1 clinical research training program 2021 anova and ancova fall 2004

34
1 Clinical Research Training Program 2021 ANOVA and ANCOVA ANOVA and ANCOVA Fall 2004 www.edc.gsph.pitt.edu/faculty/dodge/ clres2021.html

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Page 1: 1 Clinical Research Training Program 2021 ANOVA and ANCOVA Fall 2004

1

Clinical Research Training Program 2021

ANOVA and ANCOVAANOVA and ANCOVA

Fall 2004

www.edc.gsph.pitt.edu/faculty/dodge/clres2021.html

Page 2: 1 Clinical Research Training Program 2021 ANOVA and ANCOVA Fall 2004

2

ANOVA vs. REGRESSION

• ANOVA can be regarded as a special type of linear regressions.

• By using dummy coding, we can get coefficients which indicate difference in means in various groups.

Page 3: 1 Clinical Research Training Program 2021 ANOVA and ANCOVA Fall 2004

3

REGRESSIONREGRESSION METHODSMETHODS

Regression

ANOVA

ANCOVA/Regression

Page 4: 1 Clinical Research Training Program 2021 ANOVA and ANCOVA Fall 2004

4

Analysis of VarianceAnalysis of Variance

The null and alternative hypotheses are

H0:

H1: for some

kμμμ 21

ji μμ kji ,1,,

, where i represents the mean of population i

Hypotheses - Whether all group means are equal versus at least two group means are different

Page 5: 1 Clinical Research Training Program 2021 ANOVA and ANCOVA Fall 2004

5

Assumptions - k independent random samples from k

normal populations with distributions N(

1, 2), …, N(

k, 2), respectively.

Outcome variable should be continuous. All the populations have the same unknown

variance 2 (homogeneous variance).

Analysis of VarianceAnalysis of Variance

Page 6: 1 Clinical Research Training Program 2021 ANOVA and ANCOVA Fall 2004

6

1x 2x• •

• •1x 2x

• • • • • • •• • • • • • •

• • • • • • •• • • • • • •

• • • • • • •• • • • • • •

••••••••••••••

Page 7: 1 Clinical Research Training Program 2021 ANOVA and ANCOVA Fall 2004

7

Analysis of VarianceAnalysis of Variance

The main idea for comparing means: what matters is not how far apart the sample means are but how far apart they are relative to the variability of individual observations

ANOVA compares the variation due to specific sources within the variation among individuals who should be similar. In particular, ANOVA tests whether several populations have the same mean by comparing how far apart the sample means are with how much variation there is within the sample

Page 8: 1 Clinical Research Training Program 2021 ANOVA and ANCOVA Fall 2004

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Analysis of VarianceAnalysis of Variance

Between Sum of Squares (SSB)

Within Sum of Squares (SSW)

Total Sum of Squares (SST)

SST = SSB + SSW

k

i

n

j

i

i

xx

1 1

2)(

k

i

n

j

ij

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1 1

2)(

k

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iij

i

xx

1 1

2)(

Page 9: 1 Clinical Research Training Program 2021 ANOVA and ANCOVA Fall 2004

9

Analysis of VarianceAnalysis of Variance

Hypotheses: H0:

H1: for some

Test statistic:

kμμμ 21

ji μμ kji ,1,,

knkF 1,~ )(

)(

)1(

)(

1 1

2

1 1

2

kn

xx

k

xx

k

i

n

jiij

k

i

n

ji

i

i

MSW

MSB

samples within sindividual amongVariation

means sample theamongVariation F

Page 10: 1 Clinical Research Training Program 2021 ANOVA and ANCOVA Fall 2004

10

Analysis of VarianceAnalysis of Variance

Between Mean Squares (MSB)

Within Mean Squares (MSW)

kn

xxk

i

n

jiij

i

1 1

2)(

1

)(1 1

2

k

xxk

i

n

ji

i

knnnn 21

Page 11: 1 Clinical Research Training Program 2021 ANOVA and ANCOVA Fall 2004

11

Analysis of VarianceAnalysis of VarianceSummary Table

Sourceof

variation

Sum of Squares(SS)

df MeanSquares

(MS)

FStatistic

P-value

Between

k

i

n

ji

i

xx1 1

2)(SSB 1k 1

SSBMSB

k MSE

MSBF ) calculated Pr( FF

Within(Errors)

k

i

n

jiij

i

xx1 1

2)(SSEkn kn

SSE

MSE

Total

k

i

n

jij

i

xx1 1

2)(SST1n

(ANOVA Table)

Page 12: 1 Clinical Research Training Program 2021 ANOVA and ANCOVA Fall 2004

12

ANOVA vs. REGRESSION

SSR: Between Sum of Squares (SSB)

SSE: Within Sum of Squares (SSW)

SST: Total Sum of Squares (SST)

SST = SSB + SSW

k

i

n

jiij

i

xx1 1

2)(

k

i

n

ji

i

xx1 1

2)(

k

i

n

jij

i

xx1 1

2)(

Page 13: 1 Clinical Research Training Program 2021 ANOVA and ANCOVA Fall 2004

13

ANOVA vs. REGRESSION

• By using a reference coding, we can get similar results to ANOVA with additional information.

