Health Care Law and Legislation, Statistics Policies

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Chapter 9

Multivariable Methods

Learning Objectives (1 of 2)

  • Define and provide examples of dependent and independent variables in a study of a public health problem
  • Explain the principle of statistical adjustment to a lay audience
  • Organize data for regression analysis

Learning Objectives (2 of 2)

  • Define and provide an example of confounding
  • Define and provide an example of effect modification
  • Interpret coefficients in multiple linear and multiple logistic regression analysis

Definitions

  • Confounding—the distortion of the effect of a risk factor on an outcome
  • Effect modification—a different relationship between the risk factor and an outcome depending on the level of another variable

Confounding

  • A confounder is related to the risk factor and also to the outcome.
  • Assessing confounding
  • Formal tests of hypothesis
  • Clinically meaningful associations
  • We wish to assess the association between obesity and incident cardiovascular disease.

Example 9.1.
Confounding (1 of 2)

Example 9.1.
Confounding (2 of 2)

  • Is age a confounder?

  • A clinical trial is run to assess the efficacy of a new drug to increase HDL cholesterol.

H0: m1 = m2 versus H1:m1 ≠ m2

Z = –1.13 is not statistically significant.

Example 9.2.
Effect Modification (1 of 2)

  • Is there effect modification by gender?

Example 9.2.
Effect Modification (2 of 2)

Effect Modification

Cochran-Mantel-Haenszel Method

  • Technique to estimate association between risk factor and outcome accounting for confounding
  • Data are organized into stratum and associations are estimated in each stratum and combined.

Correlation and Simple Linear
Regression Analysis

  • Two continuous variables

Y = dependent, outcome variable

X = independent, predictor variable

  • Relationship between age and SBP, number of hours of exercise and percent body fat, caffeine consumption and blood sugar level.

Correlation and Simple
Linear Regression

  • Correlation—nature and strength of linear association between variables
  • Regression—equation that best describes relationship between variables

Scatter Diagram

Chart1

10
14
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17
19
21
25
28
30
35
39
Y
X
Y
5
8
3
4
9
12
16
10
17
18
21

Sheet1

X Y
10 5
14 8
15 3
17 4
19 9
21 12
25 16
28 10
30 17
35 18
39 21

Sheet2

Sheet3

Correlation Coefficient

  • Population correlation r
  • Sample correlation r, –1 ≤ r ≤ +1
  • Sign indicates nature of relationship (positive or direct, negative, or inverse).
  • Magnitude indicates strength.

Direct Relationship Between
X and Y, r = 0.6

Chart1

10
14
15
17
19
21
25
28
30
35
39
Y
X
Y
5
8
3
4
9
12
16
10
17
18
21

Sheet1

X Y
10 5
14 8
15 3
17 4
19 9
21 12
25 16
28 10
30 17
35 18
39 21

Sheet2

Sheet3

Inverse Relationship Between
X and Y, r = –0.6

Chart1

40
37
38
32
28
25
17
19
12
15
10
Y
X
Y
5
8
3
4
9
12
16
10
17
18
21

Sheet1

X Y
40 5
37 8
38 3
32 4
28 9
25 12
17 16
19 10
12 17
15 18
10 21

Sheet2

Sheet3

Sample Correlation Coefficient

Example (1 of 6)

  • Suppose we are interested in the relationship between body mass index (BMI; computed as the ratio of weight in kilograms to height in meters squared) and systolic blood pressure in males 50 years of age.

Example (2 of 6)

  • A random sample of 10 males 50 years of age is selected and their weights, heights, and systolic blood pressures are measured.
  • Their weights and heights are transformed into body mass index scores (see next slide).
  • In this analysis, the independent (or predictor) variable is BMI and the dependent (or response) variable is systolic blood pressure.

