Otsuka Pharmaceutical

Kazuto Yamada

Clinical trials have undergone significant changes over the decades, both strategically and operationally. These changes have been driven by advancements in technology and a recent emphasis on patient-centered outcomes. For instance, the direct data capture (DDC) methods have enabled electronic data collection directly from the source, which is then automatically transferred to a central database for visualization, eliminating the need for source data verification (SDV). Artificial intelligence (AI) can also play a role in the design and efficiency of non-traditional trials, such as ones incorporating the use of real world data (RWD). Additionally, blockchain technology has the potential to incentivize participants in clinical trials through token rewards or other forms of compensation.

The diversification of clinical trials has allowed for more personalized and effective treatments for patients. Digital biomarkers, in particular, have a significant impact on the future of clinical trial. These technologies can be seamlessly integrated into patient-centric and decentralized clinical trials, providing benefits to participants, clinicians, and sponsors. Sensor technology and digital devices have enabled the real-time collection of patient data in their daily lives without requiring frequent hospital or clinic visits. This has accelerated the development of digital biomarkers in digital health technology (DHT). In Japan, there have been moderate use cases of digital biomarkers in clinical research, focusing on evaluating daily activity, sleep and mobility through activity or fitness trackers. However, the use of digital biomarkers as clinical trial endpoints to support labeling claims for therapeutic products is still uncommon, although efforts are emerging.

 There have been randomized clinical trials (RCTs) that have employed wearable devices to measure clinical endpoints such as stride velocity in patients with Duchenne Muscular Dystrophy and 24-hour cough count in patients with Refractory and/or unexplained chronic cough. The severity of cough can alternatively be assessed by the patient's own visual analog scale (VAS) as a patient-reported outcome (PRO). It can be, however, subjective and may not sufficiently reflect the nocturnal status, while wearable devices can electronically acquire data on patients' biological responses. Continuous glucose monitors are also well-established as passive measurement devices through wearables. However, there are still technical hurdles to overcome for active measurement using digital biomarker, such as cognitive assessment.

“Digital biomarkers used in pivotal clinical trials as primary endpoints need to undergo verification, analytical validation, and clinical validation before seeking acceptance from regulatory authorities”

Biomarkers are particularly compatible with central nervous system (CNS) disorders, including psychiatric and neurological diseases, where subjective clinical assessments are often relied upon for diagnosis. The development of digital biomarkers aided by AI algorisms could be a breakthrough in this area. Among the various biological responses that can be measured, the digital voice biomarker shows promise as a continuous, non-invasive disease monitoring tool that can be also utilized in screening and diagnosis of a broad range of conditions, not only CNS diseases but cardiovascular and respiratory diseases.

The use of digital biomarkers in clinical trials offers several advantages. They can accurately measure clinically meaningful aspects of patient health outcome, predict disease progression or treatment responsiveness to stratify participants, and address unmet measurement needs that are not currently assessed in standard clinical trials. However, there are challenges to overcome.

Digital biomarkers used in pivotal clinical trials as primary endpoints need to undergo verification, analytical validation, and clinical validation before seeking acceptance from regulatory authorities. Usability assessment is also crucial to establish the tolerability and acceptability of the technology by participants.

The productivity in drug development has not been high enough, with the overall probability of success of drug development at 9.6 percent, and even lower for psychiatric or neurological disorders. Developing novel digital biomarkers can offer real-time and more sensitive indicators of efficacy and safety that are clinically meaningful to patient outcomes. This may lead to earlier determination of a therapeutic product’s potential assessed with a smaller sample size in pilot trials and smarter go/no-go decisions. In later stages of development, these indicators can be allowed as primary or secondary clinical endpoints with better patient engagement in supporting labeling claims.

To drive the development of digital biomarkers, pharmaceutical companies, tech companies, academia, and the health care industry need to collaborate. These partnerships can lead to the investment in new technologies and the development of digital biomarkers that capture unmet measurement needs in a wide range of diseases. In the context of future drug development, digital biomarkers can play critical roles in the successful launch of a product, particularly in the field of CNS diseases, where they are envisioned as a coming revolution.