Design, validation and reimbursement of digital therapies: the state of the art in Italy

The domain of digital therapies is one of the most promising trends in digital health. This is confirmed by the growth data and projections of investments in digital therapies worldwide.

But what is the current situation with respect to the design, development, approval and reimbursement of digital therapies in Italy?

What digital therapy is and what it isn’t

Not everything that is digital in healthcare is a digital therapy.

A possible definition, highlighted during DTX 2019, the Italian event dedicated to DTx, describes digital therapies as

Patient-centric software (only or primarily) interventions able to provide a positive clinically measurable effect, which is scientifically validated.

Digital Therapies would thus be considered those instruments based on software that, alone or in association with other instruments, are able to bring some real benefit, clinically measurable and scientifically validated, on specific health needs of patients

The therapeutic areas in which DTx are expanding the most and are being particularly effective are chronic disease and diseases with behavioural and psychological factors, for example: type II diabetes, hypertension, cardiovascular diseases, chronic respiratory problems such as asthma and COPD, obesity and insomnia, Alzheimer’s, various forms of dementia or addiction (smoking, alcohol, drugs), anxiety, depression, autism, learning disorders or attention deficits (ADHD) and all those diseases that can benefit from real-time monitoring of behaviour and health status.

Many of the diseases in which the investments of digital therapies are focused, such as chronic diseases or neurological disorders, are also the most expensive for healthcare systems, which are not always able to manage them properly. In this context, digital therapies have the potential to represent a significant revolution since they are both more affordable and more accessible than traditional therapies.

How to design and develop digital therapies

Digital therapies have to answer to one or more unmet needs and bring measurable and scientifically validated benefits on some aspect of the patient journey. DTx are intended to be integrated into clinical practice and prescribed by healthcare professionals to meet clinical needs and therapeutic objectives.

What is evident is that the framework under which digital therapies have to be designed cannot be too different from the way in which traditional medications are studied and tested. For DTx, as for drug therapies, it is essential to demonstrate efficacy and clinical safety through:

• design of the clinical study,
• activation of randomised pilot clinical trials,
• extended clinical trial validation,
• introduction into clinical practice.

In addition to medical, scientific and regulatory, technological and digital skills are also included in the process of design for DTx.

Although it may seem obvious to say, applications that do not positively pass the efficacy and safety studies can never be defined as digital therapies.

Approval and certification of digital therapies

While in the USA there is already a regulation on software to replace pharmacological therapies, in Europe no reference legislation exists yet.

From a legal and regulatory point of view, digital therapies fall within the framework of the “Software as a Medical Device (SaMD)“.  A medical device is considered a software that, alone or in combination, is used for medical purposes (such as diagnosis, prevention, monitoring, prediction, prognosis or treatment) but that does not act in the human body through pharmacological, immunological or metabolic ways.

While awaiting a specific regulation on DTx, in Italy digital therapies are thus treated as medical devices and must pass the quality certifications required by EU law to ensure compliance with safety requirements: from ISO standards regarding safety criteria of electronic devices, to FDA and EU regulations for the management of software as medical devices to manage and treat diseases.

The current recommendation is also to manage the approval procedure based on the claim of the solution (the promise of benefit declared by the producer) and its “level of risk”. The higher the risk to human health using the tool, the more thorough and scrupulous controls on safety and security must be. In this regard, four risk classes have been identified in order to categorise the DTx (from level 1 – low risk for health to level 4 – high risk, which can have irreversible effects and impacts on health and/or mortality) and which define, consequently, the approval processes and the controls that they must follow.

In addition to the indication of risk, and awaiting to build a single document of reference for Europe and Italy, the approval and certification of digital therapies is based on the following references:
Food and Drug Administration (FDA – United States)

• Guidances with Digital Health Content
• Software as a Medical Device (SaMD)
• Digital Health Innovation Action Plan
• Digital Health Software Precertification (Pre-Cert) Program

Medicines and Healthcare Products Regulatory Agency (MHRA – United Kingdom)

• Medical devices regulations: compliance and enforcement
• Medical devices: software applications (apps)

National Institute for Health and Care Excellence (NICE – United Kingdom)

•  Evidence standards framework for digital health technologies

Accessibility and refundability of DTx

To enter the circuit of refundability and prescription, the digital solution must positively exceed the levels of:

• Validation of efficacy, to evaluate its clinical benefit for the patient
• Testing and validation ISO 62304 2006 (and new draft 2019) to ensure its safety and technical performance
• Validation of constant quality, even after periodic and obligatory updates of the technological system.

In terms of prescription and refundability (public or private) Italy is still a long way off, but in the rest of the world, some DTx are already recognised and validated as digital therapies and have already been introduced into the treatment circuit, reimbursed and prescribed by doctors to patients.

Here are a few examples:

• Big Health’s Sleepio product receives coverage by the NHS (20 May 2019)
• WellDoc’s BlueStar product receives coverage by Business Health Care Group (14 May 2019)
• Omada Health’s product receives coverage by Priority Health (3 October 2018)
• Palo Alto Health Sciences’s Freespira product receives coverage by Highmark Inc. (24 September 2018)
• Omada Health’s product receives coverage by Cigna (18 September 2018)
• Propeller Health’s product receives coverage by Anthem Blue Cross and Blue Shield (16 August 2018)
• Voluntis’ Insulia product receives coverage by WellDyneRx (14 May 2018)
• Pear Therapeutics con reset (2018)
• Propeller Health’s product receives coverage by Express Scripts (16 November 2017)
• Tinnitraks, l’app per la cura dell’acufene, rimborsata dal Sistema Sanitario Nazionale in Germania (2015)