Digital Progression Biomarkers as Novel Endpoints in Clinical Trials: A Multistakeholder Perspective

Abstract

The burden of Parkinson’s disease (PD) continues to grow at an unsustainable pace particularly given that it now represents the fastest growing brain disease. Despite seminal discoveries in genetics and pathogenesis, people living with PD oftentimes wait years to obtain an accurate diagnosis and have no way to know their own prognostic fate once they do learn they have the disease. Currently, there is no objective biomarker to measure the onset, progression, and severity of PD along the disease continuum. Without such tools, the effectiveness of any given treatment, experimental or conventional cannot be measured. Such tools are urgently needed now more than ever given the rich number of new candidate therapies in the pipeline. Over the last decade, millions of dollars have been directed to identify biomarkers to inform progression of PD typically using molecular, fluid or imaging modalities). These efforts have produced novel insights in our understanding of PD including mechanistic targets, disease subtypes and imaging biomarkers. While we have learned a lot along the way, implementation of robust disease progression biomarkers as tools for quantifying changes in disease status or severity remains elusive. Biomarkers have improved health outcomes and led to accelerated drug approvals in key areas of unmet need such as oncology. Quantitative biomarker measures such as HbA1c a standard test for the monitoring of diabetes has impacted patient care and management, both for the healthcare professionals and the patient community. Such advances accelerate opportunities for early intervention including prevention of disease in high-risk individuals. In PD, progression markers are needed at all stages of the disease in order to catalyze drug development—this allows interventions aimed to halt or slow disease progression, very early, but also facilitates symptomatic treatments at moderate stages of the disease. Recently, attention has turned to the role of digital health technologies to complement the traditional modalities as they are relatively low cost, objective and scalable. Success in this endeavor would be transformative for clinical research and therapeutic development. Consequently, significant investment has led to a number of collaborative efforts to identify and validate suitable digital biomarkers of disease progression.

Virtual exam for Parkinson’s disease enables frequent and reliable remote measurements of motor function

“…Sensor-based remote monitoring could also help increase representation for groups whose data have historically not been included in clinical trials 9 , 10 . Before such measurements can be used as endpoints in clinical trials to quantify disease progression, a careful evaluation of the clinical validity, reliability, and sensitivity to change is required 11 , 12 .…”

Opportunities and Challenges for Decentralized Clinical Trials: European Regulators’ Perspective

“…30 Data quality of data generated by decentralized means It has been suggested that digital technologies could lead to more clinically meaningful end points than conventional end points, as data could be collected more frequently, and more objectively due to the reduced impact of observer and recall bias. 31,32 Although the opportunity to collect richer data via digital technologies was recognized by the regulators, they were cautious about the impact of large data sets on end points. In addition, missing data due to technical defects or poor technology adherence were found to be a potential challenge.…”

Counting What Counts: How to Reach Outcomes That Truly Matter to Parkinson's Patients

“…This approach, however, does not include additional important measures, such as monitoring a patient in their home, work, or social environment, which can provide insight into the patient's lived experience 9 with much more relevance than snapshots of their condition that is garnered at intermittent clinical visits. Wearable technology has the potential to provide such information, particularly as it relates to motor symptoms, gait, functional mobility, falls, and tremor, but limitations in assessing nonmotor symptoms and lack of standardized measurements that may be used universally in the clinical and research arenas are problematic 10 …”

“…Wearable technology has the potential to provide such information, particularly as it relates to motor symptoms, gait, functional mobility, falls, and tremor, but limitations in assessing nonmotor symptoms and lack of standardized measurements that may be used universally in the clinical and research arenas are problematic. 10 What this consensus does reveal is that there is an extensive number of determinants of health for patients with PD, which can be complicated to measure. But there is a common thread: all these parameters, to differing degrees, ultimately affect a patient's quality of life, and perhaps this is, in fact, the most telling outcome measure.…”