ISO/TR 11147:2023

TECHNICAL ISO/TR
REPORT 11147
First edition
2023-06
Health informatics — Personalized
digital health — Digital therapeutics
health software systems
Informatique de santé — Santé numérique personnalisée — Systèmes
logiciels de santé pour la thérapeutique numérique
Reference number
© ISO 2023
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ii
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Context . 5
5 Considerations .6
5.1 DTx Attributes . 6
5.2 Impact on patient care . 6
5.3 Relationship to SiMD . 6
5.4 DTx in context of a DTx System . 7
6 DTx in relation to ecosystem constructs . 8
6.1 Existing ecosystem constructs . 8
6.2 Medical device . 9
6.3 Software as a Medical Device (SaMD). 9
6.4 Software in a Medical Device (SiMD) . 10
6.5 Digital Health Technology (DHT) Frameworks . 10
6.5.1 DHT Overview . 10
6.5.2 Digital Therapeutics Alliance (DTA) . 10
6.5.3 National Institute for Health and Care Excellence (NICE) . 11
6.5.4 European Commission DG communications networks, content, and
technology .12
7 Medical device software standards . .13
Annex A (informative) Landscape analysis .14
Annex B (informative) DTx use cases .15
Bibliography .19
iii
Foreword
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iv
Introduction
As the healthcare sector evolves, there is an increasing demand for the production and appropriate use
of digital health technologies (DHTs) across patient care settings. DHTs represent a broad spectrum
of products ranging from clinician-facing electronic prescribing systems, telemedicine platforms, and
decision support systems, to patient-facing wellness apps, diagnostic tools, monitoring products, digital
biomarkers, and therapeutics.
Given the diversity of digital products available, it is important for patients, clinicians, and healthcare
decision makers to have the ability to clearly distinguish between the numerous types of DHTs on the
market. Without harmonized international guidance, healthcare decision makers and users are often
unable to differentiate between, assess, and optimize the appropriate use of DHTs in practice based on
the intended use of each product.
Digital therapeutics (DTx), as defined in this document, represent a type of medical product that can
be used as standalone therapy, incorporated into a multi-functional DHT, or integrate into clinical care
pathways alongside clinician-delivered therapies, pharmaceuticals, medical devices, or other DHTs.
Standards exist for various non-DTx DHT product categories and varying DTx product definitions, best
practices, and country-level standards exist at the industry level (see Annex A), yet no DTx-specific
international standards exist. This document centres on the ability of DTx to generate and deliver
validated and measurable medical interventions directly to patients. It is relevant to patients, clinicians,
healthcare decision makers, and product manufacturers.
v
TECHNICAL REPORT ISO/TR 11147:2023(E)
Health informatics — Personalized digital health — Digital
therapeutics health software systems
1 Scope
This document lists characteristics of a category of health software: digital therapeutics (DTx).
DTx products generate and deliver medical interventions that are based on clinical evidence, have
demonstrable positive therapeutic impacts on patient health, and produce real-world outcomes.
Product use cases (see Annex B) demonstrate the variety of products represented in this quickly
growing industry.
This document provides an overview of how DTx relates to other ecosystem constructs, including
medical devices, software as a medical device (SaMD), software in a medical device (SiMD), and other
digital health technologies (DHT). It also addresses relevant health and medical device software
standards that have various degrees of applicability to DTx.
The focus of this document is on therapeutic products that are used in the context of a disease, disorder,
condition, or injury for human use. It does not address products that are intended for veterinary use
or for general wellbeing. Additional exclusions of this document include DTx market access pathways
(i.e. prescription, non-prescription pathways), medical device requirements, product risk assessment,
clinical evidence requirements, data security, patient privacy considerations, and product authorization
pathways.
2 Normative references
There are no normative references in this document.
