MINI REVIEW

published: 09 June 2021

doi: 10.3389/fdgth.2021.667016

The Impact of Digital Therapeutics

on Current Health Technology
Assessment Frameworks
Kevin Yan 1,2 , Chakrapani Balijepalli 1 and Eric Druyts 1*
1
Pharmalytics Group, Vancouver, BC, Canada, 2 Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada

Historically healthcare has been delivered offline (e.g., physician consultations, mental
health counseling services). It is widely understood that healthcare lags behind
other industries (e.g., financial, transportation) whom have already incorporated digital
technologies in their workflow. However, this is changing with the recent emergence
of digital therapeutics (DTx) helping to bring healthcare services online. To promote
adoption, healthcare providers need to be educated regarding the digital therapy to
allow for proper prescribing. But of equal importance is affordability and many countries
rely on reimbursement support from the government and insurance agencies. Here we
briefly explore how national reimbursement agencies or non-profits across six countries
Edited by:
Harry Scarbrough,
(Canada, United States of America, United Kingdom, Germany, France, Australia)
City University of London, handle DTx submissions and describe the potential impact of digital therapeutics on
United Kingdom
current health technology assessment (HTA) frameworks. A targeted review to identify
Reviewed by:
HTA submissions and guidelines from national reimbursement agencies or non-profits
Milena B. Cukic,
Amsterdam Health and Technology was conducted. We reviewed guidelines from the Institute for Clinical and Economic
Institute (AHTI), Netherlands Review (ICER) in the USA, the Canadian Agency for Drugs and Technologies in Health
Neal Kaufman,
Canary Health, United States
(CADTH) in Canada, the National Institute for Health and Care Excellence (NICE) in the
*Correspondence:
United Kingdom (UK), the Institute for Quality and Efficiency in Health Care (IQWIG) in
Eric Druyts Germany, Haute Autorité de Santé (HAS) in France, and the Pharmaceutical Benefits
eric.druyts@pharmalyticsgroup.com
Advisory Committee (PBAC) in Australia. Our review identified one set of guidelines
Specialty section:
developed by NICE in the UK. The guidelines by NICE outlined an evidence standards
This article was submitted to framework for digital health technologies (DHT). Depending on the organizational impact,
Health Technology Innovation,
financial commitment, and economic risk for the payer, different economic analyses are
a section of the journal
Frontiers in Digital Health required. Economic analyses levels are separated into 3 categories, basic, low financial
Received: 11 February 2021 commitment, and high financial commitment. All economic analyses levels require a
Accepted: 17 May 2021 budget impact analysis. A cost-utility analysis is recommended for DHTs categorized
Published: 09 June 2021
in the high financial commitment category. Whereas, for DHTs that are in the low financial
Citation:
Yan K, Balijepalli C and Druyts E
commitment category, a cost-consequence analysis is typically recommended. No HTA
(2021) The Impact of Digital guidelines for DTx submissions were identified for the remaining countries (Canada, USA,
Therapeutics on Current Health Germany, France, and Australia)
Technology Assessment Frameworks.
Front. Digit. Health 3:667016. Keywords: digital therapeutics, digital health, digital health technology, health technology assessment,
doi: 10.3389/fdgth.2021.667016 reimbursement

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Yan et al. Digital Therapeutics Health Technology Assessment

