Using the information provided in the case study, complete Sections B, C, and D (pp. 5-10), typing your answers into a separate document.
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.
|
|
Autism
|
No Autism
|
Total
|
|
Exposed -Received the MMR vaccine
|
263
|
440,339
|
440,655
|
|
Non-exposed- did not receive the MMR vaccine
|
53
|
96,595
|
96,648
|
263/440,655 = 0.00059684*100 = 0.059%
53/96,648 = 0.00054838*100 = 0.054%
Relative risk = 0.059/0.053= 0.11. If RR<1
Atributable risk (AR)
Incidence of autism among vaccinated children : 263/440,655
Incidence of autism among unvaccinated children: 53/96,595
0.000596 -0.000548 = 0.000048 or 0.048 autism cases per 1000 people per year. The proportion of cases due to vaccine administration is not relevant.
Calculating the Relative risk and comparing the incidence of Autism with those not exposed to the MMR vaccine, the incidence of disease over the incidence of the exposed includingall in the denominator for each group.
The Exposed children were 0.11 (RR = 1: no evidence of association or RR >1 : exposure is harmfull) which demonstrates that the strength of the relationship is weak and there is no level of association between children that received the vaccine compared with those that did not receive the vaccine.
The likehood of an of children that received the MMP vaccine with a o.o1 ratio compared to the group that did not received the MMR vaccine is weak.
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.
|
PDD
|
PPD (cases)
|
No PPD (control)
|
Total population
|
|
Had MMR vaccine
Didn't have MMR
|
a 1010
|
B 3671
|
4681
|
|
|
c 284
|
D 798
|
1082
|
a*d = 1010*798
b*c = 3671*284
= 805980/1'042,564 = 0.77
Total 1294 4469 5763
The Odds Ratio (OR) included children that already had the disease and measured the association or the Odd Ratio aproximating the Relative Risk (RR).
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.,
FIGURE I: Table 1 from Madsen et al., 2002
TABLE 1. CHARACTERISTICS 01: 'HIE 537,303 Cutt.os.P.N IX 1111‘: DANISH COHORT.
|
|
VACCINATED
CHILDREN
|
UNVACCHATED
CHLOREN
|
|
|
Cummins=
|
=440,(65)
|
(N=96,648)
|
P VALUE'
|
|
|
number Ipercont)
|
|
|
Sex
|
|
|
0.55
|
|
Male
|
226,042 (51.3)
|
49,680 (51.4)
|
|
|
Female
|
214,613 (48.7)
|
46,968 (48.6)
|
|
|
Birth weight c2499 g
|
21,633 (4.9)
|
5,164 (5.3)
|
|
|
2500-2999 g
|
53,874 (12.2)
|
12,062 (12.5)
|
|
|
3000-3499 g
|
135,630 (30.8)
|
29,262 (30.3)
|
|
|
3500-3999 g
|
135,255 (30.7)
|
29,143 (30.2)
|
|
|
4000 g
|
66,358 (15.1)
|
14,563 (15.1)
|
|
|
Data missing
|
27,905 (6.3)
|
6,454 (6.7)
|
|
|
Gestational age
|
|
|
<0.001
|
|
c36 wk
|
19,029 (4.3)
|
3,129 (3.2)
|
|
|
37-41 o*
|
272,345 (61.8)
|
40,609 (42.0)
|
|
|
2 wit
|
27,349 (6.2)
|
3,986 (4.1)
|
|
|
Data missing('
|
121,932 (27.7)
|
48,924 (50.6)
|
|
|
Socioeconomic statust
|
|
|
<0.001
|
|
Manager (sent high)
|
41,367 (9.4)
|
9,940 (10.3)
|
|
|
Wage earner (high)
|
85,772 (19.5)
|
16,187 (16.7)
|
|
|
Wage earner (medium)
|
70,906 (16.1)
|
13,753 (14.2)
