For Julian Summers, it was a long time coming. For his brother John it was too late: he had passed away a year ago, succumbing to Alstrom Syndrome. What could have been done to save him?
In December 2018, the FDA published a Framework for its Real-World Evidence (RWE) Program. Among other matters, the Framework provides guidance to assist researchers interested in using real-world data (RWD) to develop RWE to support FDA regulatory decisions. The Framework applies to both drugs and biologics products. It defines RWD as “data relating to patient health status and/or the delivery of health care routinely collected from a variety of sources”; RWE is defined as “the clinical evidence about the usage and potential benefits or risks of a medical product derived from analysis of RWD”. With personalized medicine, both John and Julian could have been diagnosed earlier. While there is currently no treatment for Alstrom Syndrome, many of its potentially fatal symptoms can be managed better if people know the cause.
Alstrom Syndrome is typical of many rare diseases, in that it often takes years for a patient to get a diagnosis and this delay allows the symptoms to proceed unchecked. Sadly, like most rare diseases, there is not yet a treatment or cure. RWE provides not only a route to aid diagnosis, but provides information about the course of the disease that is useful for researchers and pharmaceutical companies. Properly collected and curated, RWE offers more information and insights around causes and treatments, even a cure, for rare medical conditions. The FDA has taken a significant step with its announcement of a framework for RWE, enabling both clinical researchers and commercial entities to focus on the collection of this vital information.
A key component of the Framework is the use by the FDA of RWE/RWD to support regulatory decisions about drug effectiveness, as opposed to its current use of RWD primarily to evaluate drug product safety. In other words, the FDA is trying to shift the emphasis from “how safe is this drug?” to “how well does this drug work?” To do so, the FDA also recognizes the necessity of developing common data standards to maximize the utility of RWD; merely because information is stored in a database does not mean that the data is meaningful. Sources of data such as patient registries need to be curated to ensure that the data is valid so that what is captured is a good source of RWD that can then be used to generate RWE. As noted in the Introduction, the FDA has, in part, created the Framework to implement its mandate under the 21st Century Cures Act which was “designed to accelerate medical product development and bring new innovations and advances faster and more efficiently to the patients who need them.” Pioneering efforts using RWE/RWD have already demonstrated the effectiveness of this approach.
The Framework’s themes of “real”, “reliable”, and “relevant” can be achieved. There are already numerous examples of well-curated RWD, providing RWE in several current and successful collaborative rare-disease research efforts. These groups work together to accelerate medical product development and have brought new innovations and advances faster and more efficiently to patients who need them most: those who suffer from rare diseases, such as Castleman’s, LMGD2, and CDKL5 and melanoma, lung, and breast cancers.
Traditionally, advances in the clinical study of disease etiology and treatment in these areas have been hampered by lack of collaboration, incentive misalignment and the selection of research studies based on an individual’s area of expertise and/or interest. These approaches did not tend to prioritize the research questions that need to be asked and answered to advance knowledge of a given disease and its treatment and/or cure. Patient numbers are small so that global reach is required. Key to addressing these challenges is the development of a patient registry that can manage data from diverse inputs, including patient-reported outcomes (PROs). These patient-reported data can support clinical trial recruitment, accelerate treatment outcomes for patients, provide information to payers to support their decision-making processes, inform clinicians who need to decide of a particular treatment will be effective for their patient and to pharmaceutical companies to identify the most promising areas of drug development.
It is apparent that a number of the rare disease and cancer research challenges are similar to those that must be overcome before we as a society can transition from a disease/population-based model of healthcare to a patient/person-based model (i.e. “personalized medicine”). Advances in technology and genetics enable a personalized approach; the recognition that medical treatments designed for the “average patient” can be successful for some patients but not for others is a driver for change. Moreover, not only may some treatments be ineffective, they may be harmful to certain groups of individuals. RWE can proactively identify the characteristics of those patients who will benefit most from treatments while experiencing the least adverse effects.
Using the FDA’s RWE Framework, successful solutions can be implemented to achieve the present and future vision of personalized medicine — “the right medicine to the right person at the right dose at the right time”.
 Canadian Institutes of Health Research, and Institute Affairs. “Personalized Medicine”. Canadian Institutes of Health Research, Government of Canada, March 24, 2017. http://www.cihr-irsc.gc.ca/e/43627.html