Study asks, "Would you take a risky flu vaccine?"

As the two dozen or so posts on the topic over the past few months suggest, there's a lot of attention being given to the development of vaccines in response to a possible avian flu pandemic. Much of the media focus of late has been on allocation strategies, largely in response to the Emanuel/Wertheimer piece in Science several weeks back (our most recent related post is here).

Largely ignored in all this is that the medical (and political) climate during anything even approaching a 'worst-case scenario' would mean that a vaccine would be hurried through development and clinical testing years more quickly than any in recent history. As a result, clinical trials would include fewer subjects, and lengths of follow-up would be well below the minimum numbers normally required for licensure. It's overwhelmingly likely that, if needed in an emergency, our understanding of an avian flu vaccine's safety profile will be far less clear than would be acceptable in normal conditions.

How would a vaccine be received by the public in these circumstances? That's the topic approached (in a slightly different way) by Zikmund-Fisher, et al., in a paper in the current issue of the Journal of General Internal Medicine ("A Matter of Perspective: Choosing for Others Differs from Choosing for Yourself in Making Treatment Decisions," 21:618-622 -- free abstract, subscription required for full text). The researchers asked subjects to consider a scenario in which they faced a 10% chance of death from a (particularly severe) flu virus. However, a vaccine exists that would provide complete protection against the virus, but would itself carry a 5% chance of death as a result of vaccination. Asked to respond if they would support vaccination in this scenario, subjects were randomly assigned one of four roles: patient, parent of a small child, physician advising a patient, or public health director setting policy.

The results: Support for vaccination varied widely, depending on the role subjects were asked to assume. 48% of 'patients' would choose the vaccine, 57% of 'parents', 63% of 'physicians', and 73% of 'public health directors'. WebMD has a detailed story about the study with comments from its authors.

It's hard to imagine a scenario so dire that a vaccine known to have a 5% chance of causing death would ever be made widely available (but nothing's impossible, presumably). Also, it should be noted that the early pandemic flu vaccines being developed suggest a far more palatable safety profile (as we wrote here).

Actually, the questions asked in this study are easier than those we would likely face in a real pandemic. Here, the precise risk of the vaccine was presumed to be known, as was the precise risk of rejecting the vaccine. In reality, neither would be even the least bit certain, making the decisions faced by patients, parents, physicians, and health officials alike all the more difficult amid the chaos of a public health emergency.

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.

"Who lives? Flu crisis may make us pick"

Yesterday's St. Petersburg Times was the latest publication to run a feature talking about which groups should receive vaccines first in the event of a shortage in the early stages of an avian flu pandemic. It's another of the stories surfacing in response to the Emanuel/Wertheimer piece in Science earlier this month (which we've discussed here and here.)

The story includes the perspectives of Greg Poland, director of the Mayo Clinic Vaccine Research Group and a member of ACIP, Bruce Gellin, director of the National Vaccine Program Office at HHS, and our own Art Caplan.

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.***

"Pandemic planning puts ethics in spotlight"

The Center for Infectious Disease Research & Policy at the University of Minnesota has posted an excellent story exploring the potential for the ethics community to contribute to preparedness efforts for a potential flu pandemic or other public health emergencies. (We'd have recommended the story even if our project wasn't a prominent part of the piece, though it happens to be.) The story has also been picked up by the website of the Association for Professionals in Infection Control and Epidemiology.

Welcome to those visiting this site for the first time as a result of that story. Take a look around, as we have nearly three months worth of posts in the archives available to the right. As the perspectives in the CIDRAP story suggest, we believe that the perspective of ethics has a great deal to contribute to discussions of vaccines and vaccination efforts, particularly when offered long before 'ethical controversies' occur. As a result, the range of material covered on this site extends well beyond the traditional terrain of the ethics of vaccines, as every aspect of vaccine science and policy relies upon stated or unstated beliefs relating to ethical considerations. Enjoy the site.

Philadelphia Inquirer on avian flu vaccine allocation strategies

In an editorial today titled "Who gets the shots?", The Philadelphia Inquirer reflects on the paper in Science this month by Emanuel and Wertheimer (which we wrote about on May 12) challenging the current paradigm for avian flu vaccine distribution when supplies are limited.

The Inquirer's four-sentence summary of the Science paper does not quite do justice to the authors' argument in favor of vaccinating those in the middle of life (roughly, 13-40 years old) ahead of the very old or very young. The original paper is very much worth reading, but a subscription is required to access it here.

The editorial's position? "Ultimately, the country will need one set of priorities, designed federally, implemented locally. The discussion needs to happen now, long before a crisis arrives."

