E-DRUG: HPV vaccine (2)
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E-drug colleagues:
In response to Dr. Lambert's message of March 29, I would like to share some information that may be helpful in developing a more accurate understanding of the various characteristics of the new HPV vaccines:
· It is true that Phase III data on the Merck vaccine (Gardasil) have not yet been published in the literature, but all of the data were reviewed by the scientists at USFDA prior to licensure in the US and by the scientists at the Advisory Committee on Immunization Practices (ACIP) of the US Centers for Disease Control prior to recommendations being made for use of the vaccine. The scientists at the European Medicines Agency (EMEA) also have reviewed the studies and approved the vaccine. So we feel that it is unfair to suggest that the data have "never been submitted to scientific scrutiny." E-drug readers also have the opportunity to examine the Phase III data as they are available for public review at the USFDA website referenced in Dr. Lambert's posting.
· Why have the data not yet appeared in the literature? We at PATH are not involved in this process, but we know that the studies included more than 20,000 women in multiple countries and we are aware that it takes time to ready such data for publication (getting agreement among researchers, resolving reviewer inquiries, etc.). Perhaps this explains the delay. But like Dr. Lambert, we look forward to publication of the papers.
· Regarding the Phase III outcomes-persistent infection and CIN 2/3-these were the agreed upon outcomes as a result of a WHO meeting and, again, were considered appropriate by both the USFDA and the EMEA. One might prefer to be able to measure prevention of actual cancer, but in a clinical trial population that is by design receiving regular follow-up, it was considered unethical to overlook recognizable pre-cancers and allow them to progress to cancer. In addition, it would require waiting 2-3 decades for cancer to develop given the natural history of HPV infection and resultant invasive cancer.
· We are a bit confused by the statement "a few conference abstracts report on the efficacy of the vaccine...but only due to vaccine type." We assume that the author meant "...only due to HPV type." But in fact that is not true-D. Harper et al. 2006 report on the impact on all high-risk HPV types (not only HPV-16 and -18) and Merck included all types in their USFDA filing.
· Regarding the statements "...the efficacy does not look nearly as good as some try to make us believe" and "...overall vaccine efficacy in preventing CIN2 or above...was 39%)," we feel that these figures, while true, are being presented out of context. The 39% efficacy figure is for all women, including those who have already been infected by one or more HPV types. But the vaccines are meant for HPV-naïve women-those who have never been infected by HPV-and this is why the recommendation is to vaccinate young women prior to sexual debut.
· In our opinion the clinical trial data are clear: vaccine efficacy against HPV 16 and 18 among HPV-naive women is incredibly high-the vaccines are at least 95 percent effective in preventing persistent HPV infection and 100 percent effective in preventing type-specific cervical lesions.
We hope that these clarifications are helpful to move the discussion along.
Vivien Tsu
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Vivien Davis Tsu, PhD, MPH
Senior Program Officer
PATH
1455 NW Leary Way, Seattle WA 98107
tel: +1.206.285.3500 | fax: +1.206.285.6619 www.path.org <http://www.path.org/> | PATH: A catalyst for global health