• Additional information Difference in means between the

reference group and other groups Difference in means between each group

and overall mean (when each group has equal N).

Page 14: 1 Clinical Research Training Program 2021 ANOVA and ANCOVA Fall 2004

14

REFERENCE CODING

• Each variable takes on only values of 1 and 0.

• 3 groups: groups 1, 2, and 3

need 2 dummy variables

X2 1 if group 2

0 Otherwise

X3 1 if group 3

0 Otherwise

Page 15: 1 Clinical Research Training Program 2021 ANOVA and ANCOVA Fall 2004

15

REFERENCE CODING

For Group 1: X2=0, X3=0:

For Group 2: X2=1, X3=0:

For Group 3: X2=0, X3=1:

ˆˆˆ Y

33 ˆˆˆˆ Y22 ˆˆˆˆ Y

3322 ˆˆˆˆ XXY

Page 16: 1 Clinical Research Training Program 2021 ANOVA and ANCOVA Fall 2004

16

REFERENCE CODING

33

22

1

ˆˆˆ

ˆˆˆ

ˆˆ

1333

1222

1

ˆˆˆˆˆ

ˆˆˆˆˆ

ˆˆ

Page 17: 1 Clinical Research Training Program 2021 ANOVA and ANCOVA Fall 2004

17

REFERENCE CODING

• Intercept μ is the mean of group 1 (mean of reference group).

• α2 indicates difference in mean between group 1 (reference group) and group2

• α3 indicates difference in mean between group 1 (reference group) and group3

Page 18: 1 Clinical Research Training Program 2021 ANOVA and ANCOVA Fall 2004

18

• . list y x x2 x3 x4 x5

• y x x2 x3 x4 x5 • 1. 5 1 0 0 0 0 • 2. 8 1 0 0 0 0 • 3. 7 1 0 0 0 0 • 4. 7 1 0 0 0 0 • 5. 10 1 0 0 0 0 • 6. 8 1 0 0 0 0 • 7. 4 2 1 0 0 0 • 8. 6 2 1 0 0 0 • 9. 6 2 1 0 0 0 • 10. 3 2 1 0 0 0 • 11. 5 2 1 0 0 0 • 12. 6 2 1 0 0 0 • 13. 6 3 0 1 0 0 • 14. 4 3 0 1 0 0 • 15. 4 3 0 1 0 0 • 16. 5 3 0 1 0 0 • 17. 4 3 0 1 0 0 • 18. 3 3 0 1 0 0 • 19. 7 4 0 0 1 0 • 20. 4 4 0 0 1 0 • 21. 6 4 0 0 1 0 • 22. 6 4 0 0 1 0 • 23. 3 4 0 0 1 0 • 24. 5 4 0 0 1 0 • 25. 9 5 0 0 0 1 • 26. 3 5 0 0 0 1 • 27. 5 5 0 0 0 1 • 28. 7 5 0 0 0 1 • 29. 7 5 0 0 0 1 • 30. 6 5 0 0 0 1

Page 19: 1 Clinical Research Training Program 2021 ANOVA and ANCOVA Fall 2004

19

• sort x

• . by x:summarize y

• _______________________________________________________________________________• -> x = 1

• Variable | Obs Mean Std. Dev. Min Max• -------------+-----------------------------------------------------• y | 6 7.5 1.643168 5 10

• _______________________________________________________________________________• -> x = 2

• Variable | Obs Mean Std. Dev. Min Max• -------------+-----------------------------------------------------• y | 6 5 1.264911 3 6

• _______________________________________________________________________________• -> x = 3

• Variable | Obs Mean Std. Dev. Min Max• -------------+-----------------------------------------------------• y | 6 4.333333 1.032796 3 6

• _______________________________________________________________________________• -> x = 4

• Variable | Obs Mean Std. Dev. Min Max• -------------+-----------------------------------------------------• y | 6 5.166667 1.47196 3 7

• _______________________________________________________________________________• -> x = 5

