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.

Perspectives on vaccine safety, exemptions, and autism links

Tuesday's Washington Post included a story about religious and other non-medical exemptions to state vaccine requirements. The article, "Faith lets some kids skip shots," examines the increase in personal belief exemptions by parents to forgo vaccination and its implications on disease rates as seen by the medical community. Interviewed for the story were Paul Offit, Saad Omer, and Barbara Loe Fisher.

This piece appears a few weeks after the cover story of Time magazine titled "The Truth about Vaccines." The story detailed the ongoing worries about alleged links between MMR or other vaccines with increases in autism rates and the response of the medical community to these concerns. Of particular note is the reporter's discussion of research using genetics and genomics to understand individual responses to vaccination. The story included a useful diagram (.pdf) tracing the recent increase in measles cases in the U.S., an increase suspected of being linked to trends in exemptions.

The Time cover story was likely motivated -- at least in part -- by the case of Hannah Poling which received significant attention this spring. In March, CDC acknowledged that vaccines Poling had received had exacerbated an underlying genetic condition related to mitochondria (a cellular component) leading to symptoms resembling those of autism. The case has been viewed by proponents of the vaccine-autism link as a 'smoking gun,' but CDC officials and others have noted that Poling's diagnosis and condition are exceptional and do not speak to a more general connection between vaccines and autism. The case was the subject of a commentary in the New England Journal of Medicine last month by Paul Offit that focused on the confusion surrounding many aspects of the decision.

Finally, returning to exemptions and their consequences, the New York Times' Ethicist column -- an often light-hearted Q&A on ethical dilemmas -- featured this question last weekend:

"My daughter’s play group consists of children ranging in age from infancy to 4 years old. One mother revealed that she does not vaccinate her son. After much frank but cordial discussion and opinions from pediatricians — some thought she endangered our vaccinated kids; others did not — she felt pressured to leave the group. Did the group behave ethically?"

Based on pediatricians' opinions that the unvaccinated child did not pose a significant threat to her vaccinated playmates (a view that is not held by all in the medical community), 'The Ethicist' concludes that the other parents were wrong to exclude the unvaccinated child.

Journal roundup: Racial disparities and school requirements, Parental comprehension, MMR media coverage, and more

As we do periodically, here are some papers of note published recently in the medical literature. (Most require a subscription in order to view the full text.)

• "Effect of a School-Entry Vaccination Requirement on Racial and Ethnic Disparities in Hepatitis B Immunization Coverage Levels Among Public School Students" (Pediatrics, Vol. 121, No. 3); Included in an issue with several papers on vaccination, this study analyzes racial/ethnic differences in Hepatitis B vaccination status among adolescents in Illinois before and after the establishment of a school-entry requirement. The authors conclude, "There was a dramatic decrease in the disparity of hepatitis B vaccination coverage between white and black or Hispanic students. School-entry requirements effectively increased hepatitis B vaccination coverage levels regardless of race or ethnicity and should be considered for other recently recommended adolescent vaccines."

• "Parents' vaccination comprehension and decisions" (Vaccine, Vol. 26, No. 12, 1595-1607); Based on a series of in-depth interviews with parents, the researchers report on the attitudes and mental frameworks that shape feelings about vaccination. They conclude that the parents were generally favorably toward vaccination, but "many had limited understanding of how [vaccination] works, making them potentially vulnerable to misinformation (or disinformation)."

• "Media Coverage of the Measles-Mumps-Rubella Vaccine and Autism Controversy and Its Relationship to MMR Immunization Rates in the United States" (Pediatrics, Vol. 121, No. 4); This paper published by our colleagues at Penn and The Children's Hospital of Philadelphia examines changes in U.S. vaccination rates in the wake of papers published in the scientific literature suggesting a link between MMR vaccine and autism compared to mainstream media coverage of the same controversy. The authors conclude, "There was a significant increase in selective MMR nonreceipt that was temporally associated with the publication of the original scientific literature, suggesting a link between MMR and autism, which preceded media coverage of the MMR-autism controversy."

• "On message, off target: Official advice on vaccination is too often poorly transmitted" (Nature, Vol. 452, No. 128); An editorial published in response to press reports noting presumptive Republican presidential nominee John McCain's sympathy toward arguments suggesting a link between vaccines and autism. The editors argue that new, enhanced communication strategies from CDC and other agencies are necessary to counter allegations of vaccine safety concerns.

