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Overview of Biostatistical Methods

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Overview of Biostatistical Methods

Overview of Biostatistical Methods

~ GOLD STANDARD ~

Designed to compare two or more treatment groups for a statistically significantdifference between them – i.e., beyond random chance – often measured via a “p-value” (e.g., p < .05).

Examples: Drug vs. Placebo, Drugs vs. Surgery, New Txvs. Standard Tx

- Let X = cholesterol level (mg/dL);

possible expected distributions:

Treatment population

Control population

RANDOMIZE

Treatment Arm

Experiment

End of Study

T-test

F-test (ANOVA)

Patients satisfying inclusion criteria

RANDOM SAMPLES

X

0

significant?

Control Arm

Overview of Biostatistical Methods

~ GOLD STANDARD ~

Designed to compare two or more treatment groups for a statistically significantdifference between them – i.e., beyond random chance – often measured via a “p-value” (e.g., p < .05).

Examples: Drug vs. Placebo, Drugs vs. Surgery, New Txvs. Standard Tx

- Let X = cholesterol level (mg/dL)

from baseline, on same patients

Post-Tx population

Pre-Tx population

Pre-Tx Arm

Experiment

End of Study

Paired T-test,

ANOVA F-test “repeated measures”

Patients satisfying inclusion criteria

PAIRED SAMPLES

X

significant?

Post-Tx Arm

0

Overview of Biostatistical Methods

~ GOLD STANDARD ~

Designed to compare two or more treatment groups for a statistically significantdifference between them – i.e., beyond random chance – often measured via a “p-value” (e.g., p < .05).

Examples: Drug vs. Placebo, Drugs vs. Surgery, New Txvs. Standard Tx

- Let T = Survival time (months);

population survival curves:

survival probability

Kaplan-Meier

estimates

S(t) = P(T > t)

End of Study

Log-Rank Test,

Cox Proportional Hazards Model

AUC difference

1

significant?

S1(t)

Treatment

S2(t)

Control

T

0

Overview of Biostatistical Methods

Observational study designs that test for a statistically significantassociation between a disease D and exposure E to a potential risk (or protective) factor, measured via “odds ratio,” “relative risk,” etc. Lung cancer / Smoking

Case-Control studies

Cohort studies

PRESENT

cases

controls

reference group

E+ vs. E– ?

D+ vs. D–

E+ vs. E–

D+ vs. D– ?

PAST

- relatively easy and inexpensive
- subject to faulty records, “recall bias”

- measures direct effect of E on D
- expensive, extremely lengthy…
- Example: Framingham, MA study

FUTURE

Both types of study yield a 22 “contingency table” for binary variables D and E:

where a, b, c, d are the observed counts of individuals in each cell.

End of Study

Chi-squared Test

McNemar Test

(for paired case-control study designs)

H0: No association between D and E.

Overview of Biostatistical Methods

As seen, testing for association between categorical variables – such as disease D and exposure E – can generally be done via a Chi-squared Test.

But what if the two variables – say, X and Y – are numericalmeasurements?

Furthermore, if sample data does suggest that one exists, what is the nature of that association, and how can it be quantified, or modeled via Y = f(X)?

Y

Correlation Coefficient

measures the strength of linear association between X and Y

JAMA. 2003;290:1486-1493

Scatterplot

–1 0 +1

r

negative linear correlation

positive linear correlation

X

Overview of Biostatistical Methods

As seen, testing for association between categorical variables – such as disease D and exposure E – can generally be done via a Chi-squared Test.

But what if the two variables – say, X and Y – are numericalmeasurements?

Furthermore, if sample data does suggest that one exists, what is the nature of that association, and how can it be quantified, or modeled via Y = f(X)?

Y

Correlation Coefficient

measures the strength of linear association between X and Y

JAMA. 2003;290:1486-1493

Scatterplot

–1 0 +1

r

negative linear correlation

positive linear correlation

X

Overview of Biostatistical Methods

As seen, testing for association between categorical variables – such as disease D and exposure E – can generally be done via a Chi-squared Test.

But what if the two variables – say, X and Y – are numericalmeasurements?

Furthermore, if sample data does suggest that one exists, what is the nature of that association, and how can it be quantified, or modeled via Y = f(X)?

Y

Correlation Coefficient

measures the strength of linearassociation between X and Y

JAMA. 2003;290:1486-1493

Scatterplot

–1 0 +1

r

negative linear correlation

positive linear correlation

X

Overview of Biostatistical Methods As seen, testing for association between categorical variables – such as disease D and exposure E – can generally be done via a Chi-squared Test.

