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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 http://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:

http://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.

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