Digital Health Advances: How Digital Biomarkers Are Changing the Rare Disease Landscape

The Rare360 Editorial Team
7h
6 min read

Smiling man in a wheelchair, wearing a blue shirt and smartwatch in a bright room with plants and shelves in the background.

For families navigating the unpredictable journey of rare diseases, where diagnosis can be delayed, symptoms subtle, and care fragmented, digital biomarkers are rapidly emerging as a transformational tool in diagnosis, monitoring, and treatment planning. These measurable physiological or behavioural signals, captured via smartphones, wearables, and sensor-enabled devices, offer new precision and continuity that traditional medical visits can’t match.

A key perspective from the Rare Diseases International Research Consortium (IRDiRC), published in Nature Reviews Drug Discovery (April 2025), emphasizes the role of digital biomarkers in accelerating therapeutic development for rare diseases by enabling continuous, objective measurement in decentralized settings. These include motor function tracking, gait assessment, and sleep patterns, all powered by technology.

In clinical trials, the European Medicines Agency (EMA) recently qualified stride velocity (95th centile) as an approved digital endpoint for Duchenne Muscular Dystrophy. It’s now under review by the U.S. FDA as a valid outcome measure, demonstrating regulatory recognition of technology-derived endpoints in rare disease research. Although validation remains ongoing, these technologies have demonstrated feasibility across ALS, SMA, Duchenne muscular dystrophy, and others.

In 2025, growing acceptance of tools backed by FDA guidance on digital health and biomarker qualification is accelerating investment into this emerging field. Digital biomarkers are enabling more robust decentralized clinical trials, lowering barriers to participation for patients in underserved or remote areas, and reducing reliance on subjective assessments or infrequent clinic visits.

Further, narrative reviews published in early 2025 emphasize the need for patient-centred design and ethics in digital health solutions tailored to rare disease communities. These resources highlight concerns around data privacy, digital equity, and the importance of co-designing tools with the rare disease lived experience in mind.

With science and advocacy in sync, digital biomarkers have the potential to become a true digital lifeline for rare disease patients, fostering earlier diagnosis, more inclusive trials, and truly personalized care.

What Are Digital Biomarkers?

Digital biomarkers are objective, quantifiable physiological and behavioural data points that are collected and measured through digital devices, like smartphones, wearables, implantables, and biosensors. Unlike traditional biomarkers, which are often obtained through invasive procedures like blood draws or imaging tests, digital biomarkers are collected passively or actively through continuous monitoring in real-world settings.

They can capture a wide range of signals, including:

Motor function (e.g., gait, tremors, dexterity)
Cognitive performance (e.g., memory, attention)
Cardiovascular indicators (e.g., heart rate variability)
Sleep patterns
Voice and speech changes
Social interaction metrics (e.g., typing speed, phone usage)

This data is analyzed using algorithms and artificial intelligence to detect deviations, trends, and potential health risks long before traditional symptoms become apparent.

For rare disease patients, digital biomarkers offer an opportunity to track subtle physiological changes that may otherwise go unnoticed in routine clinical assessments. Since many rare conditions involve nuanced or intermittent symptoms, continuous monitoring enables better detection, earlier intervention, and more precise evaluation of treatment responses. For example, researchers studying Duchenne Muscular Dystrophy (DMD) have used wearable sensors to track ambulation and muscle fatigue in real time, enabling remote monitoring of disease progression outside of clinical visits.

Bridging Diagnostic Gaps in Rare Diseases Through Continuous Monitoring

One of the greatest challenges in rare disease care is the diagnostic odyssey—a long and often painful journey marked by misdiagnoses, delayed answers, and unnecessary testing. Studies suggest that it takes an average of 5 to 7 years for a person with a rare disease to receive an accurate diagnosis. The reasons are multifaceted: low prevalence, non-specific symptoms, lack of awareness among healthcare professionals, and limited access to diagnostic tools.

Digital biomarkers offer a revolutionary approach to closing these diagnostic gaps. By enabling passive and continuous health monitoring, they can detect patterns and subtle changes in a person’s behaviour or physiology long before traditional symptoms become apparent. For example:

A progressive decline in mobility or coordination captured through gait sensors might indicate a rare neurological disorder.
Voice changes and facial expression analysis could be early markers for conditions like ALS or myasthenia gravis.
A child’s cognitive development and social interaction patterns—monitored via app-based assessments—might reveal red flags for rare pediatric neurodevelopmental disorders.

Rare disease patients may experience symptoms that don’t appear during routine clinic visits. Wearable devices can detect these subtle, real-time changes, such as irregular heart rhythms, movement abnormalities, or respiratory irregularities. Digital biomarkers can reduce the reliance on episodic clinical visits, which often fail to capture intermittent symptoms or early-stage abnormalities. Instead, these tools provide clinicians with a rich, contextualized dataset that enhances decision-making and supports earlier intervention.