BACKGROUND connection, complimentary cellular device, or proficient user

interaction. When conducting a health technology assessment
The majority of healthcare is currently delivered offline (e.g., and determining parameters such as epidemiology estimates of
physician consultations, pharmacy prescriptions, mental health the disease and the associated economic costs for implementing
counseling services). It is widely understood that healthcare lags a DTx intervention, a stakeholder must consider if the end user
behind other industries (e.g., financial, transportation) which (i.e., patient) has the adequate technology and/or user ability to
have already incorporated digital technologies in their workflow operate the technology. Due to the nature of DTx, only patients
(1). However, this is changing with the recent emergence of who can operate and afford technological hardware may benefit
digital therapeutics (DTx) helping to bring healthcare services leading to potential bias. Studies have shown individuals of
online. Digital therapeutics can be defined as a regulatory higher socioeconomic and education status tend to be healthier
approved digital system or application that is prescribed to treat and have healthier behaviors (13–15). Age is also an important
medical conditions, similar to that of new drug molecules or factor as older individuals may not own or be familiar using smart
medical devices (2–6). As developers of digital therapeutics pass technologies (i.e., smartphones, tablets) (16). Moreover, other
regulatory approval, the next step is to gain widespread adoption. identified barriers for older individuals include the complexity
To promote adoption, healthcare providers need to be educated and lack of guidance when using these technologies (16). The
regarding the digital therapy to allow for proper prescribing. elderly may also not be interested in learning how to use new
But also, of equal importance is patient affordability of which DTx interventions even if this could potentially be the population
a key determinant in many countries relies on reimbursement that would receive the largest benefit (17). These older individuals
support from the government and insurance agencies. Transition would not need to physically visit their physician’s office for
to incorporate digital technologies into clinical practice have every appointment and could use remote monitoring as a tool
been slow due to strict regulations and the disparity between to improve overall health.
stakeholder views of this new change (7). If proven effective, with Age and socioeconomic factors need to be examined (e.g.,
the introduction to virtual care, it will lead to great advances education level, family income) as these digital interventions
in convenience, accessibility, and potentially better outcomes for require the necessary user ability and hardware to function. Thus,
patients (8, 9). Moreover, it will allow for healthcare providers to when DTx are indirectly compared to pharmacologic treatments
conveniently monitor, educate, and adjust therapeutic regimens for HTA purposes, baseline characteristics may potentially
for an increased number of patients (8, 10). However, this will need to be adjusted more heavily for socioeconomic factors.
not be without challenges, including the need to prove value Unlike pharmacological drugs whereby it impacts a biological
compared to current interventions and demonstrate potential mechanism (e.g., SGLT2 inhibitor for diabetes or antiplatelet
cost savings for payers. agents to prevent cardiovascular events), DTx heavily relies on
There has been doubt to whether cost savings can truly be an individual’s behavior and attitudes toward health. Contrary
achieved when using DTx (11). Experts have argued that if these to pharmaceutical drugs whereby consideration for human
DTx were proven to be cost-effective, it would likely result in a biological factors is necessary to assess for potential therapeutic
net overall increase in healthcare spending (12). Governments effectiveness (e.g., ancestry, genetics), in digital therapeutics
are exploring to introduce additional billing codes to support technology literacy, age and other socioeconomic factors (e.g.,
digital care monitoring which can potentially lead to increased income, nationality) may potentially play a larger role when
spending (9). Moving forward, as a DTx software evolves when conducting reimbursement decisions.
incorporating more data, this may impact current and future As DTx is implemented and evolve with capabilities, will
HTA submission recommendations. Here we explore how health payers be expected to pay for initial and future training and
technology assessment (HTA) agencies handle DTx submissions. operation costs associated with these technologies? Moreover,
We conducted a targeted review to identify HTA submissions and as the technology accumulates increasingly more data, the
guidelines from national reimbursement agencies or non-profits evidence will also need to be consistently updated. Assuming
across six countries (Canada, USA, United Kingdom, Germany, the technology evolves, this may impact prior HTA results,
France, Australia). The following agencies were reviewed: the potentially making the intervention more or less cost-effective. In
Institute for Clinical and Economic Review (ICER) in the USA, contrast, with pharmaceutical drugs, the effectiveness of the drug
the Canadian Agency for Drugs and Technologies in Health does not change. A potential solution would be incorporating
(CADTH) in Canada, the National Institute for Health and Care dynamic HTAs whereby the evidence is consistently updated
Excellence (NICE) in the United Kingdom (UK), the Institute throughout predetermined time intervals as a part of post-market
for Quality and Efficiency in Health Care (IQWIG) in Germany, surveillance. However, challenges to this include accurately
Haute Autorité de Santé (HAS) in France, and the Pharmaceutical isolating therapeutic effectiveness as a result of the intervention’s
Benefits Advisory Committee (PBAC) in Australia. technology or other associated factors.

PHARMACEUTICAL DRUGS VS. DIGITAL DIGITAL THERAPEUTICS AND HEALTH

THERAPEUTICS TECHNOLOGY ASSESSMENT
Unlike pharmaceuticals whereby a drug is administered into the Our review identified one set of guidelines developed by
body, a DTx relies on extraneous factors such as a stable internet NICE in the UK (18). NICE has outlined an evidence

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Yan et al. Digital Therapeutics Health Technology Assessment

