Novartis New Mobility Digital Biomarker in Clinical Trials

The 7th Annual Digital Biomarkers in Clinical Trials conference featured a compelling presentation by Tilo Hache, Director of Strategy and Planning at Novartis Biomedical Research. Hache shared valuable insights and learnings from the Innovative Medicines Initiative (IMI) Mobilise-D project, a public-private partnership to address the challenges of integrating mobility as a vital sign in clinical trials. His presentation underscored the importance of mobility in health, the challenges in measuring it, and the consortium’s digital biomarker achievements and learnings.

The Importance of Mobility in Health

Hache emphasized the significance of mobility as an emerging “6th vital sign,” highlighting a study by Stephanie Studensky published in 2011. The study demonstrated a correlation between walking speed and mortality, underscoring the potential impact of mobility on health outcomes. Specifically, the study found that faster walking speeds were associated with lower mortality rates, suggesting that walking speed could be a predictive marker for overall health and longevity. Despite its importance, mobility has not been widely adopted in clinical practice or pharmaceutical studies due to measurement challenges. Hache pointed out that while the study’s findings were groundbreaking, they did not translate into widespread clinical application. This gap between research and practice is partly due to the difficulty in consistently and accurately measuring walking speed in a clinical setting.

Traditional methods often require patients to visit clinics for assessments, which can be cumbersome and impractical for patients and healthcare providers. These assessments usually involve walking tests that must be conducted under controlled conditions to ensure accuracy. However, this setup introduces variability, as patients’ performance can be influenced by factors such as fatigue, stress, or the unfamiliar clinical environment. Additionally, the logistical burden of frequent clinic visits can be a significant barrier for patients, particularly those with mobility issues or chronic conditions. Hache’s presentation highlighted the need for innovative solutions to overcome these challenges and effectively integrate mobility measurements into clinical practice.

Challenges in Measuring Mobility

Hache outlined three primary challenges in measuring mobility, each with its complexities. First, traditional methods for measuring mobility require patients to visit clinics, where they undergo assessments that can be both time-consuming and costly. These assessments often involve walking tests that must be conducted under controlled conditions to ensure accuracy. However, this setup introduces variability, as patients’ performance can be influenced by factors such as fatigue, stress, or the unfamiliar clinical environment. Additionally, the logistical burden of frequent clinic visits can be a significant barrier for patients, particularly those with mobility issues or chronic conditions.

Second, mobility is not typically connected to standard outcome measures used in clinical trials, which challenges integration. For instance, in multiple sclerosis (MS) trials, the effectiveness of a drug is often measured using the Expanded Disability Status Scale (EDSS), which focuses on neurological function rather than mobility. Similarly, in Parkinson’s disease trials, outcomes are frequently measured by the frequency of falls or other motor symptoms rather than walking speed. Despite its potential relevance, this disconnect makes incorporating mobility as a meaningful endpoint in these studies challenging. Third, ensuring agnosticism to devices and the interests of trial sponsors adds another layer of complexity. Studies may use various devices to measure mobility, such as accelerometers, pedometers, or smartphone apps. Each device has its specifications, data formats, and potential sources of error, making it challenging to standardize measurements across studies.

The Mobilise-D Consortium

The Mobilise-D Consortium was initiated by Ronenn Roubenoff in 2017 and brought together a diverse group of stakeholders to tackle these challenges. The consortium included ten pharmaceutical companies, two clinical research organizations, and 22 European academic partners. This collaborative effort aimed to leverage the strengths and expertise of each partner to develop innovative solutions for measuring mobility in clinical trials. With a budget of €25 million from the European Commission, the consortium created a comprehensive framework for integrating mobility as a vital sign. The project involved more than 300 experts designing and implementing studies, developing data standardization approaches, and engaging with regulatory authorities.

Hache highlighted the importance of this collaborative approach, noting that the diverse perspectives and expertise of the consortium members were crucial for addressing the multifaceted challenges of the project. The consortium’s efforts were not just limited to Europe; they aimed to set a global standard for mobility measurements in clinical trials. By bringing together such a wide array of stakeholders, the Mobilise-D Consortium was able to pool resources, share knowledge, and develop a more robust and comprehensive approach to integrating mobility as a vital sign in clinical trials.

