ACIP: No HPV vaccine preference for females, no recommendation for Gardasil in males

News from the meeting of the Advisory Committee on Immunization Practices underway today in Atlanta:

In their morning session, the committee voted to expand its recommendation for HPV vaccination to include the newly-licensed Cervarix, making minor modifications reflecting technical differences regarding the administration of each vaccine.

More importantly, the ACIP expressed no preference between the two vaccines, instead simply noting that both Cervarix and Gardasil are recommended for cervical cancer prevention, while only Gardasil is recommended for prevention of both cervical cancer and genital warts.

By ACIP standards, in which most decisions are largely resolved by working groups prior to public meetings of the full committee, the decision not to express a preference generated significant discussion. Several members questioned the decision not to express preference for Gardasil, with one suggesting it may be perceived as suggesting that the ACIP did not view genital warts as important.

The majority opinion, voiced by ACIP chair Carol Baker, held that cervical cancer prevention was the primary goal of HPV vaccination. This goal would be best served by having two vaccines available, particularly in case of shortages, a common occurrence for vaccines with a single manufacturer. (The implication being that a preferential recommendation could jeopardize the market for and viability of the non-preferred vaccine.) In the end, only one member voted against the recommendation expressing no preference, an action that followed ACIP precedent when two similar vaccines are available against the same disease.

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Later this morning, the ACIP approved only a 'permissive statement' regarding vaccination of males against HPV with Gardasil, essentially stating that males may be vaccinated but stopping far short of the routine, universal recommendation common for most vaccines (including HPV vaccination in females). Despite endorsements for a routine recommendation from several liaison groups participating in the meeting, cost effectiveness data for male vaccination and concerns over the use of limited public health resources appeared to steer the committee away from a broad endorsement of male HPV vaccination.

The 'permissive statement' means that private insurers will be less likely to provide coverage of HPV vaccination for males, according to a representative from America's Health Insurance Plans (AHIP) in attendance at the meeting. Male vaccination will still be included in the Vaccines for Children program for uninsured and underinsured children, however. Historically, vaccines lacking a routine recommendation from the ACIP -- as is now the case for Gardasil in boys and men -- have had significant difficulty gaining widespread use.

We'll add links to coverage of today's developments as they're posted online.

FDA advisors support Gardasil for males, Cervarix for females

Yesterday was the busiest day in months for news on HPV vaccines, as the FDA Vaccines and Related Biological Products Advisory Committee met to consider applications by GSK for initial U.S. licensure of its HPV vaccine, Cervarix, for girls and women ages 10 to 25, and by Merck for an expanded licensed indication for its vaccine, Gardasil, for males (ages 9 to 26 -- the same age range for which it has been approved for use in females since 2006). Information and extensive materials related to the meeting are available here and here.

The committee found both vaccines to be safe and effective in their target populations, actions likely to mean FDA approval in the coming months for Cervarix (already available in over 100 countries) for women and Gardasil for both sexes. (The usual caveat: agencies such as FDA are not obligated to follow the recommendations of their advisory committees, but they almost always do in these circumstances.)

Here is coverage of the meeting from the New York Times, Philadelphia Inquirer, and Associated Press. Also of note are press releases from GSK and Merck on yesterday's news.

Assuming FDA follows the recommendations voted on yesterday, we are likely to see in 2010 a spirited advertising campaign by each manufacturer asserting superiority of its product over the competition. (This is an easier case for Merck to make, given the additional protection Gardasil provides against genital warts in both sexes. Early indications are that GSK will argue that Cervarix provides better protection against cervical cancer-causing HPV strains, including 'cross-protection' against additional strains not included in either vaccine.)

Also on the horizon is a decision by CDC (namely, the Advisory Committee on Immunization Practices) in the coming months regarding its recommendation for HPV vaccination. The history of the ACIP suggests that it is highly unlikely that the group will preferentially recommend one vaccine over the other for use in females. Instead, the current recommendation will probably be reworded to reflect the availability of both products and the slight differences between them with respect to administration.

More interesting will be its recommendation (or lack thereof) regarding male vaccination with Gardasil. Merck will no doubt be pushing for a universal recommendation that all males within the target age group receive the vaccine, and it will certainly have support from some corners of the medical and public health communities. However, the cost of the vaccine and the non-life-threatening nature of genital warts may make justifying universal vaccination of males difficult. (Another argument sure to surface is the indirect benefits for women resulting from male vaccination -- targeting a potential reservoir of cervical cancer-causing HPV. Despite its logical appeal, this strategy has not fared well in cost-effectiveness and other economic studies of HPV vaccination.)

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Speaking of male vaccination, our colleague Arthur Caplan co-authored (with Sarah Hull) a paper in the latest issue of Public Health Genomics titled, "The Case for Vaccinating Boys against Human Papillomavirus," (free abstract, subscription required for full text). As the title suggests, the authors argue for universal male vaccination against HPV, paying special attention to ethical arguments for such a policy.

Vaccines figure prominently in Time's "Year in Medicine"

The December 1 issue of Time magazine included several stories on health and medicine, including a feature titled "The Year in Medicine: From A to Z". Of the 33 items listed (some letters had multiple entries, others were skipped), three were related to vaccination:

• A -- "Autism: Debate Rages over a Rare Case". Reviews the Hannah Poling case; the links among vaccines, mitochondrial dysfunction, and autism; and the implications for the overall vaccine-autism debate.

• G -- "Gardasil: Vaccine Battle". Discusses the reports earlier this year about serious side-effects, including deaths, linked to Gardasil. As the item notes, governmental officials are working to assure the public of the vaccine's safety, including through this CDC website.

• H -- "HIV: The Hunt for the Elusive Vaccine Goes On--and On". Details the ongoing failures of HIV vaccine clinical trials and current plans for smaller-scale testing of novel ideas.
  

Positive results for Gardasil trial in males

News came from Merck last week that results from its clinical trial of Gardasil in males showed the vaccine's efficacy in preventing HPV-related genital warts and other lesions. No serious safety concerns were found. Here's coverage from the Associated Press and the Merck press release detailing the (as yet unpublished) results which were presented at this European conference last week.

The trial included nearly 4,000 males between the ages of 16 and 26. The vaccine was 90% effective at preventing external genital lesions, the most common of which are genital warts.

Dr. Bernadine Healy, in the news earlier this year for comments seen as supporting a possible link between vaccines and autism, was pleased by these research results about Gardasil, writing about the many benefits of vaccinating males against HPV.

These findings will be part of Merck's eventual application to the FDA to license the vaccine for use in males in addition to females, a decision that has been widely expected for some time.

More interesting, however, will be the decision faced by the Advisory Committee on Immunization Practices regarding its recommendation for Gardasil in males. In particular, it remains to be seen if the direct protection provided against genital warts in males will be sufficient to recommend broad use of the vaccine, and/or what role the indirect benefits of male vaccination (i.e., aiding in the prevention of HPV-related disease in women) will play in the ACIP's recommendation.

No timetable has been set for these actions, but they are sure to be in the news in 2009.

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One other item related to HPV vaccines: The November 15 supplement to the journal Cancer is titled, "Assessing the Burden of HPV-Associated Cancers in the United States". It has a number of papers examining the burden of cervical cancer and other HPV-related conditions as well as several papers on the potential impact of HPV vaccination programs. Very interesting reading.

HPV Roundup: Gardasil safety worries, Cervarix FDA delays, more on mandates

There's been a flurry of media coverage this week about possible safety issues related to Gardasil. It appears that the attention was initiated by this report released by Judicial Watch, the conservative watchdog group. Like its previous reports alleging numerous deaths and illnesses caused by vaccine, this Judicial Watch report is based on unconfirmed submissions to VAERS, the government's clearinghouse for reports of possible vaccine-related adverse events. Reports to VAERS -- widely described as a 'hypothesis-generating mechanism' -- are later examined by government officials to determine what, if any, role a vaccine may have had in the reported condition.

Numerous other outlets have raised questions about Gardasil's safety in the past few days, most notably this CBS News story by Sharyl Attkinson, the media member who is increasingly at the forefront of reporting on alleged vaccine risks. Other media outlets examining the topic include CNN and WebMD.

In the meantime, officials from CDC and FDA have assured the public that the vaccine remains safe and effective and that reports of possible adverse events will continue to be investigated. Merck responded similarly yesterday, noting the limitations of reports made to VAERS.

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Meanwhile, it appears that the U.S. head-to-head battle between Gardasil and GSK's Cervarix will most likely be delayed until late 2009. Last week, the Wall Street Journal and Reuters, among others, reported the GSK announcement of its timetable for submitting additional trial data requested by FDA. Here is the GSK press release. It notes that Cervarix is already approved in 67 countries, including the E.U., but it's no secret that the U.S. market is by far the most lucrative, as Merck's sales figures from earlier this year illustrated.

From a business standpoint, this is decidedly good news for Merck, as it extends its head start in the U.S. (The news has not all been good, however, as it was announced late last month that Merck's application to expand the indication for Gardasil for women through age 45 will face additional scrutiny and delays. Here's a story from Reuters and the Merck press release.)

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In other news, two papers have recently been published in academic journals on HPV mandates (joining a growing literature on this topic -- including papers by Schwartz, et al., Colgrove, and Zimmerman.) One paper, "Assessing Mandatory HPV Vaccination: Who Should Call the Shots?" (Javitt, et al.) appears in the Summer 2008 issue of the Journal of Law, Medicine & Ethics (subscription required). In short, the authors conclude, "...Mandating HPV vaccination at the present time would be premature and ill-advised."

Also, the May 2008 Harvard Law Review published a paper titled "Toward a 21st Century Jacobson v. Massachusetts (pdf), alluding to the 1905 case that is widely seen as the foundation for state public health powers. The authors argue that a distinction should be drawn between vaccines that are 'medically necessary' (such as smallpox) and those that are 'practically necessary' (such as hepatitis B and HPV, for which other preventive measures are available but not widely used). The paper suggests that current law and policy fail to acknowledge the implications of this distinction.

