Wakefield: Proquad claims. Liar or incompetent?

[noblegiraffe]

This just came up on another thread, and I thought it was worth wider publicity, given Wakefield's apparent continuing influence, and the current measles outbreak.

I was discussing whether 'vaccine overload' had any basis in science, or any evidence for it. (No, btw).

I was directed to the claim that giving a 4 in 1 jab against measles, mumps, rubella and chicken pox (called the MMRV) doubled adverse reactions. I found an interview with Wakefield where he claimed this showed that giving extra vaccinations at the same time was dangerous. He said:

"If you just take for example, MMR and you add in the varicella vaccine, the chickenpox vaccine, MMRV as ProQuad what happens is you double the rate of convulsions as an adverse reaction. So just adding one and not 999,000 but just one extra vaccine in, you double the rate of an adverse, a potentially serious adverse reaction. To the extent that that ProQuad vaccine had to be withdrawn. So the notion that you could give a child a hundred thousand vaccine antigens on one day is utter nonsense. And what is extraordinary, what is telling I suppose is that no other immunologist or vaccinologist or any other person with any credible standing has stood behind Dr. Offit and said yes, you can go for it."

2 points need to be made

1. Proquad has not been withdrawn. It is still licensed for use. The advisory body in the US did amend their recommendation in light of the extra adverse reactions (4.3 extra febrile seizures per 10,000). ProQuad used to be their preferred injection for both initial and booster jab, now it is just recommended for the booster jab.
   www.merckvaccines.com/Products/ProQuad/Pages/recommendations

2. Wakefield suggests that it was giving an extra vaccine that caused the extra adverse events (vaccine overload), however the comparison of adverse events was not between the MMRV and the MMR (4 vaccines versus 3) but the MMRV versus the MMR plus the chickenpox vaccine given on the same day (4 versus 4). Nothing to do with an extra vaccine, and he is trying to use this to make a point which simply isn't valid.
   www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm123798.htm

Now Wakefield still has an agenda regarding spaced out single vaccines (as recent headlines show).
Was he lying when he made these easily researched incorrect claims about ProQuad, or was he simply too thick to correctly assess the information widely available?

Now if he wanted to discuss why there were more adverse events to the 4 in 1 versus the 3+1, he might have a point (I'm not sure they contain exactly the same vaccines) but he didn't. He made a completely false point, one which is proudly featured on an antivax website.

Please treat anything Wakefield says with the caution it deserves.

Apologies that the next few posts will be disjointed, I'm having problems with copying and pasting from other tabs and keep losing my post when I do it.

Beachcomber, you appear to have missed the fundamental point regarding the California data which is that Wakefield was using it for something the authors quite clearly stated it wasn't intended for.
The report the graph came from is here
www.dds.ca.gov/Autism/docs/autism_report_1999.pdf
It's on page 8. See how Wakefield amended the label on the axis? Why did he do that unless to hide that the numbers of people were enrolled in a centre?

The authors state "Unfortunately, the quality and type of information examined in this report were not suitable for measuring incidence in the population of persons with autism. "

And "This report was not an investigation of incidence, but was rather an official counting and reporting of the numbers of persons with autism and other developmental disabilities served by the regional center system over time. This report does not include any data on those persons in California who are not part of the Developmental Services system. "

Wakefield, however, is presenting it as if it were exactly an investigation of incidence of autism in the general population.

Basically they looked at the people enrolled in their centre in 1991 who had autism and plotted their dates of birth on a graph. There were lots of young people registered in the centre, and comparatively fewer older people. Now, I've no idea how you get registered in the centre or what it's for, but I imagine that would be quite important.
It's obvious to me that there would be fewer older people registered with autism automatically, regardless of whether incidence of autism is on the increase, simply because of the increase in diagnoses. There are lots of people out there with undiagnosed ASD out there in the older generations who would have been picked up had they been born now.

The report also says "Compared to characteristics of 11 years ago, the present population of persons with autism are younger, have a greater chance of exhibiting no or milder forms of mental retardation, are more likely to live at home, and are more likely to receive an earlier diagnosis."

So, it's also possible that in the older age groups, the people with autism who exhibit no mental retardation and are able to live at home slipped through the system, but due to more awareness of autism, they are now being picked up.

The data isn't controlled in any way, so many confounding variables make it meaningless to look at the spread of ages of people with autism registered at that centre, stick an arrow on it and say 'look, that's precisely when the problem started and it precisely links to this event.'

There's no doubt (and if you read the report it's clear) that the number of people being referred to the centre with autism is increasing, and that it is increasingly younger children who are being referred. So autism referrals are on the increase. Does that mean autism is on the increase? Or just autism diagnoses? Or something else? You can't tell at all from this data. If the centre had become renowned for its excellence in dealing with young children with autism, you'd see exactly the same thing.

Do you see? Wakefield shouldn't have touched this data with a barge pole. But not only did he do that, he tried to hide the source - an enrollment in a centre.

So, you have the authors of the UK data saying that Wakefield has misinterpreted their data, and you have the authors of the US data saying that their data shouldn't be used at all in the way Wakefield has used it.

