By MAGGIE MAHAR

I first wrote about Gardasil on The American Prospect online in the summer of 2006, just weeks before the Merck vaccine designed to protect against cervical cancer went to market.

There, I noted that “the hullabaloo began in June when the FDA approved Gardasil, a vaccine widely described as ‘100 percent effective’ in preventing cervical cancer, a disease that kills some 233,000 women worldwide each year. The drumbeat grew louder last month when a federal panel recommended that all American girls and women ages 11 to 26 should be inoculated. And now there is talk that states may mandate the vaccine for all school-age children.

“But before prescribing for the entire population,” I suggested, “it’s worth asking a few questions: Why does the vaccine cost $360 for a three-shot regimen? How much do we know about the new product? And is this a cost-effective use of health-care dollars?”

I reported what we knew at the time: Although Gardasil was commonly described as “100 percent effective” if you scrolled down far enough in most news stories, you would find that the vaccine is “100 percent effective” against  “only two strains of HPV (human papillomavirus) that causes cervical cancer. And those two account for just 70 percent of all cases. The vaccine has no effect on the viral strains which account for the other 30 percent.”

Read a little further and you would discover that because the vaccine protects against less than three-quarters of all cases, inoculated patients still will need regular Pap smear tests to check for signs of the disease.

Meanwhile, in the United States, the $30 Pap smear had already proved remarkably effective in winning the war on cervical cancer. Thanks to this relatively simple test, the National Institute of Health lists cervical cancer as a “rare disease.”

Merck Needs a Blockbuster— Sowing the Seeds of Fear

Why, then the sudden need for a vaccine against what had become a rare disease?

The simple truth is that after Merck was forced to withdraw Vioxx from the market it desperately needed a new blockbuster. Vioxx was the popular pain-killer that, it turned out, caused heart attacks and strokes in some patients. (Vioxx, like Gardasil had been “fast-tracked” through the FDA.) Merck now faced some 11,500 lawsuits. Meanwhile other Merck drugs were facing stiff competition from generics. Merck needed a new best-selling drug—and it needed it quickly.

In the mainstream media, the only publication that seems to have truly understood from the outset, what this story was really about is The Wall Street Journal. This was, after all, a business story. As the Journal explained early in 2007: “Mandatory vaccination across the U.S. would make an automatic blockbuster for Merck at a time when the patents on some of its bestselling drugs are expiring and it’s desperate to replace their revenue streams.”

Merck’s marketers skillfully laid groundwork for their new product. Even before Gardasil was approved by the FDA, Merck funded an elaborate television and magazine campaign which stressed the connection between HPV and cervical cancer. The “Tell Someone” ads depicted mothers, with arms around their daughters, expressing surprise as they learn how many people are infected by HPV:

“Millions? That’s insane,” says one woman, wide-eyed.

“You can have HPV and not even know it,” says another professional actress.

Merck’s logo flashes briefly on the screen with no mention that it has a product on the way. Many women thought that they were watching a public-service announcement.

The ads exaggerated the threat. While the vast majority of sexually active women can expect to be infected by HPV at some point during their lives, most of these infections clear up without doing harm. Only a small percentage lead to changes in the cervix that can develop into cancer. Even then, years elapse between the initial infection and the development of malignancy, leaving plenty of time for a Pap smear to detect and prevent the cancer.

Merck made sure that the FDA fast-tracked the product — as if the nation faced a sudden scourge of cervical cancer. Because the drug was pushed through the FDA, the average patient in the Gardasil trials was followed for just three and a half years. As a result, no one knew how long the vaccine would last.

Merck could only say that it believed the vaccine will remain effective “for at least five years.” After that, patients might well need expensive booster shots. And that expense could easily wipe out any savings achieved by avoiding “false positive” Pap tests.

Meanwhile, of the more than 25,000 patients who participated in clinical trials of Gardasil, only 1,184 were preteen girls. No one knew what the long-term effect would be if 12 and 13 year olds were vaccinated. As the Journal noted early in 2007, “A growing number of parents are worried about exposing their children to the unforeseen side effects of a new vaccine to protect them from a disease that is no longer very common in the U.S…Adding to some parents’ concern, 82 adverse events among both teens and adult women have been reported since Gardasil became available last June.”

Nevertheless, Merck launched an aggressive lobbying campaign to persuade politicians that every 12 and 13 year-old girl in the U.S. should be vaccinated and that the states should pay for it.

The campaign was not about saving women’s lives. It was, as the Journal so clearly understood, about money. It was about Merck’s frantic need to replace the revenue that it lost when it was forced to pull Vioxx from the market.  Some called Gardasil the “Help Merck Pay For Vioxx Vaccine.”

