Types of Biostatistics

1) Descriptive Statistics

Exploratory Data Analysis

often not in literature
Lecture 17: Review Lecture
Summaries

"Table 1" in a paper

Goal: visualize relationships, generate
hypotheses
Sandy Eckel
seckel@jhsph.edu 2) Inferential Statistics

Confirmatory Data Analysis (Methods Section of
paper)
20 May 2008
Hypothesis tests

Confidence Intervals

Regression modeling
1

Goal: quantify relationships, test hypotheses 2

Summary of the approach to modeling I Summary of the approach to modeling II

A general approach for most statistical modeling
is to:

Define the Population of Interest

State the Scientific Questions & Underlying
Theories

Describe and Explore the Observed Data

Define the Model

Probability part (models the randomness / noise)

Systematic part (models the expectation / signal)

Estimate the Parameters in the Model

Fit the Model to the Observed Data

Make Inferences about Covariates

Check the Validity of the Model

Verify the Model Assumptions

Re-define, Re-fit, and Re-check the Model if
necessary

Interpret the results of the Analysis in terms
of the Scientific Questions of Interest

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 Key Descriptive Statistics Ideas

Visualizing data

Stem and leaf plots
Descriptive Statistics
Histograms

Boxplots

Scatterplots

Describing data

ALWAYS look at your data
Distribution shapes (especially skewness)

If you can't see it, then don't
Quartiles

Measures of central tendency
believe it
Median, Mean, Mode

Measures of spread

Variance, Standard Deviation, Range, Interquartile Range
5 6

Stem-and-Leaf Plots Histograms

Age in years (10 observations)
Pictures of the frequency or relative

frequency distribution
25, 26, 29, 32, 35, 36, 38, 44, 49, 51

Age Interval Observations Histogram of Age

4
2* 569
3
3* 2568
Fre quency
2

4* 49
5* 1
1

7 1 2
A ge C a te g o ry
3 4 8
Box-and-Whisker Plots (Boxplot) 2 Continuous Variables

Box Plot of Age

Scatterplot
50
Age by Height in cm
45

190
Age in Years
40

180
Height in Centimeters
35

170
30

160
25

150

IQR = 44 29 = 15 25 30 35 40 45 50
Age in Years

Upper Fence = 44 + 15*1.5 = 66.5
Scatterplots visually display the relationship between

Lower Fence = 29 15*1.5 = 6.5 9
two continuous variables 10

Skewness Skewness

Positively Skewed
Negatively Skewed

Longer tail in the high values
Longer tail in the low values

Mean > Median > Mode
Mode > Median > Mean

Mode Mean Mean Mode

Median 11 Median 12
Symmetric Other descriptive statistics Review on your own

Right and left sides are mirror images
Quartiles

Left tail looks like right tail
Measures of central tendency

Mean = Median = Mode
Median, Mean, Mode

Measures of spread

Variance, Standard Deviation, Range,
Interquartile Range

Mean Median Mode 13 14

Key Ideas of Probability/Distributions

Mutually exclusive
Concepts from Biostat I
Statistically independent
used in this class

Addition rule

Conditional probability

Common distributions

Continuous: Normal, t-distribution,
Chi-square, F-distribution

Discrete: Binomial

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Key Ideas of
The Normal Distribution and Statistical Inference 68 95 99.7 Rule
Normal distribution

Parameters: mean, variance
68% of the area under the curve is

Standard normal within 1 standard deviation of the mean

68-95-99.7 Rule

Areas under the curve relation to p-values
Statistical Inference

Population: parameters

Sample: statistics

We use sample statistics along with theoretical results
to make inferences about population parameters

Sampling distribution of sample mean

Central Limit Theorem
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68 95 99.7 Rule 68 95 99.7 Rule

95% of the area under the curve is
99.7% of the area under the curve is
within 2 standard deviation of the mean within 3 standard deviation of the mean

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Sampling Distribution of the Sample Mean

Usually is unknown and we would like to
estimate it

We use to estimate

We know the sampling distribution of

Definition: Sampling distribution
The distribution of all possible values of some
statistic, computed from samples of the same
size randomly drawn from the same
population, is called the sampling distribution
of that statistic
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Confidence Intervals
Inferential Statistics
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The Central Limit Theorem

Given a population of any distribution with
mean, , and variance, 2, the sampling
distribution of , computed from samples of
size n from this population, will be
approximately normally distributed with
mean, , and variance, 2/n, when the sample
size is large.

In general, this applies when n 25.

