Wednesday, April 28, 2010

How Can You Tell if a Hot Dog is Really Made of Beef?

(Answer: Trust. You have to trust the person who slapped the label on the hot dog.)

Madsen, Kreesten M. et al. 2002. "A population-based study of measles, mumps, and rubella vaccination and autism." New England Journal of Medicine 347: 1480-1482.

This paper by Madsen et. al. is perhaps one of the most widely cited as "scientific proof" there is no link between the MMR vaccine and autism. On the face of it, the study appears to be a straightforward comparison of autism incidence rates between those who had received the MMR and those who hadn't. The authors studied half a million children born between 1991 and 1998 in Denmark. They identified MMR vaccination status (MMR or no MMR) and followed these children to see how many in each group were diagnosed with autism disorders. So far, so good.

The problem is that all risk calculations were done using person-years (persons x years) rather than with the number of children in two groups and how many of each group got autism.

Here were their "rules" for sorting person-years into the vaccinated vs. unvaccinated group.

1. Children were counted in the unvaccinated person-years group until they were vaccinated. Both vaccinated and unvaccinated person-years came from some of the same children.
2. Early-diagnosis (and likely severe, congenital) autism cases were assigned to the unvaccinated group because they were diagnosed prior to vaccination.

So imagine this.

Jack: MMR at age 2. Diagnosed age 4. Followed until age 6.
Unvaccinated group: 2 person-years.
Vaccinated group: 4 person-years.
1 case of autism in vaccinated group.

Bob: MMR at age 2. Followed until age 6.
Unvaccinated group: 2 person-years.
Vaccinated group: 4 person-years.
0 case of autism in vaccinated group.

Bill: MMR at age 2. Followed until age 6.
Unvaccinated group: 2 person-years.
Vaccinated group: 4 person-years.
0 case of autism in vaccinated group.

Ben: MMR at age 2. Followed until age 6.
Unvaccinated group: 2 person-years.
Vaccinated group: 4 person-years.
0 case of autism in vaccinated group.

Henry: Diagnosed age 1. MMR at age 2. Followed until age 4.
Unvaccinated group: 4 person-years.
Vaccinated group: 0 person-years.
1 case of autism in unvaccinated group.

Charlie: No MMR. Followed until age 4.
Unvaccinated group: 4 person-years.
Vaccinated group: 0 person-years.
0 case of autism in unvaccinated group.


Unvaccinated group = 16 person-years.
Vaccinated group = 16 person-years.
One case of autism in each group. No difference between the two groups.

In reality, the above scenario should show 2 cases of autism in 5 vaccinated children vs no case of autism in 1 unvaccinated child. If early diagnosis of autism muddies the vaccinated picture, those cases should have been been pulled from the larger 2 groups and analyzed separately. It would have provided a useful baseline of severe congenital cases to compare against later-onset cases that could possibly be triggered by the MMR.

So, taking Henry of the scenario, there would be 1 case of autism amongst 4 vaccinated children vs. no case of autism in 1 unvaccinated child. Notice how different this picture looks as opposed to the comparison of person-years.

Please note I am not saying that the authors manipulated data until both groups were even. The imaginary scenario simply demonstrates that the use of person-years is NOT the same thing as a straightforward comparison of incidence in both groups. It provides a very distorted picture that does not reflect reality as we know it, which is very malleable to offer whatever kind of results we want, simply based on how long each child is followed.

Other concerns include:

1. Vaccination status of children born before 1996 was inferred from a secondary database. How accurate was this inference method and its resulting data on vaccination status?

2. Many subjects were too young to be diagnosed with autism when the study ended. How much effect did this have on true autism rates in either group?

3. A LOT of calculations were "adjusted." We don't know how. That should always be a red flag, when we are asked to trust that the authors manipulated the data with integrity.

4. How did they diagnose autism? We already know they didn't distinguish between congenital (and likely severe) autism from milder forms or from regressive autism. When investigating whether MMR could be a factor in autism, severity and type of onset should be carefully defined.

5. The study did not exclude the use of other vaccines. Even if the person-years comparison was valid (in that it reflected reality well), the best one can say is that the MMR is not more likely to cause autism than other vaccines, as opposed to being truly "unvaccinated."

The bottom line is, instead of presenting the straight data so we could judge for ourselves how many cases of autism were found in each group, the authors chose to present data that has been processed and diluted and manipulated beyond recognition. Instead of serving us what could have been a sirloin steak of science, we got a hot dog that claims to be made of beef--but in the end, we can't be sure. We just have to take the authors' word for it.

And whenever authors present unrecognizable data with a lot of question marks and ask you to trust them, don't. It's bad science.

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