Additionally, digital biomarker platforms powered by machine learning and artificial intelligence can help detect symptom clusters that might otherwise go unnoticed. For underserved or geographically isolated rare disease patients, this technology holds the promise of equitable and earlier access to diagnosis.

Enhancing Disease Monitoring and Treatment Evaluation with Digital Tools

Once a diagnosis is made, managing a rare disease often requires frequent monitoring to track disease progression, assess treatment efficacy, and adjust care plans. Traditional monitoring methods, such as clinical visits, imaging, or lab tests, offer only snapshots in time, missing critical fluctuations that may occur between appointments.

Digital biomarkers offer a more patient-centric, real-time alternative. This real-time insight into a patient's daily life provides a more accurate picture of how a disease behaves and how a patient is responding to treatment. For example:

Wearables like smartwatches and biosensors can measure heart rate variability, oxygen saturation, or tremor frequency in neuromuscular or cardiovascular rare diseases like muscular dystrophy or mitochondrial disorders.
Mobile applications can prompt patients to log symptoms or complete brief daily symptom check-ins that assess memory, speech, or mood, which can be useful for rare conditions like Huntington’s disease or Wilson’s disease.
Smart inhalers and connected devices can track medication adherence and breathing patterns for patients with rare respiratory conditions like cystic fibrosis or primary ciliary dyskinesia.

Digital biomarkers also allow for patient-specific baselines, reducing the "one-size-fits-all" approach to care. This is especially valuable in clinical trials for rare diseases, where small sample sizes make individualized data even more important.

In the context of decentralized clinical trials, these tools improve both feasibility and efficiency. Rather than requiring frequent travel to study sites, participants can engage remotely while their health data is continuously collected and transmitted securely to researchers.

Ultimately, digital tools empower both clinicians and patients to engage in proactive, rather than reactive, care, leading to better health outcomes and an improved quality of life for those living with rare diseases.

Challenges and Limitations in the Adoption of Digital Biomarkers

Despite their promising potential, digital biomarkers face several barriers to widespread adoption, especially in the rare disease space, where regulatory pathways, data standardization, and infrastructure gaps pose unique barriers.

Regulatory and Validation Hurdles: Digital biomarkers must meet rigorous standards to be considered clinically valid and acceptable to regulators like the FDA or EMA. However, current frameworks are still evolving, particularly for algorithm-driven or AI-based tools. Rare diseases complicate validation further due to limited patient populations, making it harder to generate the robust datasets needed for regulatory approval.

Data Privacy and Security Concerns: Digital tools often collect sensitive health data continuously. Ensuring compliance with privacy laws (like HIPAA or GDPR) and protecting against breaches is critical. Patients with rare diseases may be especially vulnerable to re-identification due to the uniqueness of their conditions. Many rare disease patients already face marginalization and may feel uneasy about the misuse or commercialization of their health information.
Accessibility and Digital Divide: Access to digital biomarker technologies is not evenly distributed. Patients in low-resource settings or underserved communities may lack access to smartphones, wearables, or reliable internet connectivity. Without careful planning, this digital divide could exacerbate existing healthcare disparities, especially within underrepresented rare disease populations.
Integration into Clinical Workflows: Healthcare systems are often fragmented and slow to integrate new technologies into routine care. Clinicians may not be trained to interpret digital biomarker data, and electronic health record systems may not yet support seamless integration. This limits the practical utility of digital tools in real-world settings.

Conclusion and Future Outlook

Digital biomarkers are rapidly emerging as transformative tools in the landscape of rare disease diagnosis and care. By enabling continuous, remote, and real-time health monitoring, they offer new ways to detect disease onset earlier, track progression more precisely, and tailor interventions more effectively, particularly in conditions that are historically difficult to diagnose or manage.

While challenges remain—especially around validation, equity, and regulatory clarity—the momentum is undeniable. Strategic collaborations between technology developers, regulatory bodies, clinicians, researchers, and rare disease communities will be key to advancing the safe and ethical use of digital biomarkers. Furthermore, incorporating the voices of patients and caregivers during design and deployment is essential to ensure that digital solutions are equitable, ethical, and aligned with real-world needs.

Looking ahead, the integration of AI, machine learning, and real-world data into digital biomarker development may further personalize care and reshape clinical trials by reducing patient burden and capturing more nuanced outcomes. As digital health continues to evolve, it is critical that rare disease patients and advocacy groups remain central to the conversation, ensuring these innovations are inclusive, ethical, and truly patient-centred.