The approximation to normality becomes better as
n increases
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Point estimation

An estimate of a population parameter

Interval estimation

A point estimate plus an interval that expresses the uncertainty
or variability associated with the estimate
100(1 )% Confidence interval:
estimate
(critical value of z or t) (standard error of estimate)

Critical value is the cutoff such that the area under the
curve in the tails beyond the critical value (both positive
and negative direction) is
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Interpretation of confidence interval?
Use a CI for as an example:

Before the data are observed, the probability
is at least (1 alpha) that [L,U] will contain ,
the population parameter

In repeated sampling from a normally
distributed population, 100(1 )% of all
intervals of the form above will include the
population mean

After the data are observed, the constructed
interval [L,U] either contains the true mean or
it does not (no probability involved anymore)
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MANY types of hypothesis testing
We discussed

A single mean

H0: = 3000 vs. Ha: 3000

A single proportion

H0: p = 0.35 vs. Ha: p 0.35

Difference of means

H0: 1 - 2= 0 vs. Ha: 1 - 2 0

Need to decide whether to assume equality of
variance

Difference of proportions

H0: p1 p2 = 0 vs. Ha: p1 p2 0

Others for regression modelling
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Steps of Hypothesis Testing

Define the null hypothesis, H0.

Define the alternative hypothesis, Ha, where
Ha is usually of the form not H0.

Define the type 1 error, , usually 0.05.

Calculate the test statistic

Calculate the P-value

If the P-value is less than , reject H0.
Otherwise fail to reject H0.
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Which test statistic do I use for each kind of test?

Usually, the form of the test statistic
depends on

Population distribution

Sample size

Population variance

Whether known or estimated

Or assumptions about equality

To find out which test statistic to use,
check the summary sheets

Not something you really have to memorize
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Example
Summary: Hypothesis test for a single mean Relation between CI and hypothesis testing

General rule on the 100(1- )% confidence

interval approach to two-sided hypothesis
testing

If the null hypothesis value is not contained in the
confidence interval, you reject the null hypothesis
with p-value

If the null hypothesis value is contained in the
confidence interval, you fail to reject the null
hypothesis with p-value>

29 30

Why is the power of a test important? Were not always right

Power indicates the chance of finding a

significant difference when there really
is one

Low power: likely to obtain non-significant
results even when significant differences
exist
Aim: to keep Type I error () small by specifying
a small rejection region

High power is desirable!
is set before performing a test, usually at 0.05

Low power is usually cause by small sample
Aim: To keep Type II error () small and thus
size power high

Power = 1
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: Probability of Type II Error

The value of is usually unknown since it
depends on a specified alternative value.

depends on sample size and .

Before data collection, scientists decide

the test they will perform

extreme or more extreme (in the

the desired

They will use this information to choose the
sample size
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Regression Modeling
35
P-Values

Definition: The p-value for a
hypothesis test is the probability of
obtaining by chance, alone, when H0 is
true, a value of the test statistic as
appropriate direction) than the one
actually observed.
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Correlation

Measures strength and direction of the
linear relationship between two
continuous variables

The correlation coefficient, , takes
values between -1 and +1

-1: Perfect negative linear relationship

0: No linear relationship

+1: Perfect positive relationship
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Association and Causation Why use linear regression?

In general, association between two
Linear regression is very powerful. It

variables means there is some form of can be used for many things:
relationship between them
Binary X

Continuous X

The relationship is not necessarily causal

Categorical X

Association does not imply causation, no
Adjustment for confounding
matter how much we would like it to
Interaction

Example: Hot days, ice cream, drowning
Curved relationships between X and Y

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Simple Linear regression: Y= 0+ 1X1+ Assumptions of Linear Regression

Linear regression is used for continuous
L Linear relationship

outcome variables
I Independent observations

0: mean outcome when X=0 (Center!)

N Normally distributed around line

Binary X = dummy variable for group

1: mean difference in outcome between groups
E Equal variance across Xs

Continuous X

1: difference in mean outcome corresponding Most often assess with graphs
to a 1-unit increase in X
- One type: AV plots

Center X to give meaning to 0

visualize the relationship between the outcome and

Test 1=0 in the population a continuous predictor after adjusting for the
effects of a third variable
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In Simple Linear Regression Regression Methods

In simple linear regression (SLR):

One Predictor / Covariate / Explanatory Variable:
X

In multiple linear regression (MLR):

Same Assumptions as SLR, (i.e. L.I.N.E.), but:

More than one Covariate: X1, X2, X3, , Xp
Model:

Y ~ N(, 2)

= E(Y | X) = 0 + 1X1 + 2X2 + 3X3 +... pXp

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Regression Methods Nested models

Interactions can allow us to draw separate lines for two
groups
One model is nested within another if
the parent model contains one set of
X1 = Year variables and the extended model
X2 = Group
contains all of the original variables plus
one or more additional variables.

H0: all new s are zero

Assess using F-test

If only one additional variable, use t-test

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Effect Modification Confounding: the epidemiologic definition

In linear regression, effect modification C is a confounder of the relation

is a way of allowing the association between X and Y if:
between the primary predictor and the
outcome to change with the level of Outcome Y
another predictor.

