Feb 18, 2010 (CIDRAP News) – In an updated analysis of scores of studies spanning four decades, researchers at the Cochrane Collaboration in Rome say reliable evidence on the effectiveness of influenza vaccination in elderly people is very sparse and shows only a modest benefit.
To clarify the situation, the researchers call for a publicly funded, randomized controlled trial (RCT) lasting several years—a type of study that has been called unethical, given that flu vaccination is widely recommended for older people, who face an increased risk of serious flu complications.
The authors, led by Tom Jefferson, examined 75 studies and found that the vast majority were flawed by various kinds of selection biases, meaning the vaccinated and unvaccinated groups differed or might have differed in health status or other characteristics that may have affected the outcomes. The group found only one RCT that they regarded as fully reliable.
"The available evidence is of poor quality and provides no guidance regarding the safety, efficacy or effectiveness of influenza vaccines for people aged 65 years or older," the report states. "To resolve the uncertainty, an adequately powered publicly funded randomized, placebo-controlled trial run over several seasons should be undertaken."
In response to the report, a spokesman for the US Centers for Disease Control and Prevention (CDC) agreed that better studies are needed but said limited data from randomized trials and studies in nursing homes, combined with the disease burden, support the current US recommendation for flu vaccination in the elderly.
The Cochrane Collaboration is an international not-for-profit organization that studies the effects of healthcare with the aim of ensuring that healthcare decisions are based on high-quality research evidence.
The group has reported on the effectiveness of flu vaccination in older people before. For example, in 2005 the group reviewed 64 studies and concluded that vaccination was modestly beneficial for seniors overall, with greater effects in nursing home residents than in community residents.
Of the 75 studies the authors reviewed, 68 were used to assess vaccine effectiveness and 8 were used to examine vaccine safety; one trial was included in both assessments. Many of the studies were cohort studies in long-term care facilities.
The researchers found only five RCTs published in four decades, and only one of these, reported in 1994, "assessed currently available vaccines and reached satisfactory completion," their report says. An analysis of the best RCTs indicated that flu vaccination reduced the risk of flu-like illness by 43% and of actual flu by 58%.
Overall, the authors write, "Our findings show that according to reliable evidence, the effectiveness of trivalent inactivated influenza vaccines in elderly individuals is modest, irrespective of setting, outcome, population, and study design. Our estimates are consistently below those usually quoted for economic modeling or decision making."
In nursing home studies, the overall findings suggest that vaccines have little effect on influenza-like illness (ILI) but a greater effect on flu complications, which suggests that vaccination is beneficial, the report says. But in community studies, the effectiveness of vaccination seems modest.
The authors conclude that all the non-RCTs were flawed to some degree by selection biases. In particular, they say that selection biases probably account for the perplexing pattern of findings in community-dwelling older people: that vaccines are apparently ineffective in reducing flu, ILI, pneumonia, and hospital admissions or deaths from any respiratory disease, but are effective in preventing hospital admission for flu or pneumonia and in preventing deaths from all causes.
The Cochrane group also assessed vaccine safety findings and reported no major problems on that score, observing, "The public health safety profile of the vaccines is acceptable. However, relatively few studies reported assessing safety outcomes."
In a separate assessment, the team examined 259 studies for relationships between study design quality, funding source, and journal of publication. They found that higher-quality studies and those funded by governments were less likely to support vaccine effectiveness. Also, they concluded that studies partly or fully funded by industry tended to be published in more prestigious journals as measured by journal impact factor.
In calling for controlled trials of flu vaccines in older people, the group says the studies should be publicly funded. "Unfortunately, because of the global recommendations on influenza vaccination, placebo-controlled trials . . . are no longer considered possible on ethical grounds," they observe.
CDC spokesman Tom Skinner defended the CDC recommendation for flu immunization of people older than 65, who now are among vaccination target groups that include most of the population.
"We do need better studies to determine the effectiveness of influenza vaccine in the elderly, and CDC is working on such studies," Skinner commented. "However, it's a fact that influenza causes a heavy burden of illness and death among people 65 and older. This burden, combined with limited data from randomized trials as well as studies in nursing homes and other settings, support the current vaccination recommendations of the United States and many other countries."
The Cochrane report does not discuss the possibility of improving the effectiveness of flu vaccines in older people by increasing the antigen dose. Because of concern about a reduced immune response to standard flu vaccines in this age-group, a high-dose flu vaccine has been developed and was approved in December by the Food and Drug Administration (FDA). The vaccine, made by Sanofi Pasteur, contains four times as much antigen as standard vaccines—180 micrograms (mcg), or 60 mcg for each flu strain. It is expected to be available next fall.
Jefferson T, Di Pietrantonj C, Al-Ansary LA, et al. Vaccines for preventing influenza in the elderly. Cochrane Database of Systematic Reviews 2010(2) [Abstract]
Dec 28, 2009, CIDRAP News story "FDA licenses high-dose flu vaccine for elderly"
Oct 9, 2007, CIDRAP News story "Fresh doubts, new support for flu shots for seniors"
Sep 23, 2005, CIDRAP News story "Flu vaccination benefits for elderly called modest"