Wrong Rx for the FDA

The congressional legislators who oversee the Food and Drug Administration and control the nation’s coffers have shown again that they neither understand drug development nor the regulatory problems that plague it.

In February, Sen. Barbara A. Mikulski(D-Md.) unveiled a bipartisan bill intended to spur innovation in research and drug development for chronic, costly health conditions such as Alzheimer’s disease, cancer, diabetes and heart disease.

According to the press release, the bill will invest “in public-private partnerships to ensure scientists and researchers are able to develop new safe and effective drugs,” shrink product development timelines, increase the number of drugs in the development pipeline and expedite the FDA review process.

However, there is currently plenty in the development pipeline. The federal government is boosting funding for research and development on Alzheimer’s disease; the Department of Health and Human Services alone will allot more than $500 million to it in fiscal year 2013. Moreover, drug companies spend more than $65 billion annually on R&D.

For example, there are now nearly 100 drugs in development for Alzheimer’s disease, dementias and other cognitive disorders, and almost 900 medicines being tested for cancer.

It is government regulation that has become a significant obstacle for drug developers and a disincentive for potential investors. Bringing a new drug to market now requires 10 to 15 years and costs more than $1.3 billion, and the number of drugs approved by the FDA annually is trending downward. Perhaps the most ominous statistic is that manufacturers recoup their R&D costs for only one in five approved drugs, down from one in four about a decade ago.

Many of the challenges to pharmaceutical development are caused by the FDA’s excessive risk aversion, unchecked by congressional oversight, that has forced companies to perform ever-larger, longer, more complex and more expensive clinical trials.

The bill does nothing concrete to drain the regulatory swamp. Instead, it allocates $50 million for activities already underway and offers only vague, boilerplate language: “facilitate innovative and expedited review” and “regular and ongoing communication” between the FDA and drug developers, and promote “regulatory science.”

There are many FDA regulatory issues that Congress should address.

One is the agreement that gives the drug review and drug safety offices within the FDA equal responsibility for “significant safety issues” pertaining to medicines that are under review or have already been approved for marketing. The drug safety group is so narrowly focused on “safety” that it seems oblivious to the fact that because all drugs have side effects, safety cannot be evaluated in a vacuum. Instead, “safety” must be part of a risk-benefit judgment. The group’s motto might be: “If you don’t approve new drugs, you avoid safety problems with them.” These drug safety zealots should be returned to a purely advisory role.

Another issue that should concern congressional overseers is that the FDA considers the “accelerated approval” route to be too lenient. Introduced two decades ago, this process permits the agency to issue a limited, or conditional, approval of a new drug that is intended for a “serious or life-threatening disease” and for which there is an “unmet medical need” — that is, no alternative treatment. Intended as a “quick on, quick off the market” mechanism if the original positive results don’t pan out, it has worked well and saved countless lives.

Congress could also outsource some of the FDA’s functions. Dozens of independent studies over several decades have recommended transferring some tasks performed internally by the FDA to outside experts.

In fact, there is already a successful (but largely ignored) model for the evaluation of clinical data by an independent laboratory. In a two-year pilot program that lasted from 1992 to 1994, the FDA contracted out reviews of supplements to new drug applications and compared the results of these evaluations to in-house analyses. In all five of the supplements reviewed by a nonprofit technical consulting company, the recommendations were congruent with the FDA’s own actions, and the process was faster and cheaper.

The European Union offers an apposite, successful example of outsourcing in the regulation of medical devices that relies heavily on various sets of product standards and typically does not involve government regulators directly in product oversight. For low-risk devices, manufacturers themselves are allowed to certify that their products meet the necessary standards. For higher-risk products, manufacturers must obtain third-party review from nationally accredited, private-sector, profit-making entities — “notified bodies” — that test products, inspect manufacturing systems and ultimately verify that EU standards have been met.

Another improvement would be to make regulators accountable for unnecessary obstruction of drug development and delays in approval, by means of a vigorous ombudsman whose actions could encourage regulators to act in the public interest. The office would need independence from the agency and the FDA commissioner; access to independent expertise in relevant disciplines, including medicine, pharmacology, medicinal chemistry, regulation and law; and the power to levy sanctions against FDA employees found to be responsible for flawed decisions or policies that constitute severe, avoidable errors.

Instead of such reforms, the proposed legislation is as grandiose as it is clueless. Its sponsors’ magniloquence reminds me of a Monty Python skit in which a character says to viewers: “Well, last week we showed you how to become a gynecologist. And this week on ‘How to Do It’ we’re going to show you how to play the flute, how to split an atom, how to construct a box girder bridge, how to irrigate the Sahara Desert and make vast new areas of land cultivatable. But first, here’s Jackie to tell you all how to rid the world of all known diseases.”

Maybe they should give the $50 million to Jackie.

Henry I. Miller, a physician and molecular biologist, is a fellow at Stanford University’s Hoover Institution. He was the founding director of the FDA’s Office of Biotechnology from 1989 to 1993.