Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis

[tetano]

The Lancet Infectious Diseases, Early Online Publication, 26 October 2011
doi:10.1016/S1473-3099(11)70295-XCite or Link Using DOI
Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis
Prof Michael T Osterholm PhD a Corresponding AuthorEmail Address, Nicholas S Kelley PhD a, Prof Alfred Sommer MD b, Edward A Belongia MD c
Summary
Background
No published meta-analyses have assessed efficacy and effectiveness of licensed influenza vaccines in the USA with sensitive and highly specific diagnostic tests to confirm influenza.
Methods
We searched Medline for randomised controlled trials assessing a relative reduction in influenza risk of all circulating influenza viruses during individual seasons after vaccination (efficacy) and observational studies meeting inclusion criteria (effectiveness). Eligible articles were published between Jan 1, 1967, and Feb 15, 2011, and used RT-PCR or culture for confirmation of influenza. We excluded some studies on the basis of study design and vaccine characteristics. We estimated random-effects pooled efficacy for trivalent inactivated vaccine (TIV) and live attenuated influenza vaccine (LAIV) when data were available for statistical analysis (eg, at least three studies that assessed comparable age groups).
Findings
We screened 5707 articles and identified 31 eligible studies (17 randomised controlled trials and 14 observational studies). Efficacy of TIV was shown in eight (67%) of the 12 seasons analysed in ten randomised controlled trials (pooled efficacy 59% [95% CI 51?67] in adults aged 18?65 years). No such trials met inclusion criteria for children aged 2?17 years or adults aged 65 years or older. Efficacy of LAIV was shown in nine (75%) of the 12 seasons analysed in ten randomised controlled trials (pooled efficacy 83% [69?91]) in children aged 6 months to 7 years. No such trials met inclusion criteria for children aged 8?17 years. Vaccine effectiveness was variable for seasonal influenza: six (35%) of 17 analyses in nine studies showed significant protection against medically attended influenza in the outpatient or inpatient setting. Median monovalent pandemic H1N1 vaccine effectiveness in five observational studies was 69% (range 60?93).
Interpretation
Influenza vaccines can provide moderate protection against virologically confirmed influenza, but such protection is greatly reduced or absent in some seasons. Evidence for protection in adults aged 65 years or older is lacking. LAIVs consistently show highest efficacy in young children (aged 6 months to 7 years). New vaccines with improved clinical efficacy and effectiveness are needed to further reduce influenza-related morbidity and mortality.
Funding
Alfred P Sloan Foundation.

http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(11)70295-X/abstract

 

[tetano]

Re: Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis

More effective flu shots needed, study shows

Seasonal flu shots prevent only about 59% of infections in adults — and that's not effective enough to protect people in a global outbreak, says a new analysis that may help accelerate research on an improved vaccine.

Scientists are currently working on a "universal flu shot" that would last for years.



Scientists are currently working on a "universal flu shot" that would last for years.

"Today's flu shot is like an iPhone 1.0," says study author Michael Osterholm of the University of Minnesota. "What we need is an iPhone 10.0."

H1N1 shots do slightly better than seasonal flu shots, preventing infection in 69% of adults under 65. Nasal sprays do even better, preventing infections in 83% of children under age 7, according to the analysis of previous studies, published online today in The Lancet Infectious Diseases. One study found that flu shots reduce hospitalizations by 8%. That's significant, however, given that the flu hospitalizes about 200,000 Americans a year.