Discussing HPV with teens; Overlooking genital warts; New data on South Asian HPV prevalence

A potpourri of recent publications on various aspects of HPV vaccination:

• "Genital warts: Mountains or molehills?" (Lancet Infectious Diseases, Vol. 8, No. 5, 277-278 -- free abstract) -- Co-authored by Sarah Hull and our own Art Caplan, this commentary focuses on genital warts, protection for which is included Merck's Gardasil but not in GSK's Cervarix. The authors discuss how the additional benefit provided by Gardasil may factor in to debates over pricing and the market battle between the two products sure to occur in the U.S. in the years ahead.

• "Informing adolescents about human papillomavirus vaccination: What will parents allow?" (Vaccine, Vol. 26, No. 18, 2203-2210) -- A study by British researchers Vallely, et al., this paper reports on a study using an informational film to improve adolescents' knowledge about HPV, cervical cancer, and HPV vaccinations. The key messages of the film were: 1) HPV causes cervical cancer, 2) HPV is sexually transmitted, 3) Condoms may not fully protect against HPV, and 4) HPV vaccination protects against cervical cancer. A post-screening test revealed improved knowledge regarding the information presented in the film. The adolescents' parents found the messages of the film acceptable.

• "A meta-analysis of human papillomavirus-type distribution in women from South Asia: Implications for vaccination" (Vaccine, Vol. 26, No. 23, 2811-2817) -- One of the unanswered questions regarding the use of HPV vaccines in the developing world is the extent of protection provided by the cervical cancer-causing HPV strains (16 and 18) included in the vaccine. In the U.S., these strains account for approximately 70% of cervical cancer cases. Studies examining the prevalence of these strains in other parts of the world have generally found them to be less common by as much as 10%. This paper, by Bhatla et al, examines nine previously published studies from India. The researchers conclude that HPV 16/18 vaccines could provide over 75% protection against invasive cervical cancer. While an encouraging finding, it is important to note that this data is largely the product of a mathematical estimate, and it does not speak to the challenges of implementing a large-scale vaccination program in India or elsewhere.
  

Lessons from the Failure of HPV Vaccine State Requirements

That's the title of a paper written by a group from the Penn Center for Bioethics -- including the editor of this site -- and the Johns Hopkins University Berman Institute of Bioethics. The article, a review of the events surrounding Gardasil state requirement proposals and their impact on long-term HPV vaccination efforts, will appear in the December issue of Clinical Pharmacology & Therapeutics but is already available on its website.

From a Penn news release on the paper:

“The arrival of Gardasil was a major achievement for cervical cancer prevention efforts worldwide,” says Jason Schwartz, MBE, Researcher, Penn’s Center for Bioethics and Department of History & Sociology of Science, and lead author. “Much of the initial enthusiasm for the vaccine was lost amid the controversy surrounding state proposals that would require teenage girls to be vaccinated in order to attend school. The events of the past year reveal important lessons regarding ways to introduce new vaccines successfully and in an ethically responsible manner."

In the months leading up to the June 2006 approval of Gardasil, there was unprecedented media coverage and support from even socially-conservative groups. However, this support for the vaccine began to slow in September 2006 following the introduction of a bill in the Michigan state legislature that would require the vaccination of girls attending public schools. Additional states also were quick to propose similar legislation. In response to the legislation, numerous groups expressed their opposition by arguing that it was either too soon to consider an HPV requirement, or that the sexual transmission of the virus did not warrant requiring the vaccine in schools.

The opposition grew when the governor of Texas issued an executive order requiring HPV vaccination for all girls entering the sixth grade. Critics of state HPV requirements called attention to how these policies violated obligations to respect parental autonomy. However, many critics often overlooked opt-out provisions, implying that the proposals made vaccination compulsory.

The authors note that, “Quite apart from whether it was prudent public health policy to implement state requirements for HPV vaccination so soon after the vaccine’s licensure, these attacks on the state initiatives may have exacted a very real ethical price in terms of the public’s understanding of the justifications for state vaccination requirements generally, as well as the public’s understanding of the merits of the HPV vaccine itself.” Additionally, they suggest that issues of price gouging, corporate profits, and political motives, may have also added to the opposition.

In order to move forward with cervical cancer prevention efforts, the authors suggest that attention be focused on assessing the long-term safety of the vaccine, while implementing effective patient and provider educational programs about HPV and the HPV vaccine, as this is the model that other successful vaccination programs have followed. "With a second HPV vaccine expected to be approved in early 2008, it is vital to understand the strategies that are most likely to lead to the long-term success of this remarkable weapon against cervical cancer," says Schwartz.

The authors also discuss the importance of designing and implementing HPV vaccination programs in developing countries. "Cervical cancer is a worldwide concern, but its impact is particularly severe in the developing world,” says Schwartz. “It would be tragic if the negative attention created by the debate over HPV vaccine ‘mandates’ in the U.S. hamper efforts to make the vaccine available to those internationally who could benefit most from it."

Only the abstract is available free. Those without access to the full text are welcome to contact us to receive an offprint.

Gardasil, RotaTeq sales top Merck quarterly report

As we've written previously, corporate financial reports aren't exactly our forte. However, the price of Gardasil (and, to a lesser extent, RotaTeq) have been prominent in policy discussions both in the U.S. and internationally, so this week's sales news from Merck is worth noting here.

This Merck document includes a table listing sales for various vaccines in the third quarter of 2007. Among the highlights:

• Gardasil: $418 million in sales
  
• RotaTeq: $171 million in sales
  
• Zostavax: $61 million in sales
  
• All other vaccines: $593 million in sales
  

Remembering that these numbers represent only three months of sales, we can see clearly that the days in which vaccines were not thought of as potential profit centers for the pharmaceutical industry are long over. (Moreover, most European vaccine sales are not included in these figures, making the true totals even higher.)

Here's coverage from Reuters and the Associated Press, which reports that total Gardasil sales for the first 9 months of 2007 is $1.14 billion. Also of interest is the detailed news release from Merck. According to is, Gardasil has now been approved in 86 countries (with 50 more pending) and RotaTeq is approved in 69 countries.

There's no doubt that many hope that these remarkable sales figures is the U.S. and elsewhere will encourage Merck to expand its programs (like this one) to deliver free or low-cost vaccines to those parts of the world that would benefit most from them.

More good news on Gardasil cross-protection?

An Associated Press story published last week began with what seemed to be remarkable news:

"New data show that a vaccine against the virus that causes cervical cancer partially blocks infection by 10 strains of the virus on top of the four types targeted. That boosts protection - at least partially - to 90 percent of strains causing the deadly cancer, according to data presented yesterday at a medical conference by Merck & Co., maker of Gardasil."

90% protection? Recalling that 70% had long been the number used to quantify the percentage of cervical cancer-causing HPV strains covered by the vaccine, this would be a major development.

As is often the case with unpublished data presented at medical conferences, specifics on the research results are difficult to come by. However, this WebMD story published at CBSNews.com adds more detail, explaining, "The new study, which involved about 11,000 young women aged 15 to 26, shows that the vaccine is also 38% effective against 10 additional HPV types, which are responsible for an additional 20% of cervical cancers."

The fact that the vaccine is only 38% effective against these additional strains is never clearly stated in the AP story. (Research has shown the vaccine to be 100% effective against the 70% of cancer-causing strains included in the vaccine.)

The findings are still good news, but readers of the AP story -- published in our hometown Philadelphia Inquirer and no doubt many other newspapers -- could be excused for thinking it was even more noteworthy.

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In other Gardasil news, Merck announced today plans to donate 3 million doses of the vaccine for use in the developing world. Here's coverage from the Associated Press and a Merck press release.

HPV: Is adolescent consent sufficient?; Data on vaccine effectiveness post-infection

The August issue of Pediatrics included a commentary related to HPV vaccine ethics and policy that is worth noting, even several weeks after its publication. Ruth Farrell and Ellen Rome from the Cleveland Clinic offer a well-reasoned argument in favor of adolescent consent being sufficient for HPV vaccination in their commentary, "Adolescents' Access and Consent to the Human Papillomavirus Vaccine: A Critical Aspect for Immunization Success." (free extract).

The authors argue that HPV vaccination could reasonably be given the same status as other reproductive health matters among teenagers, for which parental consent is not required. They outline some of the reasons why teenagers might seek the vaccine without parental involvement or knowledge and note the missed opportunity that would occur if physicians postpone discussion of the vaccine or vaccination itself until a future visit with a parent present. They write:

"Lack of parental authorization, whether because the adolescent's mother or father may not be reachable or the adolescent truly seeks confidentiality in immunization, should not overshadow the chance to initiate or continue immunization administration. By the time the adolescent returns for health care (with or without a parent), she may have initiated sexual activity, with the vaccine losing its maximum potential efficacy."

While these authors are not the first to suggest waiving parental consent for HPV vaccination, the publication of their argument in the nation's premier journal for pediatric medicine is likely to influence the policy discussion in the coming months.

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Data that could be seen as supporting Farrell and Rome's argument could be found in an August issue of JAMA. There, Allan Hildesheim and colleagues explore the "Effect of Human Papillomavirus 16/18 L1 Viruslike Particle Vaccine Among Young Women With Preexisting Infection" (In layman's terms, "Does Gardasil Help if a Woman Already Has HPV?") At the risk of oversimplifying a nuanced study, the answer is an unsurprising "NO!" This finding confirms what had long been known about the vaccine (and the reason why vaccination is recommended for 11-12 year old girls prior to first sexual contact).

An accompanying editorial "HPV Vaccines--Prophylactic, Not Therapeutic" reinforces this point and explains how the vaccine's lack of therapeutic action shaped the ACIP recommendations.

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Finally, a new issue of HPV Today was released earlier this summer. Included in it are status reports on HPV vaccination in the U.S. and worldwide and a short paper explaining why HPV subtype replacement is unlikely to occur as a result of widespread vaccination with Gardasil or Cervarix.

