CDC cautions against White House H1N1 death forecast

Yesterday, we wrote about the report issued by the President's Council of Advisors on Science and Technology (PCAST) on H1N1 (swine) flu preparedness. We argued that the daily stream of reports, recommendations, and announcements from an ever-changing cast of government bodies ought to be replaced (or at least supplemented) by a single source and spokesperson for H1N1 information and guidance from the federal government.

It took only a day for the potential hazards of offering so much information from so many different government sources to become clear. In today's New York Times, Donald McNeil's story, "Agency Urges Caution on Estimates of Swine Flu," details efforts by CDC officials yesterday to ever-so-politely distance themselves from the rather alarming estimates of H1N1 impact included in the White House advisors' report.

The PCAST report wrote that in a 'plausible scenario,' H1N1 influenza could infect up to half the American population, causing 1.8 million hospitalizations, and as many as 90,000 deaths. In today's Times, CDC staff respond:

“We don’t necessarily see this as a likely scenario,” said Dr. Anne Schuchat, director of the National Center for Immunization and Respiratory Diseases.

A press officer for the disease centers, speaking carefully to avoid a feud with the White House press office, said, “Look, if the virus keeps behaving the way it is now, I don’t think anyone here expects anything like 90,000 deaths.”

The story later quotes Harold Varmus, the Nobel Prize-winning former NIH director and co-chairman of PCAST. Varmus defended his group's report but expressed displeasure over the way it was released.

These types of intra-governmental squabbles are all but inevitable given the number of agencies involved in some aspect of H1N1 planning, many such groups having little in-house experience or expertise regarding public health or disease control and prevention. (PCAST, with its illustrious roster of members from fields in science and technology, has not traditionally addressed clinical medicine or public health in its work. Its reports dating back to 1995 have focused on R&D issues, biotechnology, and energy policy.)

So while disagreements such as this CDC/PCAST debate over H1N1 forecasts may be inevitable, it is greatly preferable that they occur somewhere other than the pages of the New York Times. While the diversity of opinions on the severity of the H1N1 threat reflects, to some degree, the uncertainty that continues to abound, this public back-and-forth is unhelpful. To an American population already seemingly unconcerned by the threat of H1N1 flu, the lack of a single, coherent voice from government makes the challenge of educating and preparing the public in the coming months that much more difficult.

Vaccination programs rely foremost on public trust in the importance of vaccines and confidence in the individuals crafting policy. H1N1 influenza vaccination will be no exception. Implementing a mass vaccination program so quickly is already a staggering logistical challenge, saying nothing of addressing the ethical and safety debates sure to emerge. A federal government seemingly at odds with itself regarding its messages to the public only adds to the difficulty of building support for the programs it eventually hopes to implement.

Presidential and HHS advisors on H1N1 mortality scenarios and vaccine plans

Observers of American vaccine policy (and readers of this site) are well aware of the veritable alphabet soup of government offices and advisory bodies with responsibilities for aspects of vaccination in the U.S., including ACIP, NCIRD, VRBPAC, CBER, NVAC, NVPO, NVICP, NIAID, and their parent agencies, CDC, FDA, and NIH, all part of HHS. Despite the potential for overlapping jurisdiction and regulatory gridlock, each of these groups has a clearly defined set of duties and, in normal circumstances, outward appearances suggest a relatively well-functioning bureaucracy.

The situation surrounding H1N1 (aka swine) influenza has meant even more executive branch interest in planning a possible vaccination program, most notably within DHS (Department of Homeland Security) and ED (Department of Education).

Lately, rarely a day passes without an executive branch department, agency, or committee offering a new report on some aspect of the planning efforts. Yesterday, PCAST became the latest addition to the H1N1 'initialese' lexicon, as the President's Council of Advisors on Science and Technology (part of OSTP in the EOP, for those keeping score), issued an 86-page report to the president on H1N1 preparations.

