The long-term clinical impact of digital endpoints and biomarkers in data collection

KEYWORDS:

• Medication Safety
• patient outcomes
• digital endpoints
• data collection
• quality of care

1. Introduction

Traditional endpoints in clinical trials are predefined outcomes used to measure the efficacy and safety of interventions. They have been the cornerstone of regulatory approval for new treatments [1]. However, these endpoints often face challenges when applied to chronic and complex diseases like Parkinson’s and heart diseases. This is because they rely on in-clinic measurements and subjective evaluations, which can lead to costly clinical trials with the potential for inaccurate results [1]. Between 2008 and 2021, a survey of 293 registered trials on Parkinson’s highlighted the extensive use of traditional endpoints [2].

Digital endpoints, defined by sensor-generated data from outside clinical environments, offer a potential solution to the limitations of traditional endpoints [1]. These endpoints employ a variety of sensors available in an array of devices and can be applied in a diverse set of contexts. They are primarily used to understand patients’ biologic processes and responses, as well as how they feel, function, and survive in both clinical trials and routine clinical care. From 2000 to 2017, connected digital products saw a compound annual growth rate of 34%, emphasizing their increasing significance as research tools [3].

However, there is a scarcity of research concerning long-term clinical impact of these tools. Addressing this gap, this editorial embarks on an exploration of the profound impacts of digital endpoints from clinical perspective. We seek to elucidate how such innovative data collection techniques can potentially metamorphose clinical research, optimize data acquisition processes, and pave the way for the genesis of highly effective therapeutic strategies

2. Clinical impact of digital endpoints

While definitive evidence concerning the long-term clinical impacts of digital endpoints is still emerging, an analysis of current literature and the historical evolution of technology in other domains offers insights into how digital endpoints may shape clinical care in the future.

2.1. Medication safety

Drug related problems (DRPs) and Medication errors (MEs) have been increasingly seen as a global health concern, with severe consequences on patient outcomes [4,5]. Integrating digital endpoints into clinical practice has shown their potential in enhancing medication safety in several ways. Technologies such as smart pill bottles and ingestible sensors have become essential in adherence monitoring, offering real-time data on medication consumption [6]. This real-time monitoring enables healthcare providers to ensure that patients follow their prescribed regimens, a critical element for the efficacy and safety of treatment. Additionally, wearable devices, which continuously track vital signs and physiological metrics, have shown promise in detecting adverse drug reactions early [7].

The data from wearable devices is increasingly used for pharmacovigilance. In this context, biopharmaceutical manufacturers collect information from patients in clinical trials, spontaneous adverse event reports, and real-world evidence collection. Such data prove invaluable in swiftly and reliably identifying and reporting adverse drug reactions. This rapid detection allows for prompt interventions, potentially reducing the risk of severe complications [8].

Recent studies underscore the potential of digital endpoints in enhancing medication safety. One notable development is Digital Therapeutics (DTx), which melds digital technology with standard clinical care to optimize outcomes [9]. Furthermore, there is a growing interest in developing innovative digital endpoints to supplant traditional ones like clinical rating scales in trials. These new metrics aim to offer a more detailed understanding of medication safety and effectiveness [10].

2.2. Precision medicine, patient outcomes, and quality of life

Digital endpoints are poised to have profound long-term clinical implications, revolutionizing patient-centric healthcare. Their ability to consistently collect and analyze patient data facilitates early detection of health anomalies, paving the way for timely interventions and, consequently, improved patient outcomes. Digital health technologies enable remote data collection, epitomizing a patient-centric approach to drug development. This real-time data collection in real-world settings aligns with the principles of precision medicine, which aims to customize therapeutic approaches based on individual patients’ genetic, environmental, and lifestyle factors [7].

In the field of oncology, studies have endorsed the utilization of digital health solutions for collecting electronic Patient Reported Outcomes (ePROs) and allowing remote monitoring, which demonstrated benefits in symptom reporting and management, reduction in symptom distress, decrease in unplanned hospitalizations, thus enhancing the quality of life and survival rates of patients [11]. Digital endpoints are instrumental in refining therapeutic choices and ensuring treatments are as individualized as possible. These data-driven and patient-focused digital outcomes have demonstrated their merit by assisting clinicians in making more personalized decisions [12].

This real-time, data-centric approach not only potentially shortens hospital stays and prevents severe health episodes, but it also dovetails with precision medicine’s overarching goal: optimizing patient outcomes and overall well-being. The amalgamation of digital endpoints and precision medicine is spurring patient-centric innovation in the pharmaceutical realm. Clinical studies leveraging digital endpoints are emerging as potential avenues to mitigate costly late-stage trial failures [11]. The synergy of technological advancements with human biology is broadening the scope of healthcare [13].