Belgian parents face jail over non-vaccinated children

The Associated Press today reported on a fascinating story out of Belgium, where two sets of parents were sentenced to five months in prison as a result of failing to vaccinate their children against polio. The story notes that Belgium and France are the only two countries to require polio vaccination as a matter of national law. (Recall that U.S. vaccination requirements occur at the state level, and include various exemption protocols.) The parents' jail terms have been delayed to allow them another opportunity to vaccinate their children. Fines equivalent to approximately $8,000 were also assessed.

The website of the Belgian Federal Public Service includes information on polio and notes that it is the only mandatory vaccine in Belgium.

The story brings to mind the controversial jail threat levied against parents of unvaccinated children in Prince George's County, Maryland, last fall. (Our coverage here.)

According to this WHO website, there have been a total of three confirmed cases of polio in Belgium since 1980, the last occurring in 1989. (For comparison, there were 1307 cases worldwide in 2007 according to the Global Polio Eradication Initiative, the vast majority found in India and Nigeria.) Authorities in Belgium would likely point to the scarcity of polio cases as evidence supporting a strong vaccination requirement.

Threatening (or imposing) imprisonment is perhaps the most forceful tool at the disposal of public health authorities. It is unclear from the AP story whether such action is appropriate here or whether these measures should be reserved for more imminent threats to public health than the comparative minor threat of polio in Belgium given the very high vaccination rate overall.

Recent papers on vaccine-autism history, mandates, vaccine law, and YouTube

There have been an exceptional number of papers published in medical journals over the past several weeks that are worth mentioning...

• "Mercury, Vaccines, And Autism: One Controversy, Three Histories" -- American Journal of Public Health (subscription required for full text; published online ahead-of-print). From Jeffrey Baker, a physician and historian of medicine at Duke, an examination of the multiple histories that have contributed to the nature of current arguments linking vaccines to autism. Baker traces the parallel histories of thimerosal as a vaccine preservative, mercury as a health risk, autism as a diagnosis, and the relatively recent intersection of these stories.

• "Mandating Vaccination: What Counts as a "Mandate" in Public Health and When Should They Be Used?" -- American Journal of Bioethics (subscription required for full text). By Matthew Wynia of the American Medical Association, a commentary on the imprecise usage of the term 'mandate' (with respect to both vaccination and other public health activities) and the implications thereof. A nice introduction to a topic that deserves more attention from scholars.

• "Vaccine Law 101" -- Journal of Law, Medicine, and Ethics (subscription required for full text). Exactly what the title suggests, a high-altitude overview of the many laws, regulations, and types of litigation related to vaccines. A summary of a conference panel session of the same name. Short on insights and argument, but a very useful starting point for those interested in legal aspects of vaccination.

• "YouTube as a Source of Information on Immunization: A Content Analysis" -- JAMA (subscription required for full text). From a research team at the University of Toronto, a review of vaccine-related content posted on YouTube, examining claims made about vaccines and vaccination as well as the general attitude expressed toward vaccines. Slightly more than half of all videos were not expressly positive about vaccination, and those critical of vaccination tended to receive higher ratings from YouTube visitors. Here's a press release about the paper.
  

Jail threatened for parents of unvaccinated children in Maryland

It's a rare day when the same story gets noticed by both the Drudge Report and our site, but this story in today's Washington Post is already raising eyebrows. Titled "Get Kids Vaccinated or Else, Parents Told," the story reports that 2,300 parents in Prince George's County, Maryland, could be fined $50/day or be jailed for 10 days if their children are not vaccinated against hepatitis B and varicella, as required by the state.

The parents have received a letter from a state prosecutor and judge ordering the parents to attend a court hearing this weekend where free vaccinations will be available. The action comes after several months of failed efforts by local officials to resolve this issue which has resulted in the 2,300 children being barred from attending school.

As this excerpt from Maryland state law details, medical and religious exemptions from vaccination requirements are permitted, but Maryland is not one of the 20 states that allows philosophical exemptions.

There's certainly more to this story than today's Post account suggests. At first glance, however, it would seem that threatening to jail parents of unvaccinated children in the absence of a public health emergency is, to say the least, a dramatic action. While state officials are presumably well intended, it is unclear that such rhetoric is the best strategy to promote widespread support for the value of vaccination.

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.

Home-schooling and state vaccination requirements

A paper by our own Art Caplan and Penn Law student Donya Khalili in the current issue of The Journal of Law, Medicine, and Ethics explores the complicated landscape of vaccination requirements for home-schoolers. Titled "Off the Grid: Vaccinations among Home-schooled Children" (free abstract, subscription for full-text), the paper argues that extending state vaccination requirements to home-schooled children is ethically appropriate and legally justifiable.