..


http://yourlife.usatoday.com/health...ctive-flu-shots-needed-study-shows/50913008/1

 

[tetano]

Re: Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis

The Lancet Infectious Diseases, Early Online Publication, 26 October 2011
doi:10.1016/S1473-3099(11)70289-4Cite or Link Using DOI
Estimating the effect of influenza vaccines


Heath Kelly aEmail Address, Marta Valenciano b
In The Lancet Infectious Diseases , Michael Osterholm and colleagues report a meta-analysis 1 on the efficacy and effectiveness of influenza vaccines licensed in the USA. Although not confined to country of licensure, similar analyses have been published by the Cochrane collaboration. 2 However, this new study 1 differs in several ways from the Cochrane analyses.
Osterholm and colleagues' meta-analysis 1 uses the classic epidemiological definitions of efficacy and effectiveness, in which efficacy refers to ...


http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(11)70289-4/fulltext

 

[Gert van der Hoek]

Re: Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis

Strict meta-analysis raises questions about flu vaccine efficacy

Robert Roos News Editor

Editor?s Note: This article covers research conducted in part by CIDRAP researchers. Please note that CIDRAP News operates independently in relation to CIDRAP's research and policy programs.

See also: Public health groups say flu vaccine is best tool, despite limitations

Oct 25, 2011 (CIDRAP News) ? A rigorous new analysis of 44 years' worth of studies is raising questions about the evidence for the effectiveness of influenza vaccines in elderly people and, for certain types of vaccines, in children and younger adults as well.

Applying very strict criteria to filter out potential bias and confounding, a US research team sifted more than 5,000 studies and found only 31 that they felt provided reliable evidence about the efficacy and effectiveness of flu vaccines. The findings were published online today by Lancet Infectious Diseases.

Overall, the researchers found that existing flu vaccines can provide moderate protection from laboratory-confirmed flu, but protection is much lower in some groups and during some seasons. Pooled evidence from randomized controlled trials (RCTs) showed that standard trivalent inactivated vaccines (TIVs) had an efficacy of 59% in young adults (18 to 65), but the authors found no RCTs demonstrating TIV efficacy in adults 65 and older or children aged 2 to 17. (In the United States, because of the recommendation that seniors should be vaccinated, RCTs of flu vaccination in those over 65 have been considered unethical since the 1960s.)

For the live attenuated flu vaccine (LAIV)?the nasal spray version?evidence from 10 RCTs showed 83% efficacy in children 6 months to 7 years old, but no RCTs supported its efficacy in older children or adults. The authors' main conclusion is that use of existing flu vaccines should continue, but better ones are needed.

Please read more : CIDRAP

 

[tetano]

Re: Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis

Effectiveness of flu jab studied

?The annual flu jab given to hundreds of thousands of people this winter provides only limited protection against the illness,? reported The Independent.

This news story is based on a systematic review of studies looking at the effectiveness of two common flu vaccines in the prevention of seasonal flu infection. The vaccines assessed were:

trivalent inactivated vaccine (TIV): the most widely used vaccine in the UK
live attenuated influenza vaccine (LAIV): which is less commonly used

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http://www.nhs.uk/news/2011/10October/Pages/effectiveness-flu-jab-studied.aspx

 

[tetano]

Re: Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis

Vincent Racaniello

How good is the influenza vaccine?


I hear from many readers that they routinely get the flu vaccine every year, yet they often contract the disease. I usually tell them that the vaccine is not perfect: it doesn’t protect everyone who gets it. Now we have the numbers to back up this statement, and they are not pretty.

There have been 5,707 studies since 1967 on how well influenza vaccine protects against infection. Many of them did not properly assess whether individuals were infected with influenza, leading to overestimation of the protective effect of vaccines. In many studies a four-fold increase in serum hemagglutinin antibodies were used to confirm infection. Immunization also increases these antibodies, making it difficult to confirm viral infection.

A review of the influenza vaccine studies was done by focusing on reports in which viral infection was confirmed by viral culture or polymerase chain reaction (PCR). The results of 31 studies show that the trivalent inactivated influenza vaccine is overall 59% effective in individuals 18-65 years of age. That means of every 100 individuals immunized, 41 will be susceptible to influenza. This number is far too low – it should be above 90%. The infectious, attenuated vaccine fared better – it is overall 83% effective but only in children 6 months to 7 years of age. It was not significantly effective in protecting individuals 18-49 years old.

