Friday, October 27, 2006

Influenza Vaccination: What Are the Benefits?

Blue study of a young boy with fluRecently, I've been reading arguments by various experts in newspapers and various web sources that flu vaccination should be universal to provide herd immunity for the vulnerable. I've even even seen the claim that universal provision would be cost-effective as it would reduce the number of hospital admissions and treatment costs for those or normal health who developed complications, and vulnerable people who developed significant complications.
Universal immunization would eliminate a lot of misery and lost work and school days while keeping the virus from spreading to sick or older people (family members, friends or strangers) who might die from it.

And the immunization need not be 100 percent. In medicine, there is a concept is called "herd immunity" — that is, if enough members of a group of animals (including humans) are immunized against a disease, the entire group is more likely to escape infection.
Contrast that glowing call to civic responsibility with the Daily Telegraph's account of a Cochranesque study on the efficacy of flu vaccination that questions its usefulness. The article in based on a fascinating evaluation of the flu vaccination programme in the British Medical Journal: Influenza vaccination: policy versus evidence. Dr. Jefferson is the author, and he reports a systematic review of flu vaccination studies: he criticises them as mostly poor quality and showing evidence of bias.
The large gap between policy and what the data tell us (when rigorously assembled and evaluated) is surprising. The reasons for this situation are not clear and may be complex. The starting point is the potential confusion between influenza and influenza-like illness, when any case of illness resembling influenza is seen as real influenza, especially during peak periods of activity. Some surveillance systems report cases of influenza-like illness as influenza without further explanation. This confusion leads to a gross overestimation of the impact of influenza, unrealistic expectations of the performance of vaccines, and spurious certainty of our ability to predict viral circulation and impact. The consequences are seen in the impractical advice given by public bodies on thresholds of the incidence of influenza-like illness at which influenza specific interventions (antivirals) should be used.
Dr Jefferson argues that vaccination programmes should have verifiable and measurable targets; e.g., reducing the number of cases and deaths and reducing absenteeism from workplaces and school. Remembering Jefferson's comments on the poor quality of many of the studies, and the small numbers of people assessed in some of them, the summary of his findings is as follows:
  • Flu vaccination is worthwhile for people with bronchitis.
  • Inactivated vaccines reduce the incidence of exacerbations after three to four weeks by 39% in those with chronic obstructive pulmonary disease.
  • For infants up to 2 years old, vaccination was no better than placebo; in older children there was little evidence of benefit.
  • Although a review of study data suggested that vaccination of all children mimimises transmission to other family members, the weakness of the study design made it impossible to quantify the benefit.
  • Jefferson did not find enough evidence of benefit for vaccination for people with chronic chest problems, asthma and cystic fibrosis.
  • For healthy adults the evidence indicates that, on average, flu vaccination of the population would prevent 0.1 per cent of a working day lost. Vaccination does not affect hospital stay, time off work, or death from influenza and its complications.
  • Combined studies of the elderly showed a variation from no effect to a 60 per cent difference when "all cause mortality" was measured.
With reference to the last, Jefferson writes that:
These findings are both counter-intuitive and implausible as other causes of death are far more prevalent in older people even in the winter months. It is impossible for a vaccine that does not prevent influenza to prevent its complications, including admission to hospital.
Jefferson makes a strong argument for the necessity of high quality randomised control trials.
the inception of a vaccination campaign seems to preclude the assessment of a vaccine through placebo controlled randomised trials on ethical grounds. Far from being unethical, however, such trials are desperately needed and we should invest in them without delay. A further consequence is reliance on non-randomised studies once the campaign is under way. It is debatable whether these can contribute to our understanding of the effectiveness of vaccines. Ultimately non-randomised designs cannot answer questions on the effects of influenza vaccines.
Jefferson concludes that:
The optimistic and confident tone of some predictions of viral circulation and of the impact of inactivated vaccines, which are at odds with the evidence, is striking. The reasons are probably complex and may involve "a messy blend of truth conflicts and conflicts of interest making it difficult to separate factual disputes from value disputes" [22] or a manifestation of optimism bias (an unwarranted belief in the efficacy of interventions).[23]
It is a fascinating paper and will probably generate some controversy. One of the areas for discussion is the claim that the dose in adult flu shots is too low (as discussed in the first referenced piece). It is unquestionable however that Jefferson is correct about the poor quality of the studies that do exist and the need for better, randomised trials.

The BBC carries comments from the Dept. of Health and other interested bodies that emphasise their confidence in the value of flu vaccination, but in the light of Jefferson's analysis, it is difficult to accept the assertion that:
There is good evidence from clinical trials that flu and its more serious effects are prevented by vaccination when you look at the community effect.
Jefferson does not argue that people should forego their influenza jabs: he does argue that we need better quality trials and evidence before we can be confident that the jabs are effective and have cost-benefits.