• Variable | Obs Mean Std. Dev. Min Max• -------------+-----------------------------------------------------• y | 6 6.166667 2.041241 3 9

Page 20: 1 Clinical Research Training Program 2021 ANOVA and ANCOVA Fall 2004

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• regress y x2 x3 x4 x5

• Source | SS df MS Number of obs = 30• -------------+------------------------------ F( 4, 25) = 3.90• Model | 36.4666667 4 9.11666667 Prob > F = 0.0136• Residual | 58.50 25 2.34 R-squared = 0.3840• -------------+------------------------------ Adj R-squared = 0.2854• Total | 94.9666667 29 3.27471264 Root MSE = 1.5297

• ------------------------------------------------------------------------------• y | Coef. Std. Err. t P>|t| [95% Conf. Interval]• -------------+----------------------------------------------------------------• x2 | -2.5 .8831761 -2.83 0.009 -4.318935 -.6810648• x3 | -3.166667 .8831761 -3.59 0.001 -4.985602 -1.347731• x4 | -2.333333 .8831761 -2.64 0.014 -4.152269 -.5143981• x5 | -1.333333 .8831761 -1.51 0.144 -3.152269 .4856019• _cons | 7.5 .6244998 12.01 0.000 6.213819 8.786181• ------------------------------------------------------------------------------

MeanGroup1=7.5Group2=5 α2=5- 7.5= -2.5Group3=4.3 α3=4.3-7.5= -3.2Group4=5.2 α4=5.2-7.5= -2.3Group5=6.2 α5=6.2-7.5= -1.3

Page 21: 1 Clinical Research Training Program 2021 ANOVA and ANCOVA Fall 2004

21

ANOVA vs. REGRESSION

SSR: Between Sum of Squares (SSB)

SSE: Within Sum of Squares (SSW)

SST: Total Sum of Squares (SST)

SST = SSB + SSW

k

i

n

jiij

i

xx1 1

2)(

k

i

n

ji

i

xx1 1

2)(

k

i

n

jij

i

xx1 1

2)(

Page 22: 1 Clinical Research Training Program 2021 ANOVA and ANCOVA Fall 2004

22

ANOVA vs. REGRESSION

• anova y x

• Number of obs = 30 R-squared = 0.3840• Root MSE = 1.52971 Adj R-squared = 0.2854

• Source | Partial SS df MS F Prob > F• -----------+----------------------------------------------------• Model | 36.4666667 4 9.11666667 3.90 0.0136• |• x | 36.4666667 4 9.11666667 3.90 0.0136• |• Residual | 58.50 25 2.34 • -----------+----------------------------------------------------• Total | 94.9666667 29 3.27471264

Page 23: 1 Clinical Research Training Program 2021 ANOVA and ANCOVA Fall 2004

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EFFECT CODING

• 3 groups: groups 1, 2, and 3

need 2 dummy variables

X2 1 if group 2

0 if group 3

-1 if group 1

X3 1 if group 3

0 if group 2

-1 if group 1

Page 24: 1 Clinical Research Training Program 2021 ANOVA and ANCOVA Fall 2004

24

EFFECT CODING

For Group 1: X2=-1, X3=-1:

For Group 2: X2=1, X3=0:

For Group 3: X2=0, X3=1:

32 ˆˆˆˆˆ Y

33 ˆˆˆˆ Y22 ˆˆˆˆ Y

3322 ˆˆˆˆ XXY

Page 25: 1 Clinical Research Training Program 2021 ANOVA and ANCOVA Fall 2004

25

EFFECT CODING

3

ˆˆˆˆˆ

3

ˆˆˆˆˆ

3

ˆˆˆˆ

32133

32122

321

33

22

32

ˆˆˆ

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Page 26: 1 Clinical Research Training Program 2021 ANOVA and ANCOVA Fall 2004

26

EFFECT CODING

• Intercept μ is the unweighted average of the K group means. In the example here, K=3. If all groups have equal sample size, this is a grand mean.

• α2 indicates difference between mean of group 2 and unweighted average of K group mean.

• α3 indicates difference between mean of group 3 and unweighted average of K group mean.