Merck report: $358m in Gardasil sales for Q2; $1 billion total for vaccines

While we don't typically highlight corporate earnings reports or similar news, the quarterly report released Monday by Merck for April-June 2007 provides some new information about the growing market for vaccines, and, in particular, Gardasil. Here's coverage from yesterday's New York Times, "Another Quarter of Strong Results by Merck," and a similar story from Reuters.

Since this news comes directly from the company, the Merck press release is particularly useful. Here's part of what it says about vaccines:

"Total vaccine sales, as recorded by Merck, were $1.0 billion for the quarter, compared to $349 million in the second quarter of 2006. The growth in vaccine sales was led by the performance of GARDASIL along with strong contributions from ROTATEQ and other pediatric vaccines. Vaccines in most major European markets are sold through the Company’s joint venture, Sanofi Pasteur MSD, and the results from its interest in the joint venture are recorded in equity income from affiliates.

Total sales as recorded by Merck for GARDASIL, the Company's cervical cancer vaccine, were $358 million for the second quarter. As of the second quarter, GARDASIL has been approved in 80 countries, many under fast-track or expedited review; and launched in 59 of those countries. The vaccine remains under review in approximately 40 other countries.

ROTATEQ, Merck's vaccine to help protect children against rotavirus gastroenteritis, achieved worldwide sales, as recorded by Merck, of $119 million for the quarter. As of the second quarter, ROTATEQ has been approved in 61 countries and it has launched in 22 of those countries."

The release goes on to note sales figures for Proquad ($89 million), Varivax ($147 million), and Zostavax ($47 million).

A companion document released by Merck breaks down sales between the U.S. market and internationally. Nearly 80% of Gardasil sales were in the U.S. ($286 million), as were an amazing 96% of RotaTeq sales ($114 million). There's little doubt from these data that the U.S. is leading the way in the uptake of these two fairly new vaccines, despite the far greater need for cervical cancer and rotavirus prevention internationally.

Overall, $1 billion in vaccine sales for a single company in a three-month period is perhaps the best evidence to date of the potential profitability of vaccines to an extent not previously seen. As for Gardasil, it is difficult to work backwards from the sales figures given ($358m) to ascertain the number of doses sold during the April-June period, since governments and insurance companies pay less than the well-known $120/dose 'sticker price'. This CDC price list shows a cost of $96.75/dose for Gardasil as part of the Vaccines for Children program. Using those figures as endpoints, a very rough estimate would suggest 3-4 million doses were sold, or enough doses to fully vaccinate slightly more than 1 million girls.

Given the size of the population for whom vaccination is recommended (all females 11-26), the potential growth of the Gardasil market is staggering, perhaps explaining, in part, the company's apparent enthusiasm to promote its vaccine in advance of the arrival of GSK's Cervarix.

Gardasil: CDC response on safety/efficacy; survey on parental support for mandates

The weekly news update from the Immunization Action Coalition alerted us to this CDC Q&A released last week titled "CDC Questions and Answers Concerning the Safety and Efficacy of Gardasil." The three-page document outlines the current status regarding safety monitoring, known safety concerns, the potential need for boosters, and the ongoing necessity of Pap screening.

It seems likely that the fact sheet was this breathless press release from JudicialWatch.org asserting (based on VAERS reports) that "three deaths were related to the vaccine." The CDC fact sheet clearly explains how and why this statement is a misinterpretation of VAERS data, reaching conclusions that are no possible from that information alone. Not surprisingly, a search of Google News suggests that the press release garnered virtually no attention from the print media. While safety concerns linked to Gardasil could still surface, there's no evidence at present to suggest such a connection.

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One other item related to Gardasil: The headline from a survey released by a group at the University of Michigan C.S. Mott Children's Hospital reads: "Majority of U.S. Parents Not in Favor of State HPV Vaccine Mandates." The report is available here, and here is coverage from CBS News and the Washington Times.

However, the headline -- while likely shrewdly written to generate the media coverage sampled above -- is very misleading. The report's own data (Table 1 in the report) lists 26% of parents disagreeing with an HPV mandate, 44% of parents agreeing, and a very significant 30% as 'neutral.'

Therefore, the same data could also carry the headline, "76% of parents not opposed to HPV mandate," which would actually more accurately capture the large percentage of respondents with no opinion for or against a mandate.

More Benefits of Gardasil?

With GSK's HPV vaccine -- Cervarix -- about to enter the final stages of FDA review prior to its all but certain licensure in the coming months, the marketing battle between GSK and Merck is about to begin in earnest.

One precursor of what's to come has been the occasional announcements and published papers noting protection against additional HPV strains beyond those specifically included in the vaccine. We've linked to many of those items previously.

Another sign is this headline: "Gardasil Guards Against Vaginal, Vulval Cancers: Researchers found cervical cancer vaccine reduced risk of lesions by 49%". The story is based on a paper in the latest issue of The Lancet by Joura and colleagues (abstract available here with free registration).

HPV Roundup -- CQ Report, Texas Aftermath, N.H. Success, and More

Another look at recent news and perspectives on Gardasil and HPV vaccine policy appearing in print or online...

• The latest issue of CQ Researcher -- the issue-focused publication affiliated with Congressional Quarterly -- looks exclusively at HPV vaccines and the debate over mandates. The 24-page report is well researched, extensively cited, and offers an incredible range of information as to the scientific, political, public health, and economic considerations in play. It might be the single best source for non-scientists looking to understand 'what all the fuss is about.' Sadly, access requires a subscription to www.cqresearcher.com, but it's likely that readers with university affiliations can access it through their libraries.

• This story in the New Scientist -- US Conservatives Block Cancer Vaccine for Girls -- updates the US state mandate landscape, particularly this month's Texas law effectively overriding Gov. Rick Perry's executive order in February. (More on the Texas legislation can be found here and here. Also, here is the text of Gov. Perry's remarks upon the bill's passage with veto-proof majorities.)

• A major contrast to the Texas saga is what's been happening with Gardasil in New Hampshire, as described in this story from the New York Times: "In New Hampshire, Soft Sell Eases Vaccine Fears." Instead of mandates, the state's practice of voluntary, free vaccination has led to a surge in demand for Gardasil, the story explains.

• We're just about exhausted with op-eds on HPV mandates. At this point, all one hears are the same arguments (for or against) over and over. Here's one that does attempt to say something new, courtesy of The Hastings Center's "Bioethics Forum": In "Choosing Paternalism?", Karen Maschke explores lessons from the U.S. Gardasil experience thus far that might be useful when considering the vaccine's implementation in the developing world.

• Earlier this month, this story in the Washington Post -- "Who Gets Stuck? Doctors, Patients Want Insurers to Pay More for Vaccines" -- looks at some of the reimbursement issues being raised by physicians, particularly the (small) amounts provided for vaccine-related costs beyond the price of the dose itself.

HPV mandates and more in JAMA and NEJM

There is a lot of discussion on HPV vaccination and mandates in recent issues of the New England Journal of Medicine and the Journal of the American Medical Association.

In the May 2 JAMA, Lawrence Gostin -- a professor of health law at Georgetown -- and Catherine DeAngelis -- the editor of JAMA -- wrote an editorial titled "Mandatory HPV Vaccination: Public Health vs Private Wealth." Gostin and DeAngelis reject mandates for HPV at this time, referring to any use of state mandates as "a last resort." Specifically, they point to questions regarding cost/payment, long-term safety, injury compensation, and the fact that HPV is not "a highly infectious airborne disease" to support their argument against mandates.

The latest NEJM includes seven pieces on HPV vaccines, including two commentaries, two reports, two editorials, and a letter. All are available for free here. Of note is the commentary by Alta Charo -- professor of law and bioethics at the University of Wisconsin -- titled "Politics, Parents, and Prophylaxis -- Mandating HPV Vaccination in the United States." Charo argues in favor of state mandates, pointing to the easy-to-secure exemptions available in every state in which a mandate has been explored. With essentially any parent objecting the vaccine having the ability to receive such an exemption, the overall merits of a state mandate greatly outweigh the slight inconvenience the exemption process imposes on parents seeking it, she suggests.

Also of interest is "Introducting HPV Vaccine in Developing Countries -- Key Challenges and Issues" by Agosti and Goldie. The authors point to availability, access, and cost concerns related to the international implementation of HPV vaccination programs.

New Mexico HPV bill vetoed

Following up on an earlier post, New Mexico Gov. Bill Richardson vetoed a bill earlier this month that would have added a school entry requirement for HPV vaccination among all sixth grade girls. The decision was a reversal from his earlier public comments, from which his signature seemed all but certain. Here's the AP story from the Santa Fe New Mexican.

Gardasil: Recommendations published, views on industry role, male vaccination, N.M. mandate, and more

Some updates from the past 10 days or so on recent news about Gardasil and the ongoing discussions about mandates...

• Last Monday, the official ACIP recommendations on Gardasil were published online in MMWR. These are essentially the same recommendations that were announced in June 2006 (which we first wrote about here) -- there is an increasingly longer lag between such announcements and publication in MMWR. One important consequence of publication is that it typically pressures insurance companies who have not yet agreed to cover the cost of the vaccine to do so.

• A story in today's Detroit Free Press asks, "Why aren't more girls getting HPV vaccine?" The story relies more on anecdotal reports than any real data, however. The two million doses of Gardasil shipped in the 9 months since licensure is a not-insignificant number, particularly considering the delays in insurance coverage in many cases. Nevertheless, it may be a question worth asking. This AP story may be relevant to the discussion, examining continued public ignorance about HPV, despite the attention it's received in the past year.
  

