Clinical and real-world evidence (RWE) must be at the heart of digital therapeutics (DTx) development and strategy to achieve regulatory approval, payer reimbursement, provider adoption, and improved patient outcomes. Articles previously published on our blog discuss using digital technologies to aid in the collection of RWE.
This article focuses on how RWE differs from traditional clinical evidence and examines why RWE is vital to DTx, necessitating standardized guidance for manufacturers and healthcare organizations. Equipped with this information, payer and provider leaders can rely on a full spectrum of evidence for making purchasing, adoption, and reimbursement decisions.
The growing value for RWE in clinical research
The passing of the 21st Century Cures Act in 2016 put increased focus on RWE usage. Today, the role that RWE plays in clinical research is growing globally.
According to the Digital Therapeutics Alliance (DTA), randomized controlled trials (RCTs) and RWE have shown that DTx can demonstrate clinical benefits beyond traditional medical treatments. Some industry experts believe that RWE will be the primary impetus for digital therapeutics development and testing.
The FDA defines RWE as: clinical evidence regarding a medical product's usage and potential benefits or risks derived from real-world data (RWD) analysis. Both RCTs and RWE are mutually complementary, meaning there are differences in terms of reliability and how tightly the settings are controlled. Creating RWE from RWD requires collecting, combining, and validating data from disparate sources routinely collected in the clinical setting, as well as in a patient's home or via wearables. Sources can include Internet of Things (IoT) connected devices, patient health diaries, questionnaires, data pulled from claims, patient registries, electronic health records (EHRs), and the DTx app itself.
Considering that medical care is estimated to influence just 10% to 20% of health outcomes, gathering RWD can support each FDA clearance phase while providing critical insights that can affect reimbursement policy, coverage decisions, and provider pilot decisions.
Expectations for DTx RWE are growing as well
Health plans and providers are raising their expectations of DTx, looking for RWE to complement and provide additional rigor to clinical research. According to the Academy of Managed Care Pharmacy (AMCP), 55% of health plans require RWE for a DTx pilot program and 67% require FDA approval for reimbursement. Of all health plans surveyed, 56% were currently in the process of, or interested in, defining their approach for covering DTx.
The DTA looks to RWE as fundamental to market adoption and appropriate regulation. The organization sees the promise of RWE as threefold:
- RWE supports more ecologically valid insights that enhance the capacities of DTx to make predictions and claims relevant to an individual's environment and context
- Clinical trials conducted in real-world contexts, incorporating RWE, may improve decision making about whether a DTx improves upon currently used care standards, interventions, or other real-world options
- RWE offers post-approval benefits for efficient monitoring to support continued evaluation
Payers and providers are looking for not only RWE for clinical effectiveness and safety, but also patient engagement, observed adherence, quality and cost impacts, and comparative analysis against traditional treatments.
DTx evidence generation is different from pharma
DTx products must be evidence-based to be accepted and adopted. RCTs that are randomized, double-blind, placebo- or active-controlled are still the gold standard. Most DTx primarily rely on RCTs for FDA clearance evidence. However, RWE gathering for DTx presents novel challenges:
- Medication evaluation for safety and efficacy is similar to DTx. However, because DTx is software, it is exempt from preclinical evaluations, unlike medications
- Blinding and assigning comparators are difficult with DTx
- Patient use may include inquiries about health behaviors, cognitive processes or beliefs, and emotions
- Device trials tend to enroll fewer participants than medication trials
- DTx research may assess iterative changes compared to previous versions of a product
- Adapting design during a trial is not uncommon
- Context for use, adherence, and engagement can be very different from medications
In addition to these differences, according to a 2022 study published in Healthcare Informatics Research, DTx evaluation should also include “early and ongoing partnerships between developers of DTx and their intended users in clinical and/or community settings," marketing claims, and guidance for patients, providers, and healthcare leaders. RWE complements other sources, demonstrating how a DTx treatment performs outside of a controlled clinical or healthcare environment.
The DTA classifies DTx into 3 categories—treating disease, managing disease, and improving health function. DTx evaluation is different from pharma because the use of a particular DTx solution evolves over time. Early DTx focused on preventing and monitoring medical diseases or optimizing medication. Recently, the focus has been shifting toward independent therapeutics and other treatment categories.
DTx needs RWE standards
Existing regulatory frameworks lack standardized guidance on how to generate RWE for DTx. Healthcare organizations lack clarity on what RWE is needed for ethical development and marketing. Without these standards, DTx manufacturers implement their own approach to evaluation, which impacts payer and provider vetting processes.
The FDA uses RWE to monitor post-market safety and adverse events alongside making regulatory decisions. While the FDA has not yet provided RWE guidance for DTx, the organization has published draft documents on how to use RWD from EHRs and medical claims for drug and biological products and other data-related recommendations. The healthcare community is beginning to use these data to support coverage decisions and to develop guidelines and decision support tools for use in clinical practice.
The DTA, however, published “The Digital Therapeutics Real World Evidence Framework: An approach for guiding evidence-based DTx design, development, testing, and monitoring" to provide a sample framework that could be used to establish a “pragmatic, iterative, milestone-driven approach for producing RWE for DTx regulation." The DTA's RWE framework leverages best practices from human-centered design, optimization trials for behavioral interventions, behavioral health research, and implementation science.
Generating equitable, inclusive, and whole-person RWE
Because of DTx's unique position as a treatment modality, it offers opportunities to generate highly valuable RWE that can be used not only to demonstrate its safety and efficacy but its value to address health disparities and engage hard-to-reach and hard-to-treat patient populations.
DTx may encompass a whole-person approach, including an individual's context, personal experiences, and social needs. RWD from DTx is rich in useful and possibly insightful information for RWE, but any research must engage in a population representative of the communities and people served. Not only does diverse research participation enhance overall effectiveness and safety, but it can also indicate to potential prescribers and insurance companies that the DTx solution aligns with their strategic and clinical priorities.
Because DTx can zero in on specific patient populations and be more personalized than most medications, it offers novel treatment options that traditional care can't achieve alone. In many cases, DTx can be combined with medication to provide a personalized and comprehensive treatment tool.
An AMCP survey uncovered factors that payers believe adversely impact reimbursement for DTx. Level of evidence, which can include RWE, topped the list. Also, RWE can supplement RCT data, provide a vital avenue for patient engagement, and provide education alongside capturing new data points.
Below are the factors health plans believe negatively affect their decision to cover DTx and their corresponding response rates:
- 71% Inadequate level of evidence for coverage determinations
- 71% Cost or other barriers to implementing the technology to collect data
- 62% Small size of clinical trials
- 48% Lack of hard endpoints (e.g., surrogate outcomes)
- 48% Perceived issues with clinical trial design
- 43% Lack of coverage by Medicare or state Medicaid
- 43% Low patient or prescriber education
- 43% Low patient acceptance or engagement
- 38% Lack of experience with or knowledge of DTx
- 24% Number of clinical trials
Real-world evidence offers a gateway to better DTx evidence and a pathway for expansion
RWE use is expanding to other phases of clinical research across all FDA-regulated categories. However, it's particularly important to meet the unique needs of DTx and the novel value that the field brings. With better RWE standards and an equitable, whole-person approach, payer and provider organizations can make a more thorough evaluation and decide how DTx products can support their care, cost, equity, and quality goals.
RTI Health Advanced supports payer and provider PDT assessment and adoption
Our healthcare experts span all the areas needed to assess available digital therapeutics, create a real-world data and evidence strategy, and support a healthcare organization's DTx adoption journey. Contact us.