Page 27: 1 Clinical Research Training Program 2021 ANOVA and ANCOVA Fall 2004

27

• list y x x2 x3 x4 x5

• y x x2 x3 x4 x5 • 1. 5 1 -1 -1 -1 -1 • 2. 8 1 -1 -1 -1 -1 • 3. 7 1 -1 -1 -1 -1 • 4. 7 1 -1 -1 -1 -1 • 5. 10 1 -1 -1 -1 -1 • 6. 8 1 -1 -1 -1 -1 • 7. 4 2 1 0 0 0 • 8. 6 2 1 0 0 0 • 9. 6 2 1 0 0 0 • 10. 3 2 1 0 0 0 • 11. 5 2 1 0 0 0 • 12. 6 2 1 0 0 0 • 13. 6 3 0 1 0 0 • 14. 4 3 0 1 0 0 • 15. 4 3 0 1 0 0 • 16. 5 3 0 1 0 0 • 17. 4 3 0 1 0 0 • 18. 3 3 0 1 0 0 • 19. 7 4 0 0 1 0 • 20. 4 4 0 0 1 0 • 21. 6 4 0 0 1 0 • 22. 6 4 0 0 1 0 • 23. 3 4 0 0 1 0 • 24. 5 4 0 0 1 0 • 25. 9 5 0 0 0 1 • 26. 3 5 0 0 0 1 • 27. 5 5 0 0 0 1 • 28. 7 5 0 0 0 1 • 29. 7 5 0 0 0 1 • 30. 6 5 0 0 0 1

• .

Page 28: 1 Clinical Research Training Program 2021 ANOVA and ANCOVA Fall 2004

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• regress y x2 x3 x4 x5

• Source | SS df MS Number of obs = 30• -------------+------------------------------ F( 4, 25) = 3.90• Model | 36.4666667 4 9.11666667 Prob > F = 0.0136• Residual | 58.50 25 2.34 R-squared = 0.3840• -------------+------------------------------ Adj R-squared = 0.2854• Total | 94.9666667 29 3.27471264 Root MSE = 1.5297

• ------------------------------------------------------------------------------• y | Coef. Std. Err. t P>|t| [95% Conf. Interval]• -------------+----------------------------------------------------------------• x2 | -.6333333 .5585696 -1.13 0.268 -1.783729 .5170623• x3 | -1.3 .5585696 -2.33 0.028 -2.450396 -.1496044• x4 | -.4666667 .5585696 -0.84 0.411 -1.617062 .683729• x5 | .5333333 .5585696 0.95 0.349 -.6170623 1.683729• _cons | 5.633333 .2792848 20.17 0.000 5.058136 6.208531• ------------------------------------------------------------------------------

• MeanGroup1=7.5 intercept=(7.5+5+4.3+5.2+6.2)/5=5.6Group2=5 α2=5- 5.6= -0.6Group3=4.3 α3=4.3- 5.6= -1.3Group4=5.2 α4=5.2- 5.6= -0.4Group5=6.2 α5=6.2- 5.6= 0.6

Page 29: 1 Clinical Research Training Program 2021 ANOVA and ANCOVA Fall 2004

29

Analysis of Covariance (ANACOVA)

Why we need to consider control variables?

• Need to produce accurate estimates of coefficients. interaction confounding increase precision

Page 30: 1 Clinical Research Training Program 2021 ANOVA and ANCOVA Fall 2004

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Analysis of Covariance (ANACOVA)

A Question to be answered by using ANACOVA

• If each control variables have the same distributions between group A and B, what would be the mean response value for group A and B?

Page 31: 1 Clinical Research Training Program 2021 ANOVA and ANCOVA Fall 2004

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Analysis of Covariance(ANACOVA)

• Outcome---continuous

• Covariates

– Nominal (study factors of interests)

– Control variables involve any level of measurements

Page 32: 1 Clinical Research Training Program 2021 ANOVA and ANCOVA Fall 2004

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Analysis of Covariance(ANACOVA)

• Most importantly….. This method is applicable only when

there is no interaction effect between the variable of interest with covariates.

Y=β0+ β1X+ β2Z+ β3XZ+Ε

See first whether H0: β3=0 is supported.

Page 33: 1 Clinical Research Training Program 2021 ANOVA and ANCOVA Fall 2004

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Analysis of Covariance(ANACOVA)

• Blood pressure data example (X=age, Z=sex)

14.46

89.140)14.46(96.078.96)(ˆ

40.154)14.46(96.029.110)(ˆ

96.078.96ˆ:)1(

96.029.110ˆ:)0(

51.1396.029.110ˆ

X

adjY

adjY

XYZFemale

XYZMale

ZXY

F

M

F

M

Page 34: 1 Clinical Research Training Program 2021 ANOVA and ANCOVA Fall 2004

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Analysis of Covariance(ANACOVA)

sex Unadjusted mean BP

Adjusted mean BP

Male 155.15 154.40

Female 139.86 140.89

Using the adjusted mean scores removes the influence of age on the comparison of mean blood pressures by considering what the mean BP in the two groups would be if both groups had the same mean age.