HOLLY FERNANDEZ LYNCH
A COLLEAGUE of mine is fond of reminding his students to challenge the status quo because the world as it exists is not necessarily the way it has to be. Indeed, the status quo may better reflect a range of historical accidents that led down a particular path than it does a well-thought-out, strategic set of choices. And even the best-laid plans may require revision as the world changes around them. Politics and bureaucracy aside, nearly everything is changeable.
With that principle in mind, we might ask, “Is the FDA we have today the FDA we really need, and if not, how should it be changed?” The agency as it currently exists is the product of a long history of reaction to circumstances as they presented themselves—reaction to sulfanilamide, thalidomide, HIV/AIDS, Vioxx, and on and on—with a steady vacillation between emphasis on speed and emphasis on safety. Moreover, the world around FDA has changed dramatically since the agency’s birth. The chapters in this section evaluate how well a reactionary FDA has been able to keep up with some of those changes, including globalization, patient advocacy, rising health care costs, and prospective medicine. In some ways, it seems, FDA has risen to the meet these challenges, and in others it has not, as a result of either jurisdictional limitations or cabined readings of available authority.
In this part’s first chapter, Howard Sklamberg and Jennifer Devine, deputy and then-associate commissioner for global regulatory operations and policy at FDA, respectively, tout the agency’s expansive responses to the globalization of its regulated products. Sklamberg and Devine offer numerous examples of FDA’s innovative approaches to partnering with foreign authorities, placing staff on the ground abroad, expanding facilities inspections, and sharing scientific knowledge, all of which are important steps toward keeping American medicine cabinets safe. But do they go far enough? If we think about the agency we might build from scratch, perhaps not. Rather than focusing on what globalization means for the manufacture and trade of approved drugs, we might think much more broadly about developing a global marketing approval system that goes far beyond harmonization of requirements to actual reliance on decisions made by other authorities. Especially in the information age and with increasing efforts to harness the power of big data, consider how much more efficient and accurate approval decisions and subsequent safety monitoring could be on a global scale. If we challenge the status quo, we might start to see globalization as less of a challenge and more of an opportunity.
In chapter 3, Lewis Grossman describes the myriad ways in which patient advocacy and empowered consumers have influenced how FDA regulates. Of course, patients have an important role in determining whether any given product’s benefits outweigh its risks since that is a normative rather than scientific evaluation. Grossman’s chapter demonstrates FDA’s efforts, increasing over several decades, to give patients a seat at the table. But at what cost? Do we want an agency focused on speed, on safety, on both, or on something else entirely? Perhaps the empowered consumer would prefer an agency whose mission is not to serve as a gatekeeper to products reaching the market but rather as an independent and expert evaluator of information about those products that patients can then use to make informed decisions themselves. This need not bring us back to the bad old days of snake oil salesmen—to the contrary, patients would have what they need to distinguish snake oil from gold—that is, assuming that patients are in fact empowered, which is not always the case, as Grossman reminds us. And even empowered patients are likely to be interested in more than a product’s bare risks and benefits, for example, information about how that product stacked up against the competition.
It is precisely FDA’s failure to provide this sort of comparative information that Theodore Ruger highlights in his chapter. Ruger notes that although FDA is jurisdictionally limited in some important ways, it has exhibited “willful ignorance to comparative efficacy and cost,” focusing instead on safety and effectiveness as demonstrated against the gold standard of a placebo control. Ruger suggests that this failure to innovate despite authority to do so may severely marginalize the agency, as the decision by payers whether to include a product on their reimbursable formulary begins to overshadow the regulatory decision of whether to allow a product on the market in the first place. After all, what good is a drug that no one can afford? However, it may be that even on a blank slate, we would choose to separate questions about whether a drug works and is safe from questions about how much a drug should cost or whether it should be covered, such that our current bifurcated system gets things right in at least one regard. Nonetheless, it would be important to generate reliable information about a product as compared to available alternatives, and that is sorely missing from the current equation.
In the final chapter of this part, Barbara Evans hones in on FDA’s failure to fully embrace the era of prospective medicine, or interventions to help healthy people stay well. Evans emphasizes that prospective medicine poses a number of unique challenges to FDA’s status quo, the most important of which is that a new product intended to predict or prevent disease might not be demonstrated to be definitively effective for years or decades—a three-year trial, or even ten years, would not be anywhere near sufficient to evaluate the direct effectiveness of an Alzheimer’s prevention drug, for example. A lot of the work of protecting patients will have to happen in the post-marketing time period, but FDA has not adequately advanced its authority to do so. Against this background, we might prefer a world in which drug approvals were time limited and had to be renewed, just like IRB-approved research protocols, so that there are predefined and automatic points in time to reassess based on new information and context. We might also develop a much more robust system for tapping into electronic health records to gather data outside of the research setting, which might entail bypassing patient consent or articulating some social obligation to contribute data in general or as a condition of receiving a drug. FDA has already begun to head down some of these paths, but it could go substantially further.
These chapters offer an important perspective and opportunity to assess whether we are happy with the agency we have or whether dramatic changes are in order. The topics covered reflect several leading twenty-first-century challenges, but there are many others. Is FDA as it currently stands optimally situated to regulate gene therapies, for example? What about the fact that the agency largely refuses to engage in substantial questions of research ethics that are of paramount importance in a world of multinational clinical trials? And its counterparts abroad are taking huge strides to improve transparency and efforts to share data while FDA has been much more reserved.
FDA is innovating in many important ways, and it deserves substantial recognition for its efforts to manage a massive regulatory portfolio in a changing world. But we should never get complacent. Remember, the way it is is not the way it has to be. Of course, mustering sufficient political will to implement substantial change is another story.