standards framework for digital health technologies (DHT) and answering questions and communicating results with healthcare
has compartmentalized DHTs into functional groups. These practitioners will most likely lead to a greater depreciation
functional classes are grouped into evidence tiers and are in adherence.
intended to capture the level of clinical risk associated with the Traditionally, patients are prescribed and dispensed
DHT. There are three evidence tiers; Tier A: system impact, Tier medication without knowledge of their adherence history.
B: understanding and communicating, and Tier C: interventions. Revoking reimbursement privileges due to non-adherence
Tier A includes DHTs which focus on system services and is an ethical issue and patients should not be unnecessarily
have no measurable impact on patient outcomes (ex. electronic penalized for occasionally being non-adherent when they could
prescribing systems). Tier B DHTs focus on information, possibly be overwhelmed with other parts of their life. Due to
communication, and simple monitoring (ex. cognitive behavioral the technological nature and potential ability to track software
programmes, healthy lifestyle applications). Tier C DHTs focuses usage, it is possible to restructure contemporary reimbursement
on diagnosis, treatment, and active monitoring. Examples of Tier strategies. Reimbursement agencies can potentially pay per active
C technologies may include DHTs that use data to assist in DTx use whereby the patient successfully finishes the instructions
disease diagnosis or DHTs for treating and monitoring chronic provided by the physician. In this scenario in events that the
conditions (e.g., diabetes). patient is non-adherent, it does not penalize the patient nor the
Depending on the organizational impact, financial reimbursing party. Moreover, this can complement traditional
commitment, and economic risk for the payer, different healthcare whereby non-adherent patients can be easily identified
economic analyses are required. Economic analyses levels are and early alternative interventions can be discussed to promote
separated into 3 categories, basic, low financial commitment, more personalized healthcare services. Nonetheless, when
and high financial commitment. All economic analyses levels establishing criteria for linking reimbursement to adherence, it
require a budget impact analysis. A cost-utility analysis is can create both opportunities and challenges for decision makers.
recommended for DHTs categorized in the high financial If tracking health outcomes can also be possible in real
commitment category. These include DHTs that obtain funding time, is it also possible that payers require certain incremental
by the government for health and non-health outcomes. A cost- levels of health benefit for continuing reimbursement support?
consequence analysis can also be conducted if evidence is not Similar to pharmacological therapy, patients are switched to
sufficient for conducting a cost-utility analysis, however, this alternative drug therapies if the initial treatment did not
appears to be evaluated on a case by case basis. Cost consequence demonstrate adequate effectiveness (e.g., blood glucose and A1C
analysis are also a minimum requirement for DHTs that are in levels in diabetes patients). However, the criteria for health
the low financial commitment category (18). These evidence benefit will need to be adequately defined to prevent removing
requirements are only directed toward digital technologies potential patients that are benefitting from DTx. The dearth
seeking public reimbursement and do not apply to unpaid of evidence, especially high-quality evidence, associated with
interventions. It is unfortunate that no other HTA agencies we determining effectiveness of these interventions will also be
reviewed have as of yet outlined any public recommendations to an issue (22). If HTA agencies consider evidence as a pillar
guide digital health technology submissions as many DTxs have for reimbursement, DTx will not be able to compete against
already been approved by multiple regulatory agencies. Reports traditional pharmaceutical drugs with its larger evidence base.
and case studies evaluating existing DTx have been conducted Traditional analyses such as indirect treatment comparisons
by NICE and CADTH (19, 20). It appears the assessments and or cost-utility analysis may not always be possible due to the
evaluations that have been conducted attempt to fit the mold anticipated population heterogeneity expected from DTx users.
of existing frameworks for pharmaceutical and medical devices.
However, DTx is unique in that it is unlike traditional drugs
and devices. LOOKING FORWARD
The issue of potential changes in effectiveness due to
DTx software updates and how that will impact previous With the recent FDA approval of the first game-based DTx
HTA assessments requires clarification. Assuming changes used to treat ADHD, it demonstrates the expanding scope
in effectiveness, will companies be expected to alter pricing of DTx beyond patient monitoring (23, 24). Some areas
according to local willingness to pay thresholds? A potential of healthcare may never be fully replaced by technology,
solution can be requiring original manufacturer model thereby, it will be likely that DTx will complement existing
submissions to include larger variances in their sensitivity interventions to provide improved outcomes to patients. As
analysis, thereby accounting for a wider fluctuation in input DTx evolves, new HTA strategies and methods for assessing
parameters. Non-adherence to DTx needs to also be accounted these interventions will be needed. ICER is in the process
for in economic evaluations and its potential impact on costs of conducting the first HTA review aimed to evaluate the
and effectiveness. Non-adherence to traditional pharmaceutical health and economic outcomes of DTx in addition to
drugs is already a common issue contributing costs upwards medication assisted treatment in opioid use disorder (25).
of $50,000 per patient per year (21). Compounding the Based on the recent ICER protocol documents of opioid
complexity from simply taking a pill to be added or replaced apps it appears there is a shift toward focusing on non-
with navigating through a smartphone application, meanwhile, health related and societal based outcomes (e.g., accidental

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Yan et al. Digital Therapeutics Health Technology Assessment

pediatric exposure, employment-related outcomes, housing- AUTHOR CONTRIBUTIONS

related outcomes, and relationship-related outcomes) (26).
Traditional HTA methods and guidelines will need to be KY performed conceptualization, drafted the article, and editing.
updated and revised to take into consideration technological ED and CB performed supervision, review, and editing. All
and socioeconomic factors that comes with using these authors have reviewed, added value, and signed off on the final
new technologies. version of this manuscript.

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