The US Food and Drug Administration and Cardiovascular Medicine
Reflections and Observations
The US Food and Drug Administration (FDA) is a remarkable hybrid. Part regulatory agency, part public health agency, it sits at the intersection of science, law, and public policy. The FDA’s mission can be considered in the context of 2 broad dimensions: the products it regulates and its core functions. Both fall under the rubric of protecting and promoting the public health.
The FDA’s remit is both broad and diverse: altogether, the agency has regulatory responsibility for >20% of the US economy. The products it is charged with overseeing through its various centers1 encompass food and cosmetics (regulated by the Center for Food Safety and Applied Nutrition); food and drugs for animals, including companion animals and animals used for food (regulated by the Center for Veterinary Medicine); and medical devices, drugs, and biologics (regulated by the Centers for Devices and Radiological Health, Drug Evaluation and Research, and Biologics Evaluation and Research, respectively). Tobacco products were added to the FDA’s portfolio by the Tobacco Control Act of 2009, and are overseen by the Center for Tobacco Products.
Regardless of the specific product regulated, the FDA’s core mission remains the same: to protect the US population by helping to ensure the fundamental safety of the food Americans consume and the medical products prescribed by their clinicians. At the same time, this primary mission is complemented by a mandate to promote the public health by reviewing research and taking appropriate action on the marketing of regulated products in a timely manner. Not only do people need access to advances in nutrition and medical therapies, but also the American spirit is itself characterized by a strong current of scientific and technological innovation. At first glance, differences in these 2 priorities, protecting the public safety and promoting the public health through encouraging innovation, might seem to be a potential source of conflict. However, the emerging discipline of regulatory science,2 as exemplified in the collaboration between the FDA and the National Institutes of Health on next-generation sequencing,3 is helping to define approaches to regulation that strike an appropriate balance between these 2 important considerations.
Another facet of the FDA’s mission is supporting the creation and dissemination of accurate, science-based information that enables wise decision making about the products the agency regulates. This task is much more complex than some might imagine, especially in an era of rapidly proliferating information on the Internet and social media, not all of it reliable. Finally, the FDA, in concert with other agencies, has a fundamental role to play in helping the nation counter emerging threats, whether from bioterrorism, antimicrobial-resistant pathogens,4 or epidemics of infectious diseases such as those caused by Ebola and Zika virus.
Over the years, the FDA has developed a focus on decision making. As Dr Susan Ellenberg, a colleague who has migrated from FDA to academia, once taught me, “In academia, you finish your study and say ‘more research is needed,’ while at FDA a decision must be made based on the available information.” Indeed, the FDA can be likened to a referee making calls based on a rulebook: in this case, the Federal Food, Drug, and Cosmetic Act and other statutes, plus various rules and guidance that implement these statutes.
Oversight, Governance, and Relations with Elected Officials
The FDA is one of a family of agencies within the Department of Health and Human Services that includes the National Institutes of Health, the Centers for Medicare and Medicaid Services, and the Centers for Disease Control and Prevention. All are the responsibility of the Secretary of Health and Human Services, who answers directly to the President. The post of FDA Commissioner is a direct presidential appointment and requires confirmation by the Senate. FDA’s annual budget, which includes funding derived from congressionally authorized user fees, is developed with oversight from Health and Human Services. Final decisions are made as part of the President’s proposed budget, which is then revised by Congress. Thus, the FDA is a part of the Executive Branch of government but is overseen by Congress, primarily through the Senate Health, Education, Labor and Pensions Committee and the House of Representatives’ Energy and Commerce Committee.
The FDA’s vast workforce comprises >16 000 employees (many of them career civil servants) and >5000 contractors, but fewer than a dozen political appointees. For each key agency function, a multidisciplinary team is configured, roles and responsibilities are delineated, and decision-making authority is clarified. Everyone knows their respective roles, and the team is clear about its ultimate goal: to arrive at a decision within the bounds of the FDA’s authority that will protect and promote the public health. In distinction to research and clinical care teams, lawyers and policy experts are frequently essential team members.
The FDA’s pride in its mission is profound, and the spirit of dedication to the public health and welfare is everywhere evident. There is no doubt that the agency holds as a core value the primacy of scientific information and depends on the knowledge gleaned from it to guide and inform regulatory activity. However, it also is evident that regulatory decision making requires a fundamental collaboration encompassing biomedical science, public policy, and law. Ultimately, the elected officials representing the people have the power and obligation to pass laws that provide the basis for the FDA’s determinations and actions. However, laws are rarely sufficiently specific to guide operations. This is why rules and guidance are critical, particularly in such a complex arena, otherwise it may be difficult for industry to know how to comply with the law.
Building and Sustaining the FDA Workforce
Although the primary regulatory mission of the FDA is currently well-served by its multiple systems, there are overarching critical initiatives that will prepare it for the coming years. Ensuring a future of effective regulation requires that we support our first-rate workforce at the FDA and make adequate provision for its further growth and development by hiring the best people and providing a work environment that is both exciting and rewarding.
Improving the National Evidence Base
Along with supporting and building its workforce, improving the national system for evidence generation is a key priority. The FDA excels when it has access to high-quality scientific evidence to guide its judgments. Accordingly, it is critically important to take advantage of the computational revolution we are now assimilating. Cardiovascular medicine, with its rich legacy of registries, use of electronic health records and claims data, and experience conducting large clinical outcomes trials, is in the vanguard of this effort.