• An interesting (and provocative) opinion from Adrian Fugh-Berman on "Bioethics Forum" (the blog of the Hastings Center, the bioethics think-tank) -- "Cervical Cancer Vaccines and Industry Influence". Fugh-Berman's conclusion: "Cervical cancer is uncommon in the United States. This is not an emergency; this is not SARS. Listen only to public health people without conflicts of interest. There’s time for a discussion – but ban industry from the room in which any decisions on public health are made." Worth reading, regardless of one's own opinion on the topic.
  

• Following up on our colleague James Colgrove's perspective on HPV mandates in NEJM last fall (which we noted then), several letters to the editor were published earlier this month in response. One letter highlights the potential value of vaccinating males, and another takes issue with the use of the word "compulsory" to describe vaccination requirements that allow for informed refusal. This point goes to the increasing use of the term "opt-out requirement" when discussing what have traditional been known as state mandates.

• Speaking of vaccinating males, yesterday's Los Angeles Times took a closer look at some of the unique issues regarding HPV infection in men and the potential value of vaccination.
  

• New Mexico appears to be the next state on the verge of an HPV school-entry requirement. Here's a story from last week about the passage of a bill in its state legislature. As best as we can tell, the bill is still awaiting Gov. Bill Richardson's signature, which could happen at any time. Many other states -- too many to count -- have bills at some stage of the legislative process.

• The Powerpoint slides from last month's ACIP meeting were recently posted here. Updated Gardasil efficacy data from Merck's Eliav Barr are available there, as is a general overview of the American HPV vaccine landscape by CDC's Lauri Markowitz. It's very interesting for those looking for somewhat less-filtered information than what appears in the popular media.

Gardasil round-up: Merck lobbying, ACIP chair comments, Virginia mandate, and more

There continues to be a steady trickle of news about Gardasil, largely centered on the ongoing debate regarding possible state mandates. Rather than attempt to keep up with each day's new op-eds, news stories, and the rest, we've decided to combine several of the most interesting items from the past 10-14 days into a single post. With that, here are some recent items making headlines:

• Perhaps the biggest news from the past few weeks was Merck's decision to stop participating in lobbying efforts for state mandates. Here's one account of the story from late February, courtesy of Reuters. It quotes Merck's Richard Haupt calling the company's activities a "potential distraction." Few would disagree with this assessment, and it is surprising, given the company's extensive and seemingly well orchestrated marketing and education efforts, that it would commit so significant a public relations blunder.

• Since that announcement, there has been no shortage of stories and op-eds more or less making the same point, namely, that the Texas political controversy and Merck's lobbying efforts have obscured the scientific and medical aspects of the vaccine and its potential benefits. That's the thesis of this New York Times editorial, "A Necessary Vaccine," (subscription required) which generated a number of letters in response. Also: a story in today's Times titled "A Vital Discussion, Clouded."

• Sunday's Washington Post also looked at these issues ("Parents Question HPV Vaccine: Push to Mandate Shots Rapidly Creates Backlash") Quoted in this story is ACIP chair Dr. Jon Abramson, who makes clear here and elsewhere that he is no supporter of current attempts to mandate vaccination. Abramson is also featured in this essay by Arthur Allen, "Why It's Too Soon for a Mandatory HPV Vaccine," published in the New Republic Online.

• Also mentioned in the Washington Post story above is the imminent action by Virginia Gov. Tim Kaine to sign legislation making his state the second to mandate HPV vaccination. The requirement would not take effect until 2008 or 2009 and would include the traditional types of exemptions (increasingly referred to in the media, accurately, as an 'opt-out provision'.) More information can be found in this story.
  

More on Texas HPV vaccine mandate backlash

There continues to be a tremendous amount of coverage of Gardasil in the media, most of it focused on reaction to Texas Gov. Rick Perry's nearly-three-week-old executive order rather than the vaccine itself, HPV, or cervical cancer.

Saturday's New York Times wrote about the "Furor on Rush to Require Cervical Cancer Vaccine." The story's premise:

"But a roaring backlash has some health experts worried that the proponents, including the vaccine's maker, Merck, have pushed too far too fast, potentially undermining eventual prospects for the broadest possible immunization."

Syndicated columnist Clarence Page writes, "Don't judge cancer vaccine by Austin political fallout," attempting to encourage the public to distinguish the political controversy created by Perry's actions from the merits and potential benefits of the vaccine itself. He argues,

"With emotions heated up, a lot of misinformation and unnecessary anxieties already are being stirred up over the new vaccine. The least grounded appears to be the fear that it will encourage more sexual activity outside marriage. Our society unfortunately has many larger reasons for that and it is a worthy debate for another time.

For now, Gardasil appears to be a very important and welcome life-saving step forward in the fight against cancer. Don't judge it by the political confusion it has caused."

For an example of emotions heated up, take a glance at this political cartoon at Newstarget.com.

A few more op-eds of note: In Newsday, Marc Siegel writes in favor of broad vaccination (though not explicitly addressing the question of mandates). In the Atlanta Journal-Constitution, Former Rep. Bob Barr writes against mandates, in part:

"None of these concerns will likely deter the legion of Big Government types out there who — allied with the many do-gooders populating state legislatures from California to New York, and prodded by companies willing to spend millions to make billions — will allow nothing to stand in the way of 'good government,' whether the people want it or not."

As far as news goes, the latest in Texas is an effort in the state legislature to effectively reverse Perry's executive order. According to this story, a hearing on the topic yesterday went well into the night. The Houston Chronicle has more.

Finally, the Arts and Leisure section of Sunday's New York Times took a closer look at the visual and creative elements of Merck's "One Less" television commercial.

Voices on HPV vaccination, Texas mandate

Of the many opinions expressed in the media over the past 10 days regarding the executive order by Texas Gov. Rick Perry, here are a few worth noting:

• Friday's USA Today included a point-counterpoint on the Texas mandate order. The USA Today editorial board questions the timing of the mandate. The headline and subhead of the story sums up their argument nicely: "Rush to require cancer shot threatens to promote backlash; HPV vaccine holds great promise, but Texas mandate is premature."

• On the same page, Gov. Perry (or more likely, a member of his staff) responded in a short commentary titled "My order protects life." It frames the decision less as a matter of instituting a 'mandate', but rather, implementing an 'opt-out' system of vaccination instead of an 'opt-in' system. Given the relative ease of obtaining exemptions (to the chagrin of vaccine advocates), that terminology is probably more precise than speaking about 'mandates', with its connotation of compulsion.

• Arthur Allen, author of Vaccine (which we noted previously and was reviewed this weekend in the Washington Post) wrote an op-ed that appeared in several papers last week. Titled "Idea behind the decision is sound, but Perry's timing is off," the piece makes an argument similar to that of the USA Today editorial. He writes, "By imposing the HPV vaccine in such a rushed, questionable way, Mr. Perry's action threatens to mobilize people who, under normal circumstances, would simply do what they were told, assuming it was best for them."

• In this AP story in the Seattle Post-Intelligencer, Washington Gov. Chris Gregoire voiced skepticism at Perry's decision. "'I told the medical association that I was reticent to dictate when I think there is a lot of public education that needs to go on,' Gregoire said. 'To go out and start just saying everybody mandatorily has to have this is a little bit troublesome for me.'"

• Finally, Art Caplan and James Colgrove appeared on "Radio Times," a Philadelphia-based NPR program, to discuss HPV vaccination, the Texas mandate, and related topics regarding the ethics of vaccines. You can listen to the one-hour program here.

Texas HPV vaccine mandate in the news

There has been a great deal in the news this week about Gardasil (and a corresponding spike in our traffic), much of which has been triggered by Texas Gov. Rick Perry's executive order on Friday requiring sixth-grade girls to be vaccinated against HPV. Here's the text of the executive order and an accompanying press release from the governor's office. Quoting Perry, "Requiring young girls to get vaccinated before they come into contact with HPV is responsible health and fiscal policy that has the potential to significantly reduce cases of cervical cancer and mitigate future medical costs."

Perry, a Republican, has received criticism for this decision from members of his own political party and conservative organizations, as this AP story and this Houston Chronicle story explain. Perry released a second statement over the weekend, saying, in part,

"Providing the HPV vaccine doesn’t promote sexual promiscuity anymore than providing the Hepatitis B vaccine promotes drug use. If the medical community developed a vaccine for lung cancer, would the same critics oppose it claiming it would encourage smoking?

"Finally, parents need to know that they have the final decision about whether or not their daughter is vaccinated. I am a strong believer in protecting parental rights, which is why this executive order allows them to opt out."

Indeed, likely lost in the headlines pointing to a "mandate" is the important point that the exemption policies already in place in Texas will apply to HPV vaccination in the same way, including parents having the ability to decline vaccination for 'philosophical reasons'. In fact, proponents of vaccine mandates will likely be disappointed to learn that the executive order also instructs state officials to make the exemption process easier by creating a system in which parents can decline vaccination online.

Today's New York Times includes an editorial praising Perry for the decision. In fairness, it argues far more convincingly for HPV vaccination generally than it does for a state mandate (though strong arguments can certainly be made for it.)

Independent of discussions about the appropriateness of philosophical exemptions from vaccination (such as Paul Offit's op-ed we noted here), the current state mandate system means that no parents will be forced to vaccinate their children against their will. However, years of experience have shown that state mandates provide the structures and encouragement necessary to maximize a vaccine's benefit across communities, particularly reaching those without regular access to medical care whom cervical cancer targets disproportionately.

When considering vaccine mandates, we should not focus our attention on those with strong beliefs opposing vaccination, as the exemption procedures provide, for better or worse, a relatively simple remedy. Instead, we must consider those silent in these debates, those not receiving even basic medical care, much less tracking the minute-by-minute developments regarding Gardasil. For them, state mandates have been shown repeatedly to provide the awareness and stimulus needed for the vaccine to reach all who could benefit from it.

Updates on HPV vaccination outside the U.S.

Those looking for information on the policy discussions and implementation of Gardasil worldwide will be very interested in the latest issue of HPV Today, an international newsletter on all things related to HPV research, policy, and practice.

