By Sandeep Menon, SVP and head of Early Clinical Development (ECD), Pfizer Inc.
When we take a moment to reflect on it, it’s remarkable how much our engagement with technology has evolved. Just a decade ago, smartphones came into existence, and they didn’t have a fraction of the functionality they have today. Motion trackers were still just an idea. Yet today these technologies are integral to how we work, travel, shop, dine, exercise, spend, save, and even date.
Motion trackers are even changing how we develop medicines. In Pfizer’s Early Clinical Development – Digital Medicine and Translational Imaging (DMTI) team, we are using mobile technology to make clinical development more relevant to patients’ actual experiences of living with chronic diseases. Atopic dermatitis (AD), or eczema, is one such condition. It causes intense itching, which often flares during sleep. People with AD wake up and know they have been scratching. But how often? For how long? When they wake up from a night when they scratched 10 times, does that feel different from a night when they scratched 50 times?
Our DMTI team works to gather the evidence that answers questions like these. One of our most powerful tools is a dedicated space in our Kendall Square, Cambridge site, called the Pfizer Innovation Research (PfIRe) Lab. This is where we find ways to use mobile and movement-tracking technologies to collect data in the real world. Our team of data scientists, clinicians, engineers, mathematicians, and statisticians work with internal and external partners to integrate technology into clinical trials, so we can gather robust data on how patients experience disease outside of a clinical setting.
Sending The Lab Out Into The World
AD is an important focus for Pfizer’s Immunology & Inflammation Research Unit, which researches treatments for immune-mediated conditions in gastroenterology, rheumatology, and dermatology; they were the ones who asked our team to find a way to quantify how chronic skin conditions affect sleep.
Traditionally, research like this involves asking patients to complete surveys or maintain journals, even though we know these are imperfect ways to create a record of changes in symptoms over time. Memories of symptoms and experiences are colored by recall bias, calling the accuracy of the data into question. Plus, the surveys can be cumbersome for patients. Not only do they add to the burden of the disease, but for a person who is already anxious about health and their treatment, the questioning can sometimes feel like an interrogation.
We were challenged to solve the following problem: can commercially available wearable accelerometers — basic, off-the-shelf motion trackers — measure and quantify wrist and arm movements to quantify scratching behavior and disruption to sleep?
The University of Rochester Medical Center’s departments of dermatology and psychiatry, along with its Center for Health and Technology, were the perfect partners for us as we embarked on this journey — our collaboration gave us access to experts in both sleep medicine and dermatology, in addition to experience in the use of digital technologies. We set up a sleep lab with monitors to confirm when patients were fully asleep and video cameras so that members of our research teams could remotely observe activity. We then expanded the initiative to include Boston University, where experts in dermatology and sleep medicine collaborated with us to identify the movements we observed, because it was essential to understand the difference between scratching and other unrelated fidgeting. Taken together, these observations allowed us to calibrate our tracking system and document the motions that indicate scratching. Now we can send patients home with just the wearable motion tracker, which will give us data that our algorithm can correlate to incidence, frequency, and duration of scratching during sleep.
The partnership between the DMTI team and Pfizer’s Immunology & Inflammation team helps bridge the clinical lab and real-world environments, so that clinical development can be focused on objectives that will make the most day-to-day difference for patients. We can now design clinical trials with endpoints that weren’t so easily accessible before. We’re not limited to measuring in a lab. We’re measuring in the real world where patients actually live their lives.
Adding Dimensions To Our Observations
We know from work in other conditions that lab measurements are not always reflective of what happens in daily life. For example, when clinical studies measure patients’ gaits in a lab setting, even when trying to establish a baseline for measuring improvement, patients, feeling self-conscious, make a point of doing their best. It’s just human nature; the way we walk when scientists are watching probably isn’t going to be the same way we walk to the kitchen to make our tea. We know because we have used motion trackers to reveal that patients walk more quickly — and better — when they know they are being observed.
We can also devise digital measurements with the sensitivity to complement a physician’s expertise and training with a degree of precision that has never been possible before. For example, physicians have been diagnosing liver conditions by hand for hundreds of years – there are even records from ancient Greece about doctors using palpation to assess the firmness of internal organs. The stiffness of the liver can indicate when a patient has non-alcoholic steatohepatitis, or NASH, a condition that can advance to a severe stage before symptoms are present. A biopsy can be used in diagnosis, but it’s painful, invasive, and only provides information about a small sample of the liver, so physicians still rely on palpation as well for a more complete picture.
DMTI is working to give that process a 21st century upgrade, employing 3D imaging techniques we are testing in conjunction with researchers at the University of Wisconsin and the University of California at San Diego. A small external paddle called an acoustic driver placed on the abdomen can send sound waves through the body, from which an MRI can estimate liver stiffness, which is a surrogate marker of fibrosis or scarring. Ongoing research is evaluating the ability of this technology to measure other drivers in chronic liver disease such as inflammation. Currently, the fibrosis score derived from this technology helps guide management in patients at risk for or with chronic liver disease.
Driving Smarter Drug Development
Whether we are using technology for more accurate real-world measurements or more minute perceptions inside the body, we can use that data to design trial endpoints reflecting the real impact of treatment. Sharing our validated data with regulators helps them become familiar with these advanced tools and the evidence that they can generate in clinical trials.
Augmenting subjective information with validated data helps us understand disease more completely and design treatments more precisely. Counting the exact number of times someone is scratching their skin during sleep yields valuable information. Connecting that measurement with how the patient feels after a night of more or less intense scratching uncovers invaluable insight. We can use those insights to more thoughtfully develop medicines that can change lives.
Special thanks to Tim McCarthy, Carrie Northcott, Shyamal Patel, James Goodman, and Theresa Tuthill for both their diligent collaboration in the PfIRe Lab’s work and their contributions to this article.
About The Author:
Sandeep Menon works to advance Pfizer’s clinical development portfolio with scientific rigor, quantitative decision-making, innovation, and operational excellence. As senior VP and head of Early Clinical Development, he oversees the PfIRe Lab and leads a global team of experts in clinical study execution, biostatistics and bioinformatics, clinical pharmacology, precision medicine, digital medicine and translational imaging (DMTI), and early scientific planning and operations. He also sits on Pfizer’s Worldwide Research, Development and Medical Leadership Team. His passion for discovery is matched only by his enthusiasm for sharing discoveries through his adjunct faculty positions at universities in the U.S. and India.