If I use any of these questions on the final exam, I will attach to the exam copies of Geier and Geier (2003) and Parker et al. (2004). 1. Parker et al. (2004) identify a number of problems with the Geier and Geier (2003) study. Describe 3 specific problems with the Geier and Geier study. Write a paragraph on each problem. Your paragraph should be sufficiently detailed that it is clear that you understand how each problem you identify calls into questions the conclusions of Geier and Geier (2003).

2. Parker et al. (2004) identify a number of problems with the Geier and Geier (2003) study, as listed below. For each problem identified by Parker et al. (2004, pp. 795-796), write a paragraph that demonstrates that you understand what the problem is:

2a. "The key outcome measure, calculation and comparison of AE incidence for thimerosal-exposed and unexposed infants, requires accurate and unbiased assessment of the numerator (children with defined AEs) and denominator (exposure/no exposure to thimerosal-containing DTaP) for the two groups. Several factors contribute to substantial inaccuracy in the numerator of AEs."

2b. Explain what "underreporting" of AE is. How might this have caused Geier and Geier (2003) to draw the incorrect conclusion regarding the safety of thimerosal-containing vaccines?

2c. "This is particularly troubling because the disorders reported have a long differential diagnosis and because the mean age reported for children with autism (1.7 +/- 1.1 year) is below the age at which a reliable diagnosis of that disorder is made."

2d. "Demonstrating the statistical fragility of analysis of this database, if only 1 child who has autism and did not receive thimerosal-containing DTaP were misclassified into the thimerosal group or if 1 such child were not reported to the VAERS systems, then the reported risk ratio would be reduced by half and the P value would be >.05."

2e. "In addition, several biases may have led to differential reporting of events in children who received DTaP vaccines that did or did not contain thimerosal as a preservative affecting the ability to compare relative reporting rates."

2f. "An additional problem affecting numerator data is the inability to define accurately total thimerosal exposure in children with reported AEs."

2g. "Substantial questions regarding the accuracy of the denominator data for the incidence calculation also exist." (Summarize these problems in your own words.)

3. The Parker et al. (2004) paper specifically compares Geier and Geier (2003) (finding an effect of thimerosal) to several other studies with found no effect of thimerosal. Identify 3 specific study design features not included in the Geier and Geier (2003) study that are present in the studies which found no effect.

4. In science it is sometimes the case that a result is unquestionably statistically significant, but still not believable. Provide an example. For your example, explain why the result is not believable, even though it is statistically significant. Hint: Geier and Geier (2003).

5a. Using your own words, explain the Danish Civil Registration System study described by Parker et al. (2004) on pp. 795 & 800. In answering this question use the words "control group," "treatment group," "natural experiment."

5b. In theory, unwanted confounders might make the interpretation of the Danish Civil Registration System study ambiguous. Explain why confounders are unlikely to be an important factor in this study.

6. Is the major criticism of Geier and Geier (2003) that they had an inadequate sample size? Answer Yes or No. And then explain your answer in one or two sentences.

7. Parker et al. (2004) discusses the "Vaccine Safety Data Link group" study "from the CDC in the United States." On page 797 (2nd column) they state that "The authors found an association between thimerosal exposure and upper respiratory tract infection, suggesting that increased health care use may be a confounder." What exactly does this mean? Does it mean that thimerosal causes upper resiratory tract infections? Explain your answer (1 to 3 sentences).