AstroNutrition Health & Fitness Blog

Ian Hislop was interviewed by Radio 5 Live’s Simon Mayo on Friday. In a discussion about the Eye’s campaigning journalism Mayo brought up the Eye’s coverage of MMR vaccine. The Eye published a special edition about MMR in May of 2002 subtitled “The story so far: a comprehensive review of the MMR vaccination/autism controversy”. It was an appalling piece of scare-mongering journalism. Here are the views of David Elliman and Helen Bedford on the Private Eye publication at the time:

Perhaps not surprisingly the style is of a journalistic expos rather than a well argued scientific treatise, with Andrew Wakefield held up as a crusader for truth, opposing the mighty drug companies and Department of Health. Private Eye seems to have used the kind of lay, anecdotal information that you might read in What Doctors Don’t Tell You and the Informed Parent rather than what you would find in the BMJ or Lancet. Understandably, much space is given to the harrowing accounts of parents who believe that the triple vaccine caused their child’s autism. However, the overwhelming evidence suggesting no link between the vaccine and autism and bowel problems is either not mentioned or dismissed out of hand, while the suggestion of a link is given uncritical prominence.

For example, in telling the story of the evolution of Wakefield’s hypothesis the report fails to mention that at almost each stage independent researchers as well as the original investigators have been unable to replicate the findings. The scientists/researchers listed in the “Who’s who in the MMR story” is nowhere near complete (but then to publish the names of all those who continue to support the vaccine would leave little space for anything else) and reflects the Eye’s bias with seven of the nine doubting the safety of the vaccine. If one were to quantify the evidence for and against a link, the ratio would be in the other direction.

Having read that, have a listen to Ian Hislop’s admission that MMR vaccine is not related to MMR vaccine, and his utter failure to take responsibility for the actions of his publication over MMR vaccine. Simon Mayo’s quiet interview technique can be quite effective at times.

   Ian Hislop on Radio 5 Live 12/12/2008: Play Now | Play in Popup | Download

The Washington Post reports on an FDA decision on long-acting beta agonists (LABAs) in asthma:

The risks of two widely used asthma drugs outweigh their benefits for both children and adults, a U.S. Food and Drug Administration advisory panel said Thursday.

The health panel targeted GlaxoSmithKline’s Serevent [salmeterol] and Foradil [formoterol], made jointly by Novartis AG and Schering-Plough, for restrictions, but it excluded Advair [salmeterol and fluticasone], Glaxo’s biggest-selling drug in the class of medications known as long-acting beta-agonists. It also left alone a fourth such drug, AstraZeneca’s Symbicort [formoterol and budesonide].

The health experts did not say that the use of Serevent and Foradil should be abandoned altogether. Instead, they said the medications’ labeling should be reworded to urge doctors to use the drugs along with an inhaled corticosteroid — as guidelines already recommend.

There was some talk that FDA staff wanted LABAs removed from the market for under 18 year olds. The briefing documents the FDA advisory panel considered are freely available on the FDA site:

Overall, the meta-analysis showed that LABAs were associated with an increased risk of asthma-related events relative to non-LABA treatment as measured by the asthma composite endpoint consisting of asthma-related death, asthma-related intubation, and asthma-related hospitalization. Non-LABA treatment included ICSs [inhaled corticosteroids], short-acting betaagonists, other non-LABA treatments, placebo, or a combination of treatments. The risk difference estimate for the asthma composite endpoint of the LABA rate minus the non-LABA rate was 2.80 (95% CI: 1.11, 4.49) per 1000 subjects. This overall finding for the asthma composite endpoint was supported by both the asthma-related hospitalization and the asthma-related death components. However, findings for individual drugs and subgroups were driven by the asthma-related hospitalization component.

Three of the four drugs (Foradil, Serevent, Symbicort) had positive risk difference estimates for the asthma composite endpoint; however, only Serevent had a statistically significant estimate. The risk difference estimates for the asthma composite endpoint were positive both when (1) LABA without assigned ICS was compared to non-LABA treatment and (2) LABA with assigned ICS was compared to assigned ICS treatment. However, only comparison (1) was statistically significant [3.63 (95% CI: 1.51 – 5.75) per 1000 subjects], and comparison (2) had a small risk difference estimate [0.25 (95% CI: -1.69 – 2.18) per 1000 subjects].