From the authors' conclusion:

"While homeschooling and childhood vaccination laws vary substantially among states, the most direct way to encourage more parents to have their children vaccinated is to require that homeschoolers follow the same rules of mandatory immunization and standard exemptions that parents of public schooled students must follow. With improved vaccination rates, all Americans will be more protected against disease, and it is critical to the health and safety of our nation that we protect the health and safety of homeschooled children."

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.

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.

Offit on vaccine exemptions

Our colleague Paul Offit published an op-ed in the Wall Street Journal last week titled "Fatal Exemption" (Unfortunately, subscription is required for full access). In it, Offit notes the findings published in JAMA last month showing a significant increase in the number of vaccine exemptions and the corresponding increase in vaccine-preventable illnesses. The chief culprit, says Offit: the growing use of 'philosophical exemptions'. He writes, in part:

"When it comes to issues of public health and safety, we invariably have laws. Many of these laws are strictly enforced and immutable. We don't allow philosophical exemptions to restraining young children in car seats, to smoking in restaurants or to stopping at stop signs. And the notion of requiring vaccines for school entry, while it seems to tear at the very heart of a country founded on the basis of individual rights and freedoms, saves lives. Given the increasing number of states allowing philosophical exemptions to vaccines, at some point we will be forced to decide whether it is our inalienable right to catch and transmit potentially fatal infections."

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.

Michigan HPV mandate bill fails; similar bill introduced in Kentucky

This story from the Grand Rapids Press reports on the rejection of the bill in the Michigan legislature that would have mandated HPV vaccination for sixth-grade girls (while keeping the exemption system common to other vaccines). The bill, which passed the Michigan senate in September, was rejected by the state house during its last day in session prior to the holidays. The story above notes the intentions of two legislators to reintroduce the bill during the new session that has just begun.

Similar efforts are underway in Kentucky, according to this story from Friday's Lexington Herald-Leader. A bill that would require vaccination of girls prior to entering middle school was introduced by Rep. Kathy Stein and currently is being evaluated by the house's Health and Welfare Committee.

From NEJM: Ethics and Politics of HPV Mandates

This week's New England Journal of Medicine includes a commentary titled "The Ethics and Politics of Compulsory HPV Vaccination" by James Colgrove, an Associate Research Scientist at Columbia's Center for the History and Ethics of Public Health.

Colgrove -- a contributor to our Ethics of Vaccines Project -- does an excellent job outlining the many competing considerations that will influence states' decisions regarding possible mandates of HPV vaccination as a condition of school or day-care attendance. While there is not much new in the essay (particularly for regular visitors to this site), Colgrove's essay is, by far, the best available synopsis of the topic in print to date. Thanks to the folks at NEJM, its full text is available for free.

One problem (perhaps the only one) with the essay is Colgrove's simplistic characterization of the perspectives of bioethicists on the topic, a description that comes perilously close to caricature. He writes:

"Bioethicists, who generally hold the values of patient autonomy and informed consent to be preeminent, tend to be skeptical about compulsory vaccination laws. Not surprisingly, some have expressed wariness about or opposition to mandating HPV vaccination."

Colgrove surely must be aware that any attempt to describe how "bioethicists tend" to think about a specific policy issue is about as useful as trying to capture in one sentence what "politicians tend to think" about Iraq or what "judges tend to believe" about civil liberties, as though a single, dominant position exists on these topics. In fact, many bioethicists, particularly those coming from a public health background, are quite comfortable with state vaccine mandates, including those for HPV vaccination.

As for the "some" bioethicists expressing wariness, Colgrove cites only two papers on ethical aspects of HPV vaccination, one of which is written by Pitt's Richard Zimmerman (a paper we previously discussed here). While Zimmerman has written frequently on ethical topics in journals of the vaccinology community, it is a stretch to identify him as a bioethicist, let alone as one of two who represent how the discipline as a whole tends to think about vaccine mandates.

These criticisms aside, Colgrove's essay is well worth reading for anyone thinking seriously about the appropriateness of HPV mandates.

The Lancet calls for mandatory HPV vaccination

An editorial in the current issue of the The Lancet is making news. (Free registration required.) It says, in part:

"For effective and long-term eradication of HPV, all adolescents must be immunised. Data from the vaccine trials in boys are urgently needed; in the mean time, EU member states should lead by making the vaccinations mandatory for all girls aged 11-12."

Here's coverage of the editorial from Forbes.com, the BBC, and the Telegraph. The Lancet is a bit imprecise about the status of the Michigan bill that would mandate vaccination -- while it did pass the Michigan Senate last month, House consideration of the bill will not begin until after next month's election, and its passage is by no means assured.