Perhaps even more telling is those age groups in which there are no efficacy data for influenza vaccines. No trial results for the inactivated vaccine in 2-17 year olds or adults 65 years and older were considered adequate for inclusion in this study. Furthermore, there were no acceptable data for the attenuated vaccine in the 8-17 year group. Nevertheless, seasonal influenza vaccine is recommended by the Advisory Committee on Immunization practices for all people over 6 months of age.

The 65 and older age group is a main target for influenza immunization to prevent serious illness and mortality. However, there are few data for this age group on the ability of influenza vaccine to reduce illness or death. The infectious attenuated vaccine was shown to have significant efficacy in this age group in only one study, but it is not licensed for use in adults 50 years old or more in the US.

This study sends a strong message that better influenza vaccines must be developed. Why does the inactivated vaccine confer such poor protection? This vaccine is produced by inactivating the virus with formalin and disrupting it with detergents. In this dissociated state it not only does not replicate after intramuscular injection, but it lacks many of the components that induce a strong inflammatory response. Consequently the antibody response is weak. The attenuated influenza vaccine, which replicates in the respiratory tract, is more protective (83%) in the 6 month-7 year age group. If shown to be efficacious in other age groups it would make sense to increase the use of this vaccine, which currently accounts for only 9% of vaccine given in the US. But we should aim for greater than 90% protection and that may require developing entirely new vaccine approaches using novel antigens, delivery systems, and adjuvants.

These findings will provide a rationale for those do not feel it is necessary to be immunized against influenza. But the study authors do not condone abandoning the inactivated influenza vaccine:

…We should maintain public support for present vaccines that are the best intervention available for seasonal influenza.

In other words, it’s better than nothing, surely not a ringing endorsement. I suspect that the results of this study will lead to a decline in influenza immunization rates in the US.

Update: Alan Dove has a slightly different view of this study.

Osterholm MT, Kelley NS, Sommer A, & Belongia EA (2011). Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. The Lancet infectious diseases PMID: 22032844

http://www.virology.ws/2011/11/03/how-good-is-the-influenza-vaccine/

 

[tetano]

Re: Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis

Alan Dove

So Does The Flu Vaccine Work Or Not?


A paper that came out Wednesday on influenza vaccine efficacy has generated a new round of speculation about what is probably the hardest sell in the vaccine business. There?s a lot to complain about with our current flu vaccines: everyone needs a new shot every year, vaccine makers don?t always guess right about which strains of flu will be circulating that season, and plenty of people can tell stories about how they got the shot and still got sick.

Now, in the middle of flu vaccine season, we get a new peer-reviewed report ? and of course an accompanying press release ? that seems to bring more bad news:

?Evidence for consistent high-level protection is elusive for the present generation of vaccines, especially in individuals at risk of medical complications or those aged 65 years or older. The ongoing health burden caused by seasonal influenza and the potential global effect of a severe pandemic suggests an urgent need for a new generation of more highly effective and cross-protective vaccines that can be manufactured rapidly?, explains Michael Osterholm from the University of Minnesota, USA, lead author of the study.

The news coverage was a mixed bag, ranging from predictable rantings from the antivaccination nuts (no links ? you can find them yourself) to balanced, nuanced explanations such as this. Most of it was somewhere in between, no doubt confusing plenty of regular folks.

While Mark Crislip provided a typically excellent and thorough overview of flu vaccine efficacy back in ?09, I?m just going to highlight a few important features of the new paper from Osterholm?s group.

First, there?s not really any news here. Yes, Osterholm and his colleagues did yeoman?s work mining the literature and compiling their data, but they could not escape the fundamental limitations of all meta-analyses. In a meta-analysis, researchers look at existing publications, pick the ones that meet a particular (and in this case extremely strict) set of criteria, and compile the results into a new paper. There?s no new experimentation involved.

