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Last Updated

31 Dec 2002

Source: Newsday, December 31, 2002

Vaccine Test For Children Unlikely

Debate clouds chance for smallpox trial

By Delthia Ricks, STAFF WRITER

By the time smallpox vaccinations are offered to the public in 2004, researchers will have gathered reams of information on dosage for virtually every age, with the likely exception of children.

Key researchers close to a major pediatric test of the vaccine told Newsday last week they doubt the trial will proceed, the result of negative public response to the prospects of a trial.

The issue of smallpox-vaccine testing in children has inspired debate and sidelined clinical testing, a controversy underscoring a broader issue: Many drug therapies ultimately administered to children are never tested in them.

Though the Bush administration two weeks ago vowed support for a new measure requiring drug companies to routinely test medications in children, officials did not say whether the pediatric trial of the smallpox vaccine should go forward. If the vaccine is not tested and licensed for pediatric use, children whose parents want them vaccinated in 2004 would be barred from receiving the shots.

Medical historians say use of the smallpox vaccine in children has a long and storied past.

Dr. J. Michael Lane, a retired immunization director at the U.S. Centers for Disease Control and Prevention, said the standard dose was established by consensus among physicians a half century ago, not by way of clinical testing.

Even though the vaccine was administered for more than a century before smallpox was declared eradicated in 1980, the potential for side effects was commonly accepted as a risk of preventing a dangerous disease, experts say.

"Until the 1970s and even into the '80s, the smallpox vaccine dose was driven by our desire to have maximum 'take' rates," Lane said, referring to evidence of immunity. "When there was smallpox in the world, we did everything possible to ensure good take rates."

There was a lot of questioning about how much vaccine should be put on the needle used to administer the vaccination, Lane said. "It was almost like asking how many angels could dance on the head of a pin.

"Now the game is different. It would be nice to get good takes, but it would be even better to do that with a minimalist dose. That has never been worked out. There's no good pediatric data. What I'm saying here is there's no data - period - for this population."

Federal health officials solicited public opinion in October on the issue of testing diluted doses in children, in response to opposition from anti-vaccination group leaders as well as the public. The clinical trial, which was to have begun before year's end, is on hold.

Patricia El-Hinnawy of the federal Office of Human Research Protection, which solicited public reaction, said the decision now rests with Health and Human Services Secretary Tommy Thompson.

"We have no idea when he will decide," El-Hinnawy said.

Given the opposition - during the comment period, more than 300 responses opposed to such testing were submitted - Lane said doctors face a difficult situation.

"You can't license a vaccine for kids until you test it in kids," he said. "Despite the fact that many people in the medical community want to test it, it's difficult to move beyond those who say it's unethical. But I think the FDA [Food and Drug Administration] is correct in saying we can't license it without testing it first."

Groups such as the National Vaccine Information Center, based in Vienna, Va., contend that, with only a theoretical threat of smallpox, the risks of the live-virus vaccine outweigh its benefits.

Smallpox vaccine at standard dosage is estimated to cause up to 2.7 deaths, as well as 15 adverse reactions, in 1 million people who receive it. Reactions range from flulike symptoms to encephalitis. Doctors do not know - but some suspect - that adverse outcomes would be lessened with a weakened vaccine.

Results of a major clinical trial of 680 adults between the ages of 18 and 32, reported in March, showed that diluted vaccine - up to one-tenth the standard strength - worked as well as the so-called standard dose in producing immunity.

The trial is instructive, scientists say, because it demonstrates that a weaker dose works in an age group never before vaccinated against smallpox. The last case of the disease in the United States occurred in 1949; routine vaccinations ceased in 1972. A new trial, headed by medical investigators in New York, is enrolling 1,000 volunteers across the country to test the vaccine in adults between the ages of 32 and 75.

Experts on bioterrorism in the Bush administration have said an attack using the virus as a weapon is probably remote, but they nevertheless believe terrorist groups possess the virus.

Despite a freeze on the pediatric vaccine trial, administration officials want to establish keener dosages for all other medications given to children. Thompson last week said the administration would support the new measure, a new Pediatric Rule, calling for testing medication dosage levels in children.

Even if the smallpox vaccine is never tested in children, experts say a new Pediatric Rule would eliminate guesswork when it comes to establishing doses for other medications administered to children. The FDA had made a rule in 1998 requiring drug companies to test medications in children, but it was shot down in October by a federal judge in Washington, who said the agency was exceeding its authority.

"We have strongly defended the Pediatric Rule in court," said FDA Commissioner Dr. Mark B. McClellan, "because public health will be best served by enabling the FDA to require testing of drugs for pediatric use. But continued litigation is likely to take years, and its outcome is uncertain."

"This is a very complex issue," Lane said. "I am passionately pro-vaccines. I was director of a national immunization program, and part of my job was aggressively promoting vaccination.

"I can understand people who say it's unethical to administer smallpox vaccine to children. But it's also an awkward situation for people who want to run the vaccine trials" to determine the best dose.