The report, discussed today by the Washington Post, the Associated Press, and the New York Daily News, among others, has generated most attention for its estimates of potentially 90,000 deaths and 1.8 million hospitalizations caused by H1N1 influenza in a 'plausible scenario,' according to the council. Among its recommendations were to accelerate availability of vaccine, increase communication efforts and disease surveillance capabilities, and appoint a point-person in the White House to coordinate planning and response. The White House released a document accompanying the report that details progress made toward these recommendations.

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Also yesterday, the previously mentioned NVAC (National Vaccine Advisory Committee) met via teleconference to discuss H1N1 preparations. The meeting, covered only by the indispensable CIDRAP News, focused on communication strategies surrounding vaccine safety concerns (real or alleged) all but certain to emerge once vaccination begins. According to Robert Roos' story, the committee approved a recommendation stating that HHS:

..."develop, and where possible test in advance, a strong and organized response to scientific and pubic concerns about vaccine safety that may emerge during the 2009 H1N1 vaccination campaign."

"The challenge will be to communicate effectively and to differentiate rapidly between adverse events that may be causally related to the vaccine and those which would be expected by chance alone," states the recommendation.

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The takeaway from the latest round of reports, meetings, and recommendations? Both groups in the news yesterday seem to be correct in emphasizing the critical importance of coordination within the federal government (not to mention among state and local governments) and communication to the general public. With so many government hands involved in H1N1 planning and response, many of them unfamiliar with public health and vaccination, the risk of conflicting and confusing policy and public guidance is real.

In addition to the PCAST-proposed White House "Flu Czar" (as some have dubbed it) to coordinate policy-making, identifying a single individual to serve as the public face and voice of the federal government on H1N1 influenza this fall seems essential. During the virus' first wave this spring, then-acting CDC director Richard Besser served in this role to overwhelmingly positive reviews. (Dr. Besser is soon leaving CDC for a television position at ABC News.) Such an individual will be vital to translating reports and recommendations from the aforementioned alphabet soup of government bodies into a single, coherent set of messages for the American public.

Assessing public attitudes toward H1N1 vaccination

This month, CDC has been holding 10 public meetings around the country soliciting input on H1N1 vaccination planning. The meetings, organized through a contact with The Keystone Center, a Colorado-based non-profit, continue through this weekend.

This past Saturday's meetings included one in Bucks County, PA, just north of Philadelphia. We attended the meeting, which was covered by The Philadelphia Inquirer, The Intelligencer, and WFMZ-TV. As those stories describe, several attendees were sharply critical of U.S. vaccination policy generally and, in particular, ongoing H1N1 vaccine activities. CDC communications specialist Marsha Vanderford was peppered with questions related to a range of concerns circulating on the internet. These questions/criticisms (and answers from Vanderford) included:

• The presence of thimerosal in multi-dose vials of influenza vaccines (thimerosal-free vaccine will be available for those who prefer it),
  
• The possible use of novel adjuvants (such as squalene) in the final formulation of the vaccine (none are included in the vaccine currently being tested),
  
• The possibility that vaccination will be made mandatory (it will be voluntary),
  
• The adequacy of clinical testing currently underway with respect to determining safety, (the vaccine is subject to the same requirements as any new influenza vaccine, but the timeline is accelerated in light of the urgency of the potential threat), and
  
• The decision by HHS secretary Kathleen Sebelius to grant legal immunity to H1N1 manufacturers and federal officials.

After this somewhat tense start to the day, the majority of the meeting was spent with participants in small groups considering the relative merits of three broad strategies to promote and implement H1N1 vaccination in the coming months. Dubbed "Go Slow," "Moderate Effort," and "Full Throttle," each approach included a set of promotion, funding, safety monitoring, disease surveillance, and other activities reflecting increasing "levels of effort," in the parlance of the meeting organizers.

Most groups favored elements from each strategy rather than supporting one particular approach wholesale. Nevertheless, when polled at the end of the day, a plurality of participants (49%) favored the "Moderate Effort" approach, with 30% preferring "Go Slow" and 21% advocating going "Full Throttle."

Participants also expressed preferences for a vaccination program that is flexible to changing circumstances, avoids safety concerns as much as possible, and prevents the maximum number of deaths and hospitalizations caused by H1N1.