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
ISO and IEC maintain terminology databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at https:// www .iso .org/ obp
— IEC Electropedia: available at https:// www .electropedia .org/
3.1
digital health technology
DHT
system that uses computing platforms, connectivity, software, and sensors for healthcare and related
uses
Note 1 to entry: These technologies span a wide range of uses, from applications in general wellness to
applications as a medical device. They include technologies intended for use as a medical product, in a medical
product, or as an adjunct to other medical products (devices, drugs, and biologics). They can also be used to
develop or study medical products.
[1]
[SOURCE: BEST Resource ]
3.2
system
combination of interacting elements organized to achieve one or more stated purposes
[SOURCE: ISO/IEC/IEEE 15288: 2015, 4.1.46, modified — Notes to entry deleted.]
3.3
user
person using the system for a health-related purpose
Note 1 to entry: The user can be the subject of care directly, or an individual assisting (as proxy for) the subject
of care.
[SOURCE: ISO 81001-1:2021, 3.1.14]
3.4
intended use
intended purpose
use for which a product, process or service is intended according to the specifications, instructions and
information provided by the manufacturer
Note 1 to entry: The intended medical indication, patient population, part of the body or type of tissue interacted
with, user profile, use environment, and operating principle are typical elements of the intended use.
[SOURCE: ISO/IEC Guide 63:2019, 3.4, modified — Added admitted term "intended purpose".]
3.5
digital therapeutic
DTx
health software intended to treat or alleviate a disease, disorder, condition, or injury by generating and
delivering a medical intervention that has a demonstrable positive therapeutic impact on a patient’s
health
Note 1 to entry: Many jurisdictions consider DTx a medical device.
Note 2 to entry: DTx can integrate with ancillary components to form a DTx system by:
— using general purpose hardware or platforms (i.e. smartphone, tablet, computer, watch, headset), input or
output components (i.e. wearables, sensors), pharmaceuticals, or patient or clinician support components
necessary for DTx functioning;
— using patient- and context-specific data to generate a medical intervention.
Note 3 to entry: DTx can function independently or in addition to other interventions, such as integrating with:
— other DHT components (i.e. monitoring, diagnostic, clinical decision support) as part of a multi-functional
DHT product;
— tandem medical interventions (i.e. clinician-delivered therapies, pharmaceuticals, medical devices, DHTs).
Note 4 to entry: DTx includes secondary prevention and tertiary prevention.
Note 5 to entry: DTx is produced in compliance with good product life cycle (PLC) management practices,
through use of a quality management system which encompasses demonstrated safety and effectiveness, and
post-market surveillance.
3.6
medical device
instrument, apparatus, implement, machine, appliance, implant, reagent for in vitro use, software,
material or other similar or related article, intended by the manufacturer to be used, alone or in
combination, for human beings, for one or more of the specific medical purpose(s) of
— diagnosis, prevention, monitoring, treatment or alleviation of disease,
— diagnosis, monitoring, treatment, alleviation of or compensation for an injury,
— investigation, replacement, modification, or support of the anatomy or of a physiological process,
— supporting or sustaining life,
— control of conception,
— disinfection of medical devices,
— providing information by means of in vitro examination of specimens derived from the human body,
and which does not achieve its primary intended action by pharmacological, immunological or metabolic
means, in or on the human body, but which can be assisted in its intended function by such means
Note 1 to entry: Products which can be considered to be medical devices in some jurisdictions but not in others
include:
— disinfection substances,
— aids for persons with disabilities,
— devices incorporating animal and human tissues,
— devices for in-vitro fertilization or assisted reproductive technologies.
[SOURCE: ISO/IEC Guide 63:2019, 3.7]
3.7
medical intervention
activity intended to maintain or improve an individual’s health or functioning, or to alter the course of a
disease, disorder, or condition for the better, or to restore function lost through disease or injury
3.8
health software
software intended to be used specifically for managing, maintaining or improving health of individual
persons, or the delivery of care
Note 1 to entry: Health software fully includes what is considered software as a medical device.
[SOURCE: IEC 82304-1:2016, 3.6, modified — Note 2 to entry deleted.]
