TCS Daily

Dying for FDA Reform

By Henry I. Miller - June 9, 2003 12:00 AM

Critics of the pharmaceutical industry and apologists for the FDA have for years been trying to convince politicians and consumers that federal regulators have been forced to relax the oversight of prescription drugs and, thereby, compromised consumer safety. Sidney Wolfe, of the Washington-based Public Citizen Health Research Group, wrote, for example, "Egged on by its sponsors in the drug industry, Congress has systematically set about weakening a drug-approval process that for years ensured Americans the safest pharmaceutical supply in the world."

Now, along comes Philip J. Hilts, long an FDA defender, with another, book-length defense of the agency, and of the need for stultifying, centralized regulation. Blinded by his convictions about the intrinsic goodness and competence of government - which is there "to protect citizens from some kinds of commerce rather than just to protect commerce" - Hilts has produced a misleading and distorted paean to food and drug regulation.

Hilts fails to perceive that Americans now might need protection from the protectors. He offers chapter and verse of more than a century of the cupidity and mendacity of unscrupulous purveyors of dangerous products, but he gives short shrift to the capriciousness, risk-aversion and obstruction of innovation by federal regulators. Hilts does raise the most common criticism of the FDA - that it takes too long to approve new drugs - but only in order to attack it. And by focusing on the time required for marketing approval, which is merely the last step in a lengthy and complex process, he is disingenuous.

In fact, the total time required for drug development, from synthesis of the molecule to marketing approval, has more than doubled (from 6.5 to about 15 years) since 1964. In spite of more powerful and precise technologies for drug discovery, purification and production, development costs have skyrocketed. According to the Tufts Center for the Study of Drug Development, between 1970 and 2003 companies' average expenditures to develop a single new drug exploded, increasing from $138 million to $897 million. And while between 1970 and 2000, research-based companies' R&D outlays soared from about $2 billion to $30 billion, the number of approvals of new drugs barely budged. An important reason is that the highly risk-averse FDA keeps raising the bar for approval, especially for innovative, high-tech products.

The FDA contends that it's getting better and moving drugs through the pipeline more rapidly - thanks, they say, to user fees paid by drug companies (in effect, a huge, discriminatory tax) - but the data tell a different story. Although the time FDA takes to grant the final approval for marketing a biopharmaceutical has not changed appreciably during the past 20 years, the time required to meet the FDA's requirements for gathering clinical trials data has more than doubled: 32 months during the 1980s, 48 months during 1990-94, 64 months during 1995-99, and 72 months during 2000-02.

The trend in cancer drug approvals is illustrative. Vanderbilt University researchers who study the development and approvals of cancer drugs have concluded that projected out over the period from 2000-2004, we can expect to see a 68 percent reduction in new drug approvals and a 37 percent reduction in the number of claims approved for new cancer indications (uses), compared to the preceding five-year period (1995-1999).

When the FDA sneezes, the pharmaceutical industry gets pneumonia. Often, the infection is fatal. A chilling example is the delay of an injectable antibiotic called Tigecycline, for infections caused by antibiotic-resistant pathogens. Its manufacturer, Wyeth-Ayerst Laboratories, had done two human studies to show that the drug is safe and effective, and was planning a third and final one. However, in 2000 the FDA changed the rules for measuring efficacy in trials of antibiotics, which would have required the company to double the number of patients in the trials from 4,000 to 8,000. That would make the investment required by Wyeth much greater, take longer, and possibly require the enrollment of patients outside the United States. The company responded by placing the last trial on hold.

This kind of decision has a pernicious ripple effect. "As a result [of FDA's change in policy], we've got fewer companies involved in the antibiotic discovery business at a time when antibiotic resistance to existing drugs is becoming more of a problem," according to Dr. Robert C. Moellering, Jr., chairman of the department of medicine at Beth Israel Deaconness Medical Center in Boston. This is something to think about when you contract a particularly nasty antibiotic resistant infection during a hospital stay, and there are no more drugs available to treat it.

The FDA's actions on the vaccine against rotavirus, a common diarrheal disease spread by the fecal-oral route, are another example of regulatory policy gone awry. The virus infects some 2.7 million children under age five in this country annually - infections that cause half a million physician visits, 50,000 hospitalizations, and dozens of deaths. Direct medical costs are almost $300 million, and overall societal costs amount to several times that.

The first live oral vaccine against rotavirus was approved in 1998 and was soon added to the list of recommended childhood vaccinations. After approximately 800,000 American children had received a million and a half doses, public health surveillance detected what appeared to be a statistical association between vaccination and a rare bowel abnormality called intussusception (a kind of telescoping of a portion of the bowel that cuts off the blood supply). Although the condition affected only about one in 11,000 vaccinees and is easily correctable with surgery, the FDA forced the company to withdraw the vaccine from the market. Consequently, although a recent study suggests that the vaccine does not actually increase the overall incidence of intussusception, but only shortens the susceptible period to a short time after vaccination, we are now without a rotavirus vaccine.

More than 100 studies, inquiries, and congressional hearings have documented the negative impacts of the existing system for regulating foods and drugs. According to a report from the Tufts Center for the Study of Drug Development, "the regulatory activities of the FDA may constitute the most thoroughly investigated and studied program of government regulation in history." Between 1982 and 1992 alone, the activities and policies of the FDA were the subject of nine major reports or sets of recommendations from government sources and independent commissions. Their recommendations for reform now sit on government-issued shelves, gathering dust.

What's going on here? Don't regulators care about public health?

The short answer is that the system they work in is biased against innovation. A regulator can commit an error by permitting something bad to happen (approving a harmful product), or by preventing something good from becoming available (delaying or denying approval of a beneficial product). Both outcomes are bad for the public, but the consequences for the regulator are very different. The first kind of error is highly visible, and the regulators are attacked by the media and patient groups and investigated by politicians. But the second kind of error - keeping a potentially important product out of consumers' hands - is usually a non-event.

The bottom line is that regulators make decisions defensively - in other words, to avoid approvals of harmful products at any cost - so they tend to delay or reject new products of all sorts, from fat substitutes to vaccines and painkillers. That's bad for public health and for consumers' freedom to choose.

Americans are, literally, dying for better regulation.

Henry Miller, a physician, is a fellow at the Hoover Institution and the Competitive Enterprise Institute. He was an FDA official from 1979 to 1994.

TCS Daily Archives