ID Consult

Check Gardasil Adverse-Event Data


 

pdnews@elsevier.com

Since July 22nd, you have no doubt received phone calls from anxious parents who heard the news report about adverse events associated with the human papillomavirus vaccine, Gardasil. As usual, the media did a good job of creating anxiety both among parents and prescribing physicians. I've heard how much time clinicians now are spending discussing vaccine safety with their patients, and that some have begun administering the HPV vaccine separately from other recommended adolescent vaccines and others have just stopped giving it altogether.

I'd like to review what we know so that you can be prepared to answer questions and, I hope, alleviate fears about Gardasil and other recommended childhood and adolescent vaccines. A statement, issued jointly by the Centers for Disease Control and Prevention and the Food and Drug Administration, summarized all reports concerning Gardasil that were filed with the Vaccine Adverse Events Reporting System (VAERS) from the time the vaccine was licensed on June 8, 2006, through June 30, 2008.

A total of 9,749 adverse events were reported to VAERS in association with administration of Gardasil, of which 94% were classified as nonserious events, and 6% as serious events. It's important to keep in mind the denominator: At the time the statement was issued, Merck & Co. had distributed over 16 million doses of Gardasil in the United States.

Also remember that VAERS is a passive reporting system that receives unconfirmed reports of possible side effects following the use of all vaccines licensed in the United States.

Data from the system are reviewed on an ongoing basis to look for possible signals that require further investigation. Data from VAERS cannot and should not be viewed as implying causation.

The 9,164 nonserious reports included syncope, injection site pain, headache, nausea, and fever. Indeed, fainting after receipt of any vaccine is common among teenagers. Providers are reminded to keep patients seated for at least 15 minutes after vaccination to avoid injury from a possible fall.

The 585 serious adverse events included 20 deaths. There was no common pattern to these deaths that would suggest they were caused by the vaccine. Where autopsy results were available, the cause of death was unrelated to vaccine.

Other serious adverse event reports following receipt of Gardasil were attributable to Guillain-Barre Syndrome, a rare neurologic disorder for which the typical attack rate is highest during adolescence. Further investigation by FDA and CDC found no increase in GBS cases beyond the expected number among Gardasil recipients.

Thromboembolic disorders also were reported following vaccination with Gardasil, most of which occurred in individuals with risk factors for clotting, such as oral contraceptive use.

In addition to VAERS, there also is a safety monitoring system called the Vaccine Safety Datalink Project, a collaboration between CDC and eight managed care organizations that is set up to investigate any possible safety signals arising from VAERS. Gardasil and all other vaccines are monitored with these systems on an ongoing basis. In the meantime, the CDC has not made any changes to its recommendations for the use of Gardasil based on the available information, nor has the FDA revised its prescribing information.

Gardasil, the first HPV vaccine to be licensed, was approved for use in girls and women aged 9-26 years. It was recommended by the CDC's Advisory Committee on Immunization Practices (ACIP) as a three-dose series for routine vaccination of girls aged 11-12 years, and for catch-up in girls and women aged 13-26 years.

The vaccine is made from noninfectious particles, not live or attenuated virus. It contains no thimerosal. It protects against HPV strains 16 and 18, which cause 70% of all cervical cancers, and strains 6 and 11, responsible for 90% of all genital warts in the United States. Data show that the vaccine is most effective when given prior to onset of sexual activity.

When speaking with a worried parent, I think it's critical to explain that association does not imply causation. I also would review the rationale behind giving the HPV vaccine and reiterate that maximum benefit is achieved by immunization before sexual debut.

Every year, about 12,000 women in the United States are diagnosed with cervical cancer and almost 4,000 die from it. Worldwide, cervical cancer is the second most common cancer in women, causing an estimated 470,000 new cases and 233,000 deaths per year. I don't think you can put a price on the value of saving lives by administering a vaccine, although of course plenty of health economists have tried to do just that.

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