Experts Debate Whether Gardasil Marketing Clouds Risk/Benefit Decision
Daniel J. DeNoon
WebMD Health News
Reviewed By Louise Chang, MD
Aug. 18, 2009 – Merck's Gardasil won the Pharmaceutical Executive 2006 "brand of the year" award for "creating a market out of thin air." But is the HPV vaccine oversold?
The charge comes from a "special communication" and an editorial in the Aug. 19 issue of The Journal of the American Medical Association.
The articles say professional medical associations worked with Merck to overstate the vaccine's ability to prevent cervical cancer -- even before studies proved Gardasil can prevent precancerous cervical lesions.
Overselling the HPV vaccine's benefits makes it impossible for parents and young women to judge whether the vaccine's risks are worth taking, says editorialist Charlotte Haug, MD, PhD, editor-in-chief of the Journal of the Norwegian Medical Association.
"If it were a perfect vaccine you would never have to think about cervical cancer again. But it is effective against two of the strains of the virus, and there are at least 20 cancer-causing strains out there," Haug tells WebMD. "It is true these strains cause 70% of cervical cancers, but what happens when we take these two strains away? If you kill the weeds in your lawn, there will not always be a hole there. Something will take their place."
Just because we don't know this doesn't mean the vaccine isn't valuable, says Janet Englund, MD, an infectious disease pediatrician at Seattle Children's Hospital. Englund chairs the HPV Working Group of the CDC's Advisory Committee on Immunization Practices (ACIP).
"It is true we don't know for sure about the vaccine's long-term ability to prevent high-grade cancer," Englund tells WebMD. "My assessment, my personal viewpoint, is there is very good evidence for both reduction of [precancerous] cervical intraepithelial neoplasia -- it is really clear -- and that there is reduction of genital warts."
For Englund, it's not merely an abstract opinion.
"I have vaccinated my children," she says. "I take the risks and benefits into consideration, and I think the benefits outweigh the risks."
HPV, human papillomavirus, is a very common sexually transmitted infection. Most sexually active women and men get the virus -- often more than once, and often with more than one strain. Usually, the immune system clears the virus. But sometimes it sticks around. Some strains of the virus cause genital warts. Other strains cause cancer.
Gardasil protects against four of the more than 100 strains of HPV: the two strains that cause most cervical cancers, and two strains linked to genital warts. The vaccine is most effective if given to girls before they become sexually active. It can be given as early as age 9; the CDC recommends it for 11- and 12-year-old girls. The vaccine costs $300 to $500, but is covered by the U.S. Vaccines For Children program.
Gardasil Oversold by Medical Groups?
Columbia University researchers Sheila Rothman, PhD, and David Rothman, PhD, suggest that at least three medical associations used funds and other assistance from Merck to create educational materials for non-specialist doctors that promoted Gardasil.
"Doctors may not know that this education is not being done by a group of experts in the field but that it is all being orchestrated by the drug company," Sheila Rothman tells WebMD.
Stewart Massad, MD, ethics chair for the American Society for Colposcopy and Cervical Pathology -- one of the groups named by the Rothmans -- says that although the Rothmans are right that his group supports HPV vaccination, they are wrong to say Merck wrote their educational materials.
"HPV vaccine is a revolutionary advance that promises to change the way cervical cancer is prevented," Massad tells WebMD. "We thought our members needed to know about it. We sought funding from elsewhere, but we were not able to find nonprofit or government funding to fill the costs. We disclosed Merck's support in all the materials we distributed, and Merck had no role in writing them. They signed off on the concept but were not allowed to have any input on material that was developed."
The Society of Gynecologic Oncologists said in a statement provided to WebMD that its materials are unbiased. The third group named by the Rothmans, the American College Health Association, did not respond to WebMD's request for comment.
But the Rothmans' article suggests that these medical associations overemphasized the risk posed by HPV and overstated the scientific evidence supporting Gardasil's ability to prevent cancer.
"The fact is that most of the HPV infections are symptomless; most of it goes away by itself," Rothman says. "Only 10% of infections go on to become lesions. Yes, we have causative agent and a disease. But it is not a straight line to get there. And what the company did was create a straight line and get the organizations to go along with it and legitimize it."
Richard M. Haupt, MD, MPH, Merck's executive director of clinical research, says Rothman is wrong.