P.S. - Phillip Gordon has mentioned the comments on this post. For reasons that Blogger alone can fathom - they are split between Haloscan and Blogger comments. To see the Haloscan comments, you need the home page loaded and to scroll down to the post and click on comments. If you came here from the PGR 1:15 link, then the Blogger comments should automatically load with the piece. I can't wait until I'm offered the Blogger Beta option.

For more information about the images used in the illustration, click on it or visit the detail on Flickr.

9 Comments:

Blogger Flea said...

Shinga,

Check out this abstract by my former colleague, Ken Mandl. It doesn't support vaccination for the 2 and unders, but it makes a strong case for school-age-children, who themselves are not at risk for excess mortality and only moderate morbidity.

Vaccinating these kids saves the lives of their grandparents.

best,

Flea

5:58 pm  
Blogger Shinga said...

Thanks, Flea. I did wonder about that as I had previously read/believed that vaccination of school-aged children would reduce the morbidity and mortality among their grandparents. Unfortunately, I have to admit that I haven't seen the systematic review from which Jefferson draws his conclusions:
Jordan R, Connock M, Albon E, Fry-Smith A, Olowokure B, Hawker J, et al. Universal vaccination of children against influenza: are there indirect benefits to the community? A systematic review of the evidence. Vaccine 2006;24: 1047-62

I don't know why but the Jordan et al. paper isn't in Entrez Pubmed although other papers from that journal, are.

Without seeing the Jordan review, I don't have a feel for whether the paper you referred to was included or excluded. I think it is quite bad to leave readers questioning this omission.

Regards - Shinga

6:40 pm  
Blogger Rob said...

What about the NEJM study of Japanese chilren from 2001 that showed that vaccinating school-aged children also offered protection for the community (mostly the frail)? I agree that this is far more compelling than that data regarding the under 2's.

3:39 pm  
Blogger Shinga said...

Hi Rob - I'm beginning to think that it was unacceptable that this paper relies on its conclusions from another paper. It is one thing to perform your own meta-analysis, it is another to accept the conclusions from another systematic review for which the investigation criteria haven't been explained.

There have been several papers that indicate the community value of vaccinating school-aged children. If Jefferson is discounting these (irrespective of how they were handled in the Jordan et al. paper) because of poor methodology, then I think that he should say that more explicitly (the BMJ link is to the full paper).

I think that overall, Jefferson's main point holds, which is that there seems to be a paucity of well-run RCTs that illustrate the value of vaccination. Otherwise, the exclusion of both the Mandl and NEJM paper makes little sense - unless they were discounted in the Jordan paper (which I really have to get).

Incidental to this, is the issue that it seems as if there should be some experimentation with the dosage of flu vaccines with older people.

Regards - Shinga

12:11 pm  
Blogger purple_kangaroo said...

Very interesting post. I had to stop taking the flu shot because it made me so sick every time, but my mom who's a kidney transplant recipient gets one every year per her doctor's orders.

11:39 pm  
Blogger Shinga said...

Hello Purple_Kangaroo,

What a pest for you. Are your children offered flu vaccination (the older ones) - assuming that they are around you and their grandmother?

Thanks for stopping by.

Regards - Shinga

12:46 pm  
Blogger purple_kangaroo said...

My oldest is 5, and we haven't given any of our 3 kids the flu shot.

My 15-month-old was offered a flu vaccine when she was younger, but we didn't do it. At this point we don't know what's wrong with the baby, and she has severe allergies to components of most vaccines.

The pediatrician doesn't recommend getting any vaccines at this point for Baby E because of her allergies and the benefit/risk balance in her particular circumstances. He hasn't particularly recommended the flu vaccine for my older girls either (although they've had most other commonly-given childhood vaccines).

My mom avoids being around the kids if they even look like they might be getting a cold, so we pretty much just don't see her throughout the cold and flu season. The kids aren't in school, so they aren't exposed to as many illnesses, but they still get runny noses--especially Baby E, who is sick a lot.

7:42 pm  
Blogger Shinga said...

Baby E sounds so puzzling - it must be wretched for her and very inconvenient and worrying for you to have to cope with all these allergies.

Ah - the reservoir of infection avoidance technique. I know several people who accept no visitors during cold and flu season unless you are absolutely sure that you are not infectious. Tricky - because of course you can be infectious in the pre-symptomatic phase.

I do recommend that people who must remain cold and flu free should follow the new cold and flu guidelines to minimise the risk of transmission. Of course, that is both for themselves, and the people with whom they come in contact.

Regards - Shinga

12:31 pm  
Blogger purple_kangaroo said...

Thanks . . . it will be nice if we can figure out whether it's just allergies or something else going on as well.

We are pretty careful about washing hands, etc. here.

12:11 am  

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