Influenza: marketing vaccine by marketing disease

Now we are all “at risk” of serious complications

Influenza vaccine production has grown parallel to increases in the perceived need for the vaccine. In the US, the first recommendations for annual influenza vaccination were made in 1960 (table1).⇓ Through the 1990s, the key objective of this policy was to reduce excess mortality. Because most of influenza deaths occurred in the older population, vaccines were directed at this age group. But since 2000, the concept of who is “at risk” has rapidly expanded, incrementally encompassing greater swathes of the general population (box 1). As one US Centers for Disease Control and Prevention (CDC) poster picturing a young couple warns: “Even healthy people can get the flu, and it can be serious.”3 Today, national guidelines call for everyone 6 months of age and older to get vaccinated. Now we are all “at risk.”

Not to worry: officials say influenza vaccines save lives

Risk of serious illness is a problem—but, according to the official narrative, a tractable problem, thanks to vaccines. As another CDC poster, this time aimed at seniors, explains: “Shots aren’t just for kids. Vaccines for adults can prevent serious diseases and even death.”11 And in its more technical guidance document, CDC musters the evidence to support its case. The agency points to two retrospective, observational studies. One, a 1995 peer-reviewed meta-analysis published inAnnals of Internal Medicine, concluded: “many studies confirm that influenza vaccine reduces the risks for pneumonia, hospitalization, and death in elderly persons during an influenza epidemic if the vaccine strain is identical or similar to the epidemic strain.”12 They calculated a reduction of “27% to 30% for preventing deaths from all causes”—that is, a 30% lower risk of dying from any cause, not just from influenza. CDC also cites a more recent study published in the New England Journal of Medicine, funded by the National Vaccine Program Office and the CDC, which found an even larger relative reduction in risk of death: 48%.13

If true, these statistics indicate that influenza vaccines can save more lives than any other single licensed medicine on the planet. Perhaps there is a reason CDC does not shout this from the rooftop: it’s too good to be true. Since at least 2005, non-CDC researchers have pointed out the seeming impossibility that influenza vaccines could be preventing 50% of all deaths from all causes when influenza is estimated to only cause around 5% of all wintertime deaths.14 15

So how could these studies—both published in high impact, peer reviewed journals and carried out by academic and government researchers with non-commercial funding—get it wrong? Consider one study the CDC does not cite, which found influenza vaccination associated with a 51% reduced odds of death in patients hospitalized with pneumonia (28 of 352 [8%] vaccinated subjects died versus 53 deaths among 352 [15%] unvaccinated control subjects).16 Although the results are similar to those of the studies CDC does cite, an unusual aspect of this study was that it focused on patients outside of the influenza season—when it is hard to imagine the vaccine could bring any benefit. And the authors, academics from Alberta, Canada, knew this: the purpose of the study was to demonstrate that the fantastic benefit they expected to and did find—and that others have found, such as the two studies that CDC cites—is simply implausible, and likely the product of the “healthy-user effect” (in this case, a propensity for healthier people to be more likely to get vaccinated than less healthy people). Others have gone on to demonstrate this bias to be present in other influenza vaccine studies.17 18 Healthy user bias threatens to render the observational studies, on which officials’ scientific case rests, not credible.

Yet for most people, and possibly most doctors, officials need only claim that vaccines save lives, and it is assumed there must be solid research behind it. But for those that bother to read the CDC’s national guidelines19—a 68 page document of 33 360 words and 552 references—one finds that the evidence cited is these observational studies that the agency itself acknowledges may be undermined by bias. The guidelines state:

“. . . studies demonstrating large reductions in hospitalizations and deaths among the vaccinated elderly have been conducted using medical record databases and have not measured reductions in laboratory-confirmed influenza illness. These studies have been challenged because of concerns that they have not controlled adequately for differences in the propensity for healthier persons to be more likely than less healthy persons to receive vaccination.”19

CDC does not rebut or in any other way respond to these criticisms. It simply acknowledges them, and leaves it at that.

If the observational studies cannot be trusted, what evidence is there that influenza vaccines reduce deaths of older people—the reason the policy was originally created? Virtually none. Theoretically, a randomized trial might shine some light—or even settle the matter. But there has only been one randomized trial of influenza vaccines in older people—conducted two decades ago—and it showed no mortality benefit (the trial was not powered to detect decreases in mortality or any complications of influenza). This means that influenza vaccines are approved for use in older people despite any clinical trials demonstrating a reduction in serious outcomes. Approval is instead tied to a demonstrated ability of the vaccine to induce antibody production, without any evidence that those antibodies translate into reductions in illness.

Perhaps most perplexing is officials’ lack of interest in the absence of good quality evidence. Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases, told the Atlantic that it “would be unethical” to do a placebo controlled study of influenza vaccine in older people.20 The reason? Placebo recipients would be deprived of influenza vaccines—that is, the standard of care, thanks to CDC guidelines.

