Basic Biostatistics Part 2

1st March, 2017

 Content

• Part 1 Summary
• Sampling
• Statistical Hypothesis Tests
• Errors in Hypothesis Tests
• Power and Sample Size
• Examples
• Correlation and Regression
 Part 1 Summary

• What were the key learning points from Part 1?

− In groups, identify 3 key learning points from

the first session
Sampling
 Sampling
• An investigation of a population is said to be a survey or study of the
population
• A population is a group of individuals or objects that meets a set of
pre-defined criteria; e.g.
- All people with permanent residence in the UK
- All patient records held in a database
- All patients with schizophrenia
- All staff members of an organisation
- All patients registered to a particular specialist
- All members of the population diagnosed with a particular health
condition
• A survey or study that collects information from every member of a
population is referred to as a census
 Sampling

• Not always possible to collect information from every

member of a population due to time and resources
• A ‘good sample’ can be used to reliably estimate
characteristics (e.g. the mean) of the population
• Sample – any subset of a population

Sample

Population
 Sampling Error

• Errors in surveys can be divided into two categories

• Sampling error - error due to taking a sample rather
than studying the whole population

- e.g. if a psychiatrist randomly selects a sample of

patients and records the duration of each appointment,
the average treatment time can be calculated
- if the times for all patients were recorded (i.e. the entire
population) then the population average would most
likely differ from the sample average
 Non-sampling error

• Non-Sampling error is error due to:

- poor selection of strata or sample (coverage errors)
- poor data entry (processing errors)
- inaccurate responses (measurement errors)
- non-response errors
• In surveys, non-sampling errors can be more of a
problem than sampling errors
Statistical Hypothesis Tests
 Hypothesis Testing

• A process called Hypothesis Testing is used

to quantify a belief against a particular
hypothesis about the population
• There are many different types of hypothesis
tests
• Five stages for hypothesis testing can be
defined:
 5 Stages

1. Define the Null & Alternative Hypotheses

2. Collect data
3. Calculate the value of the test statistic
4. Compare the value of the test statistic to
values from a known probability
distribution
5. Interpret the P-value and results
 The Null Hypothesis

• The Null Hypothesis is tested which assumes

no effect (e.g. the difference in means equals
zero) in the population

• Example: Comparing the rates of

hallucinations in men and woman in the
population
− Null Hypothesis (H0): rates of hallucinations
are the same in men and woman in the
population
 The Alternative Hypothesis

• The Alternative Hypothesis is holds if the Null

Hypothesis is not true

• Example
− Alternative Hypothesis (H1): rates of
hallucinations are different in men and
woman in the population
 The test statistic

• After data collection, the sample data is used

to calculate a test statistic

• The test statistic is effectively the amount of

evidence in the data against H0

• Generally, the larger the value (irrelevant of

sign), the greater the evidence against H0
 The P-value

• The test statistic is compared to values from

the relevant probability distribution to obtain a
P-value
• The P-value is the probability of obtaining
our results, or something more extreme, if
the Null Hypothesis is true
• The smaller the P-value, the greater the
evidence against H0
 Rejecting H0

• Conventionally, if the P-value < 0.05, there is

sufficient evidence to reject H0

• There is only a small chance of the results

occurring if H0 is true
– H0 is rejected, the results are statistically
significant at the 5% level
 Not rejecting H0

• If the P-value ≥ 0.05, there is insufficient

evidence to reject H0
– H0 is not rejected, the results are not
statistically significant at the 5% level

• NB: This does not mean that the null

hypothesis is true, simply that we do not have
enough evidence to reject it!
 Parametric vs. Non-Parametric tests

• Tests which are based on the assumption that the

data follows a known probability distribution (often the
Normal) are known as parametric tests

• Sometimes data does not conform to the assumption

so non-parametric tests can be used

• Non-Parametric tests make no assumption about

the probability distribution
 Non-parametric tests
• Useful when:

− sample size is small

− data is measured on a categorical scale (though
they are used for numerical data as well)

• However:

− they have less power of detecting a real difference

than the equivalent parametric tests
− they lead to decisions rather than generating a true
understanding of the data
 Statistical tests