Agreed. The key question, however, is how to determine the aforementioned set of priorities, particularly when analyses based on public health and ethics don't necessarily lead to the same conclusions. Should the first goal be to minimize loss of life in absolute terms, thereby valuing the life of an 85-year-old with a host of other medical problems as equal to (or perhaps greater than) that of a healthy teenager? Or should the first goal be to minimize the virus' spread, thus prioritizing those groups known to be better vectors for transmission (e.g., young schoolchildren). These and other questions are difficult enough when thinking in general terms, but become all the more wrenching when the generic '85-year-old' or 'schoolchild' are more accurately thought of as someone's grandmother or grandson.

Discussion is vital, but reaching any degree of consensus on these topics seems to be, at best, an uphill battle. More difficult still will be ensuring widespread public buy-in once it becomes clear who is at the bottom of the list to receive the vaccine. As if this weren't tall enough a task, the agreed-upon system must then somehow be faithfully adhered to even in the worst days of a potential crisis, when the best, non-controversial disaster plans typically fail amid the chaos.

Much to be done, and The Inquirer is right to shine a light on the urgency and importance of the work.

HPV vaccines: "Everything's been said, but..."

There's a quote that often surfaces in Congress during confirmation hearings or at other times when a long list of senators wish to speak on the same topic. The last in line, having nothing new to add to the debate, will say almost apologetically, "There's a famous quote about times like this. 'Everything's been said, but not everyone has said it.'"

That's about where we are with respect to the public discussion about HPV vaccines. With virtually no developments for months (last week's favorable FDA recommendation was long-expected) but several approaching, we're left with hundreds of stories in papers large and small presenting the same overview of the vaccine, the same potential obstacles the vaccine faces, etc.

So while we won't link to the vast majority of these types of stories until there's news to report, this first-person commentary in today's New York Times caught our eye. Some excerpts:

"There have been only a few times in my life as a physician when I've been able to say (at least to myself), "This is truly big news." My colleagues are saying the same thing. But they are also asking how this promising new treatment will be made available to women and girls worldwide."

• 
  

"...and we can now see the opening act of another sophisticated "ask your doctor" advertising campaign on the evening news. This one begins with a well-dressed, hip young woman who reflects, while contemplating the middle distance: "There's a common virus that can cause cancer? I didn't know that!"

We've been meaning to mention the ad campaign referred to above. Sponsored by Merck and linked to www.tell-someone.com, the television and print ads mention no products but only stress the link between HPV and cervical cancer. The television ad briefly features a small Merck logo at its end, but the website (which can also be reached via hpv.com and cervicalcancer.com) prominently features the Merck branding and layout.

Notably, nowhere in any of the advertisements or in the website content are HPV vaccines so much as mentioned. It's safe to say this is part of a strategy to build awareness and acceptance incrementally over the coming months, thereby reducing the impact of objections to the vaccine before they're given substantial attention.

Washington Post looks at NIH-funded HIV vaccine trial in Thailand

The front page of today's Washington Post includes a lengthy story on the controversy surrounding the lone phase III HIV vaccine trial currently underway and details its links to the failed VaxGen trial of a few years ago. No news here, but a good feature recounting the failures of every large-scale trial of HIV vaccine candidate to date. An excerpt:

"For the past three years, such [research subject enrollment] gatherings have been held all over Thailand, exhorting young adults to take part in the largest, most expensive, most resource-intensive AIDS vaccine trial ever. Funded by the National Institutes of Health, it ultimately will involve 16,000 people and last 3 1/2 years.

But as the trial moves forward, at a cost of more than $120 million, some researchers are raising questions about its validity. They disparage its science, question its ethics and doubt its efficacy."

Unlike most large clinical trials in which there is significant confidence that the product being tested will likely be approved for public use, there's almost no one who would claim with a straight face that the vaccine in this trial has any chance of being the vaccine. Even in today's Post story, unnamed NIH scientists attempt to lower expectations, saying that the trial "may reveal new things about HIV" even if the vaccine itself fails.

This may be true, but it's a radically different goal to set for a 16,000-subject clinical trial. The ethical questions of asking for so many research volunteers for this type of exploratory work are many, as are the criticisms from the scientific community that the limited public research dollars for HIV vaccine research could be far better spent.

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.)

CDC update on Midwest mumps outbreak

Yesterday, the MMWR website posted a dispatch with an update on the mumps outbreak in the Midwest followed by a discussion of possible causes.

Through 2 May, 2,597 cases have been reported, 57% of which coming from Iowa. Fortunately, no more than 25 hospitalizations can be attributed to mumps among these cases, with no deaths.