This is not to say influenza vaccines have no proven benefit. Many randomized controlled trials of influenza vaccines have been conducted in the healthy adult population, and a systematic review found that, depending on vaccine-virus strain match, vaccinating between 33 and 100 people resulted in one less case of influenza.21 No evidence exists, however, to show that this reduction in risk of symptomatic influenza for a specific population—here, among healthy adults—extrapolates into any reduced risk of serious complications from influenza such as hospitalizations or death in another population (complications largely occur among the frail, older population). This fact seems hard for many health commentators to grasp, who seem all too ready to take the largest statistic and apply it to all outcomes for all populations. At a press briefing this winter, CDC director Thomas Frieden said a preliminary CDC study had found “the overall vaccine effectiveness to be 62%,” He explained that this estimate of relative risk reduction: “means that if you got vaccinated you’re about 60% less likely to get the flu that requires you to go to your doctor.” On the evening news, the CDC’s message was translated into a claim that influenza vaccines will cut the risk of death by 62%, despite the fact that the CDC study did not even measure mortality (box 2). Reflecting on the same CDC study, two authors editorialized in the Journal of the American Medical Association that there exists an irrational pessimism about influenza vaccine: “A prevention measure that reduced the risk of a serious outcome by 60% in most instances would be a noted achievement; yet for influenza vaccine, it is seen as a ‘failure.’” Here, too, the authors appear unaware that the CDC study they cite did not measure any “serious outcome” like pneumonia, only medically attended acute respiratory illness with influenza confirmed by the laboratory.

Officials say influenza vaccines are safe

The CDC’s universal influenza vaccination recommendation carries the implicit message that, beyond those for whom the vaccine is contraindicated, influenza vaccine can only do good; there is no need to weigh risks against benefits. In October 2009, the US National Institutes of Health produced a promotional YouTube video featuring Fauci. Urging US citizens to get vaccinated against the H1N1 influenza, Fauci stressed the vaccine’s safety: “the track record for serious adverse events is very good. It’s very, very, very rare that you ever see anything that’s associated with the vaccine that’s a serious event.”

Months later, Australia suspended its influenza vaccination program in under five year olds after many (one in every 110 vaccinated) children had febrile convulsions after vaccination. Another serious reaction to influenza vaccines—and also unexpected—occurred in Sweden and Finland, where H1N1 influenza vaccines were associated with a spike in cases of narcolepsy among adolescents (about one in every 55 000 vaccinated). Subsequent investigations by governmental and non-governmental researchers confirmed the vaccine’s role in these serious events.2223 24 25

Selling sickness: what’s in a name?

Drug companies have long known that to sell some products, you would have to first sell people on the disease. Early 20th century advertising for the mouthwash Listerine, for example, warned readers of the problem of “halitosis”—thereby turning bad breath into a widespread social concern.26 Similarly, in the 1950s and 1960s, Merck launched an extensive campaign to lower the diagnostic threshold for hypertension, and in doing so enlarging the market for its diuretic drug, Diuril (chlorothiazide).27 Today drug companies suggest that we have underdiagnosed epidemics of erectile dysfunction, social anxiety disorder, and female sexua| dysfunction, each with their own convenient acronym and an approved medication at the ready. Could influenza—a disease known for centuries, well defined in terms of its etiology, diagnosis, and prognosis—be yet one more case of disease mongering? I think it is. But unlike most stories of selling sickness, here the salesmen are public health officials, worried little about which brand of vaccine you get so long as they can convince you to take influenza seriously.

Marketing influenza vaccines thus involves marketing influenza as a threat of great proportions. The CDC’s website explains that “Flu seasons are unpredictable and can be severe,” citing a death toll of “3000 to a high of about 49 000 people.” However, a far less volatile and more reassuring picture of influenza seems likely if one considers that recorded deaths from influenza declined sharply over the middle of the 20th century, at least in the United States, all before the great expansion of vaccination campaigns in the 2000s, and despite three so-called “pandemics” (1957, 1968, 2009) (fig 1).⇓

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Fig 1 Crude mortality per 100 000 population, by influenza season (July to June of the following year), for seasons 1930-31 to 2009-10, US. Data sources: Doshi P.Am J Pub Health 2008;98:939-45.

 

But perhaps the cleverest aspect of the influenza marketing strategy surrounds the claim that “flu” and “influenza” are the same. The distinction seems subtle, and purely semantic. But general lack of awareness of the difference might be the primary reason few people realize that even the ideal influenza vaccine, matched perfectly to circulating strains of wild influenza and capable of stopping all influenza viruses, can only deal with a small part of the “flu” problem because most “flu” appears to have nothing to do with influenza. Every year, hundreds of thousands of respiratory specimens are tested across the US. Of those tested, on average 16% are found to be influenza positive. (fig 2).⇓

All influenza is “flu,” but only one in six “flus” might be influenza. It’s no wonder so many people feel that “flu shots” don’t work: for most flus, they can’t.

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Fig 2 Proportion of specimens testing positive for influenza at World Health Organization (WHO) Collaborating Laboratories and National Respiratory and Enteric Virus Surveillance System (NREVSS) laboratories through the United States. Data are compiled and published by CDC.^28-43