DTx: where do EU regulations stand in this emerging, rapidly-growing market?

Cécile Théard-Jallu

De Gaulle Fleurance, Paris

ctheardjallu@dgfla.com

Introduction

Digital Therapeutics (DTx), which first appeared around 16 years ago, are a type of medical device (some even say a new kind of medicine),[1] designed to complement, lighten or even replace the need for medication.

While their definition may vary from one country, or one actor, to another, we may generally say that they are evidence-based therapeutic interventions driven by software to prevent, manage, or treat a medical disorder or disease. As software applications with a proven clinical benefit, DTx can be used as a standalone therapy or in conjunction with more conventional treatments such as pharmacological therapy or with certain hardware or mechanic devices.

They can support patients in self-managing symptoms or be used in coordination with or by a medical team. DTx operate with the collection and processing of digital measurements allowing data to be collected and analysed as both a progress report and a preventative measure.

DTx use digital implementers like mobile devices, apps, sensors, virtual reality, the Internet of Things, video games and other tools to support behavioural changes in patients.[2] 

Where is the DTx market standing, and what are the trends?

Considered one of the most innovative areas within digital health, DTx ecosystem has experienced an accelerated period of progress over in recent years. Targeting a wide range of conditions, including chronic diseases, diabetes, and mental illness.[3] the DTx market is booming, with US$17.7bn in revenues forecast for 2027, and nearly a thousand clinical trials underway. The market is dominated by the United States, followed by Europe and Asia.[4]

While being a disruptive force for more personalised, participatory and preventive medicine, aimed at meeting patient needs which are unmet by conventional medicine and compensating for an overheated healthcare system, DTx are nevertheless encountering a series of obstacles, such as the still-limited support of patients and caregivers, and a financing model that has yet to be secured.[5]

Their legal framework is also a challenge, as it has yet to be developed and harmonised at both European Union and international levels. But the European Medicines Agency and the European Commission are starting to explore these solutions,[6] and the first national initiatives have been launched, along with bilateral agreements. All of which bode well for a more durable framework which should support the market’s efforts and contribute to its future prosperity.

The current regulatory framework

To date, DTx are digital medical devices (when the criteria are met)[7] with a therapeutic purpose.[8] DTx differ from drugs in their method of action, since they are non-pharmacological, non-immunological and non-metabolic.[9] This brings with it a series of obligations, including that of having a medical CE mark, and complying with certain essential safety and performance requirements.

DTx also need to ensure a sufficient level of protection for personal data, including health data, which DTx may enable to process (in compliance with the GDPR[10] and applicable national texts). In this respect, the European Data Protection Supervisor (EDPS) has already started assessing potential positive and negative impacts of DTx.[11]

According to the EDPS, no positive impacts on data protection have been identified for the moment (as of 2021/2022) with DTx, taking into consideration the current design of this technology developed in the market. The EDPS adds that ‘the situation may change in the case of a different design and configuration of the technology embedding privacy enhancing features’. The DPFS also makes observations in the following areas:

• Constant observation and profiling of the patient

‘DTx allow the collect of a vast amount of personal data directly from the patient and to process them in a complex digital ecosystem. In most cases, an accurate health and/or behavioural profile of the person are created for the functioning of the solution. This practice might entail risks of being constantly observed or the possibility of repurposing patients’ profiles.’

• High impact of personal data breaches

‘As the particular sensitivity and amount of personal data processed within DTx applications, a potential data breach can be a major threat against for the person concerned.’

• Complexity might generate security flaws

‘The fact that the processing is carried out via numerous operating systems and application providers might create risks on unlawful access across devices and providers due to possible security flaws.

’ The specificity of DTx is that they complement or replace drugs, making it necessary to compare their respective effects. However, the texts governing the clinical investigation of medical devices and their life on the market[12] are distinct from those governing these same actions for drugs.[13] Among other differences, clinical trial applications and authorisations for medicinal products in EEA Member States, Iceland, Liechtenstein and Norway must be submitted via the CTIS (Clinical Trial Information System) portal, whereas clinical investigations for medical devices must be submitted via the national authority.

It is therefore necessary to adapt texts to these new ‘hybrid digital medicines’, and several countries have already done so.

Specific regulations being shaped in various countries

To date, the aim has not yet been to introduce new, autonomous, substantive regulations, rather innovative authorisation and funding procedures applying certain eligibility criteria.

In the US, the FDA has sought to solve problems such as the inefficient review and re-examination of applications as they undergo iterative improvements. This has led to the introduction of the Digital Health Software Pre-Certification Pilot Program, which regulates the company rather than the product.[14]

Germany has paved the way for DTx reimbursement via the Digitale-Versorgung-Gesetz (DVG) healthcare law. Since 2019, it has authorised all doctors in Germany to prescribe digital therapies (Digitale Gesundheitsanwendungen, or ‘DiGA’) to insured persons, even though their clinical investigations have not yet been completed. The reimbursement period is one year, allowing the manufacturer to collect clinical data and then have the technology re-evaluated for final reimbursement.[15] Belgium has adopted a similar logic with the ‘mHealth Belgium’ system enabling reimbursement through a multi-level approval. This involves CE marking and GDPR compliance with notification to the authorities, risk assessment, and where appropriate, demonstration of medico-economic benefit.[16]

In a decree dated 31 March 2023, France adopted the Prise En Charge Anticipée Numérique (‘PECAN’) scheme. This enables one-year critical funding by the French health insurance system of sufficiently mature digital medical devices for therapeutic purposes, believed to be innovative, but which have not yet completed their clinical investigation pathway. This early phase, which goes through several stages, notably with the French National Health Agency (ANS) and High Authority for Health (HAS), enables the operator to finalise the demonstration of clinical and/or organisational benefits, while already being reimbursed.[17]

Beyond the regulatory framework, many players are mobilising themselves to support this market, which has the potential to revolutionise the healthcare sector. In October 2022, an EU Taskforce, coordinated by EIT Health, was launched to develop harmonisation evaluation criteria for digital devices.[18] At the same time, bilateral collaborations are emerging, such as the one signed in November 2023 between France Biotech and the Spitzenverband Digitale Gesundheitsversorgung (SVDG), the German association for digital healthcare. Its aim is to pool expertise, support the development of a Franco-German DTx market and foster the growth of DTx in Europe in general.[19]

Numerous issues remain, including mutual recognition of clinical results, interoperability, data sharing and storage, market access, pricing. The mobilisation of the various private players and discussions with public authorities will all be necessary steps towards integrating DTx into the healthcare landscape. In addition to ensuring that standards are compatible, if not harmonised, the challenge is also to reinforce the confidence of caregivers who can prescribe them, and facilitate their use by patients.