The biggest question is what the editorial means, precisely, when referring to making vaccination mandatory in the E.U. The term implies some program of enforcement and consequences for those who refuse vaccination. (In the U.S., of course, that takes the form of being prohibited from school or day-care.) These mechanisms don't exist in the E.U.; their establishment would represent a major policy change and an equally large philosophical shift regarding European vaccination efforts.

Perspectives on HPV vaccination, Michigan mandate bill

Yesterday's Lexington Herald-Leader included a pair of items about HPV vaccines with comments from a host of vaccine experts (and not-quite-experts). One story, "Is Prevention Worth a Shot?," offers general advice to parents. The other is a sidebar, "Feedback about Michigan Law," with comments on the bill under consideration that would mandate vaccination for girls in sixth grade. I was asked by the Herald-Leader for comments on the ethical merits of such a mandate. From the story, here are my remarks:

"Ethically, electing to mandate a vaccine for children requires weighing the societywide benefits of vaccination versus the infringement, however minor, on the decision-making authority of parents. Among the factors that influence this ethical analysis are the risk of infection, the severity of disease without vaccination, and, very importantly, the likelihood that a vaccination program can succeed without state mandates. Unfortunately, history tells us that vaccines in the U.S. have great difficulty achieving high levels of support without the power of mandates.

"The points above are true for any vaccine, but the HPV vaccine has unique considerations that point in favor of a mandate. We know that groups with reduced access to medical care, and particularly regular Pap screenings, are more likely to develop cervical cancer than the general population. They are also more likely to die as a result of it than cervical cancer patients overall. Without a mandate, there remains a great risk that those not getting Pap screens or other care will similarly not be reached by HPV vaccination efforts. Without a mandate, we may miss exactly the same people who stand to benefit most from HPV vaccination. Ethically, this is of great concern.

"While a mandate is not a silver-bullet solution to these potential problems, it would signify the importance of HPV vaccination and very likely lead to novel strategies by local health departments and school districts to deliver the vaccine to all girls in the target age group. A mandate puts the vaccine in the best position to save the most lives, while still allowing parents with philosophical or religious objections to opt out by means of the generally straightforward exemption policies."

Michigan bill would mandate HPV vaccination

It was only a matter of time until a state legislator offered a bill mandating HPV vaccination as a condition of school or day-care entry, yet the news from Michigan this week was somewhat surprising only for how quickly the time came. Here's the AP story from CNN and an editorial supporting the bill in the Detroit Free Press.

Noteworthy is the statement from the Free Press that the bill in the Michigan Senate was co-sponsored by every female member of the body, across the political spectrum. We've written previously about HPV mandates, but now that a bill has been offered, what goes on in Michigan in the weeks and months ahead will be an important test case for the reception HPV mandates receive from legislators and the public across the country in the future.

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.

Ethics of HPV vaccine policy options in Vaccine

The May 29 issue of Vaccine includes a paper that we have been expecting since first seeing a draft online back in March: "Ethical analysis of HPV vaccine policy options" written by Richard K. Zimmerman (Vol. 24, p.4812-4820 -- free abstract, subscription required for full text). Zimmerman is an Associate Professor at the University of Pittsburgh School of Medicine and a former ACIP member. (The bio on his website is out-of-date.)

Kudos to the editors at Vaccine for recognizing the importance of discussions at the intersection of ethics and policy, specifically regarding HPV vaccines. As a glance at any of its table of contents will attest, a paper on ethics is a rarity in the science-focused publication. Unfortunately, the paper doesn't quite live up to our hopes or even its own title. It reads more as a (simplified) primer to the major ethical theories than a useful discussion of the ethics of HPV vaccine policy. (See the two full paragraphs on the criticisms of utilitarianism with nary a mention of HPV therein.)

After brief examinations of HPV vaccination through the lenses of utilitarianism, the doctrine of double effect, and principlism (oddly, Kantian deontology is excluded), the paper concludes in this way:

"Given concerns for autonomy, justice, as not all persons are at risk, and non-maleficence, HPV vaccine should not be mandated for school or college entry."

Accepting the paper's ethical arguments would make it difficult to support mandating any vaccine, particularly new products with unclear risk profiles. (To be fair, Zimmerman doesn't take his argument that far, though there have been papers that do.) The most noteworthy omission from the paper is a discussion of the risks of vaccination compared to the risks of doing nothing (both the risk of infection and the consequences thereof, to individuals as well as populations). Criticisms aside, Zimmerman's offering is a laudable contribution to what should be a robust dialogue of the ethics of vaccination policy.