Accelerate Clinical Development with Patient-Centric Digital Endpoints
|Written by Christine Guo, PhD
Drug development success rates have been on the decline since 2015. Compounded by the pandemic, trial success rates fell to a 10-year low in 2021, averaging only a 5% likelihood of successful progression through all phases.1 The machinery of clinical development urgently needs some new oil.
One of the most challenging and costliest steps in clinical development is to demonstrate clinical efficacy based on the clinical outcome assessments (COAs) collected during clinical trials. Most of these COAs were developed decades ago, and they have changed very little since then. Despite known limitations in measurement precision, clinical trialists continue to rely on these traditional COAs for R&D decision making, regulatory approvals, and market access. While biomarkers have improved trial efficiency in some cases, patient-centered clinical outcome assessments remain essential – the lack of which can lead to commercial catastrophe, as witnessed in the recent controversy surrounding Biogen’s Aduhelm.2
Against this backdrop, it comes as no surprise that an increasing number of biopharma and medical device companies are incorporating digital health technologies (DHTs) such as wearable devices into their clinical development programs. Wearable DHTs offer the benefits of objective outcome assessments combined with the convenience of remote data collection. Sponsor companies are embracing these opportunities to de-risk their clinical programs, differentiate their assets, and ultimately improve the efficiency of their trials.
Since 2014, the number of clinical trials using wearables (activity tracker, actigraphy, patch, and so on) has increased steadily, with steep acceleration seen in 2021.3 Overall, about 2.2% of clinical trials in high-income countries have incorporated wearables since the beginning of 2020.3 In fact, the adoption rate is much higher among clinical programs aiming to improve patients’ real-life function.
A core aspect of clinical benefit is “function in daily life,” but this is difficult to assess accurately via established COAs. Reported outcomes are susceptible to subjective bias, and laboratory-style performance outcomes do not assess function in daily life. Wearable devices, on the other hand, are able to collect data directly on how participants function in their daily lives. Hence, digital measures of real-life functioning, such as physical activity, sleep, walking, and mobility, are the primary use cases for wearable data.
By our estimate, more than 10% of clinical trials with an interest in these functions and overall Quality of Life (QoL) have incorporated wearables over the last three years. The growth in adoption is particularly rapid in neurology, pulmonology, cardiology, and rheumatology (Fig. 1), as well as rare diseases in general.
Fig. 1 - Percentage of studies using wearables data grouped by therapeutics area
Because wearables are still relatively new to clinical trialists, they are most often used to support exploratory endpoints in studies. Exploratory endpoints in the early phase studies are great entry points for programs new to digital measures. The findings can then be used to inform endpoint design, engage with the regulators, and elevate the endpoint positioning in late phase studies. The rich dimensions of wearable data provide study teams with unprecedented opportunities to examine the potential clinical benefit of their assets and tailor their study designs to maximize the probability of success.
Based on learnings over the past five years, many clinical trialists have elevated the endpoint positioning of wearable data from exploratory to secondary and even primary to leverage the benefit. Based on internal data across 150+ Phase 1-4 trials, ~20% trials using wearables are positioning the derived digital measures as primary and/or secondary endpoints (Fig. 2). This ratio is likely to accelerate over the next five years.
Fig. 2 - Studies using wearables data for primary and secondary endpoints are growing each year
Current patient-focused drug development initiatives have emphasized clinical benefit associated with “how a patient feels or functions in daily life,” thereby encouraging study teams to take the patients’ voice into the design of clinical trials. Both FDA and EMA have called out the assessment of physical activity and physical functioning for clinical development across a wide variety of chronic conditions, including cardiopulmonary disease, rheumatoid arthritis, amyotrophic lateral sclerosis (ALS), and cancer.4-8
With the ability to directly assess “how a patient functions in daily life,” wearable quantified physical activity has been incorporated into an EMA-qualified clinical endpoint for COPD, and has been accepted into the FDA COA qualification programs for chronic heart failure and sarcopenia. Wearable-qualified walking and mobility outcomes have also been proposed as key clinical endpoints for clinical development in neurology, pulmonology, rheumatology, and beyond.9
The adoption of DHTs is poised to further accelerate with the increasing needs of decentralized clinical trials. To facilitate this growth, both FDA and EMA recently released guidance on the use of DHTs in clinical investigation to support approval of medical products.10-11 Furthermore, in June 2022, FDA included DHT use in the scientific strategy of its five-year Action Plan for the ALS act. The time is ripe to adopt DHT data as a core strategy to advance clinical development.
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- https://www.ema.europa.eu/en/clinical-investigation-medicinal-products-treatment-pulmonary-arterial-hypertension (2018)