If you are in the elderly population (over 65 years of age) you are in the crosshairs of CDC’s influenza vaccination program. The reasons seem clear — at first, anyway. Risk of influenza-related death (as measured by a specific statistical technique to estimate excess mortality during influenza seasons) increases dramatically after 65 tears of age. If you are over 80, for example, your risks of being in the excess death category is more than ten times those in the age 65 – 69 age group. Three-quaters of the flu related deaths in a normal flu season are in the 65 plus group and more than half (two thirds of these) in the 80 plus group. So it would make sense to target the 65 plus folks in a flu campaign. Data suggest that by vaccinating 100% of this group, 50% of winter deaths could be prevented.
But a closer look reveals this is highly unlikely. Similar data also show that only 5% of winter deaths are due to influenza. Lone Simonsen and her colleagues at NIAID and others have pointed this out before but their latest review, just published in The Lancet Infectious Disases, is the most pointed attack yet on the CDC vaccination policy:
Although current policy emphasizes vaccination of elderly people, the evidence that this strategy effectively reduces influenza-related morality in that age-gropu is weak. Placebo-controlled randomized clinical trial (RCT) data indicate that vaccination effectively prevents influenza illness in younger health elderly people, but no RCT data conclusively show a similar benefit in those aged 70 years or ore, the age-group that accounts for nearly all influenza-related deaths. (Simonsen et al., The Lancet Infectious Diseases [subscription required])
You’d think we would know by now whether the vaccine works or not. But it is a more difficult problem than you’d think. Flu vaccination is a recognized and accepted part of clinical practice, widely believed to be useful, effective and safe. To do a randomized trial, where half the subjects are given a fake vaccination, raises some serious ethical questions. Thus there are few RCTs in the literature and only one of a decent size that examines response in the elderly. That one shows a clear beneficial effect for the over
65 60 population as a whole, but there is some evidence the benefit is confined more narrowly to the youngest in that group, the 65 60 – 69 year olds. The effectiveness for that group is about 57% but for the 70 year old plus group only 23%, and the precision of that latter estimate is so poor the data are compatible with a very wide range of vaccine efficacy, from zero to over 60%. In other words, for the age group in the CDC vaccine program’s bullseye, the evidence is scant and not particularly encouraging.
This estimate differs greatly from other studies which compare mortality in groups of elderly who received vaccine versus those who did not. After using various conventional statistical techniques to account for any residual differences in the two groups (which were not randomly allocated), there was a large difference in overall mortality between the vaccinated versus unvaccinated elderly (68% vaccine efficacy in one study). This has been a consistent finding in observational studies of this type, which typically might take a large health plan and compare the mortality experience of patients who were vaccinated with those who weren’t. In these studies, vaccinating the elderly makes a very big difference. So what’s going on?
The authors of The Lancet paper suggest there are hidden biases that produce the difference in the observational studies not amenable to the kinds of adjustments usually employed. Two in particular are singled out: that the unvaccinated group is sicker and frailer than the vaccinated group; and that the studies use outcome measures, such as winter mortality, that are too non-speciific and magnify the effect of hidden bias. The combined effect, Simonsen et al. suggest, produces a highly inflated estimate of reduction in mortality from vaccination of the elderly.
So what’s a person (like me) to do? The question whether I personally will be helped by flu vaccination is a somewhat different question than whether people like me should be targeted in a vaccine program. The data from the RCTs still favor the utility for an individual, even of my age (I’m in the
65 60 plus group). I intend to get vaccinated again this year. As they authors observe:
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. Influenza causes many deaths every year, and even a partly effective vaccine would be better than no vaccine at all. But the evidence base concerning influenza vaccine benefits in elderly people does need to be strengthened.
On the other hand, the data present a serious challenge to the CDC program which concentrates on blanket coverage of the 65 plus age group. Both epidemiological and biological data suggest that immune response declines with age. Us older folks just don’t respond as well to the vaccines. This in turn suggests that instead of blind faith in the current program, alternative ideas should be explored, including shifting the target to younger age groups responsible for transmitting the virus in the population. If indeed it is true that there is some cross-reactivity between subtypes, vaccinating younger age groups might have special importance prior to a pandemic.
The authors also have other options:
Refocusing on the likely complications of immune senescence should help clear the way for more vigorous pursuit of other options for influenza control. These options include the development of more-immunogenic vaccines for elderly people, use of larger doses of vaccine, the combining of live and killed vaccine formulations, use of antivirals in a more aggressive manner for treatment and prophylaxis, and indirectly protecting elderly people through increased vaccination of transmitter populations. Implementation of any of these alternative approaches must be accompanied by valid assessments of their effectiveness. [cites omitted]
These are good suggestions. I fear they will fall on deaf ears at CDC, however. Those folks are “true believers.” We all know what that means: blinders and ear plugs in place and full speed ahead.