Tests of Significance · Tests of Significance Data from a Hypothetical Cohort Study Dead Alive...

Post on 10-Jul-2020

4 views 0 download

Transcript of Tests of Significance · Tests of Significance Data from a Hypothetical Cohort Study Dead Alive...

1

1

Tests of Significance

Analysis of

Two-by-Two Table Data:

Tests of Significance

UI-MEPI-J: Research Design and Methodology Workshop

2

Tests of Significance

ILL

VANILLA | + - | Total

-----------+-------------+------

+ | 43 11 | 54

- | 3 18 | 21

-----------+-------------+------

Total | 46 29 | 75

Single Table Analysis

Odds ratio 23.45

Cornfield 95% confidence limits for OR 5.07 < OR < 125.19*

RISK RATIO(RR)(Outcome:ILL=+; Exposure:VANILLA=+) 5.57

95% confidence limits for RR 1.94 < RR < 16.03

Ignore risk ratio if case control study

Chi-Squares P-values

----------- --------

Uncorrected: 27.22 0.00000018 <---

Mantel-Haenszel: 26.86 0.00000022 <---

Yates corrected: 24.54 0.00000073 <---

2

3

Tests of Significance

Objectives

Describe the reason for using statistical tests

Describe what a P-value is

Describe the two main influences on a P-value

for a two-by-two table

Properly interpret the results of chi-square

statistical tests

4

Tests of Significance

P < 0.05

P = NS

3

5

Tests of Significance

What is a Statistical Testing?

Also called “hypothesis testing”

… the process of inferring from your data

whether an observed difference is likely to

represent chance variation or a real difference

(Does NOT address bias, confounding, or

investigator error!)

For two-by-two table data, influenced by:

Number of subjects or observations in study

Size of difference in results between groups

6

Tests of Significance

Data from a Hypothetical Cohort Study

Dead Alive Total % Dead

Diabetic 2 2 4 50.0%

Nondiabetic 1 3 4 25.0%

Total

3 5 8 37.5%

4

7

Tests of Significance

Data from a Hypothetical Cohort Study

Dead Alive Total % Dead

Diabetic 10 10 20 50.0%

Nondiabetic 5 15 20 25.0%

Total

15 25 40 37.5%

8

Tests of Significance

Data from a Hypothetical Cohort Study

Dead Alive Total % Dead

Diabetic 20 20 40

50.0%

Nondiabetic 10 30 40 25.0%

Total

30 50 80 37.5%

5

9

Tests of Significance

Data from a Hypothetical Cohort Study

Dead Alive Total % Dead

Diabetic 200 200 400 50.0%

Nondiabetic 100 300 400 25.0%

Total

300 500 800 37.5%

10

Tests of Significance

Steps in Statistical Testing

1. State the null and alternative hypotheses

2. Choose a statistical test for testing the null hypothesis

3. Specify a significance level

4. Perform the statistical test, i.e., calculate probability of obtaining data you got if null hypothesis were true

5. Make a decision about the hypotheses

6

11

Tests of Significance

Mindset for Statistical Testing

2 groups – diabetics vs. non-diabetics, cases

vs. controls, etc.

Each is a sample from some larger population

Are they likely to be samples from the same

population, or different populations?

12

Tests of Significance

RR = 1

7

13

Tests of Significance

0

5

10

15

20

25

30

35

40

45

Relative Risk

RR = 1

14

Tests of Significance

1. State the Null and Alternative Hypotheses

Null hypothesis

H0: The observed difference is not real, i.e., the

observed difference is the result of chance

Alternative hypothesis

HA: H0 is not true, i.e., the observed difference is

not due to chance

8

15

Tests of Significance

Investigation: Gastroenteritis after a Wedding

16

Tests of Significance

1. State H0 and HA – Wedding Cake Study

Study 1: Wedding attendees

Attack rate, cake+ = 254 / 411 = 61.8%

Attack rate, cake− = 33 / 223 = 14.8%

H0: the attack rates in the two groups are the

same (RR=1)

HA: the attack rates in the two groups are not the

same (RR ≠ 1), or

HA: those who ate cake had higher attack rate (RR > 1)

9

17

Tests of Significance

2. Choosing a Statistical Test

Choice depends on:

study design

measurement scale of the variables

study size

Test for comparison of 2 means:

Test for 2-x-2 table data:

Student t-test

Chi-square test

18

Tests of Significance

Statistical Tests for a 2-by-2 Table

Fisher Exact Test

– use when any expected value < 5

Chi-square Test

– use when all expected values > 5

– 4 variations

– Uncorrected

– Mantel-Haenszel uncorrected

– Yates corrected

– Mantel-Haenszel corrected

10

19

Tests of Significance

ILL

VANILLA | + - | Total

-----------+-------------+------

+ | 43 11 | 54

- | 3 18 | 21

-----------+-------------+------

Total | 46 29 | 75

Single Table Analysis

Odds ratio 23.45

Cornfield 95% confidence limits for OR 5.07 < OR < 125.19*

RISK RATIO(RR)(Outcome:ILL=+; Exposure:VANILLA=+) 5.57

95% confidence limits for RR 1.94 < RR < 16.03

Ignore risk ratio if case control study

Chi-Squares P-values

----------- --------

Uncorrected: XX.XX 0.XXXXXXXX

Mantel-Haenszel: XX.XX 0.XXXXXXXX

Yates corrected: XX.XX 0.XXXXXXXX

20

Tests of Significance

Test Statistic (“Uncorrected”)

degrees of freedom = (rows−1) (columns −1)

Chi-square test determines whether the

deviations between observed and expected are

too large to be attributed to chance.

expected

expected) - (observed 2

2

Chi-Square Test for Independence

11

21

Tests of Significance

Oswego Data

Ill Well Total AR

Ate vanilla

ice cream?

Y 43 11 54 79.6%

N 3 18 21 14.3%

46 29 75

How many degrees of freedom?

What is expected in a 2-by-2 table?

1 d.f.

22

Tests of Significance

Observed number in cell A = 43

Overall attack rate (AR) = 46 / 75 = _____

Expected AR (each group) under H0 = _____

N who ate vanilla ice cream = _____

Expected # cases among those who ate vanilla

ice cream, under H0 = _______________

So, Expected (a) =

column total x (row total / table total)

What’s Expected in a 2-by-2 Table?

0.613

0.613

54

54 x 0.613 = 33.1

12

23

Tests of Significance

What’s Expected in a 2-by-2 Table?

Ill Well Total

Ate vanilla

ice cream?

Y H1V1 /T H1V0 /T H1

N H0V1 /T H0V0 /T H0

V1 V0 T

In general, expected value =

row total x column total / table total

24

Tests of Significance

Oswego: Observed vs. Expected

Observed Expected

Cell a 43

Cell b 11

Cell c 3

Cell d 18

Total 75

13

25

Tests of Significance

Oswego: Observed vs. Expected

Observed Expected

Cell a 43 33.12

Cell b 11

Cell c 3

Cell d 18

Total 75

20.88

12.88

8.12

75.00

26

Tests of Significance

Oswego: Observed vs. Expected

Observed Ill Well Total % Ill

Vanilla IC+ 43 11 54 79.6%

Vanilla IC− 3 18 21 14.3%

46 29 75 61.3%

Expected Ill Well Total % Ill

Vanilla IC+ 33.12 20.88 54 79.6%

Vanilla IC− 12.88 8.12 21 14.3%

46 29 75 61.3%

14

27

Tests of Significance

Chi-Square Tests for 2-by-2 Tables

Uncorrected (Pearson) Chi-square Test

Mantel-Haenszel Chi-square Test

Yates corrected Chi-square Test

0101

22 )(

VVHH

bcadt

0101

2

2 2VVHH

tbcadt

0101

22 ))(1(

VVHH

bcadt

28

Tests of Significance

Example: Randomized Clinical Trial

Cured Not Total Cure (%)

New Tx 7 1 8 87.5%

Old Tx 2 5 7 28.6%

Total 9 6 15

Can we use chi-square? Calculate expected value for cell d.

7 x 6 / 15 = 42 / 15 = 2.8 Use FET

15

29

Tests of Significance

3. Specify a Level of Significance

Level of significance = an arbitrary cut-off, a small

probability, for deciding whether to declare the

null hypothesis untenable

Also called alpha level

Commonly, alpha set at 0.05 (5%) or 0.01 (1%)

30

Tests of Significance

4. Perform the Statistical Test, Compute P -value

Chi-square tests provide chi-square test statistic,

which must be converted to P-value (use

computer or look-up table)

P-value = probability of observing a difference as

great or greater than the observed difference, if

the null hypothesis were true

P-value influenced by:

