Talkback: Response to Article in Nature, A To-Do List for the New FDA Commissioner, by Susan Okie, M.D.

FDA Centennial-1906-2006

FDA Centennial-1906-2006


ARTICLE: http://content.nejm.org/cgi/content/full/360/14/1373

The article in Nature by Dr. Susan Okie titled, A To-Do List for the New FDA Commissioner, was an unfair indictment of an agency that still maintains the world’s “gold standard” and has done so for over 100 years. It was a naive perspective, filled with partial anecdotes, selected excerpts, and platitudes. Dr. Okie asserts that the agency has “serious systemic problems” and recants salacious sections from reports describing the agency as “burdened by ever-expanding responsibilities, underfunded and understaffed, lacking modern scientific expertise, and equipped with a dangerously outmoded information-technology infrastructure. The problems within the FDA is not that of a “cancer,” but rather the failure of a legislature who as history demonstrates, must have tragedy, followed by public outrage, before expanded legislation or legislative authority is granted to the FDA.


Dr. Okie disingenuously surmises that the perception of the agency is “slow to act, secretive, and subject to influence by political and corporate interests.” The burden for FDA employees is that their decisions can kill millions by a single approval making the responsibilities for protecting the public from unsafe regulated products onerous. It is no secret that bureaucrats respond to incentives and FDA is no exception. Any public or congressional backlash will cause the agency to be more risk averse. The agency makes decisions that affect the lives and health outcomes of millions of Americans daily. If Dr. Okie had to sign a letter authorizing the availability of a new medical product to over 300 million Americans, what kind of information (and how much of it) would she want?


In practice, regulations are implemented in a very stylized way with ambitious goals and preambles that spell out congressional intent without practical considerations. In the case of the FDA, Congress tasked the agency with mandates to achieve certain objectives which are impossible based on allocated resources. Though FDA has discretion within its purview to set regulations which are consistent with its mission, often times these are influenced by external stakeholders such as the public, industry, congress and overlapping federal, state and local governmental authorities, all with differing interpretations of the agency’s role in fulfilling regulatory oversight responsibilities.


Dr. Okie’s perspective restates the obvious – that we are faced with problems for which the current FDA structure is inadequate to address. What we have seen out of Congress in the last twenty years tends to be performance based, placing and holding the FDA to approval targets and laborious reporting requirements without concomitant resources. Many agree that Congress needs to grant the FDA legislation that allows greater independence and less political interference. This is a tall feat for an institution that starts campaigning after the last election and is influenced by over 1,100+ registered drug lobbyists (add devices, foods, cosmetics and other regulated products and it would equal 2200+). Congress needs to empower FDA with the flexibility in meeting current and future challenges such as supply chain globalization and the sourcing of active ingredients/components from disparate sources and countries with lackluster regulatory and safety practices. These are issues that could potentially derail the confidence in the safety of the American medical product supply.


Quoted former commissioner Donald Kennedy idealistically declared that “the commissioner has legal authority to take actions to protect the public health and has considerable power to make administrative changes without congressional action.” The power is vested in the Secretary of HHS (or designates), but the real power is in the process of regulatory oversight via rulemaking which is subject to approval by the Office of Management and Budget (OMB), an executive agency. This means that new proposals for federal regulations from regulatory agencies must be submitted for review. The OMB via its unit, the Office of Information and Regulatory Affairs (OIRA) applies cost benefit analysis to new regulations before approving them. They sometimes negotiate with the agency concerned over amendments and in some cases reject changes outright. Once approved, changes are formally published in the Federal Register for public comment.


Dr. Okie fails to recognize that that the introduction of a new product to market is risky. She quotes a highly critical excerpt from the 2006 Institute of Medicine report on drug safety, but failed to mention the pronouncement that, “it is impossible to have complete information about drug safety at the time of approval, because drugs’ mechanism of action are complex; pre-approval clinical testing is generally conducted in controlled settings in defined, carefully-selected populations; and insufficient sample sizes to detect serious but rare adverse effects.” The FDA can only make decisions based on information submitted, and to imply that the agency should have a crystal ball is audacious.


If we look at the Black Box warnings required by the FDA to address the class of antidepressants called Selective Serotonin Reuptake Inhibitors (SSRIs) we can witness parallels. There were revelations of an increased risk of suicidal thoughts in teens. The Industry argued that past history of such FDA warnings revealed that they create barriers to care and unnecessarily frighten families away from seeking treatment. While this is true, had the FDA not required such label warnings and an incident occurred, the agency would once again be forced to shift the pendulum towards more stringent requirements. If the FDA did not act based on scientific evidence they received, no matter how minute, they would have been crucified in case “suicidal thoughts” manifested into suicidal acts. In essence, the FDA is damned if they do and damned if they don’t.


Safety is not absolute because it involves an overall assessment of benefit vs. risk. Absolute safety is impossible as it requires absence of injuries and death. Safety is not exclusive; it necessitates a comparison across medical products and interventions and is only known with a product’s “real world” experience. Safety is not static, as we have seen time and time again; a safe drug today may be “unsafe” and outmoded tomorrow. It comes down to experimental risk versus situational risk that is often subjective and open to various interpretations ex-post versus ex-ante.

In summary, Dr. Okie incorrectly implies that the FDA faces a crisis of confidence. The crisis of confidence is in a Congress who needs to show independence and empower the FDA legislatively and financially to increase its own scientific expertise and new skills to meet current and emerging challenges. Any failure would result in an agency outmatched by private industry with lost relevance and public trust. The agency’s reputation is damaged but it is not destroyed. They are tasked with restoring a once stellar reputation and faced with a public worried about its ability to protect it, an industry worried about declining NMEs and what they perceive as a more conservative FDA posture in light of recent events. Yes, recent withdrawals and recalls have caused appropriate concern and resurged questions regarding the FDA’s mission and whether a new framework or drastic changes are required to ensure that the FDA retains its position as the “gold standard.”The FDA’s modern history is marked by a stellar and successful dual mission of protecting the public from unsafe and ineffective regulated products. What is unacceptable is any insinuation that FDA action is based on influence or commerce and not purely science.


References:

Institute of Medicine Report, The Future of Drug Safety: Promoting and Protecting the Health of the Public. 2006

http://www.fda.gov/oc/reports/iom013007.html

Center for Public Integrity study of disclosure records shows. Spending on Lobbying Thrives,

Drug and health products industries invest $182 million to influence legislation http://projects.publicintegrity.org/rx/report.aspx?aid=823