3.9
evidence
directly measurable characteristics of a process or product that represent objective, demonstrable
proof that a specific activity satisfied a specified requirement
[SOURCE: ISO/IEC 21827:2008, 3.19]
3.10
software as a medical device
SaMD
software intended to be used for one or more medical purposes that performs these purposes without
being part of a hardware medical device
Note 1 to entry: SaMD is a medical device and includes in-vitro diagnostic (IVD) medical device.
Note 2 to entry: SaMD is capable of running on general purpose (non-medical purpose) computing platforms.
Note 3 to entry: “without being part of” means software not necessary for a hardware medical device to achieve
its intended medical purpose.
Note 4 to entry: Software does not meet the definition of SaMD if its intended purpose is to drive a hardware
medical device.
Note 5 to entry: SaMD can be used in combination (e.g. as a module) with other products including medical
devices.
Note 6 to entry: SaMD can be interfaced with other medical devices, including hardware medical devices and
other SaMD software, as well as general purpose software.
Note 7 to entry: Mobile apps that meet the definition above are considered SaMD.
[7]
[SOURCE: IMDRF 2013, modified — ‘may’ changed to ‘can’.]
3.11
software in a medical device
SiMD
software that is used as an integral part of a specified hardware medical device or is intended to drive
a hardware medical device
3.12
health
state of complete physical, mental and social well-being and not merely the absence of disease or
infirmity
[8]
[SOURCE: WHO 1948 ]
3.13
risk
combination of the probability of occurrence of harm and the severity of that harm
Note 1 to entry: The probability of occurrence includes the exposure to a hazardous situation and the possibility
to avoid or limit the harm.
[SOURCE: ISO/IEC Guide 63:2019, 3.10]
3.14
privacy
freedom from intrusion into the private life or affairs of an individual when that intrusion results from
undue or illegal gathering and use of data about that individual
[SOURCE: ISO/TS 27790:2009, 3.56]
3.15
positive therapeutic impact
favourable or useful response to, effect resulting from, or outcome of a medical intervention
3.16
component
collection of system resources that a) forms a physical or logical part of the system, b) has specified
functions and interfaces, and c) is treated (e.g. by policies or specifications) as existing independently of
other parts of the system
[10]
[SOURCE: IETF RFC 4949, modified — Note 1 deleted.]
3.17
tandem medical intervention
two or more medical interventions, each capable of producing a positive therapeutic benefit, when
implemented together, which are expected to produce a higher level of benefit than either one alone
3.18
secondary prevention
intervention for individuals or groups that demonstrate early psychological or physical symptoms,
difficulties, or conditions (i.e. subclinical problems), which is intended to prevent the development of
more serious dysfunction or illness
[11]
[SOURCE: APA ]
3.19
tertiary prevention
intervention for individuals or groups with already established psychological or physical conditions,
disorders, or diseases
Note 1 to entry: Tertiary interventions include attempts to minimize negative effects, prevent further disease or
disorder related to complications, prevent relapse, and restore the highest physical or psychological functioning
possible
[11]
[SOURCE: APA ]
3.20
quality management system
part of a management system with regard to quality
Note 1 to entry: Requirements for a quality management system are given in ISO 9001.
[SOURCE: ISO 9000:2015, 3.5.4, modified — Note 1 to entry replaced with new note 1 to entry.]
3.21
safety
freedom from unacceptable risk
[SOURCE: ISO/IEC Guide 63:2019, 3.16]
3.22
effectiveness
ability to produce the intended result
[SOURCE: ISO 81001-1:2021, 3.2.5]
4 Context
The digital health landscape encompasses a broad range of technologies, with each serving a specific
purpose. While some DHTs are used for wellness, medication adherence, monitoring, or patient
diagnosis, DTx products use software to generate and deliver a medical intervention that directly
impacts a disease, disorder, condition, or injury. Without a common international DTx definition,
healthcare decision makers are not able to consistently identify DTx products and distinguish them
from other DHTs and medical devices to determine which products best meet patient and population
needs and expectations.