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Speaking of public attitudes regarding H1N1 vaccination, a Washington Post story published late last week reported that more than 60% of those surveyed were not worried that H1N1 flu will affect his or her family this fall. 55% of respondents said they were likely to get the vaccine for themselves or a family member, a number which increases to 65% if recommended by their doctor.

Pandemic flu vaccine allocation plan released

Late last month, HHS and the Department of Homeland Security released its latest prioritization strategy for allocating limited vaccine doses in the early stages of a possible influenza pandemic. The report, "Guidance on Allocating and Targeting Pandemic Influenza Vaccine," (.pdf), incorporates public feedback and comments made in response to draft versions of the plan released over the past few years.

As the accompanying HHS press release notes, the general framework for the allocation strategy is based upon four primary objectives:

• Protect persons critical to the pandemic response and who provide care for persons with pandemic illness
• Protect persons who provide essential community services
• Protect persons who are at high risk of infection because of their occupation and
• Protect children
  

Here's coverage some CIDRAP News, including some unanswered questions and criticisms from infectious disease and public health experts. As the report itself acknowledges, a vaccine is only one part of a comprehensive response strategy for pandemic flu, and considerable challenges would be faced in implementing this or any vaccine allocation strategy consistently in the midst of a public health emergency.

Hitting the bull's eye for pandemic flu vaccine development

In this month's Lancet Infectious Diseases, a commentary by Sambhara, Bridges, and Poland offers an update on progress toward pandemic influenza vaccine development in the wake of the licensure of Sanofi Pasteur's pre-pandemic vaccine this spring.

The title of the short commentary sums up the authors' assessment: "H5N1 vaccine hits the target, but not the bull's eye." (free abstract). Complementing this metaphor is a graphic which illustrates the specific areas that need to be addressed to produce the "ideal pre-pandemic vaccine." Such a vaccine would be safe (of course), require a single dose with a small amount of antigen, provide long-lasting immunity, and be stable (i.e., capable of remaining potent even if stored for some time).

Given that the Sanofi Pasteur vaccine licensed in April falls far short of these goals, the authors advocate directing research efforts toward these aims in particular.

Speaking of pandemic influenza research, WHO posted on their website late last week a series of tables summarizing the impressive number of vaccine candidates for which clinical trials are underway. As the tables show, while H5N1 is properly commanding the overwhelming majority of attention of late, it is not the only influenza strain with pandemic potential that has attracted the interest of researchers.

With respect to pandemic planning in the U.S., another update was issued late last week by HHS secretary Michael Leavitt. Here's the full report as well as coverage from CIDRAP News. In a brief section on vaccines, the report states that the current pre-pandemic stockpile includes sufficient doses for 6 million people, with a 5-year goal of building enough capacity to produce vaccine for all Americans within six months of 'the' pandemic virus' first appearance.

Request for comments on pandemic flu vaccine allocation; federal planning update

A few noteworthy items regarding the federal government's pandemic flu activities over the last month...

First, HHS is seeking public comment regarding prioritization strategies for limited supplies of pandemic flu vaccines. The request for information (RFI) is available here. Quoting from this document, the questions of particular interest are:

"What objectives, principles, strategies, criteria, assumptions and rationales should be considered in pandemic vaccine prioritization determinations?

What is the relative importance of the three goals described above and what are the associated implications for vaccine prioritization?

Which population group(s) should have priority for receiving pre-pandemic vaccine? Which should have priority for receiving pandemic vaccine? What is the rationale?

How can fairness, equity, efficiency and related principles be reflected in the determination of priority groupings for receipt of pre-pandemic or pandemic vaccine?

For priority groups, how should vaccine be allocated, distributed and administered? Who (federal, State or local authorities) should determine when and how the vaccine is distributed and administered?"

The deadline for sending comments is January 18. Comments will be posted here once they are made available. The goal of this RFI, aside from being an excellent opportunity to assemble a variety of perspectives on this very complex issue, is to contribute to efforts to formulate guidance at the federal level to assist state and local policymakers.