|
|
|
Wage earner (low)
|
116,503 (26.4)
|
26,699 (27.6)
|
|
|
Wage earner (minimal)
|
57,408 (13.0)
|
10,996 (11.4)
|
|
|
Unemployed
|
67,841 (15.4)
|
18,519 (19.2)
|
|
|
Data missing
|
858 (0.2)
|
554 (0.6)
|
|
|
Mother's education
|
|
|
<0.001
|
|
Postgraduate education
|
26,118 (5.9)
|
5,856 (6.1)
|
|
|
College
|
67,776 (15.4)
|
14,599 (15.1)
|
|
|
Vocational training
|
178,553 (40.5)
|
34,006 (35.2)
|
|
|
Secondary school
|
42,667 (9.7)
|
10,164 (10.5)
|
|
|
Primary school
|
114,768 (26.0)
|
28,680 (29.7)
|
|
|
Data missing
|
10,773 (2.4)
|
3,343 (3.5)
|
|
|
Age at diagnosis of autistic disorder
|
|
|
0.87
|
|
c2 yr
|
48 (0.01)
|
9(0.01)
|
|
|
3-5 yr
|
187 (0.04)
|
31 (0.03)
|
|
|
3.6 7
|
34 (0.01)
|
7(0.01)
|
|
|
Age at diagnosis of another autistic-spectrum disorder c2 yr
|
32 (0.01)
|
3 (0.003)
|
0.19
|
|
3-5 yr
|
202 (0.05)
|
37 (0.04)
|
|
|
6 yr
|
118 (0.03)
|
30 (0.03)
|
|
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: Fable 2 from Madsen et al., 2002
The New England Journal of Medicine
TABLE 2. ADJUSTED RELATIVE RISK OF AUTISTIC DISORDER AND OF OTHER AUTIST1C-SPECTRUM
DISORDERS IN VACCINATED AND UNVACCINATED CHILDREN.*
|
|
|
|
|
One Aunee-Smcmum
|
|
VAceenam
|
PERSOWYEARST
|
AUTISTIC Dee>
|
Dssonoots
|
|
|
|
|
ADIUSTFD
|
|
ADJUSTED
|
|
|
|
|
RELATIVE. RISK
|
|
RELATIVE RISE
|
|
|
|
HD. OF CASES
|
(95% CI)
|
No. OF CASES
|
(95% CI)
|
|
Total
|
2,129,864
|
316
|
|
422
|
|
|
Vaccination
|
|
|
|
|
|
|
No
|
482,360
|
53
|
1.00
|
77
|
1.00
|
|
Yes
|
1,647,504
|
263
|
0.92 (0.68-1.24)
|
345
|
0.83 (0.65-1.07)
|
|
Age at vaccination
|
|
|
|
|
|
|
Not vaccinated
|
482,360
|
53
|
1.00
|
77
|
1.00
|
|
414 mo
|
200,003
|
38
|
1.18 (0.78-1.80)
|
43
|
0.88 (0.60-1.28)
|
|
15-19 mo
|
1,320/53
|
195
|
0.86(0.63-1.17)
|
270
|
0.83(0.64-1.08)
|
|
20-24 mo
|
69,242
|
17
|
1.19 (0.69-2.07)
|
12
|
0.62(0.33-1.13)
|
|
25-35 mo
|
40,935
|
11
|
1.20(0.63-2.31)
|
15
|
1.09(0.63-1.91)
|
|
>36 mo
|
16,572
|
2
|
0.56 (0.14-2.30)
|
5
|
0.64 (0.26-1.59)
|
|
Interval since vaccination
|
|
|
|
|
|
|
Not vaccinated
|
482,360
|
53
|
1.00
|
77
|
1.00
|
|
<6 mo
|
212,805
|
3
|
0.39 (0.11-1.32)
|
8
|
1.18 (0.51-2.75)
|
|
6-11 mo
|
197,931
|
21
|
1.38 (026-2.51)
|
4
|
0.31 (0.10-0.91)
|
|
12-17 mo
|
183,460
|
22
|
1.07 (0.59-1.95)
|
16
|
0.92 (0.47-1.80)
|
|
18-23 mo
|
168,045
|
31
|
0.86 (0.52-1.41)
|
16
|
0.47 (0.26-0.86)
|
|
24-29 mu
|
154,290
|
42
|
0.99 (0.61-1.58)
|
32
|
0/7 (0.46-1.27)
|
|
30-35 mo
|
139,258
|
33
|
0.86 (0.54-1.38)
|
27
|
0.69 (0.43-1.11)
|
|
36-59 mo
|
406,320
|
90
|
0.99 (0.66-1.50)
|
158
|
1.05 (0.77-1.45)
|
|
>60 mo
|
185,396
|
21
|
0.67 (0.34-1.33)
|
84
|
0/5 (0.51-1.09)
|
|
Date of vaccination
|
|
|
|
|
|
|
Not vaccinated
|
482,360
|
53
|
1.00
|
77
|
1.00
|
|
1991-1992
|
248,646
|
31
|
1.00(0.59-1.70)
|
61
|
0.75(0.51-1.09)
|
|
1993-1994
|
659,152
|
81
|
0.73 (0.50-1.06)
|
146
|
0.74 (0.56-0.99)
|
|
1995-1996
|
475,990
|
96
|
0.91 (0.63-1.30)
|
116
|
1.13 (0.81-1.56)
|
|
1997-1999
|
263,716
|
55
|
1.35(0.84-2.17)
|
22
|
0.71(0.40-1.24)
