Originally published in MedPage Today
by Crystal Phend, MedPage Today Senior Staff Writer
Failure to account for background rates when considering adverse events from pandemic H1N1 flu vaccination could spark public panic, researchers cautioned.
Coincidental cases of dramatic events including sudden death, Guillain-Barré syndrome, and spontaneous abortion can be expected to boost the true incidence of adverse events after immunization, said Steven Black, of Cincinnati Children’s Hospital, and colleagues online in The Lancet.
“The public will need frequent reassurance of vaccine safety when events that are temporally associated with vaccination are identified, even when these events have other causes and occur at the expected background rate,” they said.
Widespread belief in spurious associations can disrupt immunization programs, the researchers noted.
They cited the example of four deaths that occurred within 24 hours of seasonal flu vaccination in 2006 in Israel that derailed the program there, even though these were high-risk patients to begin with and the number of deaths was actually lower than expected from chance alone.
The risk is high for a similar situation with the mass vaccination programs underway for H1N1 influenza, they said.
A vaccination campaign in 1976-1977 against “swine” flu was associated with elevated rates of the autoimmune disease Guillain-Barré syndrome.
Since one or two diagnoses of the syndrome per 1 million people would be expected every month, 200 or more cases of Guillain-Barré will occur as background, coincidental events during the current vaccination campaign if 100 million people in the U.S. are immunized.
“The reporting of even a fraction of such a large number of cases as adverse events after immunization, with attendant media coverage, would probably give rise to intense public concern, even though the occurrence of such cases was completely predictable and would have happened in the absence of a mass campaign,” Black’s group wrote.
So, the investigators looked into background rates of some events that are most likely to raise concerns with the pandemic vaccination campaign.
A review of data from prior studies and from hospital databases showed that rates varied by year, country, age, and sex.
Overall, 3.58 cases of Guillain-Barré syndrome would be expected as background events within seven days per 10 million individuals vaccinated and 21.50 per 10 million within six weeks.
Coincident sudden death would be expected to strike 0.98 people per 10 million vaccinated people within seven days of vaccination and 5.75 cases would be expected to occur within six weeks as background events.
Among women, 14.40 cases of optic neuritis would be expected for every 10 million vaccinated within seven days and 86.30 could be expected for the same population within six weeks.
For pregnant women, 397 spontaneous abortions within one day of vaccination would occur as coincidental, background events for every 1 million vaccinated.
However, the researchers cautioned that the miscarriage rate may have been an overestimate given that vaccination rates are not uniform throughout trimesters of pregnancy.
But given the large number of events that could potentially be misinterpreted as caused by vaccination, Black’s group recommended “timely and thorough analysis of safety concerns,” taking into account the chance of temporal and geographical clustering.
For example, about 2% of practices will likely have a seemingly elevated rate — more than two standard deviations above average — of postvaccination spontaneous abortion based on the normal distribution.
Although this could lead to suspicions of a link to vaccination or a specific manufacturer’s vaccine, the investigators warned that “even random events can appear to have patterns.”
The number of cases sent to passive reporting systems alone is not an appropriate method on which to rely because the “denominator” — the number vaccinated — is usually not known, they cautioned.
Comparing observed and expected rates is a better method, although that is still subject to uncertainty and differences in populations, the researchers said.
In the U.S., the voluntary Vaccine Adverse Event Reporting System has beefed up outreach efforts, and a new Web-based active surveillance system has been implemented along with population-based, computerized database monitoring, according to an accompanying commentary in The Lancet.
The CDC’s Frank DeStefano, MD, MPH, and Jerome Tokars, MD, MPH, wrote that other countries have mounted similarly intensive monitoring for the safety of the H1N1 vaccine, which should serve as a model for tracking safety of all vaccines in the future.
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