• Numerical data (Parametric tests)

– One-sample t-test
– Independent t-test
– Paired t-test
– One-way ANOVA
 Statistical tests

• Numerical data, (non-parametric tests)

– Sign test
– Wilcoxon signed rank test
– Wilcoxon rank sum test
– Kruskal-Wallis test
 Statistical tests

• Categorical data

– z-test for a proportion

– Sign test
– McNemar’s test
– Chi-squared test
– Chi-squared trend test
– Fisher’s exact test
 Choosing a statistical test

• Useful medical statistical books will contain a

flowchart to provide guidance

• Considerations include:

– what is the data type?

– how many groups of data are there?
– can a probability distribution be assumed?
Errors in Hypothesis Testing
 Making a wrong decision
• There is the possibility of making a wrong
decision when conducting a Hypothesis test

• A wrong decision may be made when rejecting

or not rejecting the Null Hypothesis

• The possible mistakes that can be made are a:

– Type I error
– Type II error
 Type I error
• Rejecting the Null Hypothesis when it is true

• Concluding that there is an effect (difference)

when in reality there is none

• The maximum chance of making a Type I error

is denoted by alpha α

• α is the significance level of the test, we reject

the null hypothesis if the p-value is less than
the significance level
 Type II error
• Not rejecting the Null Hypothesis when it is
false

• Concluding that there is no effect (difference)

when one really exists

• The chance of making a Type II error is

denoted by beta β

• Its compliment 1- β, is the Power of the test

Power and Sample Size
 Power of the test

• The Power is the probability of rejecting the

Null Hypothesis when it is false

– i.e. the probability of making a correct decision

• The ideal power of the test is 100%

• However there is always a possibility of making

a Type II error
 Sample size

• If the number of patients/samples in the study is small,

there may be inadequate power to detect an important
existing effect – wasted resources

• If the sample is too large, the study may be

unnecessarily time – consuming, expensive or
unethical

• Need to choose an optimal sample size that strikes a

balance between the implications of making a Type I or
Type II error
Calculating an optimal sample size for a test

• The following quantities need to be specified at

the design stage of the investigation in order to
calculate an optimal sample size:

– The Power
– Significance Level
– Variability
– Smallest effect of interest
 Recall: 5 stages

1. Define the Null & Alternative Hypotheses

2. Collect data
3. Calculate the value of the test statistic
4. Compare the value of the test statistic to
values from a known probability distribution
5. Interpret the P-value and results
Examples
 Scenario 1

• A randomised double blind trial to determine

the effect of inhaled corticosteroids on
wheezing episodes in children
• An inhaled beclomethasone dipropionate was
compared to a Placebo
• Response variable was average forced
expiratory volume (FEV) over a 6 month
period
• Sample sizes: Treatment group =50, Placebo
group = 48
 Stages 1 and 2
• Stage 1: Define Ho and H1:
Ho: the mean FEV in the population of children is
the same in the two groups
H1: the mean FEV in the population of children is
different in the two groups

• Stage 2: Collect data

 Graphical Analysis
Boxplots comparing treated group to control group
2.50

2.25
Forced Expiratory Volume (FEV)

2.00

1.75

1.50

1.25

1.00

Treated Group Control Group

 Selecting a test

• What is the data type? Numerical

• How many groups are there? 2
• Are the groups Paired or Independent?
Independent
• Is Normality and equal variances of the data
assumed? Yes

→Unpaired (Independent) t-test

 Analysis Output

Stages 3 and 4: Calculate the

Sample N Mean StDev SE Mean test statistic and compare to
1 50 1.640 0.286 0.040 values from a known probability
2 48 1.537 0.246 0.035 distribution

Difference = mu (1) - mu (2)

Estimate for difference: 0.1033
95% CI for difference: (-0.0038, 0.2104)
T-Test of difference = 0 (vs not =): T-Value = 1.91 P-Value = 0.059 DF = 96
Both use Pooled StDev = 0.2670
 Stage 5: Interpret the results