If the 3rd predictor is binary, that results in Confounder C
a graph in which the two lines (for the two
groups) are no longer parallel.
Predictor X

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Confounding: example Modeling confounding and effect modification

Smoking is a confounder of the
Potential confounder(s)

relation between coffee consumption (X)
Run model without confounder (model 1)
and lung cancer (Y) since:
Run model with confounder (model 2)

Compare model 2 estimate to the model 1
Lung Cancer Y
CI of primary predictor to see whether new
parameter is significantly different
Smoking C
Effect modification

Model using interaction term
Coffee Consumption X
Test if statistically significant using a t-test

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Spline Terms Summary: Flexibility in linear models

Splines are used to allow the regression line
to bend
A spline allows the slope for a

the breakpoint is arbitrary and decided graphically continuous predictor to change at a
or by hypothesis given point; the coefficient is for the

the actual slope above and below the breakpoint is difference in log odds ratio
usually of more interest than the coefficient for the
spline (ie the change in slope)
An interaction term allows the odds ratio
Broken Arrow Model
3500 for one variable to differ by the value of
a second variable; the coefficient is for
Expenditures

3000

2500 Slope = 1 + 2 the difference in log odds ratio

Slope = 1
2000
3 5 7 9
length of stay (days)
49 50

Using R2
as a model selection criteria Logistic Regression
Basic Idea:

The coefficient of determination, R2
Logistic regression is the type of regression we
evaluates the entire model use for a response variable (Y) that follows a
binomial distribution

R2 shows the proportion of the total
Linear regression is the type of regression we use
for a continuous, normally distributed response (Y)
variation in Y that has been variable
predicted by this model
Model log odds probability, which we also call

Model 1: 0.0076; 0.8% of variation the logit
explained
Baseline term interpreted as log odds

Other coefficients are log odds ratios

Model 2: 0.05; 5% of variation explained
Transform log odds/ log odds ratio to

Model 3: 0.20; 20% of variation explained odds/odds ratio scale by exponentiating
coefficient

You want a model with large R2 51 52
 A basic logistic regression model and
Logit Function interpretation

Relates log-odds (logit) to p = Pr(Y=1) logit(pi) = 0 + 1(agei 45)

0 = log-odds of blindness among 45 year olds

logit function
10

exp(0) = odds of blindness among 45 year olds
5
log-odds

1 = difference in log-odds of blindness

0 comparing a group that is one year older than
another
-5

-10
exp(1) = odds ratio of blindness comparing a

0 .5 1 group that is one year older than another
Probability of Success
53 54

Why we can interpret the difference in log odds

as the log odds ratio

The slope in a logistic regression is

A difference in log odds associated with a 1 unit
change in X (controlling for other Xs)

A log odds ratio associated with a 1 unit change in
X (controlling for other Xs)

Why?
log(a) log(b) = log(a/b)
Multiplicative change interpretation of the slope

e 1 is the proportional increase of the
odds of not visiting a physician corresponding
to a one year increase in age
(odds for 30 - yr - old) (odds for 31 - yr - old) = (odds for 31 - yr - old)
(odds for 30 - yr - old)

so
e( )
1 10
= e101 is the proportional increase of
the odds of not visiting a physician
log(odds|X=1) log(odds|X=0) corresponding to a ten year increase in age
= log(OR for X=1 vs. X=0)
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More useful math Comparing nested models with logisitic
how to get the probability from the odds regression

Models that differ by one variable

probability
Compare models with p-value or CI using the

odds= 1 probability Wald test, a test that applies the CLT

H0: the new variable is not needed
or H0: new=0 in the population
odds

probability =
Models that differ by more than one
1 + odds variable

Likelihood ratio test (Chi-square test of
e0 +1 deviance)

so P (X = 1) =
1 + e0 +1
H0: all new variables not needed
or H0: all new=0 in the population
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Grand summary Grand summary: linear models

Exploratory analysis includes graphs and
Linear regression: for continuous

tables good to get a feel for the data (normal) outcomes

Confirmatory analysis is useful for
Logistic regression: for binary outcomes
making definitive conclusions

Linear models provide us with a
framework in which to perform
confirmatory analysis in many settings

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Grand summary: modelling

In all generalized linear models, we can
use the following tools to make models
more flexible:

Adjust for confounders using additive
covariates

Effect modification allows by interaction
terms

Curved and bent lines through polynomials
and splines
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References - textbooks
For more information

Friendly Intro Epidemiology textbook

Epidemiology by Leon Gordis

Intro to Biostatistical Modeling Textbook

Regression Modeling Strategies by Frank E.
Jr. Harrell

Slightly more theoretical intro to
statistical modeling textbook

Mathematical Statistics and Data Analysis
by John A. Rice
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Grand summary: testing

We can test significance of a single
predictor using z-test (or t-test for linear
regression)

Test significance of several covariates
using a pair of nested models by a
likelihood ratio test

Know how to interpret p-values and
confidence intervals!
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References online JHSPH open courseware
For further directed self-study
JHSPH Biostatistics Open Courseware
http://ocw.jhsph.edu/Topics.cfm?topic_id=33

Essentials of Probability and Statistical
Inference IV

Methods in Biostatistics I & II

Statistical Reasoning I & II

Statistics for Laboratory Scientists I & II

Statistics for Psychosocial Research:
Structural Models & Measurement
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