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 haveenabled electronic data collectiondirectly from the source,whichis then automatically transferred to a central database for visualization, eliminating the need for source data verification (SDV). Artificial intelligence (AI) canalso 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 significantimpact 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 enabledthe real-time collection of patient data in their daily lives without requiring frequent hospital or clinic visits. Thishas accelerated the development of digital biomarkers in digital health technology (DHT). In Japan, there have been moderateuse cases of digital biomarkers in clinical research,focusing on evaluating daily activity, sleep and mobilitythrough activity or fitness trackers.However, the use of digital biomarkers as clinical trial endpoints to support labeling claimsfor therapeutic products isstill 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 Dystrophyand 24-hour cough count in patients with Refractory and/or unexplained chronic cough. The severity of cough canalternatively be assessed by the patient's ownvisual analog scale (VAS)as a patient-reported outcome (PRO). It can be, however,subjective and may not sufficiently reflect thenocturnal status, while wearable devicescan electronically acquire data on patients' biological responses. Continuous glucose monitors are also well-established aspassive measurementdevices through wearables.However, there are still technical hurdles to overcome for active measurement using digital biomarker,such as cognitive assessment.

Biomarkers are particularly compatible with central nervous system (CNS) disorders, including psychiatric and neurological diseases, where subjective clinical assessments are oftenrelied uponfor diagnosis. The development of digital biomarkers aided by AI algorisms could be a breakthrough in this area. Among the various biological responsesthat can be measured, the digital voice biomarkershows promise as a continuous, non-invasive disease monitoringtool 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 endpointsneed to undergoverification, analytical validation, and clinical validationbefore 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. Thismay lead to earlier determination of a therapeutic product’s potentialassessed with a smaller sample size in pilot trials and smarter go/no-go decisions. In later stages of development,theseindicators 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 innew 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 biomarkerscan 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.