PRACTICAL

STATISTICS
FOR
MEDICAL
RESEARCH
Douglas G. Altman
Head ofMedical Statistical Laboratory
Imperial Cancer Research Fund
London

CHAPMAN & HALL/CRC

Boca Raton London New York Washington, D.C.

Contents
Preface

1
1.1
1.2
1.3
1.4
1.5
2
2.1
2.2
2.3
2.4
2.5
2.6
2.7
2.8

xi
Statistics in medical research

Statistics at large
Statistics in medicine
Statistics in medical research
What does statistics cover?
The scope of this book
Types of data

Introduction
Categorical data
Numerical data
Other types of data
Censored data
Variability
Importance of the type of data
Dealing with numbers

3
3.1
3.2
3.3
3.4
3.5
3.6
3.7

Describing data

4
4.1
4.2
4.3
4.4
4.5

Theoretical distributions

Introduction
Averages
Describing variability
Quantifying variability
Two variables
The effect of transforming the data
Data presentation
Exercises
Introduction
Probability
Samples and populations
Probability distributions
The Normal distribution

1
1
3
4
5
8
10
10
10
11
13
16
17
17
17
19
19
21
22
31
38
41
42
45
48
48
49
50
50
51

Contents vii
4.6
4.7
4.8
4.9
4.10
4.11

The Lognormal distributions

The Binomial distribution
The Poisson distribution
Mathematical calculations
The Uniform distribution
Concluding remarks
Exercises

5
5.1
5.2
5.3
5.4
5.5
5.6
5.7
5.8
5.9
5.10
5.11
5.12
5.13
5.14

Designing research

Introduction
Categories of research design
Sources of variation
An experiment: is the blood pressure the same in both arms?
The design of experiments
The structure of an experiment
Random allocation
Minimization
Observational studies
The case-control study
The cohort study
The cross-sectional study
Studies of change over time
Choosing a study design
Exercises

6
6.1
6.2
6.3
6.4
6.5
6.6
6.7
6.8
6.9
6.10
6.11

Using a computer

7
7.1
7.2
7.3
7-4
7.5

Preparing to analyse data

Introduction
Advantages of using a computer
Disadvantages of using a computer
Types of statistical program
Evaluating a statistical package
Strategy for computer-aided analysis
Forms for data collection
Plotting
Other uses of computers
Misuses of the computer
Concluding remarks
Introduction
Data checking
Outliers
Missing data
Data screening

60
63
66
68
71
71
71
74
74
75
78
79
80
83
85
91
91
93
96
99
101
102
103
107
107
107
108
110
111
112
114
119
120
120
121
122
122
122
126
130
132

vni Contents
7.6
7.7
7.8

Why transform data?

Other features of the data
Concluding remarks
Exercises

143
146
149
149

8
8.1
8.2
8.3
8.4
8.5
8.6
8.7
8.8
8.9
8.10
8.11

Principles of statistical analysis

152
152
153
155
160
165
171
173
174
175
176
177
177

9
9.1
9.2
9.3
9.4
9.5
9.6
9.7
9.8
9.9
9.10
9.11
10
10.1
10.2
10.3
10.4
10.5
10.6
10.7
10.8
10.9

Introduction
Sampling distributions
A demonstration of the distribution of sample means
Estimation
Hypothesis testing
Non-parametric methods
Statistical modelling
Estimation or hypothesis testing?
Strategy for analysing data
Presentation of results
Summary
Exercises
Comparing groups - continuous data

Introduction
Choosing an appropriate method of analysis
The t distribution
One group of observations
Two groups of paired observations
Two independent groups of observations
Analysis of skewed data
Three or more independent groups of observations
One way analysis of variance - mathematics and
worked example
Presentation of results
Summary
Exercises
Comparing groups - categorical data

Introduction
One proportion
Proportions in two independent groups
Two paired proportions
Comparing several proportions
The analysis of frequency tables
2 x 2 frequency tables - comparison of two proportions
2 x k tables - comparison of several proportions
Large tables with ordered categories

179
179
179
181
183
189
191
199
205
218
220
222
223
229
229
230
232
235
241
241
250
259
265

Contents ix
10.10
10.11
10.12
10.13

k x k tables - analysis of matched variables

Comparing risks
Presentation of results
Summary
Exercises

266
266
271
271
272

11
11.1
11.2
11.3
11.4
11.5
11.6
11.7
11.8
11.9
11.10
11.11
11.12
11.13
11.14
11.15
11.16
11.17

Relation between two continuous variables

277
277
278
282
285
288
291
293
297
300
300
306
309
311
316
318
319
320
321

Association, prediction and agreement

Correlation
Use and misuse of correlation
Rank correlation
Adjusting a correlation for another variable
Use of the correlation coefficient in assessing non-Normality
Correlation - mathematics and worked examples
Interpretation of correlation
Presentation of correlation
Regression
Use of regression
Extensions
Regression - mathematics and worked example
Interpretation of regression
Relation to other analyses
Presentation of regression
Regression or correlation?
Exercises

12
12.1
12.2
12.3
12.4
12.5
12.6
12.7

Relation between several variables

13
13.1
13.2
13.3
13.4
13.5
13.6
13.7

Analysis of survival times

Introduction
Analysis of variance and multiple regression
Two way analysis of variance
Multiple regression
Logistic regression
Discriminant analysis
Other methods
Exercises
Introduction
Survival probabilities
Comparing survival curves in two groups
Mathematical calculations and worked examples
Incorrect analyses
Modelling survival - the Cox regression model
Desien of survival studies

325
325
325
326
336
351
358
360
361
365
365
367
371
377
385
387
393

x Contents
13.8

Presentation of results
Exercises

393
394

14
14.1
14.2
14.3
14.4
14.5
14.6
14.7

Some common problems in medical research

Introduction
Method comparison studies
Inter-rater agreement
Diagnostic tests
Reference intervals
Serial measurements
Cyclic variation
Exercises

396
396
396
403
409
419
426
433
435

15
15.1
15.2
15.3
15.4
15.5
15.6

Clinical trials
Introduction
Design of clinical trials
Sample size
Analysis
Interpretation of results
Writing up and assessing clinical trials
Exercises

440
440
441
455
461
471
473
474

16
16.1
16.2
16.3
16.4
16.5

The medical literature

Introduction
The growth of statistics in medical research
Statistics in published papers
Reading a scientific paper
Writing a scientific paper
Exercises

477
477
478
481
493
498
499

Appendix A Mathematical notation

505

Al.l
A1.2
A1.3
A1.4
A1.5

505
505
509
510
510

Introduction
Basic ideas
Mathematical symbols
Functions
Glossary of notation

Appendix B Statistical tables

514

Answers to exercises
References
Index

546
575
589