Among the items in the issue: a short piece by Dr. Luisa Lina Villa, a Brazilian cancer researcher, updating the international regulatory landscape for Gardasil. She notes that more than 40 bodies around the world have approved the vaccine thus far. Australia, New Zealand, Peru, and Mexico are among the few to approve the vaccine for males as well as females. Dr. Villa also describes some of the implementation challenges faced by her native Brazil, among them cost and the absence of an adolescent vaccination infrastructure.

Also in the issue: a very helpful table outlining the different approvals (by age, gender, condition, etc.) that Gardasil has received by various regulatory bodies around the world and a brief report on the results of a survey in Australia exploring whether the vaccine could promote unprotected sex among Australian teens. (The short answer: no)

GSK planning head-to-head comparison of HPV vaccines

Earlier this month, GSK announced its plans to conduct a head-to-head clinical trial comparing its HPV vaccine, the still-unlicensed Cervarix, with Merck's Gardasil. Here's the GSK press release and a provocatively-headlined story from the Philadelphia Inquirer, "Area drug firms go to war over vaccine."

As the story notes, such a trial design is rare in medicine and all but unheard of for a vaccine. There's little doubt that this move by GSK is an attempt to frame an argument for the superiority of its HPV vaccine, despite the numerous advantages of Merck's Gardasil at present, among them, an increasingly longer head start in the market, immense media coverage over the past year, data showing 100% effectiveness (with respect to the HPV strains included in the vaccine), and the additional protection it provides against genital warts. Whatever their motives, head-to-head comparisons are helpful to patients and physicians, and it would by no means be a bad thing for other manufacturers of pharmaceuticals and vaccines alike to follow this lead, despite the high risks.

A sidebar piece in the same issue of the Inquirer looked at cost and access issues related to Gardasil. One interesting item: According to Merck's Richard Haupt, about $80 million worth of Gardasil had been sold through October, which he describes as "an extraordinary uptake." At Merck's listed price of $120/dose, that works out to roughly 660,000 doses, or enough to fully vaccinate 220,000 girls and women. (That number is likely higher, given the discounts offered to government programs and other groups).

More states introduce HPV mandate bills

A "wave of support" is how today's Washington Post describes the growing number of states in which bills to mandate HPV vaccination have been introduced in recent weeks. This story notes developments in Maryland, Virginia, and the District of Columbia, with many comments from politicians and physicians supporting the actions but nary a quote from opponents of the bills.

On Wednesday, a Washington Post columnist offered a very critical take on the D.C. measure and his views of the assumptions underlying the need for such a law in the city. Also of note is this counterpoint to the Post columnist's views in today's Washington Times, strongly supporting the proposed mandate.

Elsewhere, this story in Wednesday's Houston Chronicle discusses the debate likely to occur now that similar bills have been filed in both of Texas' state houses.

We're not generally in the business of forecasting the future, but it seems very likely that this momentum will lead to the passage of HPV vaccination mandates in at least some states in 2007. The fact that the exemptions (for medical, religious, and philosophical reasons) already available for other vaccine mandates are all but certain to apply to HPV requirements will likely play a significant role in how politicians react to the concerns of opponents of these bills. As a result, policy discussions of HPV mandates will be able to avoid entirely the difficult ethical questions raised by the exemption policies themselves, or, for that matter, the overall principle of mandating vaccination.

Gardasil: Profile of Merck Vaccines president; feature on early HPV-cancer link proponent

Two items worth reading for those interested in background content related to Gardasil's development and arrival:

• "Making her mark at Merck" (Business Week, 8 January) -- A profile of Margaret McGlynn, the president of Merck Vaccines. An interesting item in the story: "Analysts are counting on McGlynn to drive much of Merck's growth: Some predict revenues from her division will triple by 2010, to $6 billion." While the business of vaccines is not our area of expertise, this is point underscores the period of explosive growth for vaccines that we're just entering, one in which ethical considerations will demand that much more attention.

• "Cancer quest: How ex-Penn scientist's hunch led to cervical vaccine" (Philadelphia Inquirer, 24 December) -- A very lengthy feature (two pages in the print edition) on
  Dr. Harald zur Hausen, described in the story as a very early proponent (i.e., the 1960s) of a link between HPV and cervical cancer (the credit for proving such a link has gone to others in the early 1980s). A very interesting, seemingly well researched piece.
  

Merck launches Gardasil ad campaign

Merck today announced the launch of a national advertising campaign for Gardasil. Information on the campaign, dubbed "One Less" (as in 'one less life affected by cervical cancer'), appears in this press release. The TV ads are available for viewing on the Gardasil website.

As the press release notes, this campaign follows earlier (and continuing) HPV education efforts supported by Merck, "Tell Someone" and "Make the Connection". Back in May, we wrote about some of the questions being raised by the company's "Tell Someone" campaign here (our most widely visited post in our 8-month history), particularly the omission of any reference to the then-still-unlicensed Gardasil. (Mentioning the vaccine in an ad before it was licensed would have violated FDA guidelines, but the ads still raised eyebrows among some.)

Regardless, the "One Less" campaign is unabashedly promoting Gardasil, as is entirely appropriate for Merck to do. From all appearances, if this isn't the first major national ad campaign for a vaccine, it will certainly be the largest by far, likely to supplement ads in medical journals (the traditional domain of vaccine advertisements) with those on television and other popular media. Yet another sign that the world of vaccines has entered a new, very different, and very promising phase in its history.

Speaking of Merck, there's a notable story in today's Times of Trenton from Dow Jones Newswires -- "Merck stakes its future on demand for vaccines." In yet another story explaining the growing importance of vaccine sales to pharmaceutical companies, there are some interesting facts about Gardasil's production facilities and plans. For example...

"In a plant that Merck expanded a few years ago while Gardasil was still being tested in clinical trials, three shifts of employees now work around the clock producing the vaccine. So far, at least 750,000 doses have been shipped since Gardasil's June launch, contributing to sales of more than $80 million so far."

HPV: favorable data for male vaccination; VFC action; CDC shift in research focus

A paper published in the November issue of the journal Pediatrics includes new data from Merck on some of their ongoing trials of Gardasil in different populations. It's a highly technical paper with an equally complex title: "Comparison of the Immunogenicity and Reactogenicity of a Prophylactic Quadrivalent Human Papillomavirus (Types 6, 11, 16, and 18) L1 Virus-Like Particle Vaccine in Male and Female Adolescents and Young Adult Women." (free abstract; subscription required for full-text).

To summarize, the paper reports the results of trials examining whether the vaccine's response in 10-15 year olds mirrors what's been shown in older females (16-23 year-olds). The short answer is that it does generate a comparable ('noninferior,' in scientific jargon) immune response in younger populations. Good news. The most interesting finding from the perspective of potential ethical issues is the comparison of data between 10-15 year old boys versus girls. Boys had a nearly identical response to the vaccine as their female counterparts did as well as a virtually identical safety profile between genders. As the paper's authors (all of whom are employees or consultants of Merck, critics might note, despite that being an obvious result of a Merck trial) note:

"Our findings in boys lend support for implementation of gender-neutral immunization using this vaccine for the purpose of preventing the widespread morbidity and mortality from anogenital cancer, as well as dysplastic cervical and external genital lesions, in the general population."

Speaking of Gardasil, news earlier this week that the vaccine has officially been added to the federal government's Vaccines for Children program, ensuring its availability to uninsured children age 18 or under. Here's a brief story from UPI.

One final related item: a story from Wednesday's Washington Post, "CDC Shifts Vaccine-Data Focus," reports on the decision to refocus intensive data-collection activities on immunization in 22 major cities on teenagers rather than young children. The move is a result of multiple new vaccines recommended for adolescents, including vaccines against HPV, meningococcus, and tetanus/diphtheria/pertussis (Tdap).

ACIP: June minutes and October agenda

The folks at the Immunization Action Coalition pointed out that the full minutes from the June 2006 meeting of the CDC Advisory Committee on Immunization Practices are now available here. The 96-page PDF is the next best thing to attending the meeting yourself, as it provides comprehensive coverage of everything that took place. In June, of course, the major news was the recommendation vote for Merck's HPV vaccine, Gardasil. For those interested in the data that informed the ACIP's recommendation, the report is invaluable.

Also on the ACIP website is a draft agenda for the group's next meeting, scheduled for October 25-26. The most notable item is a scheduled vote on a recommendation for Merck's shingles vaccine, Zostavax, for use in adults.

HPV odds and ends

A few of the relevant items from the media that have crossed our desks this week...

• "How a vaccine search ended in triumph" (New York Times, 8/29) -- Tells the very interesting backstory of attempts throughout the 20th century (and even into the 19th) to understand the true cause of cervical cancer. Even after HPV was confirmed to be that cause, the road to a vaccine was by no means an easy one, including taking researchers to a convent in upstate New York, of all places. For any medical historian, this story is a book waiting to be written.

• "Parents want HPV shots, but can't find them" (MSNBC, from AP, 8/29) -- In many respects, this is a great sign -- reflecting early enthusiasm for the vaccine which may translate to significant vaccination rates long before mandates enter the discussion. That the vaccine is hard to find is no fault of Merck, it appears, but rather the result of the typical bureaucratic maneuvers that follow licensure and ACIP recommendations, including the publication of 'official' recommendations in MMWR, action required by third-party payers to cover the cost of the vaccine, and reluctance by doctors to stock it until the payment landscape becomes clearer.
  

How to explain HPV vaccination's purpose to teens?

Among the many questions regarding the implementation of Gardasil on a large scale is how the purpose of the vaccine should be explained to children as young as 9 years old (but mostly 11-12) receiving it...

• What level of detail regarding HPV, its sexual transmission, and cervical cancer is appropriate?
  
• Should the physician handle these discussions alone, should they be left to parents to deliver, or should a team effort be employed?
  
• Should parents be permitted to instruct the doctor to give an 'abridged' version of the vaccine's purpose and function vs. the 'full' version they might otherwise deliver?
  