"There is very good evidence regarding the line leading from HPV infection to cancer," Haupt tells WebMD. "If you don't get infection with these cancer-causing strains of HPV, you don't get cervical cancer."
Massad says the line between HPV infection and cervical cancer may be blurry -- but it's a line all the same.
"Most women who get HPV are never at risk for cervical cancer -- but we don't have a way to tell who is and who is not at risk," Massad says. "It seems better to do widespread vaccination than not to take any action all."
Haug says such an approach ignores the cost of the vaccine, and the risk of vaccination to women who might never get cervical cancer.
HPV Vaccine, Pap Screens, and Cervical Cancer
Rothman notes that whether or not women receive the vaccine, they still need regular Pap screening to look for early signs of cervical cancer. Screening cuts their risk of cervical cancer, and thus cuts the benefit of HPV vaccination.
Haug notes that the U.S. women who get cervical cancer are those with the least access to health care. Those who get regular Pap tests, she says, are unlikely to get cervical cancer even if they don't get vaccinated against HPV.
"We already have a way of preventing cervical cancer -- that is a major point, at least for those of us lucky enough to have health care and use it. So this can be prevented without the vaccine," Haug says.
That's not entirely true, says Haupt.
"While Pap screening is a very important intervention, it is not perfect. Not all women get Pap testing, and not all women who get Pap tests will have their lesions found," Haupt tells WebMD. "And even with 50 years of Pap testing, we see 30 cases of cervical cancer a day in the U.S. Vaccination is another tool that together with Pap screening will contribute to cancer prevention. Neither one works as well without the other."
"We still have people dying of cervical cancer here in the U.S.," Englund says. "It is easy to say we can prevent cervical cancer with Pap screening, but people are not getting Pap screens: minority women, our native people, poorer people. So when you talk of risks and benefits, people must realize that some don't have the benefit of having the wonderful health care I enjoy because I have health insurance. But they still have the risk of cervical cancer."
A CDC report -- appearing in the in the same issue of The Journal of the American Medical Association -- summarizes adverse events associated with Gardasil from its June 2006 approval through December 2008.
The report finds only one major safety issue worthy of further study: There might be a higher-than-expected number of blood clots in women who received the vaccine.
Study leader Barbara A. Slade, MD, a medical officer at the CDC, notes that the reports do not prove a link between the vaccine and adverse events. The reports do, however, point to potential risks that require further study.
"This is something worth looking at," Slade tells WebMD. "Now nearly all the people with blood clots had one of the known risks: estrogen birth control, obesity, one of the genetic mutations that puts you at risk. Most had one if not more than one of these risks."
Further study will be needed to show whether these blood clots are actually caused by the vaccine; such studies already are under way.
SOURCES: Haug, C. The Journal of the American Medical Association, Aug. 19, 2009; vol 302: pp 795-796. Rothman, S.M. and Rothman, D.J. The Journal of the American Medical Association, Aug. 19, 2009; vol 302: pp 781-786. Slade, B.A.The Journal of the American Medical Association, Aug. 19, 2009; vol 302: pp 750-757. Barbara A. Slade, MD, medical officer, immunization safety office, CDC, Atlanta. Richard M. Haupt, MD, MPH, executive director, clinical research, infectious diseases & vaccines, Merck Research Laboratories. Charlotte Haug, MD, PhD, editor-in-chief, The Journal of the Norwegian Medical Association, Oslo, Norway. Sheila M Rothman, PhD, professor of sociomedical sciences, Mailman School of Public Health, Columbia University; deputy director, Center for Study of Society and Medicine, Columbia College of Physicians and Surgeons, New York. Stewart Massad, MD, assistant secretary, board of directors; chair, practice and ethics committee, American Society for Colposcopy and Cervical Pathology. Society of Gynecological Oncologists, statement, Aug. 18, 2009. Janet Englund, MD, professor of pediatrics, University of Washington; head, pediatric transplant infectious diseases, Seattle Children's Hospital and Fred Hutchinson Cancer Research Center; chair, HPV working group, Advisory Committee on Immunization Practices;head, Pediatric Transplant ID, Seattle Children's Hospital/Fred Hutchinson Cancer Research Center; chairperson, HPV working group of the ACIP. Herskovits, B. Pharmaceutical Executive, Feb. 1, 2007; accessed online Aug. 18, 2009.
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