real-world setting for regulatory submission and reimbursement success

The Digital Therapeutic Alliance’s (DTA’s) recent whitepaper, written in partnership with Curebase, Setting the stage for a fit-for-purpose DTx evidentiary standard, states in the introductory section that “the past decade has seen a profound acceleration of digital health innovation, particularly with the rise of evidence-based digital therapeutics (DTx) and publication of an increasing number of randomized controlled trial (RCT) and real-world evidence (RWE) studies demonstrating DTx clinical benefits beyond those provided by traditional medical treatments. This has resulted in DTx regulatory approvals, favorable health technology assessments, incorporation into clinical practice guidelines, establishment of permanent reimbursement pathways, and expanded DTx access for target patient populations.” The DTA released this whitepaper in December of 2022 in an effort to “[set] the stage for this new DTx-specific evidentiary standard by providing foundational principles that apply to the DTx category of medicine, in addition to baseline expectations for healthcare decision makers (HCDMs) related to the types, quality, and timing of clinical trials necessary to evaluate and implement DTx therapies in real-world settings.” 

One of the focal points of this paper is around data collection in DTx clinical research. The paper highlights a recommendation from the NICE evidence standards for digital health technologies that states, “the choice of study design should be appropriate for the intended purpose of the DHT [digital health technology].” Real-world settings in a DTx clinical trial can give insight into feasibility, user engagement, useability, effectiveness, etc. This use of real-world settings in DTx studies can generate outcomes evidence necessary for regulatory submission,  payment pathways, and clinical use and acceptance. 

DTx in real-world settings 

In a peer-reviewed paper, Introduction to real-world evidence studies, author Deepa Chodankra, states “findings from clinical trials cannot be generalized to the population at large due to the stringent eligibility criteria. RWE studies complement clinical trials by generalizing the findings from clinical trial to general population. Furthermore, RWE can provide information on other areas, such as natural history and course of disease, effectiveness studies, outcome studies, and safety surveillance.” With growing evidence pointing to the necessity of real-world data generation, sponsors are urged to consider running their trials in settings that are or mimic the intended use setting for patients. These settings for digital therapeutics are often patients’ homes. 

Due to the fact that most digital therapeutics can be administered to patients 100% remotely through proper technology,  many digital therapeutics are inherently designed to allow for trials to take place in real-world settings. The key, however, is having a clinical research partner equipped with the right technology-driven capabilities and services to run a DTx trial from start to finish in a real-world setting while being able to collect and report the exact data necessary for study success.

Go-to-market strategy 

For sponsors of DTx research looking to obtain regulatory approval,  it is important that the evidence and data captured is the right kind of data. The previously mentioned DTA whitepaper highlights the growing need for collecting fit-for-purpose evidence. To pursue the regulatory pathway, DTx sponsors need a  strategy in place to generate and capture this type of evidence. Since RWE is key to this process, having a trial take place in a real-world setting (i.e. 

virtually, or 100% remote) is crucial. 

For sponsors looking to bring a digital therapeutic to market, having a collaborative clinical research partner to design and execute a trial that can take place in a setting where the desired evidence can be generated and properly captured can help streamline the regulatory submission process, and ultimately, clinical acceptance and commercialization. 

Designing a real-world study 

There are several ways in which DTx clinical research can take place in real-world settings. The key to a study’s success in a real-world environment however is being able to ensure that all study elements can exist in a real-world setting. For instance, if a DTx study is designed to take place in a participant’s home, sponsors have to ensure that recruitment, consent, prescreening, enrollment, ePRO collection, patient monitoring, telemedicine calls, etc., can all happen in that remote environment. This can be especially difficult when multiple components of a trial are run by different vendors resulting in patients often being burdened by having to log into different platforms, and sponsors struggling to keep up with and monitor their study. 

Sponsors need a clinical research partner that allows them the flexibility to build the study model they need with a partner that can execute all necessary study components without having to rely on a multitude of vendors and systems. A technology-driven clinical research partner offering an all-in-one solution including CRO services, recruitment, virtual site and PI’s, eConsent, comprehensive patient platform, sponsor dashboard, blinding, etc., will give sponsors the ability to execute their DTx study in a real-world setting without compromising on crucial study components. 

Example of DTx research in real-world setting: 

metaMe Health is a digital therapeutics company committed to developing FDA-cleared prescription digital therapeutics (PDTs), with an initial focus on the treatment of gastrointestinal conditions. Since PDTs are intended to be used like pharmaceuticals, they are developed under the same rigorous conditions complete with clinical trials, FDA clearance, and available only with a physician’s prescription. metaMe partnered with Curebase to help conduct this FDA registration study in a partially-remote setting. 

metaMe decided to take advantage of Curebase’s ability to rapidly activate sites with virtual 60-90 minute sessions. This dramatically increased the number of participating sites. Within two weeks, 15 additional sites were onboarded to the study, and enrollment rates increased from only a few per month to over 100 per month.  

Patient outcomes were recorded from the patients’ homes through ePROs. After patients completed their scheduled baseline exam, trial participation was facilitated through the Curebase platform. Patients could log into their account at any time to view upcoming tasks and deadlines to successfully complete the clinical trial. This included reporting daily outcomes, adding payment information, and so on. Curebase also configured automatic SMS and email alerts reminding patients when certain tasks were due and linking directly to the task item. The study health data was synced in real-time, allowing Curebase virtual research coordination team to follow up with and offer support to patients who had issues completing their given tasks.

Curebase’s ability to automate and digitize many of the steps in a typical clinical trial not only accelerated enrollment but also dramatically lowered costs. The study was executed with higher quality tools than the paper-based systems of CROs who quoted twice the price.

The Curebase eClinical software suite provided a customized single solution to remotely manage all aspects of a trial, from recruitment through close-out, and allowed Curebase to deliver FDA-grade DTx clinical research for metaMe. 

Read more information on how Curebase helped metaMe enlist virtual sites in their DTx trial in this whitepaper.