Nevertheless, it was true that cervical cancer still killed some women in the U.S. In 2006, it was estimated that 3,700 American women would die of cervical cancer. At the time, I wrote “Those deaths cannot and should not be ignored. But most could have been saved by regular Pap smears. According to a study published in The New England Journal of Medicine, “more than half of all cases occurred in women who had never or rarely” had a Pap smear. Most of these women were “poor or members of a minority.”

Here, I couldn’t help but wonder: “How many of them will receive the $360 vaccine?”

“Wouldn’t it be cheaper — and safer– to set up a government program that ensures that all girls and women are screened regularly? While the vaccine protects against just 70 percent of all cervical cancers, Pap smears detect 90 to 95 percent.

“If we had true universal screening—as in some Scandinavian countries—we probably wouldn’t need both the vaccine and screening,” acknowledged Dr. Evan R. Myers, a physician at Duke University who has served as a consultant to Merck told me. (Those Scandinavian countries’ national health insurance guarantees Pap smears—and there are no co-pays.)

In developing countries in Africa and elsewhere, regular Pap smears are not available. In these countries Gardasil could save millions of lives. But when I called Merck to ask whether it might offer discounts to poorer countries, a Merck spokesman said that the question was “premature.” For now, the company is eying the “118 to 120 million women in the 11 to 26 age range in the U.S., the EU, and other high-income countries.” [Merck still hasn’t made Gardasil available in developing countries.]

Granted, the vaccine is not without benefits. It protects against cervical warts which are not life-threatening, but are embarrassing and painful. And it could reduce the number of “false positives” following a Pap smear—false alarms that lead to follow-up tests and treatments that could lead to unnecessary tests and treatments.  Nevertheless is it worth it for taxpayers to lay out $400 to $1,000 ($360 for the three dose vaccine, plus mark-ups and the cost of three office visits) to protect against the possibility of warts and false positives?

Six Months Later:  A NY Times Editorial Hails Gardasil

As a skeptic, I was in the minority.  By the time I  again wrote about Gardasil  on The Health Care Blog in February of 2007,  the New York Times had endorsed the vaccine in a glowing editorial congratulating Texas governor Rick Perry for mandating “A Vaccine To  Save Women’s Lives.” (As it happened, Perry’s former chief of staff was a Merck lobbyist. Subsequently, it was revealed that Merck had contributed $6,000 to the governor and $38,000 to other legislators. In the wake of the scandal Perry’s mandate was overturned by the Texas Legislature, 181 to 3.)

In my 2007 post on The Health Care Blog, I noted growing concerns that once girls thought they were “vaccinated” against cervical cancer, they might begin skipping the Pap smears needed to protect against the other viruses connected to roughly one-third of all cancers.  A 2003 study published in JAMA had cautioned that “women who are vaccinated [will] perceive themselves to be at low risk for developing cancer and, as a result [will] not participate in screening as recommended.” If they are lulled into a false sense of complacency, the study acknowledged “gains from the vaccination may be offset.”

A week before I wrote that post, I saw a report on NBC which featured a young girl in Texas explaining why she was happy to have been vaccinated: “Now this is one cancer I don’t have to worry about fighting.” No one corrected her.

Flash Forward 18 months: $1.4 Billion and Tens of Millions of Girls Later; Doctors Paid $4,500 per lecture to Hawk the Drug.

“In two years, cervical cancer has gone from obscure killer confined mostly to poor nations to the West’s disease of the moment,” the New York Times reported Tuesday, in a story headlined: “The Evidence Gap:  Drugmakers’ Push Leads to Cancer Vaccines Rise.”

Finally, the Times, too, understands. This is not a story about health care. It is a story about money:

“Tens of millions of girls in the U.S. and Europe” have now been vaccinated the Times reported. “The lightning-fast transition from newly minted vaccine to must-have injection in the United States and Europe represents a triumph of what the manufacturers call education and their critics call marketing.”

“Award-winning advertising has promoted the vaccine. Before the film ‘Sex and the City’ some moviegoers in the United States saw ads for Gardasil. On YouTube and in advertisements on popular shows like ‘Law and Order,’ a multi-ethnic cast of young professionals urges girls to become ‘one less statistic’ by getting vaccinated.”

But as the Times now describes it, Merck’s much ballyhooed breakthrough offers only “some protection against infection . . . . from human papillomavirus, or HPV, a common and generally benign sexually transmitted virus that can in rare cases cause cancer after years of silent infection.

“Meanwhile, it is far more expensive than earlier vaccines against other diseases — Gardasil’s list price is $360 for the three-dose series, and the total cost is typically $400 to nearly $1,000 … But with their high price, the vaccines are straining national and state health budgets as well as family pocketbooks.”

Noting  that GlaxoSmithKline has introduced a second vaccine, marketed under the brand name Cervarix, the Times points out that  “these were the first vaccines approved for universal use in any age group that clearly cost the health system money rather than saved it.” By contrast, inexpensive vaccines to protect against measles and tetanus more than pay for themselves by protecting against costly diseases. But Merck was so successful in fueling fear of the HIV virus that it was able to ask $360.

