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Articles below by: DeStefano,   Inappropriately Brief Follow Up,   Incomplete Data in Early US Studies,   Madsen,   Makela

"Early vs. Late Administration of MMR" written by DeStefano ('04)

AD did “not have a well demarcated date of onset” –

“children who are vaccinated at younger ages would have a higher risk of …autism” – not so: this has never been substantiated as a risk factor for autism.

Early concern (Wakefield) centered on the close association of symptoms of AD occuring soon after the MMR. The recognition and diagnosis of AD/PDD occurs only months to years later. As occured with SSPE, later onset of symptoms only makes the connection more difficult to establish.

Study supports: earlier age vs. later age of administration of the MMR II shows no difference in the rate of autism.

This study does not reject an association betweeen MMR II & autism.


"Inappropriately Brief Follow Up or Insufficient Search Studies"

 Insufficient follow up studies:                    Length of f/u:

                Patja (’00)                  8 days (natural rubella incubation)
                DeWilde (’01)           compared consults 6 mo. pre- vs. post- MMR II
 
   The  recognition and diagnosis of AD occurs after months to years. These studies give short term adverse reaction but totally miss late disease.
            
Insufficient search study:
                Peltola (’98)              14 years – ending in ‘’96 – zero cases of autism!
 Good long term study but finding zero cases of autism - when incidence is clearly increased -indicates that autism was not sufficiently explored.
    
    

"Incomplete Data In Early US Studies"

Burd et al. (’87): Birth years: ‘78 – ’83 found that 66% of cases occurred in the youngest 33%  
   
ASD
 
  ’78 – ’81 oldest 66% (born 1st 4 yrs)

33% of cases

(8.25% cases/yr)

 
       
     
  ’82 – ’83 youngest 33% (born last 2 yrs) 

66% of cases

(33% cases/yr)

 
       
More cases in later years: author realized that this was: “difficult to explain”    
       
  The gradual introduction of the MMR II occurred from ’80 – ’83. The youngest were at higher risk of receiving the MMR II during the transition.  
       
  This would support an association of autism with the MMR II.  
       

Incomplete data studies:



"Insufficient Follow Up + Excess Padding of Null Group"
Madsen et al. ('02)

Born: 1/1/91 thru 12/31/98 --    Case selection stopped 12/31/99
                 
  Criticism: failed to follow minimum 2 yr post MMR II  
  53% had not reached mean age of diagnosis for AD (missed cases)  
   
  66% had not reached mean age of diagnosis for PDD (missed cases)  
   
  Some < 12 mo. age at end – i.e.: no MMR II even received  
   
  Null group: included months pre-MMR27/3 vaccination –  

      i.e.: all contributed to a false increase in the null hypothesis.

The authors allude to an "age adjustment." This study was stopped much too early to pick up all cases of ASD.


"Lack of Significant Clustering Argument"
Makela ('02)

Rejected the association of MMR with Autism: based on a lack of “significant clustering"

Deficiencies: no comparison of vaccinated vs. unvaccinated cases Clustering could support an association but only a good case-control study can negate an association (of MMR & Autism)