And you have a graph where he has forced the two together in a way that mathematically shouldn't be done, as it is exceptionally misleading.

Autism diagnoses are increasing, that's indisputable. Autism itself may be on the increase, although untangling that from the increase in diagnoses would be quite tricky, I imagine. You say that's accepted now, I haven't looked into it.

But that graph, and what Wakefield has attempted to do with it is just intellectually, scientifically, mathematically, undefendable.

Either cases of autism have risen or they have not.

No diagnosis has risen.

Before the 1940s there were virtually no cases because the term 'autism' wasn't used then.

There were still people with autism, they just didn't have a diagnosis.

In silicon valley there are a lot of children with ASD, this is unlikely to be environmental, it is probably due to the fact many computer programmers, IT geeks etc have ASD, or ASD tendencies and there is a complex genetic link.

racheael76 - I live in France where we had a measles epidemic a couple of years ago. Apparently around 10,000 cases - most French people have never heard of Dr Wakefield.

Yes, I know the rebuttal is on the same page as the letter published by Dr Wakefield - thought it was interesting to read the whole thing in context. Thanks for replies noblegiraffe, I will read and reply later.

Dr Wakefield clearly states where the California data comes from "Data from the recent California report from the Office of Developmental Services".

The Department of Developmental Services isn't 'a centre' it is a state wide system for ensuring that people with developmental issues are looked after and access services they are entitle to. They are considered to have one of the best data bases on autism in the world because they have been gathering comprehensive data since the 1970s. Many studies have been done on autism using the Californian data for this reason.

In California, the Lanterman Developmental Disabili-ties Services Act, passed in 1969 and amended numerous times over the subsequent 6 years, guarantees that all individuals with developmental disabilities can receive age-appropriate services for specified conditions (autism, mental retardation, cerebral palsy, and epilepsy). During that period, the paradigm for services to individuals with disabilities was shifting from the medical model to the developmental model, a change implemented by state and national policies. By 1976, 21 Regional Centers were established in California to administer and coordinate those services in a community rather than institutional setting. Administrative databases from these Regional Centers are now compiled centrally by the Department of Developmental Services (DDS) and have been analyzed to track trends in developmental disabilities.

From the CDC;

More people than ever before are being diagnosed with an ASD. It is unclear how much of this increase is due to a broader definition of ASDs and better efforts in diagnosis. However, a true increase in the number of people with an ASD cannot be ruled out. We believe the increase in ASD diagnosis is likely due to a combination of these factors.

That webpage states the number as 1 in 88. Their latest study shows 1 in 50 but apparently the study method was different.

The CDC was adamant for years that any increases could be accounted for by changes in diagnosis/better diagnosis so this is quite a change in their stance. Which is good because it has helped open up the possibilities for research into environmental factors.

Beachcomber, you haven't acknowledged the fact that Wakefiekd was using the data in a way the authors specifically said it wasn't suitable for. Presumably he read the report before taking the graph, no? And if there isn't a problem with the data he used, why did he amend the axis label?

Data is data. Although of course it can be 'massaged' and manipulated - in fact the Talyor et al study has been heavily criticized for doing this.

I think it is very interesting that the Californian Department of Developmental Services is careful to stress that their investigation is not an attempt to measure incidence in the population. Which of course it is not - it is a state wide report clearly showing that the Department has seen a major increase in the number of autistic people they have in their service whilst they have not seen a similar increase in other developmental difficulties. They also go on to say;

What we do know is that the number of young children coming into the system each year is significantly greater than in the past, and that the demand for services to meet the needs of this special population will continue to grow. If present rates of intake continue, there will be a need for: (1) greater emphasis on long range planning to develop suitable methods of delivering services, (2) strategies for development of new and abundant resources; (3) clinical training of regional center personnel in diagnostic and treatment standards necessary to adequately advise parents and (4) creation of forums for information exchange and collaboration between providers and the families of children with autism. In conclusion, there is a real need to accelerate multi-discipline, multi faceted research efforts in this area.

The Californian data shows an increase in autism cases entering the state wide system over that period - they don't wish to draw conclusions about the population in general based on their limited data. I also think they are being very careful as they know that this is a highly charged subject.

Wakefield does not try to draw conclusions about the population in general either. His point is that there is a temporal association. He is pointing out that there are more cases in California than before and that there are more cases in West London than before but that what is interesting is that the increase in these two areas happened 10 years apart and that in both areas the increase followed a change in vaccination policy with the first birth cohorts to receive the triple vaccine. Which is pretty solid epidemiological evidence that more, not less, investigation is needed (the Taylor study was an attempt to shut down any more investigation).

If you look at this article, they use the Californian data to examine incidence in the state.

I don't know why Wakefield amended the axes label - just as I don't know why the authors of the above article amended labels. I suppose though that it is because the DDS is making a point that the data shows that they have more people enrolled in their service and therefore need more funding/infrastructure whereas Wakefield or others are not making a case for the DDS they are using the DDS data simply to show that there are more people with autism in California than before. (As I said before, California is considered to have one of the most comprehensive data bases in the world with regards to autism and other developmental disabilities. Seems logical to use the best data available to examine a possible increase in cases.)

