Study Examines Cost-Effectiveness of HPV Vaccine

The cost of administering human papillomavirus vaccines is justified in pre-adolescent girls but becomes less so as the age of women receiving the injection increases, according to a study published Thursday in the New England Journal of Medicine, the Wall Street Journal reports. In clinical trials, the vaccines have been shown to be 100% effective in preventing infection with HPV strains 16 and 18, which together cause about 70% of cervical cancer cases (Loftus, Wall Street Journal, 8/21). FDA in July 2006 approved Merck's HPV vaccine Gardasil for sale and marketing to girls and women ages nine to 26, and CDC's Advisory Committee on Immunization Practices later that month voted unanimously to recommend that girls ages 11 and 12 receive the vaccine (Kaiser Daily Women's Health Policy Report, 2/23/07). CDC recommends that a temporary "catch-up" vaccination be given to women between 13 and 26 who were not immunized (Wall Street Journal, 8/21).

For the study, researchers at Harvard School of Public Health, led by assistant professor Jane Kim, used computer models to predict health outcomes of girls and women who are vaccinated and undergo recommended screenings. The calculations accounted for the cost of the vaccine, screenings and treating illnesses caused by HPV. To determine cost-effectiveness, researchers used widely accepted economic measures of how much society would be willing to pay to extend the life of each person by one year (Stobbe, AP/San Francisco Chronicle, 8/21).

The study concluded that vaccination costs about $43,600 per additional "quality-adjusted life year" when administered to 12-year-olds, assuming the vaccine provides lifelong protection. According to the Journal, many researchers use a $50,000-per-QALY limit to determine cost-effectiveness, while some other researchers use $100,000 as a limit. The study also found that extending the catch-up program cost about $97,300 to vaccinate girls and women through age 18, $120,400-per-QALY for girls and women through age 21 and $152,700 for girls and women up to age 26. The cost-effectiveness increases when protection against genital warts is considered, according to the Journal.

The cost-effectiveness of the vaccine would decrease if a booster is required, according to the study. The vaccine was studied for five years before receiving FDA approval and has been on the market for two years, so it is not certain whether it can provide lifelong protection against the virus, the Journal reports.

According to the Journal, the study likely will "fuel skepticism about Gardasil, which has already faced questions surrounding its safety and effectiveness" (Wall Street Journal, 8/21).

The study is available online.

Editorial
The HPV vaccines are being widely used without evidence of whether they are worth their higher cost or whether they will prevent women from getting cervical cancer, an accompanying NEJM editorial states, the New York Times reports. Charlotte Haug, editor of the Journal of the Norwegian Medical Association, writes, "Despite great expectations and promising results of clinical trials, we still lack sufficient evidence of an effective vaccine against cervical cancer," adding, "With so many essential questions still unanswered, there is good reason to be cautious." According to Haug, although it is true in theory, there is no absolute proof that protecting against the two strains of HPV targeted by the vaccine would result in reduced rates of cervical cancer. She also notes that the researchers have not shown the length of immunity offered by the vaccines, or whether protecting against some strains of HPV will decrease the body's natural immunity to other strains.

Richard Haupt, medical director for Merck, said these concerns were "very theoretical," adding that research is ongoing. He said that the vaccines would not increase vulnerability to other strains (Rosenthal, New York Times, 8/21).

The editorial is also available online.

New York Times Examines Marketing, Educational Efforts for Vaccines
The Times on Wednesday examined educational and marketing efforts by Merck and GlaxoSmithKline that have helped make Gardasil and Cervarix "must-have injections." Cervarix has not been approved for use in the U.S., and GSK said it would submit outstanding data from clinical trials to FDA early next year. According to the Times, tens of millions of girls and young women in the U.S. and Europe have been vaccinated with either Gardasil or Cervarix.

HPV causes fewer than one-tenth of the number of deaths caused by lung cancer or breast cancer, according to the Times. The virus "is nearly universal and generally benign. Eighty percent of people will contract HPV in their lifetime and most will clear it on their own," the Times reports.

The vaccines are the first approved for universal use that "clearly cost the health system money rather than saved it, in contrast to less-expensive shots -- against measles and tetanus, for example -- that pay for themselves by preventing costly diseases," the Times reports. Gardasil costs $360 for a three-dose series of shots.

According to the Times, the vaccines' quick rise in use and acceptance "represents a triumph" of what the vaccine makers call "education and their critics call marketing."

"Award-winning advertising" has been used to promote the vaccines, and Merck paid for hundreds of doctors and nurses in 2006 to attend a presentation where they learned about the vaccine, the Times reports. In addition, the vaccine makers have provided money for cervical cancer awareness activities, "sometimes in ways that skirt disclosure requirements or obscure the companies' involvement," the Times reports. Merck and GSK also lobbied lawmakers, and 24 states have considered proposals to make the vaccine mandatory for some girls.

While critics of the marketing recognize the vaccines' benefits, they also are concerned that the "aggressive marketing" could pressure some into getting the vaccines before all the risks are known, and legislative efforts to mandate the vaccine "only add to the pressure," the Times reports.

In addition, there is concern among some experts that the side effects of the vaccine might not become apparent until after the vaccine has been tested over longer periods of time. Further, it is uncertain how long the vaccines will remain effective after they are administered.

Haupt said that the five years the company spent testing Gardasil in clinical trials is a normal period of time before applying for FDA approval. He added that Merck spoke with physicians, lawmakers and the public about the vaccine to "accelerate and facilitate access." In addition, Merck and GSK spokespersons say that the vaccines are safe and effective and that there is no evidence that a booster shot would be needed (Rosenthal, New York Times, 8/20).