COMMENTARY

An Indefensible Epidemic

The acceleration of a three-year-old outbreak of an exotic, mosquito-borne infection is worrying public health experts across the country. Louisiana has been hardest-hit this year by the West Nile virus, with at least 85 cases and eight deaths, but since infections were first found in the U.S. three years ago, cases have been discovered in 35 states and the District of Columbia. By next year, the virus is expected to cross the Rockies and spread to the Western states.

There are two ways to combat such an outbreak definitively. In the short run, eliminate the vector, which in this case is the mosquito. Longer term, develop a vaccine to prevent infection even if a mosquito does inject the virus. The technology is available to accomplish both objectives, but fundamental, long-standing mistakes in public policy have put them out of reach.

DDT

Thirty years ago, on the basis only of suspicion about toxicity to fish and migrating birds (but no evidence of harm to humans), the Environmental Protection Agency imposed drastic restrictions on DDT, an inexpensive and stunningly effective pesticide once widely used to kill disease-carrying insects. During the two decades before DDT was restricted, perhaps 100 million people in Africa, Asia and South America were saved by this miracle chemical. With the ensuing decline in DDT use, the World Health Organization estimates that 300 million to 500 million cases of malaria occur annually and more than 1 million people die. About 1,200 cases of malaria are diagnosed in the U.S. each year -- and it won't be long until West Nile virus infections far exceed that level.

The gradual spread of these diseases should have afforded time to begin work on a vaccine, but that is wishful thinking. Vaccine development is out of favor, producers are abandoning the unprofitable field in droves and lately there have been shortages of vaccines that prevent even common, potentially epidemic diseases.

From 1967 to 1984, the number of U.S. vaccine manufacturers fell from 37 to 15, while the number of licensed vaccines declined from 380 to 88. Currently, there are only four major producers and a few dozen products. Largely as a result of this decreased capacity, there are now, or recently have been, shortages of several essential vaccines in the U.S., including DTaP for diphtheria/tetanus/pertussis; the Td booster shot for tetanus and diphtheria; MMR for measles/mumps/rubella; varicella (chicken pox); and pneuomococcus. As a result, many states are lowering immunization requirements for students this fall, increasing the chances of outbreaks.

Why aren't more vaccines being manufactured? Because, compared to therapeutic drugs, they offer a low return on investment and high exposure to legal liability. The entire world-wide vaccine market, estimated at approximately $6.5 billion annually, represents only about 2% of the global pharmaceutical market, an amount roughly equivalent to the sales of one blockbuster ulcer drug.

Blame wrong-headed public policy. For example, the U.S. Centers for Disease Control and Prevention, the largest domestic buyer of vaccines, uses its buying clout to compel deep discounts for purchases. Recently, Wyeth Lederle Vaccines' proposed price of $58 per dose for its pneumococcus vaccine was rejected by the CDC, which demanded a discount of more than $10 per dose. Such extortionate behavior is a powerful disincentive to innovate.

Capricious and excessive regulation is another significant obstacle to pharmaceutical development. The FDA's position on a vaccine to prevent meningitis C, a bacterial illness that infects thousands and kills hundreds of Americans annually, is particularly inexplicable. At present no conjugated vaccine (one comprised of linked components) against this infectious disease is approved for use in the U.S., although three excellent products are available in Canada and Europe. The safety and efficacy of these vaccines have been amply demonstrated; over 20 million doses have been administered. Yet the FDA refuses to recognize the foreign approvals, although such "reciprocity" is supposed to be a goal of discussions among international regulators.

It's no wonder industry has come to regard vaccine development as unattractive -- even though vaccines are a great investment for society. The costs of vaccines are far lower than the cumulative expenses of treatment, hospitalization, loss of working days by patients and so on. The measles, mumps and rubella vaccine saves approximately $16.34 in direct medical costs for every dollar spent, and the diphtheria, tetanus and pertussis vaccine saves $6.21 for every dollar.

Incentives

By offering incentives to industry in the form of enlightened economic and regulatory policy, the federal government can make vaccine development more attractive. First, reciprocity of vaccine regulatory approvals between the U.S. and the European Union would cut development costs significantly. Second, public sector agencies should also stop using their purchasing clout to obtain heavily discounted prices for vaccines. Third, extend patent terms or marketing exclusivity to make vaccine development more lucrative.

Fourth, rein in the legal sharks. One possible approach would be to have the government indemnify companies for damages caused by side effects from FDA-approved vaccines (assuming no negligence or fraud). Companies could be shielded from tort liability by a "regulatory compliance" defense -- as long as they comply with all regulatory requirements, they aren't liable for damages involving unforeseen consequences of vaccine use.

How likely is any of this to happen? Not too likely, alas. Al Gore-style eco-babble, regulators' intransigence, and the power of the trial lawyer lobby are all potent obstacles to speeding up vaccine development or bringing back DDT. So get out the insect spray and prepare to suffer.

Dr. Miller, an FDA official from 1979 to 1994, is a fellow at the Hoover Institution.

Updated August 19, 2002