• In general, it's obvious that a discussion of Gardasil with a nine or ten year old would be dramatically different than one with a 13 or 14-year old (with added individual differences even within a specific age group). However, there's no clear guide to help physicians (or the other health care providers who will administer HPV vaccinations) tailor their discussions of the vaccine to children of varying ages, particularly in cases where there isn't an established physician/patient relationship to provide guidance as to a child's maturity, etc.
• What if a parent and child/patient have different opinions regarding whether to vaccinate? Is there a place for child assent to vaccination in these circumstances (particularly among older teenagers)?
  

With all that in mind, an AP story posted this weekend considers some of these questions. Titled "HPV vaccine creates parental challenge," the story follows a 14-year old girl and her mother as they learn about HPV vaccination from the girl's doctor. It's a useful way to begin thinking about these issues less on the national policy level and more from the perspective of individual patients and families. (Thanks to Dom Sisti for the heads-up.)

Gardasil provisional ACIP recommendations posted

As shown by the series of announcements in the past six months regarding Merck's rotavirus vaccine, there's a pattern for how ACIP recommendations become official -- first a vote at one of the committee's thrice-annual meetings, then the online posting of recommendations on the ACIP website a few months later, and, finally, publication in MMWR a few months after that. Only then are the recommendations truly 'official', for what that's worth. In the case of RotaTeq, the ACIP vote came on February 21, provisional recommendations were posted in May, and final publication occurred on August 10 (as we noted here).

Using this timetable for comparison, all signs point to Merck's HPV vaccine, Gardasil, being on a faster track. Recall that the ACIP vote took place on June 29 (as we discussed then), but the provisional recommendations are already posted here at the ACIP website, where they've been available for over a week. The only real news from the document is that publication of the official version of the recommendations in MMWR is tentatively slated for November. (Thanks to the Immunization Action Coalition for the heads-up.)

June ACIP presentations available online

We neglected to mention that the slides from speakers at June's ACIP meeting were posted online in the last few weeks. For those looking for details, data, references, and scientific sophistication well beyond anything available in the media (for understandable reasons), these are great resources, particularly regarding Merck's HPV vaccine, the main item on the June agenda.

The files available include several presentations on Gardasil (safety and efficacy data from Merck, cost-effectiveness analyses, recommendation details, etc.), as well as the many other topics the committee considered, including a new recommendation for varicella vaccination, updates on influenza, mumps, rotavirus, avian flu, and much more.

Los Angeles school district planning to offer Gardasil to students

A very interesting story in Monday's Los Angeles Times -- "Schools to Offer STD Vaccine" -- explains that the Los Angeles Unified School District will make Gardasil available to students in its schools in as little as six months, administering vaccines provided by the federal Vaccines for Children program. Here are three noteworthy excerpts from the story:

"Karen Maiorca, who retired two weeks ago as L.A. Unified's director of nursing services, said the vaccine would be offered each year at dozens of clinics that the district operates. The district's 600 school nurses will be responsible for spreading the word. And though the Vaccines for Children program is designed for uninsured and underinsured children, she said, no student will be turned away."

While turning no student away is an admirable policy, it would seem that such a practice would run afoul of the eligibility requirements of the VFC program. Likewise, Gardasil's manufacturer, Merck, must not be thrilled to learn that students with adequate insurance to cover the cost of vaccine could receive doses sold to the government at significantly reduced rates as part of the VFC program.

"[Peter] Kerndt, [director of the county health department's sexually transmitted disease program], said he will soon recommend to county supervisors that all female adolescents in Los Angeles County receive the vaccine unless their parents opt out."

Only a recommendation at this point, Kerndt's 'opt out' comment seems to suggest creating a presumed consent policy for HPV vaccination, rather than requiring active parental consent to vaccinate. Again, this would presumably be an effective strategy to deliver the vaccine to as many girls as possible, but it would seem that the county would likely face legal opposition to such a policy, the resolution of which is unclear.

"County and L.A. Unified officials said they have not received opposition to the idea of providing the vaccine to students. But they have not yet publicized its availability and a number of groups said they were not aware of the school district's plans.

'Wow, that really is different,' said Linda Klepacki, a spokeswoman for Focus on the Family in Colorado Springs, Colo., who originally believed that the vaccine would be available only through private physicians and government welfare agencies."

The use of schools as a vaccine distribution mechanism is not particularly common in the U.S. today, but in a recent paper in Lancet Infectious Diseases (which we wrote about here), school vaccination programs were suggested as a way to increase Gardasil's uptake among African-American populations disproportionately impacted by HPV infection and cervical cancer mortality.

Two cautionary views on Gardasil

With essentially the same points being made repeatedly in editorial and op-ed pages across the country, we suspect that we'll be linking to far fewer opinion pieces regarding Gardasil in the weeks ahead. (Exceptions will certainly be made for essays such as Alice Dreger's that offer a unique perspective.)

Since nearly every commentary we've seen has offered unabashed praise for HPV vaccines, it seems fair to call attention to two commentaries published in the last few days offering a slightly more cautionary take while still supporting the vaccine generally (it would be hard not to).

The first was written by Peter Sprigg of the Family Research Council and published in Saturday's Washington Post. Titled, "Pro-family, pro-vaccine--but keep it voluntary," the op-ed begins by citing the positive reception the vaccine has received from the FRC and other conservative organizations. However, Sprigg then outlines two concerns: the first notes the importance of accurate communication about what level of protection the vaccine does and does not provide. His point that claims of Gardasil's "100 percent effectiveness," while accurate in their intended context, can create confusion when used less precisely is on target. (Data suggest the vaccine is 100% effective against the 70% of cervical cancer-causing HPV strains it targets.) Sprigg's second concern touches about the FRC's oft-stated opposition to mandating HPV vaccination as a condition of school entry, a decision the group (and others) believe should be left to families.

A second essay with a very similar thesis appeared in today's New York Times, titled "A new vaccine for girls, but should it be compulsory?" by Roni Rabin. Rabin advocates continued vigilance regarding pap smears (as nearly everyone does), but questions the ACIP universal recommendation for HPV vaccination due to the continued decrease in cervical cancer incidence in the past 50 years. In her essay, she suggests the funds that will pay for the vaccine could be better spent on 'preventive health care' (a category that, for Rabin, apparently doesn't include vaccination). She also wonders aloud about as-yet-unknown potential safety concerns and the limited size of the clinical trial cohort of younger girls.

Follow-up on ACIP Gardasil recommendation

Following up on last Thursday's post on the ACIP recommendation of Gardasil, here's a sampling of reaction in newspapers around the country:

• Both the Detroit Free Press and Press of Atlantic City ran 'local reaction' stories about the ACIP recommendation, surveying views from parents and physicians in their communities. Though some reservations are expressed -- both those unique to HPV as well as those common across all vaccines (i.e., safety) -- the vast majority of opinions in the story are positive.

• Two editorials specifically address the ACIP recommendation -- "A cancer vaccine triumph" (Chicago Tribune) and "Cancer prevention: Protect our girls" (Seattle Post-Intelligencer). Both pieces praise the recommendation (as the headlines would suggest), while postponing discussion of possible state mandates. The Tribune editorial ends this way:

  "But please, let's remember, this is a cancer vaccine. It's not a surrogate for the abstinence debate. Everyone is best served if this public discussion is about the safety, efficacy and cost-effectiveness of the new vaccine--and that's all."

Finally, the CDC website on HPV has been updated to reflect the Gardasil licensure and ACIP recommendation.

Gardasil receives ACIP recommendation for girls 11-26

We're in Atlanta for the summer ACIP meeting, where the biggest news coming out of the CDC is the (not unexpected) action on Gardasil. In short, the ACIP unanimously recommended that all 11-12 year old girls receive the 3-dose series, although vaccination can begin as young as 9, at the physician's discretion. Additionally, a 'catch-up' immunization program was recommended for girls and women through age 26.

Here's the coverage from the New York Times, Associated Press, Los Angeles Times, and Reuters, as well as the press releases from Merck and the CDC. Also of interest is this transcript of a CDC media briefing held this afternoon shortly after the recommendation.

In many respects, today's proceedings were rather anti-climactic, despite a standing-room-only crowd in the meeting auditorium. Coming after four hours of presentations and discussion on HPV vaccines at the February ACIP meeting, there was very little new information presented this morning. The pre-vote discussion was equally subdued, as Gardasil's trial data and FDA indications provided few alternatives beyond the recommendation as approved. That's probably a good thing, as decisions made amid uncertainty or a significant division in opinion would likely mean that things hadn't been thoroughly explored prior to the meeting. Clearly, the committee was well prepared and ready to act.

Personally, we were curious to see whether any of the groups opposing state mandates for HPV vaccination would use the "public comment" time to continue making themselves heard (as the Family Research Council did at the February meeting). Once again, however, no fireworks to report, as all nine public commenters strongly supported the vaccine. Commenters included representatives from the National Coalition for Cancer Survivorship, the Planned Parenthood Federation of America, AmeriChoice, The Balm in Gilead, the American Social Health Association, the Celebrate Life Foundation, Women in Government, and the International RRP ISA Center. Also commenting was Dr. Otis Brawley, a professor at Emory University. While unanimously praising the ACIP's recommendation, several commenters advocated broadening the vaccine's target groups in the future to include boys as well, an action that will surely occur in the not-too-distant future.

It should be noted that several opponents of state mandates, while not vocal at today's meeting, are quoted in some of the news stories linked above.

With licensure and a recommendation secured this month, the fate of Gardasil now depends on a variety of financing programs to make the vaccine available and affordable to all who should receive it, a comprehensive education program for parents and physicians alike, and the actions of all 50 state departments of health, whose decisions regarding school-entry mandates will impact greatly the degree of vaccine uptake and, thus, the overall benefit of the vaccine for society. Stay tuned.

Should Gardasil be called a 'cancer vaccine'?

