FDA Data on Gardasil May Fuel Controversy

Conservative Group Publicizes
Statistics on Adverse Events
Reported on Merck Vaccine

By JOHN CARREYROU
May 24, 2007; Page D1

In a move likely to fuel the debate over Merck & Co.'s Gardasil cervical-cancer vaccine for young women, a conservative watchdog group disseminated new reports of serious adverse events linked to the vaccine. The reports included problems in pregnant women who had received Gardasil.

Health officials and Merck dismissed the adverse events as probably unrelated to the vaccine, which targets the human papillomavirus strains linked to most cervical cancers. Adverse events with drugs and vaccines are routinely reported to the Food and Drug Administration by doctors. But they don't necessarily indicate that the medication or vaccine caused the event, which might be related to a person's underlying health or other factors.

Eighteen women who received the vaccine while pregnant experienced complications, ranging from miscarriages to fetal abnormalities, according to new FDA data. The data were obtained by Judicial Watch, a group based in Washington, through a Freedom of Information Act request. Some states are debating whether to make the vaccine mandatory for schoolgirls. Judicial Watch opposes such school requirements.

The new data also show that three female patients who received the vaccine died. However, Merck, the FDA and the Centers for Disease Control and Prevention, which helps the FDA monitor vaccine adverse events, said the deaths were unlikely to have been caused by Gardasil. Two of the women were taking birth-control pills and died from blood clots, a known risk of contraceptive medication, according to the CDC. The third, a 12-year-old girl, suffered from heart disease and died from a heart inflammation brought on by the flu, the CDC said.

So far, there have been 1,637 reports of adverse reactions, not an unusually high number given that two million to three million women may have received the vaccine. Most of the adverse events involve minor side effects such as pain at the site of injection, itching and dizziness. Merck has distributed more than five million doses of Gardasil in the U.S. since its introduction in June 2006. The vaccine is administered in three shots over a period of six months.

Karen Riley, a spokeswoman for the FDA, said the agency was closely monitoring the adverse events associated with Gardasil, including the pregnancy complications, but "we haven't seen anything at this point that would suggest we'd make any changes in the product."

Gardasil became the subject of much controversy after Merck lobbied states to make it a school requirement for pre-teen girls. Though the company halted its lobbying campaign in late February amid criticism, some 16 states are considering mandatory-vaccination bills. One state, Virginia, has passed such a bill into law.

Those opposed to school mandates range from religious conservatives, who say the vaccine conflicts with their abstinence message, to parents who worry that it is too new and untested to administer to 11- and 12-year-old girls.

Some scientists have also raised doubts about the vaccine's efficacy against cervical cancer and suggested that the billions of dollars likely to be spent on it in coming years might be better used to expand Pap screening among low-income women.

Of the 1,637 adverse-event reports, 136 have been deemed serious by the FDA, ranging from seizures to Guillain-Barre Syndrome, a rare life-threatening disorder in which the immune system attacks nerves and induces paralysis.

Of the 18 pregnancy complications, 16 have involved miscarriages. Gardasil isn't recommended for pregnant women, but at least some of the women in the adverse-events reports said they were unaware that they were pregnant when they received the vaccine.

Richard Haupt, Merck's executive director of medical affairs, said the miscarriages likely had nothing to do with Gardasil, noting that miscarriages are very common during the first trimester of a pregnancy. However, one of the 18 women was diagnosed with an abnormal fetus, and a test conducted on another woman during her pregnancy showed an increased risk of fetal defect. There is no report on the outcome.

Congenital anomalies were one issue of concern during the FDA's review of the vaccine last year. In its clinical trials, Merck reported five cases of birth defects among women who received the vaccine within 30 days of conception. Upon looking at the cases more closely, Merck says, it determined that they didn't fit any pattern and were unlikely to be connected to the vaccine.

Dr. Haupt says that Gardasil's label states that it is "not recommended for use in pregnant women" merely because the vaccine hasn't been "systematically studied" in a large population of pregnant women, not because of any concern about birth defects.

Among the postmarketing commitments Merck made upon receiving FDA approval for Gardasil, the company committed to compiling a registry of pregnant women who have received the vaccine, to monitor any effect the vaccine might have on pregnancies. The registry has more than 300 pregnant women exposed to the vaccine, and Merck says that the registry has received no reports of congenital anomalies.

John Iskander, acting director of the Immunization Safety Office at the CDC, says Gardasil isn't a live vaccine, so it shouldn't cause any infections that would affect fetuses. He also notes that 3% of all live births involve a birth defect of some sort, and some cases would be expected to occur naturally among pregnant women vaccinated with Gardasil.

"None of the information I'm aware of or have seen suggests that there's any pattern here linking birth outcomes to the vaccine," says Dr. Iskander. But, he added: "The bottom-line message to pregnant women is that, if they've received the vaccine, to make sure they're enrolled in the registry and make sure they keep up with their routine prenatal care."

Write to John Carreyrou at john.carreyrou@wsj.com