FOCUS on policy.

The healthcare industry is rapidly evolving with treatments that aim to provide both personalized and targeted care while focusing on the patient as a key information source for decision making related to their treatment. These two initiatives, precision medicine and patient centricity, have largely developed simultaneously, albeit with dramatically different paths. Recent advancements in precision medicine are rooted in the physical sciences, e.g., biotechnology, which have developed molecular- and gene-based therapies, while patient centricity has been rooted in the social and administrative sciences, which evaluate how to optimize the delivery of care for the best potential outcomes. As these advancements have converged, the boundaries of what it means to be a pharmaceutical product or medical device have also evolved to include domains related to digital health technologies. These technologies provide value both as part of the treatment paradigm, as well as through the generation of real-world evidence (RWE), that can be studied to create further developments. The U.S. Food and Drug Administration (FDA) is at the forefront of these changes as the cornerstone of public trust in overseeing the safety, efficacy, and security of the nation’s pharmaceutical products and medical devices.

The FDA, with support from the federal legislature, has taken a proactive approach to manage these changes by establishing a framework for evaluating RWE and its subsequent incorporation into regulatory decision making. The 21st Century Cures Act (“Cures Act”) was enacted in December 2016 to facilitate the continued advancement of precision medicine and the discovery of medical cures, streamlining new drug product regulatory approvals, and expanding the use of digital medicine and social media for more efficient treatment delivery. Under the Cures Act, the FDA, through the Secretary of Health and Human Services, was required to establish a program to evaluate the potential use of RWE to support the approval of new indications for approved drug products, and to support or satisfy post-approval study requirements. The development of the FDA’s “Real World Evidence Program,” opens many avenues for using real-world data (RWD) to generate RWE for demonstrating clinical effectiveness to support regulatory decisions of new drug products, and label expansion of existing drug products.

Distinguishing between RWD and RWE is essential to understanding their benefits and limitations in generating actionable insights. RWD are those data related to a patient’s overall health and delivery of healthcare as presented outside of a randomized clinical trial (RCT). The sources of RWD are varied and include third-party payer medical claims, electronic health records (EHR), patient registries, patient-reported outcomes (PROs), and data from mobile and household devices. RWE is the clinical evidence generated from analyzing RWD. This evidence is used to inform clinical decision makers, healthcare users, and increasingly regulatory authorities, about healthcare trends, benefits, risks, and costs of a medical intervention or drug product.

While findings from RCTs have high internal validity, RCTs are typically designed to control variability and are comprised of a select group of patients who lack certain elements of diversity. The result is a sample population which represents a small proportion of patients with a specific disease state, selected by strict eligibility criteria based on their demographic and clinical profile. This limits the external validity in populations beyond those studied in the trial. Conversely, RWE embraces patient variability and can provide insights on routine clinical practices and healthcare delivery with studies that are more representative of the overall patient population. Other benefits of RWE studies include targeting of healthcare markets of interest, and reduced time and cost to bring a product to market compared to a traditional RCT. However, RWE studies do possess limitations such as the risk of selection bias, lack of standardization of data, incomplete or inaccurate data, and uncertain data quality. Therefore, to ensure that these risks are mitigated, careful consideration is warranted when selecting RWD for evaluation and designing RWE studies.

One of the most important elements of an optimized healthcare system is aligning treatment goals among the various stakeholders. While alignment between physicians, payers, and patients is not always easy to achieve, recent advancements in technology have provided patients with an unparalleled ability to actively participate in treatment decisions and maintain a share of control relative to managing their desired health outcomes. Today’s patients are more sophisticated than ever due to the availability of information surrounding disease states and treatment options that empower them to make more informed decisions about their own care. The result has been an increased interest in the adoption of patient-centric healthcare models and treatment regimens: those that highly prioritize the issues most pressing to the patient and address barriers related to the costs, quality, and access to care.

Quoting Dr. Gottlieb, the former Commissioner of the Food and Drug Administration, “Digital health tools have vast potential to improve our ability to accurately diagnose and treat diseases. And to enhance the delivery of healthcare for the individual, making medical care truly patient centric -- empowering the individual.” Digital health is a broad descriptor that ranges from the technologies which receive and transmit data to the medical devices themselves. In an effort to improve access and reduce the cost of bringing these innovations to market, the FDA has initiated new directives and policies utilizing RWD to generate RWE.

The FDA has issued guidance documents and industry publications to assist in the understanding of and expectations from pre- to post-market decisions in the development and implementation of digital health products. One of the more ambitious pieces, The Digital Health Innovation Action Plan, lays out the agency’s vision for fostering digital health innovation while continuing to protect and promote public health. This plan confirms that the FDA is focused on oversight of software applications and devices that present a high risk to patient safety and also maintains an interest in developing alternative regulatory approaches to low-risk products. One such alternative approach is seen with the Software Pre-Certification Pilot Program which will shift agency focus to approving trusted software developers as opposed to reviewing individual software applications. This strategy will allow quicker commercialization of digital health technologies while conserving limited agency resources. Over time, these approaches may reduce healthcare costs and increase access to new technology that is designed for patient-centric precision medicine.

The FDA’s recent initiatives surrounding RWE create both opportunities to spark innovation and new responsibilities to design studies and generate evidence, with the onus on the RWE research community to use reliable and relevant RWD. As new technologies that capture RWD are developed, new methodologies will be necessary to validate the insights derived from their use, while never losing sight of the patient as the primary stakeholder.