Because Gardasil and Cervarix are so pricey, the Times reported, “countries that pay for the vaccines will have less money available for other health needs. “This kind of money could be better used to solve so many other problems in women’s health,” Dr. Abby Lippman a professor at McGill University in Montreal and policy director of the Canadian Women’s Health Network told the Times.

Meanwhile “Some experts are concerned about possible side effects that become apparent only after a vaccine has been more widely tested over longer periods.” They “worry about the consequences of the rapid rollout of the new vaccines without more medical evidence…They say that because of the aggressive marketing, even parents of girls who are far from being sexually active may feel pressured into giving them a vaccine that is not yet needed and whose long-term impact is still unclear. Legislative efforts to require girls to have the vaccine only add to the pressure.

In 2006 , hundreds of doctors and nurses were recruited and trained to give talks about Gardasil — $4,500 for each 50-minute talk, delivered over Merck-sponsored meals. Some have made hundreds of thousands of dollars.

“’This big push is making people crazy — thinking they’re bad moms if they don’t get their kids vaccinated,’” McGill’s Lippman added.

“And why the sudden alarm in developed countries about cervical cancer?” the Times asks. “ A major killer in the developing world, particularly Africa, where the vaccines are too expensive for use, cervical cancer is classified as very rare in the West because it is almost always preventable through regular Pap smears, which detect precancerous cells early enough for effective treatment. Indeed, because the vaccines prevent only 70 percent of cervical cancers, Pap smear screening must continue anyway.

“‘Merck lobbied every opinion leader, women’s group, medical society, politicians, and went directly to the people — it created a sense of panic that says you have to have this vaccine now,’ said Dr. Diane Harper, a professor of medicine at Dartmouth Medical School. Dr. Harper was a principal investigator on the clinical trials of both Gardasil and Cervarix.

“Because Merck was so aggressive, it went too fast,” Dr. Harper told the Times. “I would have liked to see it go much slower.”

In receiving expedited consideration from the Food and Drug Administration, Gardasil took six months from application to approval and was recommended by the C.D.C. weeks later for universal use among girls. “Most vaccines take three years to get that sort of endorsement,” Dr. Harper told the Times, “and then 5 to 10 more for universal acceptance.

“In that time, you learn a lot about safety and side effects and how to use it,” she added.

Despite the uncertainty about long-term risks and side effects, 24 states have considered proposals to mandate the vaccine for girls, generally in middle school. According to the Times, “Many bills, like ones passed in Colorado, New Jersey and New York, allocate more money for HPV and cervical cancer education or to promote the vaccine. Others, like proposals in Iowa and Louisiana, require insurers to cover it.”

Virginia has passed a bill requiring the vaccine for school entry; it takes effect in October, after school begins, so will first apply in 2009. “Merck has a growing economic interest in Virginia,” the Times noted. “In December 2006, Merck announced it would invest $57 million to expand its Elkton, Va., plant to make Gardasil, helped by a $700,000 grant from a state economic development agency that is part of the executive branch. Two months later, Gov. Tim Kaine, who has been mentioned as a possible Democratic vice presidential candidate, signed legislation requiring Gardasil for schoolgirls. Four months after that, Merck pledged to invest $193 million more in the plant to make drugs and vaccines, helped by a state grant of $1.5 million.”

What We Still Don’t Know

No one knows how long the immunity will last. Even commercials for Gardasil say — in small print — that “the duration of protection has not been established.”

According to Dartmouth’s Dr. Harper,  in the data from Merck’s clinical trials, which she helped conduct, the vaccine was no longer protective after just three years in some girls: “The immunity of Gardasil will not last — that is dangerous to assume.”

Other experts worry that eliminating the two cancer-causing HPV strains covered by Gardasil and Cervarix might allow the other cancer-causing strains of HPV to increase in frequency, reducing the vaccine’s effect.

Finally, Physicians are still trying to determine just how risky the vaccines are.

Health care centers are asked to report side effects to the Center of Disease Control. There have been 9,749 voluntary reports, almost all from doctors and nurses, of patients experiencing adverse events after receiving the vaccine, the agency announced in a joint report with the Food and Drug Administration at the end of June. According to the Times, “Ninety-four percent of them were not serious, ranging from arm pain to fainting.” But 6 percent were classified as serious, including blood clots, and paralysis. There have been at least 20 deaths.”

Maggie Mahar is an award winning journalist and author. A frequent contributor to THCB, her work has appeared in the New York Times, Barron’s and Institutional Investor. She is the author of  “Money-Driven Medicine: The Real Reason Why Healthcare Costs So Much,” an examination of the economic forces driving the health care system. A fellow at the Century Foundation, Maggie is also the author the increasingly influential HealthBeat blog, one of our favorite health care reads, where this piece first appeared.