Aug 29, 2008 (CIDRAP News) – Some healthcare experts have wondered if large mortality reductions among older people who receive seasonal influenza immunizations are real or if the findings are biased by a "healthy-user" effect. But now a study that more rigorously controlled for confounders suggests that the benefits are overstated.
The study, by Canadian researchers who evaluated data from patients admitted to six Capital Health hospitals in Alberta, appeared in the Sep 1 issue of the American Journal of Respiratory and Critical Care Medicine.
It revealed no statistical difference between in-hospital mortality rates of elderly patients receiving seasonal flu vaccination and of those not vaccinated.
It is the latest among a handful of recent studies that have cast doubt on the benefits of flu vaccines for older people and may call for a reexamination of public policy on flu vaccination among the elderly. A study that appeared in the Aug 2 issue of The Lancet suggested that the vaccine's ability to protect the group from pneumonia was less than expected.
Accounting for 'good behavior'
The research group pointed out that most evidence on the benefit of influenza vaccines in older patients is based on observational studies that suggest a 50% mortality rate reduction. However, they said many experts have suspected that such a high benefit is implausible.
For example, they wrote that though vaccination rates in the United States' elderly population have risen from 15% to 65% over the over the past 20 years the increase has not been matched by decreasing hospitalization and mortality rates.
"Previous studies were likely measuring a benefit not directly attributable to the vaccine itself, but something specific to the individuals who were vaccinated—a healthy-user benefit or frailty bias," said Dean T. Eurich, PhD, the study's first author, in a press release from the American Thoracic Society, which publishes the American Journal of Respiratory and Critical Care Medicine. Eurich is a clinical epidemiologist and assistant professor at the University of Alberta's School of Public Health.
Also, the researchers wrote that other studies have detected similar mortality reductions during the times of year when influenza viruses aren't circulating, which cast further doubt on the size of the vaccination benefit.
Sumit Majumdar, MD, MPH, principal investigator and associate professor of medicine at the University of Alberta, said in the press release, "The healthy-user effect is seen in what doctors often refer to as their "good" patients—patients who are well-informed about their health, who exercise regularly, do not smoke or have quit, drink only in moderation, watch what they eat, come in regularly for health maintenance visits and disease screenings, take their medications exactly as prescribed—and quite religiously get vaccinated each year so as to stay healthy."
"Such attributes," he said, "are almost impossible to capture in large-scale studies using administrative databases."
Majumdar and colleagues hypothesized that if a healthy-user effect was responsible for mortality benefits, then the same benefit would be seen during the "off season," when the influenza virus wasn't circulating.
The researchers had access to a large database that allowed them a unique opportunity to explore the bias, because it included a number of potential healthy-user indicators such as smoking and functional status.
Looking beyond biases
They analyzed data from 704 patients ages 65 and over who were admitted to the hospital for community-acquired pneumonia during non-flu season intervals from 2000 through 2002. Researchers matched 352 patients who had received their flu vaccines against 352 controls who did not.
Twelve percent (81) of the patients died. When the group looked at in-hospital death rates, they found that vaccinated patients were about half as likely to die as those who weren't vaccinated (28 [8%] versus 53 [15%]), which is consistent with past observational studies. However, when they adjusted for the healthy-user effects, the benefit was much smaller, and at 19% didn't reach statistical significance.
The authors concluded that a difficult-to-detect healthy-user effect is present among vaccinated patients, and that other analyses of vaccine benefit during influenza season probably overestimate the benefit of vaccination. However, they cautioned that their findings might not be generalized to healthier, lower-risk patients in a nonhospital setting.
Putting the findings to use
The findings have broad implications for public health, the authors wrote. Patients with chronic diseases, as well as their contacts, should still get their annual flu vaccines, Majumdar said in the press release. "But you also need to take care of yourself. Everyone can reduce their risk by taking simple precautions," he said, such as hand-washing, avoiding sick people during flu season, taking antiviral medication, and seeking prompt medical care.
Inflated mortality reductions noted in previous studies could hamper efforts to develop better vaccines, particularly for use in elderly populations, they wrote. Evidence-based findings, however, may help policymakers to direct their efforts more toward hand-washing and vaccinating children and healthcare workers, they added.
And for researchers, the findings might serve as a useful reminder, Majumder said in the press release. "The healthy-user effect is everywhere you don't want it to be."
Eurich DT, Marrie TJ, Johnstone J, et al. Mortality reduction with influenza vaccine in patients with pneumonia outside 'flu' season: pleiotropic benefits or residual confounding? Am J Respir Crit Care Med 2008 Sep 1;178(5):527-33 [Abstract]
Aug 29 American Thoracic Society press release
Aug 8 CIDRAP News story "Study: Flu shots may not protect elderly from pneumonia"