Furthermore, the conclusion of this particular meta-analysis should surprise exactly nobody. We?ve known for a long time that flu vaccines are imperfect, and while Osterholm has now put specific numbers on that imperfection for particular age groups, those numbers are neither definitive nor shocking.

Osterholm?s latest results weren?t exactly secret, either. He presented them at the National Influenza Vaccine Summit in May, and the conference report I wrote for them went on the NIVS web site this summer. It may not be in the top of everyone?s news feed, but anyone who?s really tracked this issue closely already knew these results were coming.

These findings don?t alter the main conclusion of decades of public health advice, either. Flu vaccines aren?t 100% effective, but given their outstanding safety record, and the very real risks involved in catching the flu, they?re a whole lot better than nothing.

Finally, while the study?s headline conclusion was that vaccine efficacy averages only around 59% in healthy adults, the team also found that the H1N1 pandemic flu vaccine was a bit above average (69% effective), and discovered even better results for the live attenuated flu vaccine (LAIV, also known as FluMist) in one of the groups at highest risk of severe flu infection:

By contrast, LAIV showed significant protection against infection in young children, preventing influenza in 83% of children aged 7 years or younger. However, the Advisory Committee on Immunization Practices (ACIP) does not currently recommend LAIV over TIV in these children.

Besides its apparently higher efficacy, FluMist has another huge advantage: it?s inhaled rather than injected. My daughter used to scream her head off each Fall before, during, and after her flu shot. Now she can barely stop giggling through the procedure. With the new meta-analysis showing that this snorted vaccine is probably more effective for her than the shot, I can feel good about it as both a virologist and a father.

http://alandove.com/content/2011/10/so-does-the-flu-vaccine-work-or-not/

 

[tetano]

Re: Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis

The Lancet Infectious Diseases, Volume 12, Issue 9, Pages 658 - 659, September 2012

doi:10.1016/S1473-3099(12)70184-6Cite or Link Using DOI
Quantifying the efficacy of influenza vaccines
Jiehui Kevin Yin a bEmail Address, Gulam Khandaker a b, Harunor Rashid a, Dominic E Dwyer b c d, Robert Booy a b d
The meta-analysis by Michael Osterholm and colleagues1 sheds fresh light on influenza vaccine efficacy and effectiveness. Their review focused on specific endpoint data of RT-PCR or culture-confirmed influenza (serological diagnoses were excluded) to ?assess the highest quality evidence? about the efficacy and effectiveness of influenza vaccine; only ?moderate protection? was reported. The median vaccine effectiveness of monovalent pandemic H1N1 (pH1N1) was shown to be 69% (range 60?93) on the basis of five case-control studies (references 48?52 in Osterholm and colleagues1), all of which were published before Feb 15, 2011. The pooled estimate of pH1N1 vaccine effectiveness might be an underestimate since at least three other relevant studies have been reported as of Nov 28, 2011.2?4 Moreover, we have identified one more study5 that was not found by Osterholm and colleagues. We have done a fresh meta-analysis with these new studies and have identified median vaccine effectiveness against PCR-confirmed influenza of 86% (range 60?95). Our new meta-analysis shows a pooled vaccine effectiveness of 88% including two new case-control studies,2, 3 and 79% based on two cohort studies (figure).4, 5 The pH1N1 vaccines in the nine studies differed in terms of antigenic content, adjuvants, and virus propagation, but they were all monovalent vaccines against A/California/7/2009 H1N1-like virus. The higher effectiveness of pH1N1 vaccine we identified can be explained partly by absence of any significant drift in the pH1N1 strain so far.

