The need to transform the clinical trial process to deliver more effective treatments to patients faster is greater than ever, and a key part of this transformation is a focus on putting the patient first. This patient-centric approach ensures that new treatments are not only effective but that they improve quality of life, enhance adherence to therapy, and ultimately achieve better health outcomes. At ActiGraph, we’re fortunate to have a front row seat to applications of wearable digital health technologies (DHTs) in many clinical trials, and it's inspiring to see how DHTs are creating new opportunities to include more patient-centric measures in clinical research.  

This is why we’re creating the Patient-Focused Digital Measures Library. With this new resource, we will provide actionable information for specific indications where there are relevant digital measures that correspond to the most significant symptoms reported by patients.  

By leveraging the comprehensive collection of patient-reported experiences from the FDA’s Patient-Focused Drug Development Initiative, we highlight opportunities for DHTs to provide a patient-centric measure for use in clinical research. We hope this information makes it easier (and compelling) for clinical development teams to include digital measures as they plan and execute their clinical trials. 

This library consists of a summary table and full indication-specific reports. The table will summarize by indication -  

• Most Significant Symptoms Reported by Patients (derived from the FDA condition specific meeting reports) 

• Meaningful Aspects of Health relevant to these symptoms, and 

• Candidate Digital Measures 

Each indication-specific Patient-Focused Digital Measure (PFDM) Report will include more detail around the reported symptoms, including how they manifest in the patients’ daily lives, and meaningful aspects of health related to those symptoms, and definitions for candidate digital measures that can track these symptoms. The reports are similar to those in our Digital Endpoint Resource Guide Series that are based on different therapeutic areas, but PFDM Reports are more specific to each indication. 

To introduce this new resource, we wanted to share more information on the evolving regulations and real-life case study that inspired us to create the library. 

Evolving Regulation: Patient-Focused Drug Development 

In the past, clinical trial endpoint selection did not directly factor in patient perspectives or primary complaints of living with their conditions. Treatments were being evaluated based on outcome measures that impact patient survival, but not necessarily how they feel or function in their daily life. 

The momentum shifted to specifically involve patient perspectives in the early 2010s, as part of overall efforts to accelerate medical product development and the launch of the FDA's Patient-Focused Drug Development (PFDD) Initiative. The rationale and activities of this initiative were described as part of the Prescription Drug User Fee Act Reauthorization VI (PDUFA VI) in 2017, when the agency shared that meeting with patients and advocacy groups had helped the FDA to better understand diseases, and this directly supports their goal of developing more effective and meaningful treatments.  

The FDA's emphasis on PFDD has been outlined in several guidance documents, the fourth and final one being released in April 2023. The PFDD initiative includes a commitment to hold public meetings each year to -  

• capture information about how diseases impact patients’ and caregivers’ lives,  

• to hear about what treatment benefits would be most meaningful to patients, and 

• to hear what treatment burdens are most important to consider. 

Condition-specific reports based on these meetings are published and available on the FDA website. The list contains almost 200 conditions with open access links to meeting reports and related information.  

Evolving Regulation: Digital Health Technology

In clinical development, the efficacy of a treatment is demonstrated based on the clinical outcome assessments (COAs) collected during clinical trials. Most of these COAs were developed decades ago, and they have changed very little since then despite known limitations in measurement precision. However, patient-centered COAs remain essential, and there is growing momentum for regulatory acceptance of digital measures as endpoints in clinical trials. Digital measures can overcome certain limitations of traditional COAs to provide continuous, objective measures of real-world patient behavior.  Regulatory agencies have recognized the potential of DHTs to capture richer information on patient functioning, enhance patient-centricity with low-burden technology, and collect measures that inform meaningful aspects of health.  

In December 2021, the FDA published draft guidance for using DHTs to collect data in clinical trials and was followed by publication of the final guidance in December 2023, "Digital Health Technologies for Remote Data Aquisition in Clinical Investigations.” The guidance outlines recommendations to facilitate DHT use in clinical trials and discusses the potential benefits of DHTs, which include providing a broader picture of how participants feel or function in their daily lives. 

Case Study: Innovating with Regulators to Leverage DHT Data as Patient Centric Trial Endpoints

The importance of incorporating the patient voice into a clinical development program and the ability to do so with digital measures is illustrated by Bellerophon Therapeutics. Bellerophon was investigating the treatment effect on inhaled nitric oxide in patients with Idiopathic Pulmonary Fibrosis (IPF) with risk of pulmonary hypertension, a fibrotic interstitial lung disease associated with reduced life expectancy and impaired functional capability.  

Bellerophon saw an opportunity to improve the clinical endpoints used in these types of trials, and CEO Peter Fernandes shared the approach Bellerophon took to obtain a new, patient-centric, DHT-based regulatory endpoint in a recent webinar. Previous trials used endpoints like time to clinical worsening and mortality/morbidity. These types of endpoints evaluate if a patient will live longer, but will they suffer during that time? How can we know if we are improving their quality of life during that time? 

Applying the PFDD Report 

Peter described how they wanted to align with the FDA PFDD Initiative’s focus to learn more about what’s meaningful to the patient and incorporate this information into how they evaluate therapies. In the PFDD Voice of the Patient Report for IPF, patients, caregivers and family identified daily physical activity as having the greatest impact on patients' lives, as activities like walking or climbing stairs triggered severe coughing and intense episodes of shortness of breath.

Here are a few excerpts from the Report: 

The most frequently mentioned impact on daily life was the decrease of physical function. This included struggling to perform basic activities such as walking up stairs, showering, housework, and other everyday tasks. One participant explained, “It's difficult to keep my house clean … I get very tired, so it's sweep the floor, sit down and rest for a long time.” 

Many described how physical activity, including walking and climbing stairs, exercise, hobbies, and household tasks, were a struggle due to IPF symptoms. “[My cough] comes with exertion … walking up a flight of stairs … putting your clothes on, bending over and tying your shoes, fixing something in the kitchen, moving around.” 

Using a Digital Measure 

In their Phase 2 trial, Bellerophon included an actigraphy-based measure of time spent in moderate-to-vigorous physical activity (MVPA) as an exploratory endpoint. They reported a 14.6 minute per day decline in MVPA in the placebo group over 16 weeks. Peter stressed how significant a loss of 14 active minutes a day is for patients with a survival of 2 – 3 years. Overall, there was a 21% difference in the time spent in MVPA in the treated group compared to placebo, which can be considered a clinically relevant change in cardiopulmonary disease populations. 

Across many meetings and correspondence with the FDA, Bellerophon innovated with regulators and received approval to use a new endpoint, MVPA measured by actigraphy, in their phase 3 pivotal trial that began in 2020 (listen to Peter Fernandes tell the story here).  

The FDA acceptance of a primary digital endpoint for the first time in a phase 3 pivotal study is reflective of regulators being open to the value digital measures can add to clinical research, and their focus to measure an aspect of health that’s meaningful to the patient.  

We are excited to share the Patient-Focused Digital Measure Library, and hope that it can help support the goal of better incorporating the patient's voice into the drug development process.