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.
  

New data on HPV prevalence; conflicting thoughts on relevance to vaccine debate

Last week's JAMA paper by Dunne, et al., -- "Prevalence of HPV Infection Among Females in the United States" -- garnered a significant bit of media attention. An accompanying editorial, "Estimating the Population Prevalence of HPV," by Weller and Stanberry, makes a point of examining the implications of this data to HPV vaccination policy, specifically cost-effectiveness calculations. (Free abstracts; subscription required for full text).

Here's some of the coverage of the paper by the popular press: Associated Press, Dallas Morning News, Washington Times, and Washington Post.

The data has provided ammunition for both sides of the vaccine mandate debate. Proponents of vaccination (and mandates, specifically) are pointing to the surprisingly high prevalence of HPV, of all types, in women: 24.8%

Those on the other side note the study's findings that the specific HPV types included in Gardasil are present in only 3.4% of females. To critics of mandates, this suggests that it is unnecessary to vaccinate all young girls when only a small percentage of females have the specific strains included in the vaccine. However, these numbers do not change the overall facts regarding cervical cancer incidence and mortality.

If anything, the ways in which the Dunne, et al., paper's findings have been used and will continue to be used in the Gardasil debate offer a valuable lesson of the potential dangers of using statistics in isolation to advance a policy argument.

Debate on continuing polio eradication efforts

That's what is being reported in this AP story from last week: "Experts reconsider goal of ending polio." The debate centers on whether efforts should be centered on containment -- polio is endemic in four countries and affects roughly 2,000 people a year -- or a continuation of the quite costly eradication program now entering its 19th year. Eliminating these remaining cases has proven to be far more difficult than smallpox eradication, which was accomplished in half as much time.

The story highlights an interesting and important debate among experts within the WHO, the infectious disease community overall, and leaders from the countries still affected by the disease.

Of note is the nearly-4,000 word feature published nearly a year ago in the New York Times on the challenges of polio eradiation, which we wrote about here.

Positive data on Hepatitis E vaccine research

Regular readers are aware of our discomfort about reporting on news of vaccines years away from licensure, at best. But when the New England Journal of Medicine decides to include results of Phase I or II clinical trials, it's generally worth noting.

That's the case for the most recent issue of NEJM, which published a paper on the "Safety and Efficacy of a Recombinant Hepatitis E Vaccine." Hepatitis E, more information about which can be found here and here, is quite rare in the United States and is not known to cause chronic conditions. Far more common, of course, are hepatitis A, B, and C (with vaccines available for the first two). Hep E does, however, lead to outbreaks in many parts of the world, particularly in Asia.

The trial reported on here included nearly 1800 volunteers from the Army of Nepal, a population at high risk of contracting the virus. The result: the candidate vaccine's efficacy was 95.5%. No serious safety concerns were identified.

Included in the same issue of NEJM was an editorial titled "Hepatitis E Vaccine -- Ready for Prime Time?"

ABC "20/20" segment on risks of vaccination

On February 23, ABC News' 20/20 featured a series of reports by John Stossel under the heading "Scared Stiff: Worried in America." Among the topics he explored was the general question "are vaccines safe?" His conclusion: Yes, they are. An article closely based on the piece is available here.

Supporting Stossel's conclusion was Dr. Paul Offit; taking the other side, as usual, was Barbara Loe Fisher. She was hardly portrayed in a positive light by Stossel. Most damning was Fisher's unwillingness to acknowledge that, on balance, vaccines have done more good than harm for society throughout history, a position that all but the most fervent opponents of vaccination readily accept.

Needless to say, Fisher was less than pleased with the program's discussion, Stossel's assessment, and the way in which she and her organization were perceived. Her response can be viewed here.

Potential supply issues for varicella-containing vaccines

Late last month, the CDC's MMWR included a "Notice to Readers" titled "Supply of Vaccines Containing Varicella-Zoster Virus." What are those vaccines? Varivax (against chickenpox), Zostavax (against shingles), and Proquad (a combination of MMR and chickenpox). All are manufactured by Merck, and no other U.S. companies manufacture vaccines providing protection against VZV.

There's no shortage to report, only news from Merck that the yield produced from early stages of the vaccine manufacturing process are less than expected (the reasons for which are not yet known). In the meantime, the plan is to prioritize production of the chickenpox and shingles vaccines, creating the potential for a limited supply of the combination ProQuad by late 2007. Again, not a major issue, as children can receive the same protection by receiving MMR and Varivax separately.

However, this announcement does remind us of the potential fragility of the U.S. vaccine supply. In addition to varicella-containing vaccines, those against measles, mumps, rubella, HPV, and rotavirus, among others, are all produced by a single manufacturer in the U.S. While the economic reasons behind this single-supplier market have been discussed by many, minor hiccups such as this announcement raise the attention of those who worry that the system is not sufficiently insulated against the risk, however small, of major production problems affecting a recommended vaccine.