New research from Canada suggests that some studies have exaggerated the benefits of the flu vaccine in reducing death rates among elderly patients and that while it confers protection against specific flu strains, other factors like unidentified “healthy user” effects have produced small but statistically insignificant reductions in all-cause mortality rates.
The study was led by principal investigator Dr Sumit Majumdar, associate professor in the Faculty of Medicine and Dentistry at the University of Alberta in Edmonton, Alberta, Canada and is published in the first issue for September of the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.
Majumdar and colleagues found that the widely held perception that flu shots reduced death risk in the elderly did not stand up to scrutiny.
For the study, they analyzed clinical data from records of all 6 hospitals in the Capital Health region in Albert. This meant they had around 700 matched patients most of whom were aged 65 and above, who had been hospitalized for community-acquired pneumonia during non-flu season.
Half of the patients had received the flu shot and half had not, and each vaccinated patient was matched to a non-vaccinated equivalent of similar age, same sex, and other demographic characteristics, plus similar medical conditions, functional status, smoking status and current prescription medications.
The records gave the researchers detailed information, including variables that had either not been considered or had not been available in the studies that had reported the reduction in mortality
Majumdar and colleagues found that:
- Overall hospital mortality revealed 12 per cent of the patients died overall.
- 29 per cent had severe pneumonia.
- The overall median length of stay was about 8 days.
- While they analyzed the figures using a model similar to that employed by previous observational studies (that had mostly showed vaccinated patients were about 50 per cent less likely to die as unvaccinated ones), there was a striking difference when they adjusted for detailed clinical information.
- The detailed clinical information they included in their adustment were things like: the need for an advanced directive, pneumococcal immunizations, socioeconomic status, in addition to sex, smoking, functional status and disease severity.
- When they controlled for these variables, the relative risk of death went down to a statistically non-significant 19 per cent.
When Majumdar and colleagues added another 3,400 patients from the same cohort to their analysis, they found the relative risk did not change very much.
They concluded that:
“The 51 per cent reduction in mortality with vaccination initially observed in patients with pneumonia who did not have influenza was most likely a result of confounding.”
“Previous observational studies may have overestimated mortality benefits of influenza vaccination,” they added.
Speculating on their findings, they suggested there was a difficult-to-correct confounding due to a “healthy user” effect in the vaccinated patients. Lead author Dr Dean T. Eurich, clinical epidemiologist and assistant professor at the School of Public Health at the University of Alberta, said:
“While such a reduction in all-cause mortality would have been impressive, these mortality benefits are likely implausible.”
“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,” he added.
Eurich said that over the last 20 years or so in the US, even though vaccination rates among elderly patients has gone up from 15 to 65 per cent, it has not been matched by an equivalent fall in hospital admissions or all cause mortality.
“Further”, added Eurich, “only about 10 per cent of winter-time deaths in the United States are attributable to influenza, thus to suggest that the vaccine can reduce 50 percent of deaths from all causes is implausible in our opinion.”
Commenting on the healthy user effect, Eurich explained that it was “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.”
He said that such attributes are nearly “impossible to capture in large scale studies using administrative databases”.
The researchers said the main message of their research was that the elderly should still be vaccinated against the flu, but as Majumdar explained:
“You also need to take care of yourself. Everyone can reduce their risk by taking simple precautions.”
“Wash your hands, avoid sick kids and hospitals during flu season, consider antiviral agents for prophylaxis and tell your doctor as soon as you feel unwell because there is still a chance to decrease symptoms and prevent hospitalization if you get sick — because flu vaccine is not as effective as people have been thinking it is.”
The message to vaccine developers is that the previously inflated reports of reductions in mortality rates may have stifled the development of newer and better vaccines for use in the elderly, and for policy makers the message is that effort to improve quality of care is best directed at evidence based precautions such as washing hands, vaccinating children and health care workers.
For researchers, Majumder had this less reassuring message: “the healthy-user effect is everywhere you don’t want it to be”.
“Mortality Reduction with Influenza Vaccine in Patients with Pneumonia Outside “Flu” Season: Pleiotropic Benefits or Residual Confounding?”
Dean T. Eurich, Thomas J. Marrie, Jennie Johnstone, and Sumit R. Majumdar
Am. J. Respir. Crit. Care Med. 178: 527-533.
First published online as doi:10.1164/rccm.200802-282OC.
Sources: American Thoracic Society.
Written by: Catharine Paddock, PhD