Industry spotlight
PUBLICATION
“Digital biomarkers have the potential to profoundly impact drug development. Digital biomarker‐enabling technologies give pharmaceutical researchers access to more continuous, objective data sets that were previously not attainable, including outside the clinic and during activities that are more meaningful to patients daily lives. They offer the promise of earlier, more sensitive, and less variable indicators of safety and efficacy, which may result in smaller, shorter duration clinical trials and faster go/no go decisions. Additionally, in late‐stage development, digital biomarkers have the potential to be used not only for internal decision making but as primary or secondary registration end points and in support of label claims.”
“Benefits to the researcher:
• Increased access and retention of patients
• More efficient and faster trial enrollment
• Increased confidence and improved medication adherence
• Augmented data sets and access to data in-between visits
• Reduced unexplained variability in data
• Improved understanding of drug and disease effect
• More rapid and informed clinical decisions• Potential for reduced sample size and earlier study readout
• Access to patient-relevant endpoints”
“Benefits to the patient:
• Increased access to trials
• Reduced patient and caregiver burden
• Reduced frequency of site visits
• Less painful sample collection
• Increased engagement and communication with the clinical trial site
• Increased precision medicine
• Patient-relevant endpoints
• Improved medication adherence and study compliance”
PUBLICATION
“…digital health technologies provide the research community with new tools that can greatly enhance the clinical trial enterprise, including the opportunity to run trials liberated from the anchor of “brick and mortar” research centers. A fully digital trial will enable access for potential participants regardless of where they live or work. For investigators, this means more efficient and real-time remote monitoring and multiple opportunities for interactive patient management and assessment (passive and active), which means that more intensive work can be done with budgets that may not require greater resources. This also means investigators can investigate traditionally collected endpoints alongside more novel endpoints—ones that can be captured in an automated fashion and over extended periods. Doing so has the potential to reduce the burden on both research teams and on study participants.”
PUBLICATION
“Digital health technologies (DHTs) offer the ability to capture data remotely, continuously, and with low patient burden. As such, DHTs are paving the way for the development of a new class of clinical outcome assessments (COAs) that reflect how patients feel, function, and survive in real-world environments. Many believe the evidence generated from DHTs provides an opportunity for a more holistic and direct understanding of the patient experience and consequently, there has been a significant investment into developing new DHT-derived outcome measures. Initial efforts were technology-driven and centered around expanding the limits of what can be measured. However, following the overall trend in the industry for a more patient-centric approach to drug development, there is an increased focus on understanding what should be measured with DHTs.”
PUBLICATION
“DHTs allow for quantitative and objective measurements of meaningful aspects of health, including symptoms of disease, that were not able to be measured previously, resulting in novel endpoints. Furthermore, DHTs can be designed to interfere minimally with patients’ daily lives and enable remote data acquisition outside the traditional clinical setting. Measurements obtained by DHTs have the potential to assess relevant aspects of disease in a less biased, patient-centric manner with ecological validity. Furthermore, potentially, these novel digital endpoints can identify early efficiency in clinical trials. The use of DHTs can facilitate decentralization of clinical trials, enabling clinical sites to recruit patients independent of location, creating more patient-centric trials, boost recruitment, especially in rare disease trials, as well as promote diversity and equity in clinical.”
PUBLICATION
“The use of DHTs in clinical trials offers several potential advantages by providing richer data sets (e.g., continuous data collection in participant’s home environment vs. snapshots/episodic recordings during clinical visits) or performing objective measurements without recall bias that flaws Patient Reported Outcomes, leading to a better understanding of the efficacy and safety of the interventions studied.
Via remote data acquisition, DHTs can also decrease the number of clinical trial sites and follow-up visits and potentially increase diversity and inclusivity in clinical trials. For these and other advantageous reasons, we have seen the use of DHTs in clinical studies increase significantly over the years.”
PUBLICATION
“By moving beyond ‘‘snapshots’’ of a disease status – at intervals defined by study protocols – and towards more continuous measurement of outcomes of interest, DHT can paint a clear picture of disease behavior and hold promise for early event and rare event detection. DHT can be used to collect multiple data types with complex characteristics, and may include information from physiological, behavioral, functional, or psychological domains. The depth, breadth, accuracy, and relevance of DHT-generated data will be key to conducting decentralized trials in which data are captured from individuals in their home environments, thereby minimizing, and sometimes obviating, the need for any visits to research sites.”