National regulatory, assessment, and reimbursement frameworks are increasingly emerging to better
enable DHT market and patient access:
— In 2010, the U.S. Food and Drug Administration (FDA) granted its first Class II 510(k) medical device
[15] [16]
clearance to a DTx product, and in 2017, its first de novo product clearance .
— In 2013, the International Medical Device Regulators Forum (IMDRF) published ‘Software as
a Medical Device (SaMD): Key Definitions’ to establish a common framework for regulators to
[7]
incorporate converged controls into their regulatory approaches for SaMD .
— In 2018, the Belgian Federal Government launched the mHealthBelgium platform for mobile apps
[17]
that are CE-marked as a medical device .
— In 2019, England’s National Institute for Health and Care Excellence (NICE) released the Evidence
for Effectiveness functional classification of DHTs that categorizes three tiers of DHTs based on
[18]
potential risk to users. The framework was updated in 2022 .
— In 2020, Germany launched a Fast-Track Process for Digital Health Applications [digitale
[19]
Gesundheitsanwendungen (DiGA)], with Class I or Class IIa medical devices under the European
Union’s Medical Device Regulation (MDR) qualifying for DiGA recognition.
— In 2020, the South Korea Ministry of Food and Drug Safety (MFDS) established a DTx-specific
[20]
regulatory framework, recognizing DTx as a subcategory of SaMD .
— In 2022, the European Taskforce for Harmonized Evaluation of Digital Medical Devices (DMDs)
launched to provide a blueprint for appropriate assessment procedures and methodologies in
Europe, with the overall goal of enabling a harmonized approach for European assessment, national
appraisal, and reimbursement by statutory health insurance organisations for distinct subclasses
[21]
of DMDs .
— In 2023, France is launching a fast-track DMD reimbursement pathway for therapeutic and remote
monitoring products. The Prise En Charge Anticipee (PECA) decree will allow a temporary one-year
[22]
reimbursement of DMD products until they provide further robust clinical evidence .
While momentum in developing and implementing national DHT, DMD, or mHealth frameworks
continues to build, there are inconsistencies in how DTx products are named and classified, in addition
to what qualification requirements these products are expected to meet (aside from the Republic of
Korea, which has developed a DTx-specific national framework).
Developing a consistent, internationally recognized definition of a DTx and eventual corresponding
quality standards will enable policymakers and other healthcare decision makers to develop appropriate
regulatory, assessment, reimbursement, or patient access frameworks that properly distinguish DTx
from other product types and establish harmonized expectations related to DTx function, reliability,
and real-world impact.
5 Considerations
5.1 DTx Attributes
According to the Digital Therapeutics Alliance (DTA), DTx products require certain fit-for-purpose
standards due to their agile development processes, mechanisms of action, ability to generate real-time
outcomes, ongoing iterative nature, lower potential risk profiles, and place in clinical therapy. Although
DTx-specific standards incorporate aspects of existing pharmaceutical and medical device frameworks,
they should include any necessary tailor-made components that enable appropriate and efficient DTx
[23]
product design, capability, and performance assessments .
5.2 Impact on patient care
DTx has direct impact on patient health, similar to how pharmaceuticals and clinician-delivered
therapies have direct impact on patient health.
DTx products can be used by patients independently (i.e. without professional guidance). Many
products, however, offer the possibility of professional guidance, referred to as guided self-management
interventions, or can be supplemented with clinician-delivered interventions, called a blended
[24]
intervention or combined treatment .
DTx are not intended to solely augment a human decision and are therefore classified differently from
clinical decision support (CDS) tools.
DTx products are autonomous and differ from Medical Device Data Systems (MDDS), a class of systems
that has no intelligence and serves as an accessory to other regulated technology that does have
intelligence.
