Using the information provided in the case study, complete Sections B, C, and D (pp. 5-10), typing your answers into a separate document.Weighing the Evidence: Misconceptions about measles-mumps-rubella (MMR) vaccine and autism

Objectives: At the end of this session, students will be able to:
- Recognize criteria for initiating experimental and observational studies
- Identify key design components of studies
- Describe the advantages and disadvantages of various study designs
- Calculate and interpret outcome measures in cohort and case-control studies
- Interpret data from observational studies looking at MMR vaccination and autism

Introduction

1. What have you heard about an association between vaccines and autism? What are some of the hypotheses you have heard about or read about?

2. What types of studies would you recommend to look at an association between vaccines and autism?

Section A: Study Design

Design a study to look at the association between MMR vaccine and autism.

1. Cohort study

a. How will you assemble your cohort ?

b. What are your inclusion/exclusion criteria for participation in the study?

c. Exposure status: How will you define and measure vaccination status?

d. Outcome status: How will you define and measure autism?

e. What measure of association will you calculate in a cohort study?

2. Case-control study

a. What is your definition of a case?

b. How will you identify cases?

c. What is your definition of a control?

d. How will you identify controls?

e. Exposure status: How will you define and measure vaccination status?

f. What measure of association will you calculate in a case-control study?

Section B: Calculating Measures of Association

Over 25 studies have been conducted which have failed to show an association between MMR vaccine and autism. Below are some data from two of these studies (one cohort and one case-control). Calculate the measure of association for each study after completing the 2x2 table and interpret the measure of association.

1. Cohort study by Madsen et al (NEJM 2002)

Of the 537,303 children in the cohort, 440,655 (82.0 percent) had received the MMR vaccine. We identified 316 children with a diagnosis of autistic disorder; 263 of the cases had been vaccinated with MMR (83%); 53 children with autism had not been vaccinated.

2. Case control study by Smeeth et al (Lancet 2004)

1294 cases of pervasive developmental disorder (PDD) and 4469 controls were included. 1010 cases (78-1%) had MMR vaccination recorded before diagnosis, compared with 3671 controls (82-1%) before the age at which their matched case was diagnosed.

Section C: Interpreting results

Review the following data from the aforementioned studies and answer the following questions.

FIGURE 1: Table 1 from Madsen et al., 2002

1. Describe the characteristics in Table 1 in terms of what type of data they are (discrete / qualitative versus continuous / quantitative).

Using the chi-square test (see footnote of FIGURE 1), authors found significant differences in certain characteristics of vaccinated and unvaccinated children.

2. What characteristics showed no differences between the two groups? What characteristics showed differences between the vaccinated and unvaccinated groups?

3. What do these differences mean?

FIGURE 2: Table 2 from Madsen et al., 2002

4. Do the data in Figure 2 above show an association between MMR vaccine and risk of autism?

5. Do the data in Figure 3 from Smeeth et al show an association between MMR vaccine and risk of autism?

FIGURE 3: Tables 1 and 2 from Smeeth et al 2004

Table 1: Association between Pervasive Developmental Disorder (PDD) and MMR vaccination before index date, before and after third birthday, and before and after age 18 months.

Section D: Conclusion

Since 1998, numerous well-designed studies have found no link between vaccines and autism (see table below). Why do you think some parents are still fearful of vaccines? What is your role as future healthcare providers in counseling patients about vaccines?