Digitally Enabled, Patient-Centric Clinical Trials: Shifting the Drug Development Paradigm
1. Challenges related to patient privacy and lack of sufficient validation for digital endpoints.
2. Lack of transparency in endpoint calculations and operational challenges.
3. Added complexities due to software version changes and regulatory unknowns.
Recommendations
1. Increase patient-centricity and reduce patient burden through digital health technologies.
2. Foster collaboration among pharmaceutical companies, regulators, academia, and technology companies.
3. Embrace innovation and ensure senior leadership support for digital health initiatives.
4. Utilize real-time data access to enrich clinical trial data sets.
5. Implement outpatient sampling to augment decision-making processes.
Regulatory Considerations
1. Request feedback from regulatory agencies as part of the development plan for outpatient sampling.
2. Consider the FDA’s guidance on bioanalytical method validation for dried blood sampling.
3. Note examples of regulatory acceptance of digital biomarkers as primary or secondary endpoints.
Some summaries are generated with the help of a large language model; always view the linked primary source of a resource you are interested in.
Digitizing clinical trials
Operational inefficiencies in participant recruitment and data acquisition inflate costs and extend timelines.
Disparities in access to research due to geographic and mobility constraints limit participant diversity.
Many digital biomarkers require further validation for use in clinical trials.
Heightened need for security measures to protect against data breaches in digital trials.
Opportunities exist to improve clinical trials using real-world data from EHRs and IoT technologies.
Recommendations
Leverage existing technologies and research platforms to transform clinical trials.
Develop partnerships with technology and computational communities.
Create standard protocol templates for automation in recruitment, retention, and data collection.
Develop validation models for new devices and analyses using existing trials.
Invest in the next generation workforce in medicine, technology, and clinical research.
Regulatory Considerations
Address data privacy and security concerns in digital trials.
Provide guidance for IRBs on consenting requirements, reporting, and oversight in digital trials.
Develop empirical research on the risks and benefits of digital trials.
Educate IRBs on digital technology and its implications for clinical trials.
Some summaries are generated with the help of a large language model; always view the linked primary source of a resource you are interested in.
Patient-centricity in digital measure development: co-evolution of best practice and regulatory guidance
Only a small number of novel digital measures have matured into regulatory qualification or efficacy endpoints.
Demonstrating that digital measures are meaningful to patients is a key challenge.
There is resistance from sponsors due to uncertainty about the value of DHT-derived endpoints in regulatory discussions.
Patient experiences are highly heterogeneous, making it difficult to generalize meaningful aspects of health.
Challenges exist in defining clinical significance and classifying digital measures as COAs vs biomarkers.
Recommendations
Engage patients and caregivers in facilitated discussions to incorporate their voices.
Determine the best method for gathering patient input on a case-by-case basis.
Engage patients to inform evidence needs, implementation, and value delivery.
Return summarized health data to participants to motivate and encourage communication with clinicians.
Regulatory Considerations
Understand the FDA’s recent guidance on patient engagement in drug development.
Recognize the shift in evidence rigor required by the FDA for demonstrating meaningfulness.
Provide evidence that DHTs are usable, acceptable, and clinically relevant.
Utilize early engagement channels like CPIM and pre-LOI programs offered by the FDA.
Some summaries are generated with the help of a large language model; always view the linked primary source of a resource you are interested in.
Why Language Matters in Digital Endpoint Development: Harmonized Terminology as a Key Prerequisite for Evidence Generation
There is a lack of alignment in concepts, definitions, and terminology related to digital health technologies, which hinders global drug development programs.
Different regulatory agencies interpret common terms like “monitoring” differently, leading to confusion and inconsistency.
The classification of digital measures impacts evidentiary requirements and regulatory acceptance, but detailed guidance on these requirements is lacking.
Recommendations
Align terminology and definitions across stakeholders to ensure consistency in understanding and communication.
Reuse existing terms where possible to avoid unnecessary complexity.
Focus on what is measured rather than how it is measured to streamline regulatory processes.
Encourage companies and regulators to reflect on and adopt a common lexicon within their organizations.
Move quickly to address critical questions about evidence needed for validation of digital measures.
Regulatory Considerations
Regulatory authorities should apply consistent standards for all endpoints, regardless of data acquisition methods.
The classification of DHTs as medical devices or not will impact their regulatory pathway and requirements.
There is a need for dialogue with regulators to clarify source data requirements for data acquired by DHTs.
Some summaries are generated with the help of a large language model; always view the linked primary source of a resource you are interested in.
