Postlicensure safety: Gardasil not associated with increased adverse events

FDA, CDC confirm safety of HPV vaccine.

A review of 12,424 incidents reported to the Vaccine Adverse Event Reporting System showed that patients assigned to the HPV vaccine Gardasil did not experience adverse events at rates greater than background rates when compared with other vaccines.

Based on these findings, the FDA and the CDC released a statement Aug. 24 that said, “Gardasil continues to be safe and effective, and its benefits continue to outweigh its risks.” The statement also indicated that neither agency has changed its recommendations for use of the vaccine.

In the August issue of Journal of the American Medical Association, researchers with the FDA and CDC concluded that the safety profile for quadrivalent HPV vaccine (Gardasil, Merck) was consistent with the prelicensure data.

The Vaccine Adverse Event Reporting System (VAERS) is a national, passive and voluntary surveillance system jointly operated by the FDA and CDC. Researchers studied incidents reported to VAERS from June 2006 to December 2008. There were 23 million doses of the vaccine administered during that time.

Vasovagal syncope was the most commonly reported adverse event (15%). Barbara A. Slade, MD, of the CDC, and colleagues said syncope was particularly prevalent among girls aged 11 to 18, a group that has a higher background rate of syncope than other age groups.

Dizziness (14%) was the second most common adverse event followed by nausea (9%), headache (8%) and injection site reactions (7.5%). The researchers said that on average, each report listed 3.7 codes for adverse effects.

Serious effects

Only 6.2% of reports were considered serious, including 32 reports of death. Two deaths were attributed to venous thromboembolism in women who had used oral contraceptives, which can increase the risk for VTE by as much as sixfold.

The researchers observed 42 cases of Guillain-Barré syndrome in patients administered the vaccine. The RR was 0.3 per 100,000 person-years for Guillain-Barré syndrome following vaccination.

“To date, there is no evidence that Gardasil has increased the rate of Guillain-Barré syndrome above that expected in the population,” FDA and CDC officials said in their statement. “While we continue to carefully analyze all reports of Guillain-Barré submitted to VAERS, the data do not currently suggest an association between Gardasil and Guillain-Barré syndrome.”

Though it appears the vaccine is safe, study researchers cautioned against making too much of these findings.

“VAERS data need to be interpreted with caution because not all reported events are systematically validated, and many may have only coincidentally followed vaccination,” they wrote. “In addition, data limitations include underreporting, inconsistency in the quality and completeness of reported data, stimulated reporting due to extensive news coverage and reporting biases.”

Marketing angle

In an editorial in the same issue, Sheila M. Rothman, PhD, of Mailman School of Public Health in New York, and David J. Rothman, PhD, of Columbia College of Physicians and Surgeons in New York, said that safe or not, the way the vaccine was sold to the public minimized the risk from sexually transmitted HPV and oversold the size of the population at risk for cervical cancer from HPV while ignoring those most at risk for the disease.

“Marketing this HPV vaccine as an anticancer vaccine appears to have enabled its manufacturer to circumvent possible parental and public unease with an antidote to STDs. But in doing so, the company bypassed public health officials who would have spearheaded a risk-sensitive vaccination campaign. So too, this manufacturer understandably wanted as many adolescents as possible to be vaccinated. But the pursuit of this goal was neither cost-effective nor equitable,” they wrote. “It meant rather than concentrating on populations in geographic areas with excess cervical cancer mortality, including African-Americans in the South, Latinos along the Texas–Mexico border and whites in Appalachia, the marketing campaign posited that every girl was at equal risk: ‘Your daughter could become one less life affected by cervical cancer.’”

There are still questions, the physicians noted, about whether the vaccine would have any effect on rates of cervical cancer. They added that economic analysis showed the vaccine was only cost-effective when administered to girls aged younger than 16 and if it demonstrated efficacy for more than five years.

Rothman and Rothman also criticized professional medical associations such as the Society of Gynecologic Oncologists and the American College Health Association for working too closely with Merck to promote the vaccine. They called for more transparency in the associations’ dealings with industry and said “under no circumstances should professional medical associations administer product-specific speakers’ bureaus, nor should they accept funding that requires them to report activity to the donor.

“It is important for professional medical associations to advocate for vaccination as a public good, but recommendations must be consistent with appropriate and cost-effective use,” they wrote. “In no other way will adolescents’ or anyone else’s health and quality of life be enhanced.”

For more information:

• Haug C. JAMA. 2009;302:795-796.
• Rothman SM. JAMA. 2009;302:781-786.
• Slade BA. JAMA. 2009;302:750-757.