Example (3 of 6)

  • Data

X = BMI Y = SBP

18.4 120

20.1 110

22.4 120

25.9 135

26.5 140

28.9 115

30.1 150

32.9 165

33.0 160

34.7 180

X = BMI (X – ) (X – )2

18.4 –8.89 79.032

20.1 –7.19 51.696

22.4 –4.89 23.912

25.9 –1.39 1.932

26.5 –0.79 0.624

28.9 1.61 2.592

30.1 2.81 7.896

32.9 5.61 31.472

33.0 5.71 32.604

34.7 7.41 54.908

272.9 286.669

= 27.29

Example (4 of 6)

Y = SBP (Y – ) (Y – )2

120 –19.5 380.25

110 –29.5 870.25

120 –19.5 380.25

135 –4.5 20.25

140 0.5 0.25

115 –24.5 600.25

150 10.5 110.25

165 25.5 650.25

160 20.5 420.25

180 40.5 1640.2

1395 5072.50

= 139.5

Example (5 of 6)

(X – ) (Y – ) (X – )(Y – )

–8.89 –19.5 173.355

–7.19 –29.5 212.105

–4.89 –19.5 95.355

–1.39 –4.5 6.255

–0.79 0.50 –0.395

1.61 –24.5 –39.455

2.81 10.5 29.505

5.61 25.5 143.055

5.71 20.5 117.055

7.41 40.5 300.105

1036.95

cov (X,Y) = 1036.95/9

= 115.22

Example (6 of 6)

Sample Correlation Coefficient

Example (1 of 2)

  • Suppose in the same study we also measure the number of hours of vigorous exercise per week.
  • Is there a relationship between the number of hours of exercise and SBP in males 50 years of age?

Example (2 of 2)

  • Data

X = Hours of Exercise Y = SBP

4 120

10 110

2 120

3 135

3 140

5 115

1 115

2 165

2 160

0 180

Sample Correlation Coefficient

Simple Linear Regression

Y = Dependent, outcome variable

X = Independent, predictor variable

= b0 + b1 x

b0 is the Y-intercept, b1 is the slope

Simple Linear Regression Assumptions

  • Linear relationship between X and Y
  • Independence of errors
  • Homoscedasticity (constant variance) of the errors
  • Normality of errors

Least Squares Estimates of
Regression Parameters

Regression Analysis: BMI and SBP

Using Regression Equation

  • What is expected SBP for a male with BMI = 20?

  • Compare two males whose BMIs differ by 2 units. How do SBPs compare?

Person with higher BMI will have SBP that is 2(3.61) = 7.22 units higher.

Regression Analysis: Exercise and SBP

Example 9.6.
Linear Regression Analysis

  • Clinical trial to assess the efficacy of a new drug to increase HDL cholesterol

where 1 = new drug and 0 = placebo

Multiple Linear Regression

Y = continuous outcome variable

X1, X2, …, Xp = set of independent or predictor variables

Multiple Regression Analysis (1 of 2)

  • Model is conditional, parameter estimates are conditioned on other variables in model.
  • Perform overall test of regression.
  • If significant, examine individual predictors.
  • Relative importance of predictors by p-values (or standardized coefficients)

Multiple Regression Analysis (2 of 2)

  • Predictors can be continuous, indicator variables (0/1), or a set of dummy variables.
  • Dummy variables (for categorical predictors)
  • Race: white, black, Hispanic

Black (1 if black, 0 otherwise)

Hispanic (1 if Hispanic, 0 otherwise)

Example 9.7.
Multiple Linear Regression Analysis

Outcome = infant birth weight, grams

Independent Regression

Variable Coefficient t p-value

Intercept –3850.92 –11.56 0.0001

Male gender 174.79 6.06 0.0001

Gestational age, weeks 179.89 22.35 0.0001

Mother’s age, years 1.38 0.47 0.6361

Black race –138.46 –1.93 0.0535

Hispanic race –13.07 –0.37 0.7103

Other race –68.67 –1.05 0.2918

Simple Logistic Regression Analysis

  • Outcome is dichotomous (1 = event, 0 = non-event) and p = P(event).
  • Outcome is modeled as log odds.

