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What are the differences between traditional and digital biomarkers?
The term “biomarker” is an abbreviation of “biological marker” which has existed since 1980. This is a marker of a biological process which can be normal, pathological, or as a response to therapy or exposure according to the definition by the FDA-NIH working group.[cite:fda-nih-biomarker-def] This is a measurement done objectively by means of, for example, laboratory instrumentation, in vivo imaging techniques, or electrophysiological methods. The biomarker identity often includes the biomarker type (e.g., molecular, histologic, radiographic, digital, or physiologic). Digital biomarker refers to the method of data acquisition that can be achieved via various forms of digital health technologies (DHTs) and may include wearable sensors, smartphones, and other types of technologies.
What advantages / benefits are there of digital biomarkers, and how can digital biomarkers revolutionize clinical trial design and process?
Digital biomarkers are aiming to address the shortcomings of current clinical trial outcome assessments which often represent snapshots in time, are prone to high variability, depend on patient motivation at the exact time of assessment, and do not reflect what is happening to patients in their natural environment. Additionally, the requirements for regular in-clinic assessments represent a burden for patients and limit participation in clinical trials. Designing and developing digital biomarkers offers an opportunity to address these challenges by providing frequent or semicontinuous monitoring of patients in the work and home settings by means of DHT. These measures may constitute digital biomarkers or eCOA, can be deployed conveniently for patients, and may provide novel datasets complementary to in-clinic assessments. The findings from DHT-enabled measures may have a significant impact on the outcome of clinical trials by reducing the sample size,[cite:huang-fev1-asthma] measure objectively signs and symptoms,[cite:lipsmeier-roche-pd] and understand better disease features and subtypes. Additionally, the emerging data indicate potential in improved and augmented healthcare delivery.
What is the role of digital biomarkers in expediting the drug development process?
Digital biomarkers have multiple applications in drug development which may vary depending on the phase of drug development. In early-stage development, these tools can be useful as safety monitoring,[cite:izmailova-wearable-heart-rate] pharmacodynamic assessments,[cite:huang-inhouse-mobile-health] (e.g., at-home blood pressure monitoring for hypertensive therapies), and early proof of concept studies aimed at establishing an efficacy signal in small clinical trials.[cite:huang-fev1-asthma] Moreover, digital biomarkers have the potential to increase the confidence in POC by measuring clinically meaningful endpoints objectively. For example, daily step count is a prognostic factor for survival in locally advanced lung cancer and a dynamic predictor of short-term hospitalizations in cancer patients undergoing chemoradiotherapy.[cite:izmailova-step-counts-oncology] For late-stage clinical trials, the biggest potential is the ability to capture objective efficacy data related to functional, physiological, or cognitive ability. Moreover, the remote nature of digital data collection can improve clinical trial accessibility, at the same time offering near real-time data for review by the medical staff. Furthermore, remote deployment of digital biomarkers makes it possible to collect the data in a natural environment, complementing standard physician assessments done during clinic visits, which can lead to a reduced sample size and/or shorter trial duration for registration studies.[cite:mori-moneyball-digital-biomarkers]
What is the FDA guidance to support novel biomarker qualification?
FDA Biomarker Qualification: Evidentiary Framework[cite:fda-biomarker-qualification-framework] guidance is a result of a multiyear precompetitive collaboration between the agency, public-private partnership consortium (FNIH), and the industry to create comprehensive requirements for qualifying novel biomarkers. This approach is agnostic to the measurement method and covers all biomarkers.
It is still important to note other regulatory documents that are pertinent to DHT-derived measures acquired in clinical trials, such as the latest FDA guidance on remote data acquisition[cite:fda-digital-health-remote-data] and the EMA’s outlook on digital technology-based methodologies that support the approval of medicinal products.[cite:ema-digital-technology-qualification]
Most pharmaceutical companies depend on technology development partners to implement digital biomarkers in clinical trials. How is Koneksa making these partnerships a success?
In the case of more traditional biomarker methods, for example based on laboratory methods, development and validation of biomarker assays done in laboratories is an internal biopharma activity as it is leveraging laboratory expertise, core to drug discovery, and development. However, DHTs and digital biomarkers are different in this regard. Successful deployment of DHT-derived measures requires in-depth knowledge of DHTs, a platform enabling data collection and integration, data analytics, and statistical analysis tailored to the specific nature of a measure of interest. This infrastructure takes place often in conjunction with data processing algorithms and development which traditionally resided outside of biopharma R&D. Koneksa provides a full capability platform and experienced staff that can effectively partner with pharma companies to make digital biomarker data collection happen in clinical trials.
What is unique about Koneksa as a company and its service offerings?
Koneksa provides a unique integrated solution that includes:
- in-depth expertise in biomarker development and validation
- full integration into clinical study protocols and procedures. Our device agnostic data integration platform offers complete adaptability, and our extensive experience in evaluating and developing algorithms yields optimal data capture and robust analysis backed by our proven experience with trial success.
How does the Koneksa platform enable a better picture of patient data?
Koneksa can improve patient generated data collection in multiple ways. Our ability to integrate different devices provides an opportunity for capturing different modalities of data including wearable sensors, patient questionnaires/ePRO, and digitally instrumented assessments. These datapoints are integrated in a single platform enhanced by a dashboard which allows data visualization for sponsors and sites to monitor data collection adherence and view trends over time. Our data processing algorithms provide a unique opportunity to capture data from multiple sensors and provide insights into patient physiology, disease characteristics, and function.
How is Koneksa evaluating and validating digital biomarkers for research use?
Our approach starts with a thorough evaluation of the technology landscape, in order to identify digital health technologies capable of capturing the measure(s) of interest. We then follow a rigorous internal assessment process in which candidate technologies are evaluated in terms of sensor performance, usability, analytical validation, and clinical validation evidence. Throughout this process, we follow community best practices such as the V3/V3+ framework [cite:goldsack-v3-biomets] and regulatory guidance [cite:fda-biomarker-qualification-framework],[cite:fda-digital-health-remote-data], to ensure identification of technologies that are fit-for-purpose within the proposed context of use.
How are digital biomarkers validated?
A reliable, clinically meaningful digital biomarker must be proven accurate and meaningful through both analytical and clinical validation [cite:pmc-article-8077605].
- Analytical validation determines whether the digital technology reliably measures its target outcome with accuracy, precision, and consistency of data, ensuring replicability, particularly against gold standards, and a clean signal.
- Clinical validation demonstrates whether the digital biomarker provides clinically meaningful insights into the health outcome of interest in people.
Both types of validation must be met in order for a digital biomarker to be considered “fit-for-purpose,” confirming that it produces clear, stable signals that are consistently representative of real-world patient outcomes [cite:pmc-article-8077605].
How do Digital Biomarkers Differ from Wearables, Digital Endpoints, or ePRO?
Although these concepts can complement each other to improve clinical research results, digital biomarkers are not the same as wearables or smart technology, digital trial endpoints, or electronic patient-reported outcomes (ePROs). Digital biomarkers are a type of measurement strategy, whereas wearables or smart technologies are tools [cite:pmc-article-11147994]. Data collected by these tools can only be considered digital biomarkers once they are analytically and clinically validated, representing a clear clinical outcome. Similarly, in clinical trials, a digital endpoint is the outcome for which data from digital biomarker measurements are used to test the study’s hypothesis [cite:nature-article-d41573]. Lastly, ePROs capture self-reported patient health and experiences directly via digital devices over the duration of a trial, whereas digital biomarker measurements are sensor-derived [cite:clinion-epro-guide].