5.3 Relationship to SiMD
DTx typically forms a subset of SaMD. Software whose sole intent is to operate a medical purpose device
(SiMD), regardless of whether the software is embedded or remote, does not qualify as a DTx. However,
if the DTx is hosted on general purpose hardware (i.e. VR headset), even if the hardware is customized,
branded, or locked for a specific function, the product qualifies as a DTx since the headset is general
purpose and not a medical purpose device.
For example, if a virtual reality (VR) headset is branded and used exclusively with DTx, the headset is
still considered to be general purpose hardware, as opposed to a medical purpose hardware. In this
case, VR software is loaded on the headset, but this software is not "embedded" in the hardware to
control a medical purpose device, as defined for SiMD devices. Further discussion is warranted related
to the relationship between VR, SaMD, and SiMD since in this example, the VR software controls the
headset hardware only to the extent needed for visual display. Yet, since the VR software needs to be
paired with a headset to function and will not be effective if displayed on another platform such as a
smartphone, it cannot be strictly classified as SaMD.
5.4 DTx in context of a DTx System
While this document focuses on software, there are other components (i.e. general purpose hardware,
input and output components, pharmaceuticals) that can be incorporated into or work alongside a DTx
system or software.
First, as shown in Figure 1, a DTx system (also commonly referred to as a DTx product) includes DTx
software and any structural elements necessary to facilitate and enable the DTx to generate and deliver
its medical intervention. Components necessary for the software to function can include hardware (i.e.
smartphone, tablet, computer, watch, headset, sensors), input or output components (i.e. wearables,
sensors, software, operating system), pharmaceuticals, or patient or clinician support components (i.e.
coaching, real-world outcomes dashboard). A DTx system can also include other required components,
such as a quality management system. While hardware components are typically general purpose in
nature, as discussed above, it is still possible for the hardware to be customized, branded, or locked for
a specific function.
Second, similar to how a pharmaceutical product can incorporate multiple active components in a
single product, a multi-functional DHT product can combine a DTx system or software with other DHT
component(s) (i.e. monitoring, diagnostic, clinical decision support features). In this case, it is important
for clinicians, patients, and other users to understand the intended use and functionality of each
individual component. Additionally, it is important for authorities with jurisdiction and policymakers
to understand the intent, performance, and outcomes associated with each component. This allows
product evaluators to assess the respective safety, efficacy, and impact of each system component based
on its intended use (i.e. therapeutic, monitoring, diagnostic, wellness, decision support), in addition to
each component’s direct impact on the safety, efficacy, and impact of the multi-functional DHT product.
Third, DTx products can work alongside other tandem medical interventions to deliver a cohesive
therapy. Components that can form this level of a DTx system include other therapeutic categories (i.e.
clinician-delivered therapies, pharmaceuticals, medical devices, DHTs).
Whether a patient uses a multi-functional DHT product, or a combination of a DTx or multi-functional
DHT product with a tandem medical intervention, they should have a clear understanding of what
components are part of the system.
a
Examples provided are representative of potential components. Inclusion in the diagram does not imply
necessity for clinical practice.
Figure 1 — Use of DTx system in clinical practice
6 DTx in relation to ecosystem constructs
6.1 Existing ecosystem constructs
Existing ecosystem constructs, as shown in Figure 2, including medical devices, SaMD, SiMD, and
DHT, directly relate to DTx, but individually, do not sufficiently define DTx products. However, when
viewed in relation to each other, they provide more context on the DTx industry’s positioning. Boxes
representing each industry do not correlate to the size of the industry they represent.
Figure 2 — Relationship of DTx, medical devices, and DHTs
6.2 Medical device
While digital therapeutics typically qualify as a medical device, there can be situations in certain
regulatory jurisdictions where DTx products cannot be regulated as a medical device or the jurisdiction
does not yet have regulations in place that pertain to digital therapeutics.
6.3 Software as a Medical Device (SaMD)
In many national regulatory frameworks, DTx products are associated with the International Medical
Device Regulators Forum’s (IMDRF) definition of SaMD. Wh
...