Key Achievements

Despite the unprecedented challenges posed by the COVID-19 pandemic, the Mobilise-D consortium achieved several significant milestones. One of the most notable accomplishments was completing two studies involving 2,500 patients across four indications: Parkinson’s disease, multiple sclerosis, chronic obstructive pulmonary disease (COPD), and hip fracture. Conducting these studies during a global pandemic required extraordinary efforts in patient recruitment, data collection, and coordination among the consortium members. The consortium also made substantial progress in regulatory engagement. They received two letters of support from the European Medicines Agency (EMA) for their approach to measuring mobility. Additionally, they initiated their first interactions with the U.S. Food and Drug Administration (FDA).

These interactions were critical for gaining regulatory acceptance and ensuring that the project’s findings could be translated into clinical practice. In addition to regulatory achievements, the consortium focused on data standardization and dissemination. They published 70 papers and held 11 webinars to share their findings with the broader scientific community. The consortium’s commitment to transparency and open science was evident in their decision to publicly share the data from the 2,500 patients and the methods and protocols used in the studies. This open-access approach aims to facilitate further research and encourage the adoption of mobility measurements in clinical trials.

Learnings from the Mobilise-D Project

Hache shared several key learnings from the Mobilise-D project, categorized into people, process, and product. First, diversity, trust, and leadership were crucial for the project’s success. Hache likened the role of project managers to shepherds guiding a large crowd of sheep, navigating through numerous challenges such as Brexit, the EMA’s relocation from London to Amsterdam, the Ukrainian war, and the COVID-19 pandemic. The consortium’s agile risk management approach allowed them to adapt to these disruptions and continue making progress. Hache emphasized that the team’s diversity, which included experts from various fields and backgrounds, fostered unique ideas and innovative solutions.

Second, the IMI framework, despite being perceived as bureaucratic, provided a structured way to kickstart the project. The framework included contract templates and terms and conditions that facilitated a quick start without the need for extensive negotiations. However, the project also faced challenges related to the IMI’s waterfall model, which is less flexible than iterative or agile approaches. The consortium’s decision to run its trials, rather than relying on pharma-sponsored trials offered greater flexibility but highlighted the need for infrastructure support from clinical research organizations. This approach allowed the consortium to recruit 2,500 patients within a year, even during the pandemic, demonstrating their close connection to patients and ability to adapt to challenging circumstances.

Third, collecting raw accelerometer data required extensive data clarification and validation. This process involved checking with study sites to ensure data accuracy and consistency. The consortium also navigated academic and corporate partners’ different cultures and priorities. Academic institutions often operate on semester schedules, while corporations follow fiscal cycles, leading to potential conflicts in scheduling and priorities. Hache highlighted the importance of internal marketing within corporations to maintain sponsorship and resource allocation for the project. The consortium also implemented a publication clearance process to ensure fairness and transparency in disseminating their findings.

Early Health Authority Interactions

Hache stressed the importance of early interactions with health authorities like the EMA and FDA to understand regulatory pathways and requirements. While resource-intensive, these interactions are essential for successfully integrating new measures into clinical practice. Given the global nature of clinical trials and the need for harmonized standards, engaging with both European and U.S. regulators was particularly important for the consortium. Early health authority interactions provided valuable guidance on the regulatory requirements for mobility measurements, helping the consortium design their studies and data collection methods accordingly.

Hache noted that these interactions also helped build credibility and trust with regulators, which is crucial for gaining approval and support for innovative approaches. The consortium’s proactive approach in engaging with health authorities early in the project ensured that they were aligned with regulatory expectations and could address any potential issues promptly. This strategy facilitated smoother regulatory processes and increased the likelihood of successfully integrating mobility measurements into clinical practice.

Conclusion

Tilo Hache’s presentation at the 7th Annual Digital Biomarkers in Clinical Trials conference provided a comprehensive overview of the Mobilise-D project, highlighting the importance of mobility as a vital sign and the challenges and successes of integrating it into clinical trials. The learnings from this project offer valuable insights for future public-private partnerships and the advancement of digital biomarkers in clinical research. The Mobilise-D consortium’s achievements and innovative approaches set a precedent for future efforts to incorporate mobility and other digital biomarkers into clinical trials, ultimately improving patient outcomes and advancing medical research.