Speaking of the federal government, on December 18, a report was issued and posted at pandemicflu.gov summarizing steps taken in response to items outlined in the National Strategy for Pandemic Influenza Implementation Plan (the document released in May 2006). This CIDRAP News story reviews the report. Overall, an impressive amount of progress seems to have been made.

WHO and state reports on ethics and pandemic flu planning

The folks at CIDRAP News report in this story that the WHO plans to issue a report in January on ethical issues associated with pandemic flu planning. Among the topics to be explored: access, the ethics of quarantine and related actions, health-care worker responsibilities, and international collaboration. All are important topics will ethical aspects that merit attention alongside the relevant science and public health considerations.

Speaking of WHO, yesterday's New York Times included an editorial, "Preparations for a Flu Pandemic," that questions the current pace of pandemic planning, particularly vaccine development and supply issues that are certain to complicate mass vaccination efforts.

Thinking about limited vaccine supply and the ethics of allocating those doses, a number of scholars and organizations have offered ethical perspectives on how best to do so. (The most notable: the Emanuel/Wertheimer essay in Science back in May, which we wrote about here.) This week, the Minnesota Center for Health Care Ethics released a very interesting report titled "Allocating Pandemic Influenza Vaccines in Minnesota." Growing out of a multi-disciplinary working group of state-wide stakeholders, the report offers a different model for prioritizing specifics groups than the current HHS plan. While the report is written for Minnesotans in particular, the discussion of ethical concerns and priorities is relevant everywhere. The report is well worth reading for anyone interested in the ethical priorities that will influence these difficult decisions.

The Minneapolis Star-Tribune wrote a story ("A Tough Call Awaits if a Killer Flu Breaks Out," October 23) on the report that includes a few quotes from us, among others.

Impact of air travel on flu season; bird flu vaccine plans

A few items in the news this week that have implications on continuing avian flu pandemic preparedness efforts...

1) While not directly vaccine-related, an interesting paper appears in the October issue of PLoS Medicine titled "Empirical Evidence for the Effect of Airline Travel on Inter-Regional Influenza Spread in the United States". In short, the paper presents evidence suggesting that the 2001 flu season was delayed as a result of reduced air travel in the U.S. following the 9/11 attacks. While starting later than usual, the trade-off was that the flu season extended farther than is typically seen. (That finding isn't altogether surprising, however, considering the resumption of domestic and international air travel shortly after the attacks.) These observations could be of use when evaluating the impact of limiting air travel in order to mitigate the spread of a potential pandemic. Here's the Washington Post story on the paper.

2) As for vaccines in a pandemic, the September 29 issue of Vaccine includes a report of a meeting of global vaccine policy leaders titled "A global pandemic influenza vaccine action plan." (subscription required for full text). It's a sobering assessment of our current vaccine production capabilities, as the paper begins by noting a worldwide production capacity of one billion doses per year (less than 1/6th the world's population). That's a best case scenario, as the need for a two-dose vaccination series would cut that capacity in half. Of course, production is in many respects the "easy" part; getting those vaccines administered to at-risk populations is an even greater challenge.

That said, the authors propose three somewhat self-evident approaches for improving the otherwise-gloomy pandemic vaccine picture... 1) Increasing seasonal vaccine demand to stimulate market forces and augment supply, 2) Increasing production capacity for pandemic vaccines, and 3) Developing new technologies that offer broader immunity or improve long-term efforts. Good ideas all, but many questions remain about how to achieve them and how much time we have to do so.

Bird flu mutation impacting vaccine planning

As always, CIDRAP News is on top of all things avian flu-related. This story from Friday covers the WHO announcement of the most recent data on avian flu mutation and the specific strains that are recommended targets of future vaccine development. Here's the WHO document.

The CIDRAP story offers a nice analysis of the relevant policy and planning ramifications of the science-laden WHO document. Here's an excerpt, featuring comments from Dr. Michael Osterholm:

"Many experts who follow the ongoing analysis of the H5N1 virus sequences are alarmed at how fast the virus is evolving into an increasingly more complex network of clades and subclades, Osterholm said. The evolving nature of the virus complicates vaccine planning. He said if an avian influenza pandemic emerges, a strain-specific vaccine will need to be developed to treat the disease."