Among other biases and confounders of observational studies, Osterholm and colleagues have raised the issue of the so-called healthy vaccinee effect, which results in overestimation of vaccine effectiveness among elderly adults. We assessed this effect in the context of a randomised controlled trial of antiviral treatment to contain influenza outbreaks in aged-care facilities in Australia.6 Further exploration of the data shows that mean number of comorbidities in the aged-care facility residents vaccinated with influenza vaccines was 4?7, which was significantly lower than those who were not (5?6; p=0?01), consistent with a healthy vaccinee effect.
Because most developed countries recommend routine influenza vaccination for elderly people and others at high risk, randomised controlled trials of vaccination are ethically inappropriate, even though present policy is based on historical reference rather than quality evidence; Osterholm and colleagues identified no trial involving adults aged 65 years or older.
Influenza vaccination is, however, not licensed or recommended for elderly people in most disadvantaged parts of the world; this provides an excellent window of opportunity for doing randomised controlled trials to assess the efficacy of influenza vaccine in elderly people and younger at-risk groups. A study from Bangladesh7 has shown that influenza is a major contributor to respiratory infections in early childhood, accounting for a tenth of pneumonias. A milestone study of influenza vaccine effectiveness in pregnant women and their offspring was also done in Bangladesh.8 Randomised controlled trials of influenza vaccines in young children are underway (NCT01319955).
Well-designed randomised controlled trials of influenza vaccine efficacy in developing countries could help address important concerns in research evidence. We suggest a developing country solution for influenza vaccine research through more high-quality randomised controlled trials answering questions of local importance. If efficacy is shown, funding should be in place to achieve local vaccine implementation. And if an influenza vaccine can be shown to be of benefit under somewhat adverse nutritional, socioeconomic, and other conditions, there will be positive implications for other countries be they developing or developed.
RB has received financial support from CSL, Sanofi, GlaxoSmithKline, Roche, Novartis, and Wyeth/Pfizer to do research and present at scientific meetings. Any funding received is directed to an NCIRS research account at the Children's Hospital at Westmead and is not personally accepted by RB. JKY, GK, HR, and DED declare that they have no conflicts of interest.
References
1 Osterholm MT, Kelley NS, Sommer A, Belongia EA. Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. Lancet Infect Dis 2012; 12: 36-44. Summary | Full Text | PDF(192KB) | CrossRef | PubMed
2 Castilla J, Mor?n J, Mart?nez-Artola V, et al. Effectiveness of the monovalent influenza A(H1N1)2009 vaccine in Navarre, Spain, 2009?2010: cohort and case control study. Vaccine 2011; 29: 5919-5924. CrossRef | PubMed
3 Mahmud S, Hammond G, Elliott L, et al. Effectiveness of the pandemic H1N1 influenza vaccines against laboratory-confirmed H1N1 infections: population-based case?control study. Vaccine 2011; 29: 7975-7981. CrossRef | PubMed
4 Igari H, Watanabe A, Chiba H, et al. Effectiveness and safety of pandemic influenza A (H1N1) 2009 vaccine in healthcare workers at a university hospital in Japan. Jpn J Infect Dis 2011; 64: 177-182. PubMed
5 Simpson CR, Ritchie LD, Robertson C, Sheikh A, McMenamin J. Vaccine effectiveness in pandemic influenza?primary care reporting (VIPER): an observational study to assess the effectiveness of the pandemic influenza A (H1N1)v vaccine. Health Technol Assess 2010; 14: 313-346. PubMed
6 Dean AS, Moffatt CR, Rosewell A, et al. Incompletely matched influenza vaccine still provides protection in frail elderly. Vaccine 2010; 28: 864-867. CrossRef | PubMed
7 Brooks WA, Goswami D, Rahman M, et al. Influenza is a major contributor to childhood pneumonia in a tropical developing country. Pediatr Infect Dis J 2010; 29: 216-221. CrossRef | PubMed
8 Zaman K, Roy E, Arifeen SE, et al. Effectiveness of maternal influenza immunization in mothers and infants. N Engl J Med 2008; 359: 1555-1564. CrossRef | PubMed

http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(12)70184-6/fulltext?rss=yes