Among the possible causes for the outbreak discussed in an accompanying editorial note are: 1) the close quarters of college dormitories, 2) the absence of 2-dose MMR vaccination requirements for college attendance in 8 of the 11 states affected, 3) delayed recognition of mumps by younger physicians with limited exposure (so to speak) to it or physicians not initially suspecting mumps among vaccinated patients, both leading to more time for transmission to occur, and 4) the long-known fact that the vaccine is less than 100% effective at preventing disease.

Friday round-up: HPV vaccine parental acceptance, bird flu vaccine allocation, and more

• The May 2006 issue of Pediatrics includes an interesting study of parental beliefs and attitudes on HPV and HPV vaccination, comparing groups receiving an information sheet on the topic versus those without it. The paper, from Dempsey, et al., is titled "Factors that are associated with parental acceptance of human papillomavirus vaccines: A randomized intervention study of written information about HPV." (117:1486-1493; free abstract, subscription required for full text) Their findings, in short: those receiving the information sheet performed better on a knowledge assessment, but there was no statistically significant difference in vaccine acceptability between the two groups. Here's the press release on the paper from the University of Michigan (the lead author's institution.)

• This story from National Geographic's website discusses a paper in the current issue of Science on how best to ration limited vaccine supply in the event of a pandemic. The paper, titled "Who should get influenza vaccine when not all can," is written by Ezekiel Emanuel and Alan Wertheimer of the NIH, though they note the opinions expressed are solely their own. (312:854-855; subscription required for full text.) In the paper, the authors challenge the current plan to allocate limited supplies of vaccine, which they refer to as the 'save-the-most-lives principle.' Their alternative? A modified 'life-cycle principle' that values giving everyone a chance to pass through various life stages while, overall, still maintaining public order. It's an interesting idea, and one that leads to a radically different ranking of which groups would receive vaccines first. Well worth reading.

• Another paper of note in this week's Science: "Is polio eradication realistic?" by Arita, et al. (312:852-854; subscription required). The authors propose that "the time has come for the global strategy for polio to be shifted from 'eradication' to 'effective control.'"

Criticism for ABC bird flu movie "Fatal Contact"

The ABC made-for-TV movie "Fatal Contact" premiering tonight has clearly attracted a lot of attention--and not just in the media. The U.S. government's PandemicFlu.gov has a section specifically about the film at the top of their homepage, complete with a viewer's guide and Q&A based on the movie. Prepared by HHS, the first bullet point in the viewer's guide is:

"The ABC Movie 'Fatal Contact: Bird Flu in America' is a movie, not a documentary. It is a work of fiction designed to entertain and not a factual accounting of a real world event."

Perhaps the two most prominent experts on avian flu outside the government, John Barry (author of "The Great Influenza") and Dr. Michael Osterholm (U. of Minnesota) held their own teleconference yesterday to express concerns about the film, as this story in the New York Times reports.

One brief excerpt about vaccines:

"(Dr. Osterholm) and Mr. Barry disagreed over a scene in which desperate New Yorkers ambush a military convoy escorting vaccine through Manhattan. Dr. Osterholm expects riots over shortages; Mr. Barry felt the scene was exaggerated."

Vaccine shortages would no doubt be a problem in almost any scenario, but whether or not riots could result depends on so many variables that it's little more than blind guessing at this point. However, the fact that the possibility can't immediately be written off as ridiculous is evidence for the need for continued planning and preparation.

Based on media coverage and comments from the film's producers, "Fatal Contact" at best will encourage the public to seek out more information about bird flu (hopefully from responsible, trustworthy sources). To the filmmakers' credit, they link to PandemicFlu.gov on the website for "Fatal Contact," and reportedly will include a similar statement at the film's start tonight. At worst, "Fatal Contact" could trigger unnecessary alarm among the public and only add to the confusion and misinformation circulating about the prospects for a pandemic and the consequences should one occur. We'll wait to judge for ourselves.

CDC fact sheet/Q&A on HPV vaccines

Likely of interest to many visitors to this site is a fact sheet recently posted by CDC on HPV vaccines. There's not much in the way of new information, but the site concisely covers most of the basic questions that might be missed by many amidst the more specific controversy surrounding the vaccine's arrival and implementation.

BioPort contracted for 5 million more anthrax vaccine doses

Back in March, we wrote about VaxGen's apparent troubles developing a new anthrax vaccine and noted the continued availability of an older anthrax vaccine produced by BioPort. Over the weekend, news that HHS has contracted with BioPort to produce 5 million more doses of vaccine, having recently completed a previous 5 million dose order for the government. The $120 million contract comes from Project BioShield. This AP story has details and a follow-up on VaxGen's problems:

"The contract would run through September 2007 and delivery of the doses would begin almost immediately, said BioPort spokeswoman Kim Brennen Root.