So, the increased risk of asthma events is related to the use of LABAs when used without inhaled corticosteroids. When concern about LABAs came up a year ago, the NPC posted a useful blog post advising on the evidence and action to take:

Healthcare professionals should follow current CHM advice and national guidance on management of asthma. LABAs should be initiated (at step 3) only if inhaled corticosteroids at moderate doses are failing to control asthma symptoms adequately. Before initiating a new drug therapy practitioners should recheck compliance, inhaler technique and eliminate trigger factors. If LABAs are introduced this should be in context of a therapeutic trial.

Professionals should take particular note that LABAs should not be initiated in patients with rapidly deteriorating asthma: they are for “stable but poorly controlled” asthma. Practitioners should consider stepping down LABA use when good long term asthma control has been achieved.

It will be interesting to see if any of these views are revised in the light of the FDA data and the Advisory Panel descisions, but it is arguable that the above advice still stands and that the focus should be on inappropriate prescribing rather than the drugs themselves.

Wakefield’s original 1998 paper, which led to the health scare over MMR vaccine driven by the UK media, was eventually retracted by ten of his co-authors. Another paper published by Wakefield is expected to be retracted by some important co-authors.

In 2002, Wakefield published a paper which is widely known as the O’Leary paper. The conclusion was that measles virus was present in childrens’ bowels, and associated with gut pathology and development disorders in children. This was taken as evidence that Wakefield’s theory on autism being linked to MMR vaccine had a plausible mechanism.

It has been know for some time that results from this study were fatally flawed because of problems with the laboratories involved in the studies. The measles virus they found was actually a contamination present in the laboratory. Additionally, other studies have failed to find the mythical measles virus (Afzal, D’Souza, and Baird).

Earlier this year the Hornig study was published. Hornig replicated the 2002 O’Leary paper and found no difference between the autistic and non-autistic children in terms of measles virus RNA in the bowel. As the author’s put it:

The work reported here eliminates the remaining support for the hypothesis that ASD with GI complaints is related to MMR exposure. We found no relationship between the timing of MMR and the onset of either GI [gut] complaints or autism. We also could not confirm previous work linking the presence of MV [measles virus] RNA in GI tract to ASD [autism] with GI complaints.

Interestingly, the O’Leary of 2002 (whose laboratories gave false positives due to contamination and the omission of a crucial step in the process to detect measles RNA) is the same O’Leary of 2008 who was involved in Hornig study. This has been seized upon by US anti-vaccinators and Andrew Wakefield who have used the fact that the Hornig study carefully checked the reliability of the laboratories performing their tests, to suggest that the Hornig study actually supports the conclusions of the 2002 paper by supporting the reliability of O’Leary’s laboratory. This is the direct opposite of the reality.

In a BMJ rapid response John Stone, of the UK’s leading anti-vaccine website JABS, puts this uber-bizarre debating point across neatly:

the study [Hornig et al] confirms the consistency of O’Leary’s results with two most higly rated labs in the US

Stone may therefore be surprised to read that O’Leary himself is expected to retract the 2002 paper. A letter from Professor Stephen Bustin in The Guardian notes the irony of the same laboratories being involved in both studies.

What makes this evidence wonderfully ironic is that it has been provided by the same individuals (Professor John O’Leary and Dr Orla Sheils from Trinity College Dublin) who reported the original evidence in favour in a 2002 publication.
[...]
It takes no scientific knowledge at all to realise that the reason for this discrepancy is that O’Leary and Sheils have taken exceptional care over their experimental protocols and improved their expertise so that contamination no longer affects their results. Clearly, O’Leary and Sheils have changed their mind on this subject and the expectation now is that both will publicly retract their 2002 publication.

My expectation, when/if this retraction is issued, is that the anti-vaccine movement will find themselves defending a paper which has been retracted by the authors. Not that this is a new experience for them. On the matter of MMR vaccine, faith surpasses reason.