Fostering Patient-Centered Approaches
The term patient-centered has perhaps been overused lately. Nevertheless, inventors and companies developing medical products would be well-served to consider and solicit the needs of patients early in product development and incorporate their perspectives throughout the product lifecycle. The development of rigorous methods for using patient-reported outcomes, and for characterizing and understanding preferences and outcomes that matter to patients, as well, are important priorities for the agency, especially because widespread proliferation of personal devices and social media are enabling direct contact with patients.
Achieving an understanding of patient characteristics that provide a shared basis for targeted therapy has been a goal at the FDA for decades. However, scientific and technological advances now allow us to combine genetic and genomic measures (for biological understanding), electronic health records and claims data (for clinical understanding), and data from personal devices (for understanding social interactions, integrated and continuous physiological measures, and geospatial mapping of social and environmental interactions). The President’s Precision Medicine Initiative5 catalyzes these approaches in a way that will enhance our capacity to target treatments to the right patient at the right time, according to the values and preferences of that patient.
All these initiatives necessarily take place in the context of globalization. Although the United States has an enormous presence in global markets, Americans make up <5% of the world’s population. With that in mind, it is unsurprising that a large part of our food supply, and significant quantities of the ingredients and components of our medical products, as well, come from outside the United States, or that an increasing proportion of clinical trial and epidemiologic data used to guide clinical decision making come from studies performed abroad. This means that, although the FDA’s core mission revolves around serving the US public, doing so effectively requires it to maintain a global perspective.
Thus far, the biggest challenges I have encountered at the FDA revolve around assimilating the breathtaking scope of responsibility, developing strategies to work effectively amid intense scrutiny and criticism, and addressing the need to engage with the evolving world, while at the same time helping to ensure the safety of products used and consumed by Americans. Decisions made by the FDA routinely disappoint significant numbers of people, and the reactions to those decisions can be strongly expressed. Nonetheless, it remains essential to maintain an agency that is (and is seen to be) fair and transparent, and whose decisions are untainted by favoritism.
Learning and Surprises
Because of my previous work with FDA, I was expecting to encounter the issues described above, but 1 important issue did surprise me: when the FDA observes a problem that could potentially jeopardize the public health, it is much more difficult and complex for the agency to take action than I had imagined. Our system of laws, with its emphasis on checks and balances, significantly constrains the actions of government agencies. Regulatory decisions with major ramifications for industry are not made lightly because of the substantial resources that can be consumed. Similarly, enforcement decisions can involve significant resources for documentation and legal proceedings. Accordingly, it is critical for the FDA to work with the industries it regulates to foster quality systems and a culture of integrity that enables as much self-correction as possible, so that FDA actions can be reserved for the most important issues.
The FDA is an exciting place to work, with an amazingly talented and knowledgeable workforce devoted to supporting the agency’s vital societal mission. It is both a joy and privilege to lead the FDA, particularly at a time in which simultaneous revolutions in biomedical science and information technology are converging to open up new horizons in treating illness and fostering health.
Just over a year ago, I arrived at the FDA after 32 years in academic medicine; in late February of this year, I was confirmed as Commissioner of Food and Drugs for the agency. In his capacity as editor of Circulation, Dr Hill has invited me to answer some questions about the FDA. It is a privilege for me to be able to offer some personal reflections on what I have learned during my time at FDA and to discuss what I hope to accomplish as Commissioner.
Dr Califf currently holds the post of Commissioner of Food and Drugs, US Food and Drug Administration. Before his appointment to the FDA, Dr Califf received research grant funding from the Patient-Centered Outcomes Research Institute, the National Institutes of Health, the US Food and Drug Administration, Amylin, and Eli Lilly and Company; research grants and consulting payments from Bristol-Myers Squibb, Janssen Research and Development, Merck, and Novartis; consulting payments from Amgen, Bayer Healthcare, BMEB Services, Genentech, GlaxoSmithKline, Heart.org – Daiichi Sankyo, Kowa, Les Laboratoires Servier, Medscape/Heart.org, Regado, and Roche; he also held equity in N30 Pharma and Portola.
The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.
Circulation is available at http://circ.ahajournals.org.
- © 2016 American Heart Association, Inc.
- 1.↵US Food and Drug Administration. FDA organization. http://www.fda.gov/AboutFDA/CentersOffices/default.htm. Accessed April 26, 2016.
- 2.↵US Food and Drug Administration. Advancing regulatory science. http://www.fda.gov/ScienceResearch/SpecialTopics/RegulatoryScience/default.htm?utm_campaign=Goo. Accessed April 26, 2016.
- 3.↵US Food and Drug Administration. Optimizing FDA’s regulatory oversight of next generation sequencing diagnostic tests—preliminary discussion paper. http://www.fda.gov/downloads/MedicalDevices/NewsEvents/WorkshopsConferences/UCM427869.pdf. Accessed April 26, 2016.
- 4.↵US Food and Drug Administration. Antibiotics and antibiotic resistance. http://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/AntibioticsandAntibioticResistance/UCM2007092. Accessed June 7, 2016.
- 5.↵The White House. The Precision Medicine Initiative. https://www.whitehouse.gov/precision-medicine. Accessed April 26, 2016.