Regulatory considerations for successful implementation of digital endpoints in clinical trials for drug development
Regulatory Acceptance is Complex: Gaining regulatory acceptance for endpoints derived from Digital Health Technologies (DHTs) is a lengthy, multifaceted, and costly process that requires a global strategy and early health authority consultation.
“Fit-for-Purpose” is Key: A DHT’s clearance or approval as a medical device does not automatically ensure it is fit-for-purpose in a clinical trial; its intended use must align with the specific context of use (COU) in the study.
Meaningfulness is a Hurdle: Demonstrating the clinical meaningfulness of novel digital endpoints, especially for abstract concepts like cognitive decline in Alzheimer’s Disease, remains a significant challenge for regulatory acceptance.
International Harmonization is Lacking: Differences in regulatory requirements for DHT validation between major health authorities can delay or prevent the successful implementation of digital measures in global clinical trials.
Technology Changes Pose Risks: Software and hardware updates to DHTs during a clinical trial can have significant implications, potentially invalidating study results if not managed through a predetermined change-control plan.
Recommendations
Engage Health Authorities Early and Often: Sponsors should conduct multiple consultations with major health authorities (e.g., FDA, EMA) early in the development process to align on the Concept of Interest (COI), COU, and the validation roadmap.
Develop a Comprehensive Regulatory Strategy: A global regulatory strategy should be an integral part of the overall development plan, tailored to the program’s objectives and endpoint hierarchy.
Establish “Fit-for-Purpose” Criteria: Before selecting a DHT, sponsors should establish the minimum technical and performance specifications required for the specific COU to guide the selection of a fit-for-purpose device.
Create a Conceptual Framework: For novel endpoints, sponsors should develop a conceptual framework that visualizes how the DHT-derived measure relates to meaningful health concepts and patient experiences.
Plan for Change and Missing Data: Sponsors should establish predetermined change-control plans with manufacturers to manage DHT updates and create risk management plans to minimize and handle missing data from remote acquisition.
Regulatory Considerations
Distinct Pathways in US vs. EU: The US FDA uses a risk-based approach for DHTs that are medical devices, while in Europe, CE marking for the intended COU is generally expected by the EMA.
Qualification is an Option, Not a Requirement: Both the FDA and EMA offer voluntary qualification programs for Drug Development Tools (DDTs), which can validate a DHT for a specific COU across multiple drug programs, though the process is resource-intensive.
Scientific Advice for Individual Programs: For DHTs used within a single drug development program, engaging with health authorities through scientific advice meetings is a more targeted and confidential pathway for gaining feedback and agreement.
Data Privacy and Security are Paramount: Sponsors must ensure that the collection, transfer, and storage of personal data via DHTs comply with all applicable regulations, such as GDPR in the EU, including cybersecurity and data transfer measures.
Some summaries are generated with the help of a large language model; always view the linked primary source of a resource you are interested in.
Digital outcome measures in pulmonary clinical trials
The need for rigorous verification and validation of DHT-generated measurements before they can be relied upon for safety, efficacy, or effectiveness.
The risk of widening health inequities due to disparities in access to healthcare and technology.
Challenges in ensuring data quality, privacy, and security.
The necessity for improved interoperability to facilitate data sharing.
The requirement for developing AI and machine learning algorithms for real-time data evaluation.
Recommendations
Improve the reach and effectiveness of DHTs, particularly among marginalized groups.
Develop and validate AI and machine learning algorithms for real-time evaluation of DHT data.
Ensure systematic protections for data privacy and security.
Enhance interoperability to unlock the full potential of DHTs.
Engage with stakeholders, including patients, to create efficient pathways for DHT adoption.
Regulatory Considerations
Compliance with rapidly changing digital health policies.
Utilization of FDA guidance documents and tools for understanding digital health regulations.
Consideration of regulatory oversight as DHTs become more integral to clinical trial design.
Some summaries are generated with the help of a large language model; always view the linked primary source of a resource you are interested in.
example
Patient advocacy groups are producing guidance on meaningful outcomes. For instance, UsAgainstAlzheimer’s has published research on outcomes that matter most to patients and caregivers in Alzheimer’s disease, such as emotional wellbeing and daily functional abilities. These community-driven findings can inform what digital endpoints to pursue in those disease areas
For reference: review the relevant regulatory guidances
Regulatory spotlight
Features essential guidance, publications, and communications from regulatory bodies relevant to this section. Use these resources to inform your regulatory strategy and ensure compliance.