I think you speak very eloquently BeachComber. If I had the energy you do I would love to debate properly about this.

My ds has mumps at the moment, which I think he caught on our holiday from a relative. He is fine and resting, just keeping him in and away from other kids. Dd is having her second bout of chickenpox :)

Beachcomber, you are now arguing a different point entirely, whether autism diagnoses are increasing. No one disputes that. There are lots of people making efforts to investigate why.

The issue here is Wakefield misusing data to try to show a link between this increase and the MMR and using wholly unsuitable data without any controls to do so.

The document you just linked to makes huge efforts to exert some control on the data they are analysing before drawing any conclusions.

They point out that the definition of autism became much broader in the 80s. Does Wakefield? No. They point out that the people currently in the system in California might not have been born in California (so would they have even got the MMR?). Does Wakefield account for that? No. Did regulations change to include milder cases? (remember the report says that far more of the recent cases are likely to have no or mild mental retardation, and are more likely to live at home). Did Wakefield discuss that hypothesis? No. He just took some raw data and plonked a big old arrow in it saying 'MMR starts here' and said that meant his argument was true.

It's nonsense.

Waynetta it may be eloquent but it,s complete nonsense.
Its excuses made for a man that has repeatedly been caught out lying, changing data etc for his own end. The consequence of which is a return of a disease that should have been eliminated by now in the UK.

Another issue to consider is that if the MMR was introduced in 1988 and causes autism at a particular rate, and most of the infant population have got the MMR post a certain date, why are autism cases rising rather than there being a big spike then a plateau? (And maybe a dip when confidence in the MMR dropped?). The graph doesn't fit the hypothesis at all.

Nor does the fact in Japan Autism continued to rise once MMR was stopped.

I would like to see a graph of the Japanese data put on top of Wakefield's graph with a big fat arrow saying 'MMR stopped here'.

Wakefield aside giving children several viruses at the same time as live measles vaccine does concern me because measles supresses cell-mediated immunity therefore reducing the bodies ability to fight other pathogens (ref 1, ref 2, ref 3). This supression results in increased susceptibility to secondary infections.

Measles does, as your links show. I can't find any evidence that the measles vaccine does. Remember, the measles vaccine doesn't give you measles. And if giving mumps and rubella vaccines with measles was dangerous because the measles vaccine surpresses the immune system, then wouldn't you expect to see cases of mumps and rubella after vaccination?

Measles vaccine can result in vaccine induced measles which is clinically indistinguishable from the wild-type virus ref. It is also not possible to distinguish between the measles antibody response from a vaccine and that to a wild type virus without molecular characterisation of viral isolates ref. Unless genetic analysis is done on every person who exhibits post-vaccine measles symptoms and not just serological tests then it is difficult to know how many cases of wild-type measles from vaccines there actually are.

Vaccine induced measles, mumps and rubella are common side effects of the MMR ref, they do tend to be milder. There are side effects which indicate secondary infections listed for Priorix here.

Some of the side effects are very serious, not to say you wouldn't get some of them with a single measles vaccine, but at least the risk of getting multiple complications relating to the measles, mumps and rubella aspect of the MMR would be removed.

Beachcomber Dr Wakefield had a rather distinguished career until he questioned MMR safety

No, he had a rather distinguished career until, after many years of lies and fraud, he was found out.

But those mild forms are experienced with monovalent vaccines anyway. The link says "Adverse reactions which might occur following the use of a combined mumps, measles, rubella vaccine correspond to those observed after administration of the monovalent vaccines alone or in combination."

Noblegiraffe, why is the data unsuitable?

And when you say that no-one disputes that autism is more prevalent than in the past, that is simply not the case. The struggle to have it admitted by the CDC and the general public and all manner of people, has been herculean. There has been MASSIVE resistance simply to the data that pays witness to the, very concerning, increase in autism. And I think that is because if we admit that there is an increase, we then need to look at why....

And, we can argue the data till the cows come home, but the only answers lie in examination of the children themselves.

I mentioned the side effects purely to illustrate that even with the vaccine the immune response can be supressed leading to secondary infections (upper respiratory infections, otitis media etc).

Yes some will occur with the single measles vaccine, but you won't get the Arthralgia of rubella or the parotitis of mumps at the same time as the measles related symptoms.

Also, Wakefield's comments were in a letter to the Lancet. The point of the letter was to say that he didn't find the Taylor et al study strong evidence that the issue of MMR and autism could be closed (and he was right, the Taylor study was very poor).

He wasn't doing research or a study - he was writing a letter to point out a flaw in the Taylor study and to point out that available data strongly suggested that more not less investigation was needed. (And he was right about that too.)

I doubt he thought that years later his letter would be scrutinised as though it was a piece of comprehensive research.

There are many reasons why cases could continue to increase (although I think the long term data does show curves - not 100% sure would have to check). The viral load of the MMR could be changed (IIRC the mumps element was tinkered with at one point). Other vaccines could be added to the schedule which could potentiate MMR, the age of vaccination could be lowered, etc.

It would be extremely interesting to see a population wide study which took these elements into account. Complex to do though, perhaps the MIND institute has done that sort of work?