2.3. Quality of care

Digital endpoints are expected to significantly improve the quality of care through enabling timely interventions and more informed decision-making by healthcare providers. This is facilitated by a more comprehensive view of patients’ health that digital endpoints provide.

2.4. Drug discovery

Digital endpoints are increasingly recognized for their potential to expedite clinical trials. They accelerate data collection, which may reduce trial durations, thus fast-tracking drug discovery. Moreover, these tools provide a deeper insight into patient conditions, which could diminish late-stage failures [1]. This is achieved by accurately charting changes in conditions over time using digital tools, conserving resources that might otherwise be expended on unsuccessful drug trials [1].

3. Conclusion

Digital endpoints offer exciting prospects for enhancing medication safety, broadening precision medicine approaches, elevating care quality standards, and streamlining the drug discovery process. The emergence of Digital Therapeutics exemplifies these remarkable potentials; collectively, they envision a future of healthcare that is both meticulously personalized and profoundly efficient.

4. Barriers to digital endpoints

Digital endpoints face many obstacles, from regulatory requirements and funding shortages to the need for compelling real-world evidence of their efficacy. Regulation requires collaboration between innovators and authorities to ensure digital health technologies meet reliability and utility criteria [14]. Funding issues related to providing broadband access for underserved populations highlight the digital divide, with initiatives like the FCC’s Connected Care Pilot seeking to bridge it by improving internet access and supporting telehealth services [15]. Aligning reimbursement policies with digital health advancements is crucial for wider adoption, as CMS guidelines begin to recognize telehealth’s value but face integration and policy alignment issues. Slow adoption rates are compounded by the absence of clear real-world evidence showing its benefits; digital health tools must demonstrate their integration capability, effectiveness, and fulfillment of unmet patient needs in order to be adopted widely by stakeholders. Through collaborative efforts among all concerned, digital health technologies can unlock their full potential for improving both patient care and healthcare efficiency.

5. Expert opinion

The findings of this editorial indicate that digital endpoints might enhance medication safety, reinforce principles of precision medicine, improve quality care delivery, and expedite drug discovery processes. These tools are appealing primarily due to their capacity to deliver real-time, objective data, potentially offsetting limitations associated with traditional endpoints, like in-clinic measurements or subjective evaluations that can vary in accuracy and reliability.

Digital endpoints research illustrates the disparity between short and long-term data through DHTs by juxtaposing an abundance of immediate DHT data against scarce long-term insights, underscoring the difficulty of using short-term results to predict long-term outcomes. A strategic framework is proposed for integrating DHTs into clinical development programs, with emphasis placed on verifying, validating, and leveraging prior work to establish strong evidence bases, accurately estimate costs and timelines, and successfully use DHTs across clinical programs, thereby closing this divide between short and long-term data insights [16].

Stride Velocity 95th Centile (SV95C), a digital endpoint that utilizes wearable technology to measure patient movements, was recently approved by the European Medicines Agency (EMA) as a secondary endpoint in Duchenne muscular dystrophy trials for participants over 5 years old. This endorsement marks an impressive recognition of digital endpoint validity and reliability, confirming its accuracy, sensitivity to change, and relevance to patients. Additionally, its ActiMyo® device, used for measuring this endpoint, underwent extensive validation testing, proving its ability to provide real-world evidence and improve clinical trial outcomes [14].

Development and regulatory acceptance of digital endpoints face many hurdles, from complex regulatory barriers to extensive validation requirements. Yet, despite these difficulties, there’s increasing interest and gradual adoption of digital health technologies (DHTs), such as activity trackers in the CNS disease space, that measure real-world mobility more accurately than traditional outcomes. Regulatory agencies are becoming more accepting of digital endpoints, with some agencies, such as the EMA, offering formal endorsement for their use in clinical trials. Such endorsements mark a shift toward wider acceptance and use of these innovative approaches within drug development and approval processes; yet, more work remains to integrate them into current frameworks [17].

The trajectory for digital endpoints in the upcoming years is promising, characterized by steady growth. As technological innovations, particularly in AI and ML, continue to progress, we can expect an ever-evolving array of digital tools with increased precision. The capabilities of AI and ML in analyzing extensive data and generating predictive models can further enhance the real-time interpretation of these tools, allowing for timely interventions and bespoke therapeutic plans. With this evolution, data privacy and ethical considerations will inevitably become more salient, necessitating robust regulatory frameworks.

DTx stands out as an exciting development in today’s healthcare landscape. Symbolizing the fusion of digital capabilities and therapeutic models, DTx goes beyond mere data collection. It emphasizes active patient engagement, offering tools that not only monitor but actively guide users through therapeutic pathways. This evolution presents a tantalizing glimpse into the future of healthcare, a realm where technology and therapy are seamlessly integrated.

Declaration of interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.