Flu Shots May Have Little Mortality Benefit in Older Adults

WASHINGTON -- Influenza vaccination may save many fewer older patients' lives than generally claimed, according to researchers here.

WASHINGTON, Sept. 25 -- Influenza vaccination may save many fewer older patients' lives than generally claimed, according to researchers here.

The reason is that estimates of a 50% or greater reduction in all-cause mortality have emerged from cohort studies fraught with selection bias, asserted a review article in the October issue of The Lancet Infectious Diseases.

But the real effect with flu shots for those 65 and older during December through March could not have been any greater than 5% to 10%, said Lone Simonsen, Ph.D., of George Washington University here, and colleagues. That's the flu-related mortality burden found in studies of excess all-cause mortality.

Aside from these cohort studies, the evidence is too weak to show any mortality benefit in older adults, who account for 90% of influenza deaths each year, Dr. Simonsen and colleagues added.

However, even a partially effective vaccine is better than no vaccine at all, the researchers said.

"While awaiting an improved evidence base for influenza vaccine mortality benefits in elderly people, we suggest that this group should continue to be vaccinated against influenza," they wrote.

The CDC has targeted influenza vaccination efforts at people at high risk for severe outcomes, including older adults. Vaccination rates have therefore risen to nearly 70% in the 65 and older population. (See: Flu Vaccine Supply Rebounds but Immunization Rates Don't)

However, these "cherished" vaccination policies may need to be revisited, commented Tom Jefferson, M.D., and Carlo Di Pietrantonj, Ph.D., both of the Cochrane Vaccines Field in Alessandria, Italy.

"We must never again allow layers of poor research to mask substantial uncertainty about the effects of a public-health intervention and present a falsely optimistic view of policy," they wrote. They called for placebo-controlled trials.

The "illusory" estimates arose primarily from methodologically weak cohort studies, the GWU researchers said.

These studies used nonspecific endpoints, typically all-cause mortality and non-laboratory-confirmed influenza outcomes, while attempting to adjust for selection bias in multivariate models with health-status covariates defined by diagnostic codes.

But, in one study, adjustment for diagnostic codes indicating severe illness and frailty was found to increase the mortality difference between vaccinated and unvaccinated groups even before the flu season. This suggested that the method left uncontrolled bias.

"If under-vaccination were a direct consequence of these individuals' poor health status, it would be a major source of bias," Dr. Simonsen and colleagues wrote.

Indeed, two studies revealed that most influenza-related deaths occurred in small subsets of older adults with low vaccine coverage who were hospitalized in autumn.

Without cohort studies, "the remaining evidence is not sufficient to show that vaccination substantially reduces the risk of influenza-related mortality among elderly people," they wrote.

Age-adjusted estimates for influenza-related mortality in excess mortality studies showed no reduction in flu-related deaths during a period when vaccine coverage increased by 50%. Nor was there any increase in mortality during the 1997-1998 flu season when the vaccine completely mismatched circulating strains.

Furthermore, vaccine efficacy at preventing the flu may drop with age because of declining immune responsiveness, they noted.

Antibody responses to the influenza vaccine in placebo-controlled randomized controlled trials were only about one-quarter to one-half as strong among older adults as they were in younger adults.

A case-control study that managed to avoid bias showed a vaccine efficacy of 29% for prevention of hospital admission with laboratory-confirmed influenza.

Although none of the randomized clinical trials were powered to evaluate mortality or other severe outcomes, the largest and best-designed trial found a 57% reduction in laboratory-confirmed influenza among healthy adults age 60 to 69 randomized to the vaccine or placebo, but only a 23% reduction for the small group of those ages 70 and older.

These studies with highly specific endpoints and low likelihood of bias "suggest that vaccine benefits are modest," the researchers said.

The way forward may be using case-control studies and potentially even placebo-controlled trials to clarify the mortality effect on older adults and allow "for more vigorous pursuit of other options for influenza control," the researchers concluded.

Dr. Jefferson reported receiving consultancy fees from Sanofi Synthelabo and Roche.