Brisbane, Calif.-based VaxGen Inc. received the first contract worth $877.5 million to develop the company's experimental anthrax vaccine, but delivery has been delayed.

Lance Ignon, VaxGen's vice president corporate affairs, said the company expects it could begin delivery 'at the end of this year if all goes well with our development program and if HHS is willing to accept vaccines based on the data that's currently called for in the contract.'

VaxGen was warned in a March 24 letter from the Food and Drug Administration about sales material handed out at a government biodefense research meeting that contained 'false and misleading statements' about the experimental vaccine and how it compared to one produced by BioPort."

Papers of note in Vaccine

Among the many interesting papers published in the journal Vaccine, two that appeared in the May 8 print edition are worth mentions here (free abstracts, subscription required for full text):

• "Parental decision-making in childhood vaccination" -- In light of the reduced uptake of MMR vaccine in the U.K. on account of parental concerns about vaccine safety, the paper explores some of the psychological factors that impact decision-making, how 'risk' is understood, the role of the media in affecting public perceptions, and other aspects of decision theory relevant to vaccination.

• "A review of vaccine research and development: The human immunodeficiency virus (HIV) -- An up-to-date, extensively-referenced review article on the current state of HIV vaccine research, future directions, and scientific challenges that need to be overcome. Heavy on science, but an invaluable starting point for anyone seeking to learn more about the field.
  

Seattle Children's Hospital to host conference on pediatric vaccine ethics

The Treuman Katz Center for Pediatrics Bioethics at Children's Hospital & Regional Medical Center in Seattle is hosting a conference July 14-15 titled "Current Controversies: Ethical Issues Related to Vaccination of Children".

The conference aims to address the following, among other topics:

• Do "wealthy" nations have an ethical obligation to develop vaccines for diseases that occur primarily in developing nations and to fund vaccination programs for children of impoverished nations?
• Is it appropriate to do human vaccine testing in developing nations and, if so, under what conditions?
• How should priorities be set regarding the development of new vaccines?
• How should vaccines be distributed in a shortage situation?
• Should vaccination programs be government funded or market based?
• Should parents be able to refuse vaccinations for their children?
• How should health care providers respond to parents who are reluctant to vaccinate their children?
• When does the community interest in public health justify restricting the freedom to choose regarding vaccination?
• Are school mandates too restrictive, too weak or appropriately written?

Quite a broad spectrum of questions to tackle in two days, but it looks to be an excellent program.

Federal government avian flu implementation plan released

The White House released a 234-page document today titled "National Strategy for Pandemic Influenza: Implementation Plan" (pdf). The New York Times story leads this way...

"Although the federal government will stockpile 75 million doses of antiviral drugs and 20 million doses of vaccine to combat any outbreak of pandemic flu, local governments and individual communities will have to shoulder most of the burden in battling the disease, the White House said today."

Courtesy of ABC News, the AP story opens...

"A flu pandemic would cause massive disruptions lasting for months, and cities, states and businesses must make plans now to keep functioning and not count on a federal rescue, the Bush administration said Wednesday."

More on the document's discussion of vaccines shortly...

News Roundup -- Measles and Bird Flu

Several items of note that appeared during our brief break from posting necessitated by the Center for Bioethics' 10th Anniversary Symposium, on the legacy of the Terri Schiavo case...

• The New York Times series 'Diseases on the Brink' (which we discussed previously) wrapped up Sunday with an extensive package examining measles eradication efforts worldwide. Of particular note is this graphic illustrating immunization rates by country. It's no surprise that the nations with inadequate measles vaccination levels are nearly all in Sub-Saharan Africa and South Asia, mirroring the trend shared with other vaccinations and most medical interventions.

• Yesterday, the Times also had a provocative 'What If?' piece that asked avian flu experts and government officials about the possibility of administering poultry flu vaccines to humans in a worst-case scenario. Described in the story as 'aghast' at the possibility, NIAID Director Dr. Anthony Fauci is quoted saying, "It's not even on the table." Others interviewed suggest that poultry vaccines might be of some benefit, but they could only be considered for humans in the most catastrophic circumstances. By any estimation, the scientific, production, safety, and ethical issues are so enormous that it's hard to imagine any scenario in which this would actually occur.

• Speaking of avian flu and worst-case scenarios, ABC has quickly assembled a TV movie on the topic, just in time for the May 'sweeps'. "Fatal Contact: Bird Flu in America" will air next Tuesday, May 9 at 8 PM eastern. The ABC press release is available here, as are a number of photos from the film overflowing with actors in biohazard suits. Despite ABC's assurances that the film will contribute to public understanding of the topic, many in the public health and medical communities are wondering whether the film is more likely to scare rather than inform, as this AP story printed in the Philadelphia Inquirer explains.