A few weeks back, we were asked by a reporter whether it was misleading to refer to Gardasil as a 'cancer vaccine'. The phrase has been widely used of late -- and not only by the media. Both the FDA and Merck refer to Gardasil as a 'cervical cancer vaccine' in their press releases this month announcing the product's licensure.

We hadn't thought much about the issue at the time, but it didn't (and still doesn't) strike us as dishonest. There's no dispute regarding the link between HPV and cervical cancer, and the data show that Gardasil prevents infection from HPV strains responsible for 70% of such cancers. The fact that the vaccine is less than 100% protective against cervical cancer has no impact on whether it can rightly be called a 'cervical cancer vaccine,' since no vaccine available provides complete protection.

Gardasil is beneficial for multiple reasons, but cervical cancer is clearly the most prominent of the group. From a medical perspective, referring to it as a cervical cancer vaccine is prudent, as public awareness of HPV (and, in particular, its close link to cancer) is lacking. A vaccine against cervical cancer is much more likely to attract patient interest than one against 'human papillomavirus,' meaning that more people who should receive the vaccine actually will. Meanwhile, there's no denying that the branding of Gardasil as a cervical cancer vaccine is a shrewd (but appropriate) marketing decision by Merck.

A story in today's Charleston (W.V.) Gazette is the first we've seen that discusses this topic. Most of those interviewed in the story appear to share our view, with the chief reservation being that the branding ignores the other benefits of vaccination. True, but the additional attention Gardasil receives as a 'cervical cancer vaccine' will likely put it in a better position to accomplish its full range of benefits for a greater number of people.

"Merck's vaccine victory not yet complete"

So notes a story on TheStreet.com, the financial news and opinion site, that looks ahead to this week's ACIP actions on Gardasil and subsequent decisions that will be made at the state level. We agree wholeheartedly with the gist of the story, particularly because it quotes at length an earlier post from this very site.

Waive parental consent for HPV vaccination?

That's the position of physicians from Brown Medical School, The Miriam Hospital, and elsewhere in a letter published in the July issue of The Lancet Infectious Diseases. The letter, "Where to begin human papillomavirus vaccination?" (subscription required), emphasizes the need to direct HPV vaccination efforts at African-American women, a group disproportionately affected by cervical cancer in the U.S. For those without subscription access, here's a press release from the lead author's institution.

The authors cite data showing that African-American women have a lifetime risk of cervical cancer 0.25% higher than in white women (0.94% compared to 0.69%) and are twice as likely to die from it. The reasons underlying these disparities aside, the authors propose a multi-dimensional, targeted HPV vaccination campaign for African-American women, including school-based vaccination clinics in schools with high percentages of African-American students as well as vaccine distribution in juvenile detention centers. Finally, the authors write,

"Parental consent ought to be waived for HPV vaccination as it is for other sexually transmitted infection-related health care."

It's a provocative claim for which no further explanation is offered. While the authors' interest in maximizing the availability of HPV vaccines is clear, it's possible that attempting to circumvent parental authority in this case would actually have the reverse effect. Such a move would greatly increase the level of criticism the vaccine receives, particularly from groups already arguing strongly that the decision to vaccinate should be left to parents in all cases.

Editorial pages on the future of HPV vaccines

A number of newspapers, both large and small, published editorials on Gardasil over the past few days. The pieces look at what lies ahead regarding the vaccine's availability, recommended use, and possible requirements. It's a good time to do so, as we're just about halfway between FDA licensure (which came June 8) and ACIP recommendations (June 30). Here's a sampling of editorial views from around the nation:

• "A major advance in women's health" (Philadelphia Inquirer): "As states address this issue in the coming months, they should remember they have a wide range of policy choices between mandatory vaccination and silence. Although abstinence is the safest choice before marriage, public health policy should not ignore the fact that nearly every person engages in sexual activity at some point in life."

• "Preventing a cancer" (Boston Globe): "But the greatest potential benefit of Merck's Gardasil vaccine will come only if parents, doctors, policymakers, public health professionals, and school officials work together to ensure that all pre-teen girls get the full vaccine regimen of three shots."

• "Vaccine will save lives" (Fort Wayne Journal Gazette): "Protecting women from cervical cancer should trump patriarchal concerns about women becoming promiscuous. Any negative reaction to a vaccine that will protect millions of women’s lives is nothing less than misogyny."

• "A vaccine that fights cancer" (Clarksville, TN Leaf Chronicle): "By all means, those families with a strong belief in sexual abstinence until marriage should share that with their children — especially with all the mass media messages that young people are constantly exposed to concerning sex. Unfortunately, though, the parents' best hopes don't always work out. It's estimated that by high school, half of all teens are sexually active. Even for a girl who is committed to abstinence before marriage, there's always the possibility that a sexual assault could leave her exposed. One also must take into account that just because a young woman waited until marriage, her groom may not have."

• "Cancer breakthrough" (Providence Journal): "Further, some conservative organizations oppose requiring the vaccine. They argue that it will promote promiscuity, and that sexual abstinence before marriage is the better route to preventing illness. That seems farfetched. Few adolescents struggling over a decision to have sex will be deterred by fears that they could contract cancer in adulthood. Moreover, depriving anyone of this life-saving vaccine for "moral" purposes is a reckless roll of the dice."

Caplan MSNBC column on Gardasil

Our own Art Caplan has written a column about Gardasil and related issues for his twice-monthly MSNBC.com column, Breaking Bioethics. An excerpt...

"Medicine is poised to take a giant leap forward in the war on cervical cancer. But every American needs to think hard about the challenge this medical opportunity creates. The issue of cervical cancer vaccine will soon come to your school, church, synagogue, mosque and doctor's office. The right thing to do is to ensure as best we can that all young women are vaccinated. Now is the time to push politicians to make sure that the money will be there to make this happen. If insurance companies don't have to pay and public health departments cannot afford to then all the other moral issues surrounding this new vaccine become moot. It's time to prevent that from happening."

Gardasil approved -- $360 for 3-dose series

By no means surprising news, but Merck's HPV vaccine, Gardasil, was approved by the FDA earlier today. Here's the initial AP story, courtesy of the Washington Post, followed by the lengthy Merck press release which carries the triumphant headline, "FDA Approves Merck's GARDASIL, the World's First and Only Cervical Cancer Vaccine," a not-so-subtle jab at GSK in winning the race to be first with a licensed HPV vaccine. More importantly, the press release includes the first mention of Gardasil's 'catalog price': $120/dose, with 3 doses required for protection. The press release also announces the launch of www.gardasil.com, which (at least for now) only carries a "Coming Soon" banner.

We'll be watching for the arrival of the next phase of Merck's "Tell Someone" campaign (which we've previously discussed here and here) that will surely promote Gardasil, both in TV ads and on the websites that (so far) have made no mention of HPV vaccines.

Plenty of media coverage tomorrow, no doubt. We'll post some of the best here.

Two more editorials in support of HPV vaccine

Yesterday, The Oregonian published an editorial in support of HPV vaccines titled "Choosing women's health over sexual politics." The piece attempts to draw parallels between Gardasil's imminent licensure with the still-undecided fate of the emergency contraception Plan B...

"[The] decision to value sexual politics over women's health has damaged the reputation of this federal agency. More important, it has needlessly hurt women and their families. Next month, the FDA has a chance to mend some of the damage by approving a new vaccine against a sexually transmitted virus that causes cervical cancer.

The idea of vaccinating young girls against a sexually transmitted disease causes discomfort among some of the same groups that oppose contraception. But the chance to prevent cancer is too powerful and extraordinary to deny."

Last week, the Palm Beach Post took a similar approach in this editorial, "Save lives, not ideology," which may have left some readers with the incorrect assumption that Gardasil was in danger of suffering the same fate as Plan B. It should be noted that there's no evidence suggesting such a move is at all likely.

While the editorial strongly supports the vaccine, the Post seems to miss the key point of contention about the vaccine's use. Without qualification or explanation, they write, "Parents, of course, should decide" about whether to vaccinate their children, despite that issue being the almost-certain focus of attention for months to come as state policies are developed.

As expected, HPV vote tops June ACIP agenda

Prior to the Memorial Day weekend, the first (public) draft of the agenda for the June 29-30 meeting of the CDC Advisory Committee on Immunization Practices was released. As usual, a wide range of topics are slated to be covered in the two days, but attention will overwhelmingly be directed at the first item on the agenda, the recommendation vote for Merck's HPV vaccine, Gardasil. (Technically, this assumes FDA licensure early next month, but all signs suggest this is all but a sure thing.)

The expected ACIP actions next month follow nearly four hours of presentations and discussions on HPV vaccines at the group's last meeting in February. The minutes for that meeting recently surfaced on the ACIP website, and are well worth reading for those interested in data galore on all aspects of HPV vaccines -- from Merck and GSK's research data, to cost-effectiveness studies, to analyses of possible behavioral consequences of vaccination, and more.

It's worth repeating that while the ACIP recommendation is very significant, the ultimate decision as to whether HPV vaccination will be mandated as a condition of school attendance is the responsibility of each state. Since that appears to be the key point of contention for critics of the vaccine, the federal actions expected in the next month will likely only mark the start of months of deliberation, lobbying, and scrutiny centering on each state's department of health.

A final 'program note': we'll be in Atlanta for the meeting and will be posting extensively here on the discussions and decisions that take place.

More on Merck's "Tell Someone" HPV awareness program

Earlier this week, we wrote about the intriguing ad campaign launched by Merck to stress the link between HPV and cervical cancer. With the imminent arrival of the company's HPV vaccine, Gardasil, it seemed obvious that the print, TV, and web presence were the first steps in the rollout of promotion for Gardasil. Not so, says Merck, in this Bloomberg.com story:

"Gary Ruskin, executive director of Commercial Alert, a consumer group based in Portland, Oregon, that is critical of drug company advertising, said Merck's promotional Web site on the viral connection to cervical cancer is 'deceptive and dishonest.''

