INFORMED: An Interview with Sean Khozin, MD, MPH

The Information Exchange and Data Transformation (INFORMED) initiative was launched by the U.S. Food and Drug Administration (FDA) and the Innovation, Design, Entrepreneurship and Action (IDEA) Lab of the U.S. Department of Health and Human Services. INFORMED is intended to promote the use of big data analytics to analyze the large and disparate clinical evidence now available to researchers and regulators. Sean Khozin, MD, MPH, Acting Associate Director, Oncology Regulatory Science and Informatics at the FDA’s Oncology Center of Excellence and a founder of INFORMED, discussed the details of the initiative for IASLC Lung Cancer News readers.

What are the goals of INFORMED?

The primary goal of INFORMED is to expand and maintain organizational and technical infrastructure for big data analytics. This is done by functioning as an incubator for conducting collaborative regulatory science research focused on supporting innovations that enhance FDA’s mission of promotion and protection of public health.

Organizationally, INFORMED is serving as a sandbox, where we’ve paired new talent such as entrepreneurs-in-residence, engineers, and data scientists with subject matter experts such as oncologists at the FDA. The synergy we’ve created among groups with complementary skill sets is quite unique and has been very productive. We’re also continuously building and expanding robust technical infrastructure through internal agile software development and pilots with the technology groups, such as Palantir, at the leading edge of big data aggregation and analytics.

How has the development of precision medicine changed the process of drug development in the field of oncology?

As we all know, precision medicine is defined as the right therapy delivered to the right patient at the right time and in the right dose. The idea of precision medicine is driving the healthcare and drug development industry from a population health outlook to a patient-centered approach: holistic and individualized, as opposed to reductionist and generalized. A holistic approach considers a variety of intrinsic (e.g., genomic and proteomic) and extrinsic (e.g., environmental) variables in making drug development and treatment decisions that are tailored to the individual, not an entire population of patients as defined by traditional diagnostic terms and traditional clinical trial designs. For example, in the past decade, we’ve recognized that not all non-small cell lung cancer (NSCLC) patients have the same kind of disease, as we discovered mutations and translocations such as EGFR and ALK that greatly influence response to therapy and outcomes. Some molecular aberrations in NSCLC, such as BRAF and ROS1, occur in less than 2% of patients and when combined with other intrinsic and extrinsic variables, we end up with very small cohorts and in some cases N of 1s.

Developing drugs and delivering care that is precisely tailored to small groups and individual patients requires fundamental changes in how we approach drug discovery, clinical evidence generation, and healthcare delivery. It requires us to capture and analyze big data sets from traditional (e.g., conventional clinical trials) and novel pipelines (e.g., realworld data and biometric sensors), using new study designs to better understand the patient’s experience in the context of a sustainable framework for precision delivery of therapies and healthcare services.

What types of organizations and researchers participate in INFORMED?

As an incubator, INFORMED conducts collaborative research with innovators in professional organizations, academia, nonprofits, and industry. For example, in the domain of real-world evidence generation, we have research collaborations with the American Society of Clinical Oncology’s CancerLinQ and a start-up called Flatiron Health. In the area of data sharing, we’re collaborating with a nonprofit called Project Data Sphere on open access data. We are also developing a framework for decentralized sharing of data at scale with IBM Watson Health based on blockchain, which allows users to access and add to a secure, shared ledger or spreadsheet of data. We’re also working with data science experts at MIT and Stanford on innovations based on artificial intelligence and algorithmic analytics that can help the drug development and the life sciences communities.

What is “systems thinking” and why is it emphasized in the INFORMED initiative

Systems thinking is a prerequisite for enabling precision medicine and, as a theoretical foundation, can be an optimal framework for making regulatory decisions. Traditional sciences are largely siloed into specific disciplines and not organically designed as multidisciplinary units. Progress in traditional sciences is characterized by intense specialization into specific disciplinary boundaries. In contrast, regulatory science, which is what INFORMED is all about, takes a systems science view of the world, where the focus is on networks and relationships, and where progress is best characterized by becoming more inclusive and holistic, as opposed to being specialized into narrowly defined fields. By quantifying networks and interconnected relationships, from the molecular level (e.g., systems biology) to the macro scale (e.g., market dynamics), systems thinking can allow for objective and data-driven regulatory decision-making in order to have the greatest positive impact on public health.

What should clinicians know about the INFORMED project?

INFORMED is a translational incubator at the intersection of data science, health tech, and the life sciences. The aim, however, is not technology for the sake of technology: we use advanced tools and methods to help diffuse innovations into the point of care by catalyzing the development and adoption of precision tools and therapeutics. Our systems view of the ecosystem is not about the system itself, but about enabling appropriate treatment decisions locally, where care is delivered. Therefore, empowering physicians and other healthcare providers is one of the focal points of our efforts, and we welcome and depend on their continued input and participation as the pillars of the healthcare delivery system.✦