Quantifying the Benefits of Digital Biomarkers and Technology-Based Study Endpoints in Clinical Trials: Project Moneyball

Abstract

<b><i>Introduction:</i></b> Digital biomarkers have significant potential to transform drug development, but only a few have contributed meaningfully to bring new treatments to market. There are uncertainties in how they will generate quantifiable benefits in clinical trial performance and ultimately to the chances of phase 3 success. Here we have proposed a statistical framework and ran a proof-of-concept model with hypothetical digital biomarkers and visualized them in a familiar manner to study power calculation. <b><i>Methods:</i></b> A Monte Carlo simulation for Parkinson’s disease (PD) was performed using the Captario SUM® platform and illustrative study technology impact calculations were generated. We took inspiration from the EMA-qualified wearable-derived digital endpoint stride velocity 95<sup>th</sup> centile (SV95C) for Duchenne muscular dystrophy, and we imagined a similar measurement for PD would be available in the future. DaTscan enrichment and “SV95C-like” endpoint biomarkers were assumed on a hypothetical disease-modifying drug pivotal trial aiming for an 80% probability of achieving a study <i>p</i> value of less than 0.05. <b><i>Results:</i></b> Four scenarios with different combinations of technologies were illustrated. The model illustrated a way to quantify the magnitude of the contributions that enrichment and endpoint technologies could make to drug development studies. <b><i>Discussion/Conclusion:</i></b> Quantitative models could be valuable not only for the study sponsors but also as an interactive and collaborative engagement tool for technology players and multi-stakeholder consortia. Establishing values of digital biomarkers could also facilitate business cases and financial investments.

Digital health technology derived measures: Biomarkers or clinical outcome assessments?

“…The line between using DHT‐derived measures to assess a response to a therapy and using a DHT to measure a patient's ability to perform a certain task that has implications on their quality of life can be very fine. This fine line creates uncertainty for drug developers in terms of their regulatory strategy; which, in turn, results in their hesitancy to develop and implement novel measures that could potentially reduce sample size for clinical studies 24 and bring much‐needed treatments to patients faster. This is particularly true in rare or slowly progressing diseases, where the number of patients participating in clinical trials can present a significant challenge.…”

Empowering drug development: Leveraging insights from imaging technologies to enable the advancement of digital health technologies

“…42,83 The deployment of DHTs in rare diseases is likely to become more important as our understanding of disease subgroups continues evolving, requiring studies in subpopulations with a robust signal in a small number of participants. 54,84 In summary, lessons from imaging biomarkers can be leveraged to advance DHT use in clinical investigations in the following ways:…”

“…These validated tools are likely to have the biggest impact in rare diseases as they may solve multiple problems, such as the need for frequent site visits, resilience to changes in environment, and attrition during the pandemic, at the same time offering convenience, inclusion, and data quality 42,83 . The deployment of DHTs in rare diseases is likely to become more important as our understanding of disease subgroups continues evolving, requiring studies in subpopulations with a robust signal in a small number of participants 54,84 …”

Assessing the Net Financial Benefits of Employing Digital Endpoints in Clinical Trials

“…Industry researchers have proposed frameworks for predicting and assessing the benefits of digital endpoints to study teams. Mori et al developed a statistical framework to simulate the impacts of digital capabilities [12]. They applied it to trial scenarios to model potential benefits to clinical development programs.…”