'Merck doesn't tell you why the site exists, which is to sell Gardasil,' Ruskin said.

[Kelley] Dougherty, the Merck spokeswoman, said the campaign isn't about Gardasil.

'This campaign is part of a broad and longstanding Merck public health commitment to encourage education about the disease,' Dougherty said in an e-mail."

Merck launches a costly, multi-platform ad campaign bringing attention to a virus for which the company just happens to have a vaccine set to arrive in the next month, and one has nothing to do with the other? More likely is that the spokesperson is trying to prevent Merck from running afoul of laws prohibiting advertising for medications (and vaccines) not yet approved for use in the U.S., a category that would include Gardasil -- at least until June 8.

That said, the Bloomberg story suggests that there is plenty of need for education about the link between HPV and cervical cancer. According to data from Merck, fewer than 20% of women in the U.S. are aware of the connection.

Health education is crucial, but many in the medical community continue to be wary of this responsibility falling to the pharmaceutical industry, whether through visits from drug reps, free meals, sponsored conferences or lectures, or direct-to-consumer advertising such as the "Tell Someone" campaign.

***Update: November 14, 2006 -- For more recent perspectives on Merck's "One Less" advertising campaign, click here.***

Merck's Gardasil moves one step closer to licensure

There's news this week about Merck's HPV vaccine, Gardasil. The headline is that an FDA committee, the Vaccines and Related Biological Products Advisory Committee, voted unanimously that Gardasil is safe and effective at preventing precancerous lesions in the cervix and genital warts caused by the four HPV subtypes included in the vaccine. The group recommends that the FDA license the vaccine, a decision expected to be made by June 8.

This news isn't much of a surprise, as the data for the vaccine's safety and effectiveness are clear. Also, it should be noted that this committee's findings are not binding, though the FDA's actions typically mirror such recommendations.

Here's an AP story on the announcement and Merck's news release. Also worth reading is this Boston Globe story, which highlights the need for continued cervical cancer screening and the ongoing debate over the benefits of vaccinating boys.

Lots of reaction pieces, including this one in the Los Angeles Times which quotes representatives from the Family Research Council and discusses the procedures for implementing state requirements for vaccination. This story on the Houston Chronicle's website includes reaction from Focus on the Family. Also, here's a statement from the president of Planned Parenthood.

(Those interested might want to explore our previous posts on HPV vaccines: here, here, here, here, here, here, here, here, here, and here.)

At least 5 years of protection from Merck HPV vaccine

A few weeks ago, we discussed the news from GSK that their cervical cancer vaccine, Cervarix, appears to provide at least 4.5 years of protection against the pre-cancerous lesions caused by HPV types included in the vaccine. Today, news from a conference in Paris that Merck's vaccine, Gardasil, offers at least 5 years of such protection. Reuters has the story.

We should expect these back-and-forth announcements every few months from each manufacturer as long-term follow-up data continues to trickle in. The question needing an answer is how long immune protection lasts following the initial HPV vaccination series. These results will help determine whether booster doses are needed, and if so, how often.

Among the advantages of these follow-up studies led by the vaccines' manufacturers is the head start it provides in advance of the vaccines' public debut. If immunity does wane at some point, we know (a) that it appears that it won't for at least 5 years and (b) there will be ample time to implement recommendations for booster doses well before the initial public vaccine recipients near the point at which immune protection would otherwise begin to fall.

Pharma sparring over which HPV vaccine is better

Aside from the controversy that likely will shadow HPV vaccines' introduction, Merck and GSK are fully engaged in a not-so-friendly debate over whose vaccine is superior. Those in attendance at the last ACIP meeting in February caught a glimpse of this jockeying, and a piece in today's Philadelphia Inquirer covers the latest round of salvos.

First, the news. A paper was published today on the website of The Lancet (subscription required) reporting new trial data of the GSK vaccine, Cervarix. It is titled "Sustained efficacy up to 4·5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial." Here's the GSK press release.

Two newsworthy items: (1) The follow-up study showed 100% efficacy over 4.5 years against the precancerous lesions caused by HPV. The data was gathered from a sample of 776 women who participated in an earlier vaccine trial, according to Forbes. For both vaccines, long-term efficacy data is not yet available, so it's unclear whether booster doses may be needed. 4.5 years of protection is a start, but ultimately, life-long protection is necessary.

(2) The paper also suggests broader protection against more subtypes of HPV than the two specifically included in the vaccine. From the press release:

"The study provided evidence that GSK’s candidate vaccine demonstrated substantial protection against infection with the third and fourth most prevalent cancer-causing types of HPV, namely types 45 and 31. This protection also extends over 4.5 years. GSK is conducting further large studies to determine the potential mechanism and extent of the demonstrated broader oncogenic protection."

If this finding holds up, it would mean that GSK's vaccine provides protection against up to 80% of cervical cancers in the U.S. (up from the 70% figure originally believed).

As the Inquirer reports, Merck scientists were skeptical of the GSK announcement:

"Merck...immediately questioned GlaxoSmithKline's study. One of its HPV researchers, Eliav Barr, called Dubin's analysis 'unorthodox' and emphasized that Merck also was testing for additional virus protections. Merck's vaccine already has been shown to help prevent HPV infections that cause genital warts.

Reacting to Merck's criticism, Dubin defended the study results as highly reliable and suggested that a reporter 'ignore' Merck's comment."

We've discussed the differences between each company's HPV vaccine and other recent developments previously (here, here, here, and here). While Merck's inclusion of additional HPV subtypes responsible for genital warts in their vaccine gave it the early competitive advantage (as males could also benefit from it), today's news signals that the battle for superiority is far from over.

Gates-sponsored effort working toward a new TB vaccine

For the second time in the last seven days, the Washington Post looks at issues related to new vaccine development. (Last Friday was this story on setbacks for VaxGen's anthrax vaccine, which we wrote about here.) Today's story highlights tuberculosis and the efforts of the Aeras Global TB Vaccine Foundation to develop the first new vaccine for the disease in over 80 years. An excerpt:

"Though nearly forgotten in rich countries such as the United States, the lung ailment sickens many millions of people every year and kills nearly 2 million of them. The 1921 vaccine, to this day the most widely used vaccine in the world, protects babies from the worst forms of TB but doesn't do much to cut the toll in adults. Backed by tens of millions of dollars from the Bill and Melinda Gates Foundation, Aeras is working on an improved vaccine that might finally banish the disease."

Here's the Aeras website. It's worth noting that 2012 is cited as the earliest date that the aforementioned vaccine could be widely available.

As is increasingly the case with any large-scale global health initiative, the Gates Foundation has played a central role in this project. Of particular interest is the model for vaccine development employed by Aeras, one that replicates that of the major vaccine manufacturers on a scale few private entities could match. The Post explains...

"Aeras, with $108 million in Gates money, has gone further than any of the other Gates-funded groups. Not only has it set up a pipeline, but it has now built a $10 million drug factory that will allow it to produce any vaccine that emerges from the far end of that pipe. Except for its nonprofit charter and its financing, Aeras is hard to distinguish from a small drug company."

In the past, a common complaint about the pharmaceutical industry has been their apparent unwillingness to invest in vaccine research for diseases most prevalent or most severe in the developing world. The thought has been that the potential profitability of such vaccines is too limited to make their development investment worthwhile. (The Merck and GSK rotavirus vaccines may partially dispel this perception, although their potential market in the U.S. and Europe is far greater than any vaccine against TB or malaria would be.)

If this Gates/Aeras TB initiative is successful (far too early to tell), it would signal the existence of a novel pathway to develop vaccines for diseases primarily of the developing world, irrespective of concerns over profitability. A story well worth following in the years ahead.

GSK submits cervical cancer vaccine for EU approval

We haven't yet posted about Merck's and GSK's vaccines against human papillomavirus (HPV), a sexually transmitted infection best known as the cause of cervical cancer (among other effects). By June, however, this will be the biggest vaccine ethics issue getting public attention.

A quick summary of where we stand today for those not following the developments closely... Both Merck (Gardasil) and GSK (Cervarix) have HPV vaccines nearing licensure. There are over 100 subtypes of the virus, but 2 are responsible for about 70% of cervical cancers. Both vaccines provide protection against these HPV subtypes. The Merck product also includes 2 additional subtypes that are the leading causes of genital warts in both males and females. As a result, both genders could directly benefit from Merck's vaccine, while the GSK product will target only females.

In the race to be the first on the market, Merck is in the lead, having submitted licensure applications in the U.S. and EU in December '05. Today's news courtesy of Reuters is that GSK submitted for EU approval of Cervarix. A decision is not expected for about a year. Their U.S. application is even farther behind; it's not expected until late 2006.

The reason why June is important is that two events scheduled for that month will determine the fate of Merck's Gardasil -- likely FDA approval early in the month followed by a recommendation from the CDC's Advisory Committee on Immunization Practices a few weeks later.

Why the likelihood of controversy? Several groups -- notably the Family Research Council -- have already expressed concerns about mandating HPV vaccination as a requirement for school entry. Why? 1) HPV is sexually transmitted. 2) To be maximally effective, the vaccine should be administered to pre-teen girls (age 11-13, perhaps as young as 9). 3) A key concern among some of these groups is that vaccinating girls of this age will encourage sexual activity -- a phenomenon known as 'behavioral disinhibition'. (It should be noted that there's no evidence that human papilloma virus is much of a factor at all in teens' sexual behavior -- factors such as pregnancy, religion, and risk of HIV dominate.) 4) These decisions should be left to families, they argue.

The FRC has tempered their position compared to comments made in this Fortune piece last October previewing the debate. Rather than broad opposition to the vaccine in principle, their key objection at this point is mandating vaccination for school attendance rather than leaving it a parental decision. The battleground is set for the June ACIP meeting and subsequent decisions by state departments of health.

The topic is more complex than this short preview allows. While it isn't on many people's radars just yet, the Fortune piece was right in dubbing it "the coming storm". We'll stay on top of it.