That the virus will continue to evolve has long been known, as has the fact that vaccines developed in advance of a pandemic are likely to be increasingly less effective as time passes. For those hoping that a vaccine currently in development would be the vaccine, this news confirms that such hopes are unrealistic. The vaccines in the pipeline today are based on clade 1 strains of the virus, while most recent human cases have been caused by clade 2 strains, according to the WHO report. While it remains unclear how effective "older" vaccines will be against the eventual pandemic strain (if one develops at all), nearly all continue to agree that the most effective vaccine can only be developed after a human pandemic begins.

The WHO document cited here provides our most specific knowledge to date of the virus' pattern of mutation, information needed to develop effective vaccines. It also makes mention of the potential to develop region-specific vaccines if the virus' mutation proceeds in such a way in the months and years ahead.

Medical groups point to importance of vaccines in pandemic planning

This story from CIDRAP News called our attention to a joint statement released yesterday by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. In response to the government's pandemic flu national strategy released in May, the two groups urge that vaccines be the primary focus of pandemic planning and response efforts. The statement explains:

"Although the federal government’s pandemic plan addresses vaccination, IDSA and SHEA believe a more comprehensive, international approach is needed for vaccine development, production, and delivery throughout the world. 'The United States must take a leading role in fostering an international effort to develop vaccines against likely and eventual pandemic strains,' said Martin J. Blaser, MD, president of IDSA. 'We must do the legwork now so that we can produce and deploy those vaccines where we need them when a pandemic hits.'"

The statement appears as a result of formal comments and recommendations sent by the two organizations to the White House. The full document is available here as a PDF.

How to make global bird flu vaccination efforts feasible

That's the focus of a paper in the current issue of the ominously-named journal Biosecurity and Bioterrorism. It's titled "Removing barriers to global pandemic influenza vaccination" (available free) and authored by Gigi Kwik Gronvall and Luciana Borio of the University of Pittsburgh. The paper begins this way:

"In an influenza pandemic, most of the world will not get vaccine. Vaccination would be the best way to prevent infection and save lives, but there simply won’t be enough. The United States, France, Australia, Canada, Japan, and other wealthy countries have contracted with manufacturers to produce pandemic vaccine for their citizens, but their demand will quickly exceed the global production capacity. The manufacturing capacity for seasonal influenza vaccine is only about 300 million doses per year globally, and the capacity for pandemic influenza vaccine will be even less."

How can this situation be improved? The authors focus on harmonizing the varying regulatory structures and requirements employed by the U.S., E.U., and Japan, among other suggestions.

"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.

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...

HHS Update on Avian Flu Preparations

HHS Secretary Michael Leavitt released an update today on U.S. preparations for a potential pandemic. The PDF is available here. After a sobering (but accurate) introduction assessing the current status of the virus and its westward spread, vaccines receive significant attention in the report.

One interesting piece of information appears in the pie chart on page 2 showing funding allocations. It notes that HHS was appropriated $3.3 billion for pandemic flu activities during the current fiscal year. Of that amount, nearly $1.8 billion (54%) has been allocated to vaccines. That’s more than the amount given to antivirals, state and local preparedness, medical supplies, surveillance, lab capacity, risk communications, and international activities combined. Look for comments in the next few days from constituencies in the medical community expressing concern over this distribution of resources, particularly among state and local public health officials.

Of the 12-page document, nearly 3.5 are devoted to vaccines. It appears to be a thorough, honest assessment of where we are regarding vaccine development and the many unknowns moving forward (which we’ve discussed previously here and here).

One statement in the report, while not new, should remind us of the many ethical issues regarding vaccine safety, manufacturer liability and the limits thereof, and the potential consequences of large-scale immunization efforts that could surface in a worst-case scenario…

“If a pandemic occurs prior to licensure of a vaccine, the FDA can use its Emergency Use Authorization authority to permit the use of unapproved products (or to permit unapproved uses for previously approved products) if there’s a reasonable belief the products may be effective and if the benefits would outweigh risks.”

More to come, no doubt.