Furthermore, if sample data does suggest that one exists, what is the nature of that association, and how can it be quantified, or modeled via Y = f(X)?

But what if the two variables – say, X and Y – are numericalmeasurements?

Correlation Coefficient

measures the strength of linearassociation between X and Y

For this example, r = –0.387

(weak, negative linear correl)

Overview of Biostatistical Methods As seen, testing for association between categorical variables – such as disease D and exposure E – can generally be done via a Chi-squared Test.

Furthermore, if sample data does suggest that one exists, what is the nature of that association, and how can it be quantified, or modeled via Y = f(X)?

But what if the two variables – say, X and Y – are numericalmeasurements?

Regression Methods

Simple Linear Regression gives the “best” line

that fits the data.

?

residuals

Want the unique line that minimizes the sum of the squared residuals.

For this example, r = –0.387

(weak, negative linear correl)

Overview of Biostatistical Methods As seen, testing for association between categorical variables – such as disease D and exposure E – can generally be done via a Chi-squared Test.

Furthermore, if sample data does suggest that one exists, what is the nature of that association, and how can it be quantified, or modeled via Y = f(X)?

But what if the two variables – say, X and Y – are numericalmeasurements?

Regression Methods

Simple Linear Regression gives the “least squares”regression line.

residuals

Want the unique line that minimizes the sum of the squared residuals.

For this example, r = –0.387

(weak, negative linear correl)

Y = 8.790 – 4.733X (p = .0055)

For this example, r = –0.387

(weak, negative linear correl)

It can also be shown that the proportion of total variabilityin the data that is accounted for by the line is equal to r2, which in this case, = (–0.387)2 = 0.1497 (15%)... very small.

Overview of Biostatistical Methods

- Extensions of Simple Linear Regression
- Polynomial Regression – predictors X, X2, X3,…
- Multilinear Regression – independent predictors X1, X2,…
- w/o or w/ interaction (e.g., X5 X8)
- Logistic Regression – binaryresponseY (= 0 or 1)
- Transformations of data, e.g., semi-log, log-log,…
- Generalized Linear Models
- Nonlinear Models
- many more…

Numerical (Quantitative)e.g., $ Annual Income

Summary ~2 POPULATIONS:

Independent e.g., RCT

Paired (Matched) e.g., Pre- vs. Post-

σ1

σ2

X

H0: 1 = 2

1

2

Sample 1

Sample 2

No

Yes

Yes

No

Normally distributed?

- Q-Q plots
- Shapiro-Wilk
- Anderson-Darling
- others…

Yes

No

Yes

No

Equivariance?

“Nonparametric

Tests”

- F-test
- Bartlett
- others…

“Nonparametric

Tests”

Wilcoxon Rank Sum (aka Mann-Whitney U)

“Approximate” T

- Sign Test
- Wilcoxon
- Signed Rank

2-sample T (w/o pooling)

2-sample T (w/ pooling)

- Satterwaithe
- Welch

Paired T

2 POPULATIONS:

ANOVA F-test

(w/ “repeated measures”

or “blocking”)

- Friedman
- Kendall’s W
- others…

Kruskal-Wallis

- ANOVA F-test
- Regression Methods

Various modifications

e.g., Income Level: Low, Mid, High

Summary ~ 2 CATEGORIES per each of two variables:

H0: “There is no association between

(the categories of) I and

(the categories of) J.”

r × c contingency table

Chi-squared Tests

- Test of Independence
- (1 population, 2 categorical variables)

- Test of Homogeneity
- (2 populations, 1 categorical variable)

- “Goodness-of-Fit” Test
- (1 population, 1 categorical variable)

- Modifications
- McNemar Test for paired
- 2 × 2 categorical data, to control
- for “confounding variables”
- e.g., case-control studies
- Fisher’s Exact Test for small
- “expected values” (< 5) to avoid
- possible “spurious significance”

Introduction to Basic Statistical Methods

Part 1: Statistics in a Nutshell

UWHC Scholarly Forum

May 21, 2014

Ismor Fischer, Ph.D.

UW Dept of Statistics

Part 2: Overview of Biostatistics:

“Which Test Do I Use??”

- Sincere thanks to…
- Judith Payne
- Heidi Miller
- Samantha Goodrich
- Troy Lawrence
- YOU!

All slides posted at http://www.stat.wisc.edu/~ifischer/Intro_Stat/UWHC

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