The Complementary Roles of Wearables and Patient-Reported Outcomes in Patient-Focused Drug Development: Spotlight on Oncology Trials

Wearables that remotely collect data from decentralized clinical trials allow for more frequent data collection and can enable long-term, real-time monitoring of a patient’s well-being and activity during and after treatment.

The patient voice in drug development

The 21st Century Cures Act highlights patient-centered research and engagement at the core of its agenda, including the use of patient experience data to support regulatory submissions and the need for U.S. Food and Drug Administration (FDA) guidance to involve patients in the drug development process. Similarly, in its Regulatory Science 2025 strategic framework, the European Medicines Agency emphasizes the need to systematically incorporate patient-reported outcomes (PROs) in drug development. Both documents also anticipate the increased use of wearable technology in drug development studies. What role can wearables and PROs play, specifically in oncology research?

One of the established methods for gaining insights into patients’ experience of symptoms and their physical, emotional and social well-being is the use of PROs. More than a decade ago, the FDA released general regulatory guidance outlining the expectations for documenting that a PRO is fit for inclusion in clinical trials. Today, a series of four additional patient-focused drug development (PFDD) guidance documents are in various stages of development, which provide updated recommendations for capturing the patient perspective.

Patient-focused drug development in oncology trials

While the inclusion of PRO measures has been standard in some disease areas, typically cancer trials have focused on assessment of overall survival and tumor growth and have used clinician reporting to evaluate adverse events. Patients with cancer suffer from multiple emotional and physical burdens related to both their diagnosis and their treatments. In a PFDD paradigm, understanding the patient experience is critical, but traditional endpoints used in oncology clinical trials do not provide this insight.

The implementation of PROs in oncology clinical trials presents specific challenges, including:

• Bias: Cancer trials often use open label and single-arm trial designs, which could cause bias in PRO assessments as study participants are aware which treatment they are receiving.
• Timing: Clinical trials often have rapid timelines, and timing of PRO assessments needs to be carefully considered to accurately interpret disease versus treatment-related symptoms.
• Data: Missing data is also a challenge, particularly when patients have advanced cancer.

The first draft of regulatory guidance for inclusion of PROs in oncology trials, which debuted in June 2021, addressed an important gap. The regulatory guidance seeks to supplement previous advice on the use of PRO measures in clinical trials by providing specific recommendations for a core set of PROs — specific to the oncology clinical trial setting — including:

1. Disease-related symptoms
2. Symptomatic adverse events
3. Overall side effect impact summary measure
4. Physical function
5. Role function

The systematic assessment of a core set of PROs using fit-for-purpose PRO measures could facilitate the collection of high-quality data on patient-reported symptoms, as well as their impact on the daily lives of patients in oncology trials.

While the guidance focuses specifically on PROs, some aspects of the concepts identified as relevant in the guidance — for example, physical function — could also be assessed through objective measures (i.e., wearable devices). The guidance instructs sponsors to select scales that measure defined concepts and assess varying levels of ability to perform activities that require physical effort.

Wearable devices were discussed as an approach to the assessment of physical function during the 6th Annual Virtual Workshop on Clinical Outcome Assessments in Cancer Clinical Trials: Characterizing Clinical Function (July 2021). There was significant discussion of the importance of measuring physical functioning in cancer trials and related conversation around the future of patient-generated physical functioning data collection — specifically with the use of electronic and wearable devices (including sensors).

How the tiniest device holds the power to improve drug development trials

From smartwatches that count steps to apps that track heart rate and blood pressure, the wearables market is expanding rapidly on both the consumer and professional-grade levels. Specifically, wearable activity monitors can be used in therapeutic clinical trials to measure a patient’s improvement or decline over the course of treatment and to assess function and performance status.

Compared to intermittent trial visits, the use of wearables to remotely collect data from trial participants (decentralized clinical trials) allows for more frequent data collection and can enable long-term, real-time monitoring of a patient’s well-being and activity during and after treatment. This may provide a broader picture of how participants function in their daily lives. In addition, this reduces the burden of traveling to trial sites, particularly for participants with physical limitations.

Momentum around wearables to deliver digital endpoints is clear. Digital Medicine Society’s growing crowdsourced Library of Digital Endpoints, for example, includes more than 91 sponsors collecting digital endpoints, many as primary endpoints. In addition, the International Society for Quality of Life 2021 conference focused on the emerging use of digital health technologies (DHTs) and digital endpoints in clinical trials. The interest in using digital endpoints specifically in oncology trials appears to be gaining traction with sponsors, signaling the growing need for regulatory guidance.

Wearables vs. PROs

As researchers consult on regulatory and market access strategies for PROs, wearables can help optimize and drive efficiency of development plans and provide accurate and unbiased data.