• The P-value is 0.059

• There is insufficient evidence (just!) to reject Ho
at the 5% level
• There is insufficient statistical evidence of a
difference between the 2 groups
• The Power of the Test should be checked
• A Type II error may be made when not
rejecting Ho
 Scenario 2

• A study was conducted to determine if a heart condition

influences the age at which children start to walk
• Response variable was age the children started to walk
• 30 children with a specific heart condition were analysed in
the study
• Children (in general) are known to start walking at an age
of 11.4 months
• Does the heart condition influence the age at which
children start to walk?
 Stages 1 and 2

• Stage 1: Define Ho and H1

Ho: the mean walking age of the children with
the heart condition = 11.4 months
H1: the mean walking age of the children with
the heart condition ≠ 11.4 months
• Stage 2: Collect data
 Graphical Analysis
Histogram showing walking age of children

4
Frequency

0
10 12 14 16 18
Months
 Selecting a test

• What is the data type? Numerical

• How many groups are there? 1
• Is Normality of the data assumed? Yes

→One-sample t-test
 Analysis Output

One-Sample T Stages 3 and 4: Calculate the test

statistic and compare to values from a
known prob distribution
Test of mu = 11.4 vs not = 11.4

N Mean StDev SE Mean 95% CI T P

30 13.158 2.583 0.472 (12.193, 14.123) 3.73 0.001
 Stage 5: Interpret the results

• The P-value is 0.001

• There is strong evidence to reject Ho
• There is statistical evidence that the heart
condition influences the age at which children
start to walk
• The Probability that a Type I error has been
made in drawing this conclusion is 0.1%
Correlation and Regression
 Correlation and Regression

• Correlation
– measures the strength of association
between two variables

• Regression
– models a relationship between two or
more variables
 Correlation
• The degree of association between two variables is
called their correlation

• Positive correlation - when the points appear in a

band running from lower left to upper right (when x
increases, y increases)

• Negative correlation - when the points appear in a

band from upper left to lower right (when x increases,
y decreases)

• No correlation - when the points are randomly

scattered about the graph
 Correlation and “Line of best fit”

Here are
some
examples
 Be Careful!

"Correlation does not imply causality"

• In other words, the scatter plot may show that

a relationship exists, but it does not and cannot
prove that one factor is causing the other

• The scatter plot can only provide a clue that

two factors may be “cause and effect”
 Correlation - example

• Driving test scores – written paper

• Outcome compared by plotting scores against

number of lessons (1-10)

– does score improve as the number of lessons

increases?
 Scatter plot for learner drivers
170

160

150

140
marks3

130

120

110

100

90
0 2 4 6 8 10
classes
 Linear Regression

• Investigates a straight line (linear) association

between variables

• Straight line fitted to the scatter diagram is

known as the regression equation

• Least squares – the sum of the squared

differences between the observed and
predicted values is minimised
 Medical example

• Does increasing hardness improve abrasion resistance

for composites?

• Does increasing etch time improve bond strength to

enamel?

• Both questions require a regression approach

– using just two or three materials of different hardness
is not acceptable

– using just two etch times would not provide answers

 Data

Composite Hardness Wear rate

1 120 56
2 168 46
3 290 21
4 42 98
5 78 80
6 90 65
7 130 32
 Regression equation 1

A regression equation is: wear = 94.6 - 0.288 hardness

Fitted Line Plot

wear = 94.65 - 0.2882 hardness
100 S 14.5829
R-Sq 75.4%
R-Sq(adj) 70.4%

80

60
wear

40

20

0
50 100 150 200 250 300
hardness
 Regression equation 2
• Etch time 5 to 60 s
• Bond strength 15 to 26 MPa
Regression equation: bond strength = 17.3 + 0.110 etch time
Fitted Line Plot
bond strength = 17.31 + 0.1103 etch time
27.5 S 2.51095
R-Sq 35.2%
R-Sq(adj) 32.2%
25.0
bond strength

22.5

20.0

17.5

15.0

0 10 20 30 40 50 60
etch time
 Summary

• Part 2 Summary
• Sampling
• Statistical Hypothesis Tests
• Errors in Hypothesis Tests
• Power and Sample Size
• Examples
• Correlation and Regression