Multiple Logistic Regression Analysis

  • Outcome is dichotomous (1 = event, 0 = non-event) and p = P(event).
  • Outcome is modeled as log odds.

Example 9.8.
Logistic Regression Analysis

  • Study to assess the relationship between obesity and incident CVD

Estimation of Regression Coefficients

  • Model parameters are estimated using maximum likelihood techniques.

b1 is the log odds ratio.

exp(b1) is the odds ratio estimate from a logistic regression model.

Interpretation of Regression Coefficients in Logistic Regression (1 of 2)

  • With a dichotomous predictor X, b1 is a log odds ratio for success for group1 versus group2.
  • With a continuous predictor X, b1 is a log odds ratio for success per unit change in X.

b1 = 0  No association between Y and X

b1 > 0  Probability of success increases as X increases

b1 < 0  Probability of success decreases as X increases

Interpretation of Regression Coefficients in Logistic Regression (2 of 2)

Multiple Logistic Regression Model for Hypertension (Y/N)

Predictor b p OR (95% CI for OR)

Intercept –5.407 0.0001

Age 0.052 0.0001 1.053 (1.044 – 1.062)

Male –0.250 0.0007 0.779 (0.674 – 0.900)

BMI 0.158 0.0001 1.171 (1.146 – 1.198)

1.78

0.086

0.153

60/700

46/300

RR

CVD

=

=

=

1.44

0.13

0.18

RR

and

1.43

0.07

0.10

RR

50

Age

|

CVD

50

Age

|

CVD

=

=

=

=

+

<

0

5

10

15

20

25

051015202530354045

X

Y

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5

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X

Y

1

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)

X

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7.73(563.6

49.33

s

s

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cov(X,

=

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2

x

-

=

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40.98

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0b = Y − 1b X =139.5− (−6.38)(3.2) =159.9

0

b

= Y-

1

b

X=139.5-(-6.38)(3.2)=159.9

ŷ = 159.9 – 6.38 x

ˆ

y = 159.9 – 6.38 x

Treatment

0.95

9.21

y

ˆ

+

=

Men: ŷ = 39.06 + 6.19 Treatment Women: ŷ = 39.24 – 0.36 Treatment

Men:

ˆ

y=39.06 + 6.19 Treatment

Women:

ˆ

y=39.24 – 0.36 Treatment

x

b

+

.

.

.

+

x

b

+

x

b

+

b

=

y

ˆ

p

p

2

2

1

1

0

X

b

b

X

b

b

1

0

1

0

e

1

e

p

ˆ

+

+

+

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x

b

b

p

1

p

ln

logit(p)

log(odds)

1

0

+

=

÷

÷

ø

ö

ç

ç

è

æ

-

=

=

ln p̂ 1 – p̂ ⎛

⎝ ⎜

⎠ ⎟= b0 + b1x1 + b2x2 + ... + bpxp

ln

ˆ

p

1 –

ˆ

p

æ

è

ç

ö

ø

÷

=b

0

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1

x

1

+ b

2

x

2

+ ... + b

p

x

p

ln p̂ 1− p̂ ⎛

⎝ ⎜

⎠ ⎟= −2.592 + 0.415 Obesity + 0.655 Age Group

ÔR = exp(0.415) = 1.52

ln

ˆ

p

1-

ˆ

p

æ

è

ç

ö

ø

÷

=-2.592+0.415 Obesity + 0.655 Age Group

ˆ

OR = exp(0.415) = 1.52

ln p̂ 1 – p̂ ⎛

⎝ ⎜

⎠ ⎟= −2.367+ 0.658 Obesity

ÔR = exp(0.658) = 1.93

ln

ˆ

p

1 –

ˆ

p

æ

è

ç

ö

ø

÷

=-2.367+0.658 Obesity

ˆ

OR = exp(0.658) = 1.93