Duty to warn?-the ethics of disclosing information about possible risks associated with H1N1 vaccination

IN THIS ISSUE OF SLEEP A LETTER TO THE EDITOR APPEARS FROM DAUVILLIERS AND COLLEAGUES1 REPORTING A POSSIBLE ASSOCIATION BETWEEN narcolepsy-cataplexy and H1N1 exposure believed to be primarily through the vaccine Pandemrix2 (GlaxoSmithKline), which contained the adjuvant ASO39. This report follows an earlier observation of an association by Swedish authorities, which led to the suspension of the use of this vaccine in Sweden and Finland.3 The publication of the letter from Dauvilliers et al.1 is likely to raise concerns about the safety of H1N1 vaccines, and in some circles, the safety of vaccines in general. Given the well-established and undeniable importance of vaccination in preventing death and disability due to influenza and other infectious diseases, the claim of an association with a disabling and dangerous condition raises key questions of ethics concerning what constitutes sufficient evidence for imputing a risk factor to a vaccine, the impact of such claims on debates about vaccine safety and use, and the role of this and other journals in publishing claims about vaccine risks. These questions are complicated by the controversial nature of the campaign to vaccinate against H1N1. In 2009 there was a global pandemic H1N1 influenza. There were grave concerns about the potential lethality of this viral strain, and massive efforts were mounted worldwide to find, manufacture, and distribute a vaccine. Some nations, fearing they would not receive any vaccine, explored utilizing unproven vaccines.4 Vaccines were developed, but were mainly utilized only after prior exposure had occurred to the virus. The number of persons infected with H1N1, the time of their infection, and the efficacy of vaccination were not known, since most suspected cases were never confirmed. Fortunately, H1N1 proved less deadly than had been feared, but still lethal. At least 540 pediatric deaths were attributed to H1N1 in the USA.5 At least 18,000 deaths worldwide were reliably attributable to H1N1.6 Still, these numbers did not reflect what many public health officials had predicted, and thus there was criticism of the effort to broadly vaccinate the world's population.7 It is this backdrop of controversy that will shape the interpretation of a claim that H1N1 vaccination may cause a medical disorder, even a rare disorder such as narcolepsy-cataplexy. The observation of Dauvilliers et al.1 alerting to a possible association between N1H1 and narcolepsy is information that the scientific community and public health officials need to know. However, the evidence they present is not yet convincing that either H1N1 or vaccination for it caused narcolepsy-cataplexy in the cases they report. There are a number of possible explanations for what they found, which as they acknowledge could include exposure to the virus and/or another infection (e.g., streptococcus) rather than vaccination per se.1 Moreover, there remains some uncertainty regarding the background rates of narcolepsy-cataplexy given recent advances in diagnostic techniques. These uncertainties are the reason the observation of Dauvilliers et al. appears as a letter in this issue rather than as an original science article. The case report observations of Dauvilliers et al. do, however, warrant further scientific study and public health surveillance for a possible linkage to H1N1 or certain vaccines for it, even if narcolepsy is a rare complication. In exploring the issue of how much scientific evidence would suffice to warrant a conclusion of causality, two factors must be considered: (1) the ability to sample a large number of persons who were vaccinated without prior exposure to the virus; and (2) the ability to control for other factors that might be associated with the observation of an increase in the incidence of narcolepsy-cataplexy in any particular population. It is crucial that public policy and public health planning regarding vaccination or any other health measures be grounded on firm evidence rather than anecdote, suspicion, or the hypothesis of an association, as was made very clear from the tragic consequences of allowing initial reports (subsequently unconfirmed) of risk associations with MMR vaccine to receive premature and undeserved credibility.7,8 Scientific proof and consensus, not speculation and suspicion, are the requisite criteria for action when lives hang in the balance. Dauvilliers and colleagues1 have a duty to inform other scientists and physicians of their concerns, including a possible elevated risk to children. It is ethically important that sleep medicine physicians and scientists, and others charged with public health surveillance follow-up on the observational report from Dauvilliers et al. It also important that those who use novel vaccines on a large scale create registries that can reveal short and long term benefits and risks, even for relatively rare disorders such as narcolepsy. The public must know what risks may be associated with novel vaccines, as well as the risks of electing not to receive vaccines, so that they can make informed decisions about their use. Truly informed decisions must ultimately involve more than concern over risk—they require evidence that can meet scientific standards of proof. As agreed by all, including Dauvilliers et al., this will have to involve carefully designed follow-up epidemiological studies.