|
4. Do the data in Figure 2 above 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.
|
|
Unadjusted OR (95% CI) Adjusted OR (95% CI)*
|
p (for adjusted OR)
|
|
MMR vaccination before index date At any age
No MMR vaccination
|
|
|
|
|
Vaccinated with MMR
|
073 (0.59-0.91)
|
oi86 (0.68- log)
|
0.21
|
|
Before and after third birthday
|
|
|
|
|
No MMR vaccinatim
|
(1,0)
|
|
|
|
MMR vaccination before third birthday
|
9'75 (0-60-095)
|
9.90 (0-70-119
|
939
|
|
MMR vaccination after third birthday
|
068 (0-50-0-94)
|
07/ (055-1-08)
|
013
|
|
Before and after age 18 months
|
|
|
|
|
No MMR vaccination
|
(1.0)
|
|
|
|
MMR vaccination before 18 months
|
0.76 (040-0.96)
|
0.90 (0.70-145)
|
0.39
|
|
MMR vaccination after 18 months
|
0.69 (0.51-0.89)
|
0.80 (041-10x5)
|
0-11
|
UK General Practice Research Database (GPRD)
|
|
Unadjusted OR (95% CI)
|
Adjusted OR (95% CI)*
|
p (for adjusted OR)
|
|
MMR vaccination before index date Autism only
|
|
|
|
|
No MMR vaccinat ion
|
(1-0)
|
|
|
|
Vaccinated with MMR
|
017 (0.60-0-98)
|
088(0.67-1.15)
|
0-35
|
|
Other PDDs only
|
|
|
|
|
No MMR vaccination
|
(1-0)
|
|
|
|
Vaccinated with MMR
|
0.60 (039-0.92)
|
0.75 (046-1.23)
|
0,25
|
5. Do the data in Figure 3 from Smeeth et al show an association between MMR vaccine and risk of autism?
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?
Table 1. Studies that fail to support an association between measles-mumps-rubella vaccine and autism.
| Source |
Study design |
Study Location |
| Taylor et al., 1999 [5] |
Ecological |
United Kingdom |
| Farrington et al., 2001 [6] |
Ecological |
United Kingdom |
| Kaye et aL, 2001 [7] |
Ecological |
United Kingdom |
| Dales et al., 2001 [8] |
Ecological |
United States |
| Fombonne et aL, 2006 [9] |
Ecological |
Canada |
| Fombonne and Chakrabarti, 2001 [10] |
Ecological |
United Kingdom |
| Taylor et al., 2002 [11] |
Ecological |
United Kingdom |
| DeVVilde et al., 2001 [12] |
Case-control |
United Kingdom |
| Makela et al., 2002 [13] |
Retrospective cohort |
Finland |
| Madsen et al 2002 [14] |
Retrospective cohort |
Denmark |
| DeStefano et al., 2004 [15] |
Case-control |
United States |
|
|
|
| Peltola et al., 1998 [16] |
Prospective cohort |
Finland |
| Patja et al., 2000 [17] |
Prospective cohort |
Finland |
References
Madsen KM et al. A population-based study of measles-mumps-rubella vaccination and autism. N Engl J Med 2002;347(19)1477-82. Retrieved from https://www.nejm.org/doi/full/10.1056/NEJMoa021134#t=articleMethods
Offit, PA. & Coffin, SE. Communicating science to the public: MMR vaccine and autism: Vaccine 2003: 22(1) 1-6.
Smeeth L et al. MMR vaccination and pervasive developmental disorders: a case-control study. Lancet 2004;364:963-9.
Simeonsson, K., Bethel, J., & Lea, S. (n.d.). Weighing the evidence: Misconceptions about measles-mumps-rubella (MMR) vaccine and autism.
Retrieved from Association for Prevention Teaching and Research website:
https://c.ymcdn.com/sites/www.aptrweb.org/resource/resmgr/prevention_modules/module_2_student_case.pdf
Using the information provided in the case study, complete Sections B, C, and D (pp. 5-10), typing your answers into a separate document.