– size of difference / strength of association

– size of the sample

16

31

Tests of Significance

Oswego: Observed vs. Expected

Observed Expected

Cell a 43 33.12

Cell b 11 20.88

Cell c 3 12.88

Cell d 18 8.12

Total 75 75.00

2.947

4.675

7.579

12.021

27.222

(O-E)2

E

32

Tests of Significance

Chi-Square Tests for 2-by-2 Tables

Uncorrected (Pearson) Chi-square Test

0101

22 )(

VVHH

bcadt

29462154

)3111843)(75( 22

222.272

17

33

Tests of Significance

Converting a X2 to a P-Value

To convert the X2 into a P-value by hand, use a

special X2 table

The bigger the X2, the smaller the P-value

For data with 1 degree of freedom, i.e., data from

a 2x2 table, the X2 value must be ≥ 3.84 to yield

a P-value ≤ 0.05

Alternatively, let the computer do the conversion

34

Tests of Significance

ILL

VANILLA | + - | Total

-----------+-------------+------

+ | 43 11 | 54

- | 3 18 | 21

-----------+-------------+------

Total | 46 29 | 75

Single Table Analysis

Odds ratio 23.45

Cornfield 95% confidence limits for OR 5.07 < OR < 125.19*

RISK RATIO(RR)(Outcome:ILL=+; Exposure:VANILLA=+) 5.57

95% confidence limits for RR 1.94 < RR < 16.03

Ignore risk ratio if case control study

Chi-Squares P-values

----------- --------

Uncorrected: 27.22 0.00000018 <---

Mantel-Haenszel: 26.86 0.00000022 <---

Yates corrected: 24.54 0.00000073 <---

18

35

Tests of Significance

36

Tests of Significance

5. Make Decision about Hypothesis

If computed P-value < alpha, reject H0, i.e.,

conclude that difference is unlikely to be due to

chance*

If computed P-value > alpha, do not reject H0,

i.e., conclude that difference could be due to

chance*

* You could be right or you could be wrong!

19

37

Tests of Significance

Two Types of Possible Errors

In reality, H0 is…

True False

Decision re: H0, based on our data

Accept OK Type II

(β) error

Reject Type I

(α) error OK

Level of significance (α) = probability of

making Type I error

1 – α = Confidence 1 – β = Power

38

Tests of Significance

What Influences a P-value?

Strength of association / size of

difference

Number of subjects (size of sample)

20

39

Tests of Significance

P- value and Strength of Association

D+ D- AR RR

E+ 10 10 20 50% 2.0 X2 = 2.67

E- 5 15 20 25% p = 0.10

D+ D- AR RR

E+ 12 8 20 60% 2.4 X2 = 5.01

E- 5 15 20 25% p = 0.03

40

Tests of Significance

P- value and Size of Study

D+ D- AR RR

E+ 10 10 20 50% 2.0 X2 = 2.67

E- 5 15 20 25% p = 0.10

D+ D- AR RR

E+ 20 20 40 50% 2.0 X2 = 5.33

E- 10 30 40 25% p = 0.02

21

41

Tests of Significance

Hypothetical Cohort Study

Dead Alive Total % Dead

Diabetic 2 2 4 50.0%

Nondiabetic 1 3 4 25.0%

Diabetic 10 10 20 50.0%

Nondiabetic 5 15 20 25.0%

Diabetic 20 20 40 50.0%

Nondiabetic 10 30 40 25.0%

X2 = 0.53

P = 0.47

X2 = 2.67

P = 0.10

X2 = 5.33

P = 0.02

42

Tests of Significance

Notes on Interpretation of Statistical Tests

Statistical testing does not address bias!

Statistical significance ≠ importance

“A difference, to be a difference, has to make a difference.” – Carl Tyler

Not significant ≠ no association

“Absence of evidence should not be taken as evidence of absence.”

– Sherlock Holmes

Statistical significance ≠ causation

22

43

Tests of Significance

Interpret the Findings (Studies 1–6)

Study P value Interpretation

1 0.007

2 0.03

3 0.08

4 0.65

5 0.0001

6 8 x 10-11

44

Tests of Significance

Interpret the Findings (Studies 7–11)

Study P value Interpretation

7 0.060

8 0.052

9 0.048

10 0.00009

11 0.9

23

45

Tests of Significance

Objectives

Describe the reason for using statistical tests – To evaluate the role of chance as an explanation

of observed differences / associations

Describe what a P-value is – Probability of observing >difference under H0

Describe the two influences on a P-value – size of difference / strength of association

– size of the sample

Properly interpret the results of chi-square test – reject H0 if P < α, but use judgment!

46

Tests of Significance

Author, Acknowledgements, References

Author

Richard Dicker

Acknowledgement

Virgil Peavy

24

47

Tests of Significance

Baking the Cake Layers

48

Tests of Significance

Filling the Cakes

25

49

Tests of Significance

Filling the Cakes

Raspberry jam

Syrup

White

Chocolate

Mousse Filling

50

Tests of Significance

The Strawberry Filling

26

51

Tests of Significance

Strawberry Filling

Strawberries

– Fresh

– Washed in sink

– Sliced in the

bake room

– Hand-spread

onto cake filling

52

Tests of Significance

Cake Composition

Cake Layer 3

Cake Layer 1

Cake Layer 2

Baked Cake

Filling

27

53

Tests of Significance

Icing, Assembly, and Decorating

54

Tests of Significance

Attack Rates by Type of WCM Filling

Type of

Filling # Ate

Attack

rate

(eaters)

Attack rate

(non-eaters) RR P-value

Strawberry 408 62% 15% 4.2 0.0001

Chocolate

and Mocha 36 53% 45% 1.2 0.3

WCM only 9 44% 45% 1.0 1.0