National report - Gardasil presents no significant safety concerns. That was the consensus of a Center for Disease Control (CDC) advisory committee following a review of safety studies of the human papillomavirus quadrivalent vaccine, manufactured by Merck, two years post-approval by the Food and Drug Administration (FDA).
- Gardasil presents no significant safety concerns. That was the consensus of a Center for Disease Control (CDC) advisory committee following a review of safety studies of the human papillomavirus quadrivalent vaccine, manufactured by Merck, two years post-approval by the Food and Drug Administration (FDA).
The vaccine protects against four strains of HPV (types 6, 11,16 and18) linked to the development of 70 percent of cervical cancers, and was also approved in September 2008 as protection against vulvar and vaginal cancers. The CDC panel reviewed reactions reported through the agency’s Vaccine Adverse Event Reporting System (VAERS), week-by-week reports from eight managed care organizations (Vaccine Safety Datalink - VSD) and the Clinical Immunization Safety Assessment network (CISA).
The VSD covered 375,000 doses administered to females ages 9 to 26 from August 2006 through July 2008.
The study found no increased risk of serious side effects, such as stroke, blood clotting, fainting, appendicitis, anaphylaxis or Guillain-Barre Syndrome.Overall, more than 20 million doses have been administered, with about 10,000 adverse events reported, including 27 deaths. Still, 94 percent of the events are rated non-serious - significantly fewer than other vaccines, which report 10 percent to15 percent serious events, according to the CDC.
John Iskander, M.D, Ph.D., associate director for the Science Immunization Safety Office, Division of Healthcare Quality Promotion, CDC, says, "The committee found the data, overall, quite reassuring with regard to the safety of this vaccine."
Still, support for the vaccine is not unanimous. Barbara Loe Fisher, founder of the National Vaccine Information Center (NVIC), a nonprofit educational organization dedicated to the prevention of childhood vaccine injuries and deaths through public health education, says her organization is not convinced of the safety, contending there are too many unexplained, troublesome reactions.
"Not all physicians report adverse reactions, so we’re concerned problems are severely under-reported.
"We know of healthy, athletic girls who had absolutely no problems before being vaccinated, who have had their health completely deteriorate. Some have even died. We think that is cause for concern," Ms. Fisher says.
Dr. Iskander says reports of deaths were examined in detail.
"If there were a link, we would expect to see a causal relationship with some pattern - similarity in age, dose number, time from vaccination to death, or similar cause of death. Those patterns just aren’t there," Dr. Iskander tells Dermatology Times.
Dr. Iskander adds that because the HPV vaccine is not a live vaccine, it doesn’t attack a compromised immune system.
A national study conducted by the University of Colorado indicates that 98 percent of pediatricians and 88 percent of family practitioners are vaccinating their patients. Half recommend the vaccine for girls ages 11 to 12, and 82 percent, for girls before they turn age 15.
A significant percentage of the doctors report that about a quarter of their parents refuse, either because the drug is too new, their daughters aren’t sexually active, or the drug isn’t covered by insurance - but not because of safety concerns.
Merck reports Gardasil sales were about 25 percent below projections in 2008. The company believes that is because doctors recommend the vaccine to younger girls, not for the 18- to 25-year-old group.
A study conducted at the Harvard School of Public Health questions the cost-effectiveness of prophylactic vaccinations in the older target population. The study indicates the cost of vaccinating girls younger than age 12 is $43,600 - below the $50,000 per quality-adjusted life year (QALY) considered cost-effective.
The study estimates the QALY cost increases quickly, however, to $120,000 at age 18 and $152,000 by age 25.
A primary factor is the assumption that older females are exposed to HPV strains through sexual activity, rendering the protection less effective.
Also, Pap smears are still needed to screen for HPV types not covered by Gardasil.
Merck disputes the QALY figures. Senior medical director Gregg Sylvester, M.D., says QALY models can differ and yet both can be valid.
"Our model shows vaccinating females from [ages] 12 to 24 costs $8,586 per QALY. Government agencies consider various models when making their recommendations," he says.
"We’re confident that immunization up to the age of 26 is still cost-effective. Just because a woman is sexually active does not mean that she’s contracted an HPV, and if exposed to one strain, [she] is still protected against the other types.
"There are many single and divorced women dating after 26. If they haven’t had all four HPV strains, there is still some protection.
"It’s not only dying of cervical cancer, but when you think of the cost and morbidity of treating cervical dysplasia, the vaccine becomes a clear-cut ‘yes,&38217" Dr. Sylvester says.
Diane Harper, M.D., M.P.H., M.S., professor at Dartmouth College in Hanover, N.H., conducted phase 2 and 3 trials on both Gardasil and GlaxoSmithKline’s Cervarix, an HPV vaccine yet been approved in the United States, and encourages Gardasil primarily for women in their 20s.
"Syncope occurs more frequently among 11- to 15-year-olds, but neurological systems have completely developed in the older age group, and there is no insult to them at this age," Dr. Harper says.
Dermatologist Jeffrey Weinberg, M.D., director of clinical research, Beth Israel Medical Center, New York City, contends cancer is not the only justification for using Gardasil.
"Genital warts are not life-threatening, but they’re aggravating, and are spreading like wildfire.
"Cancers and warts cause morbidity, mortality and social impact. You have to consider safety, but as efficacious as this drug is, it’s use is essential," Dr. Weinberg says.
"If you save young women from cancer, isn't it worth the money?"
More recently, an Australian study reported the incidence of anaphylaxis in one Australian state was 20 times higher with Gardasil than for similar, school-based meningitis vaccination programs. Dr. Iskander says no similar increased risk of anaphylaxis was found in the United States.
Houston dermatologist Stephen Tyring, M.D., considers the anaphylaxis concern over-rated.
"There’s a risk of reaction with any vaccine, even a placebo, so when we give Gardasil, we ask patients to wait to make sure there is no immediate reaction.
"But dying of cervical cancer is certainly more dangerous than the slim chance of an allergic reaction," Dr. Tyring says. DT