Wearable activity monitors offer the promise of objective measures of physical activity in oncology trials. Potential advantages include:

• Reduced patient data collection burden (e.g., from site visits, completion of study forms)
• The elimination of recall and desirability bias from patient reporting
• Collection of objective, real-time data over long periods of time or more frequent intervals, providing more direct insights into patients’ lives and reducing likelihood of missing data
• Opportunity to collect data from participants who cannot directly report their experiences, e.g., those with cognitive impairments
• Vast amounts of data can be captured by a provider of evidence-based solutions

These perceived advantages account for some of the growing interest in the use of wearables in clinical research and practice.

However, there are caveats, as wearables-based data has its own challenges that require careful consideration and planning, including:

• Lack of standardization across devices in sensors being used, including differences in device placement location and in algorithms used to transform raw data into various metrics
• Data storage concerns, especially for large or long studies with continuous data collection
• Increased data privacy risks, need for training of participants in use of devices used, and risks associated with changes, loss and damage of a device, or injury to the participant (e.g., wrist band occluding blood supply or causing skin irritation)
• Data analysis and interpretation

In comparison to wearables, using PROs to capture patient experiences presents fewer technical challenges. Generated data is of manageable volume and readily analyzed, and perhaps most importantly, can provide direct (subjective) insights into how a patient feels and functions in their lives with PROs, while wearables provide only intermittent glimpses into patients’ lives.

In this context, sponsors and researchers should consider insights from wearables and PROs as complementary; data from wearables can supplement — rather than replace — insights collected through PRO measures.

Navigating the fast-changing research landscape

To be considered for inclusion in label claims, all endpoints used in clinical trials must meet certain criteria demonstrating they are indeed fit for purpose, meaning there has been sufficient validation to support the context of use. There has been guidance in existence since 2009 outlining the information required to demonstrate a PRO is fit for purpose. Four additional PFDD guidance documents are in various stages of development and, once completed, are expected to replace the 2009 guidance.

The FDA published regulatory guidance in January 2022 on the use of DHTs for remote data acquisition from participants in clinical investigations evaluating medical products. This provides much needed guidance on important considerations associated with the development and use of digital technology-based endpoints (clinical, physiological, psychological, behavioral or functional). In line with the FDA’s Fit-for-Purpose (FFP) initiative, which provides a pathway for regulatory acceptance of tools for use in drug development programs, the latest guidance on DHTs walks through the steps required to evidence that DHTs are fit for purpose.

• Verification is confirmation by examination and provision of objective evidence that the physical parameter that the DHT measures (e.g., acceleration) is measured accurately and precisely over time.
• Validation is confirmation that the selected DHT appropriately assesses the clinical event or characteristic in the proposed participant population. In the case of wearables, validation may include comparisons of measurements made by the wearable device with reference measurements (e.g., step count by actigraphy versus step count by observation), or evaluation of factors that might affect the precision and accuracy of the measurement, such as placement of a wearable DHT (e.g., wrist versus hip).

The guidance issued on DHTs outlines some differences in the type of information and considerations in the development of clinical outcome assessments (COA) based on DHTs. While these guidance documents provide valuable information on the regulatory requirements, the design of a clinical study and the selection of an optimal and relevant set of COAs and endpoints remain the responsibility of trial sponsors.

At this stage, we recommend clinical trial sponsors consider the following options to expand usage and test the possibilities with wearables and PROs.

• Monitor agencies and publications of wearables in clinical trials. Become familiar with recent draft guidance documents and publications. A quick web search identifies multiple articles and publications sharing the results of wearables in clinical trials. Diving into the specifics of physical function in oncology yields fewer results, but a trend is emerging.
• Share, explore and grow your knowledge. Working groups are forming to explore how digital endpoints may be beneficial in clinical trials and are helping to provide proposed structure for regulatory consideration. Joining one of these efforts can build momentum around digital endpoint inclusion and regulation.
• Consult with partners you trust. Look for experts in evidence-based solutions that are dedicated to patient-centered research — and working to assess patient outcomes in a way that reduces patient burden while also improving data quality and preserving safety. Wearables appear to be part of the answer. Specifically with oncology trials, where sponsors are striving to measure physical function, consider a partner, like us, that sees wearables and PROs as complementary measures and worthy of inclusion in a regulatory submission.

Research is forging ahead, data is being gathered, and interest — fueled by burgeoning technology — is growing with sponsors. Our Evidera peri- and post-approval business can help your team navigate the landscape of wearables and PROs, providing clarity and evidence that leads to actionable insights tailored to the specific needs of your clinical program.