Drug Development Statistics & Data Management Data Handling II: Describing and Depicting your Data Dr Yanzhong Wang Lecturer in Medical Statistics Division of Health and Social Care Research King's College London Email: yanzhong.wang@kcl.ac.uk Types of data • Quantitative data – continuous, discrete – distributions may symmetric or skewed • Qualitative (categorical) data – binary – nominal, ordinal 2 Skewed Distributions Pos itively ske we d da ta Negatively Skewed data 25 30 20 Fre q u e n cy Frequency 25 20 15 15 10 10 5 5 0 0 Long tail to left Long tail to right 3 Symmetric Distribution .4 .3 .2 .1 0 0 2 4 6 4 Summary statistics • ‘Where the data are’ - location – mean, median, mode, geometric mean • Used to describe baseline data and main outcomes • ‘How variable the data are’ - spread – standard deviation, variance, range, interquartile range, 95% range • Needed (primarily) to describe baseline data in RCT and cohort study 5 Definition of the Mean The mean of a sample of values is the arithmetic average and is determined by dividing the sum of the values by the number of the values. 6 Definition of the Median The median is the middle value. not affected by skewness and outliers, but less precise than mean theoretically. 7 Ordered Blood Glucose Values 2.2 3.6 3.8 4.2 4.7 2.9 3.6 3.9 4.3 4.7 3.3 3.6 4.0 4.4 4.8 3.3 3.6 4.0 4.4 4.9 3.3 3.7 4.0 4.4 4.9 3.4 3.7 4.1 4.5 5.0 3.4 3.8 4.1 4.6 5.1 3.4 3.8 4.1 4.7 6.0 8 Definition of the Mode The mode is the most frequent value. 9 Ordered Blood Glucose Values 2.2 3.4 3.8 4.1 4.4 4.7 5.0 3.4 3.8 4.1 4.4 4.7 3.4 3.8 4.1 4.4 4.7 2.9 3.6 3.6 3.6 3.6 3.9 4.2 4.5 4.8 5.1 3.3 3.7 4.0 4.3 4.6 4.9 6.0 3.3 3.3 3.7 4.0 4.0 4.9 10 Location = Central Tendency Mode - not necessarily central (categorical data) Median - only uses relative magnitudes 7 6 Arithmetic Mean - outlier prone 5 Count 4 3 2 1 0 2 3 4 5 6 Blood glucose (mmol/litre) 11 Relation of mean, median and mode • If distribution is unimodal (has only one mode) then: • Mean=median=mode for symmetric distribution. • Mean>median>mode for positively skewed distribution. • Mean<median<mode for negatively skewed distribution. 12 Serum Triglyceride Levels from Cord Blood of 282 Babies 80 70 60 Count 50 40 30 20 10 0 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 1.1 1.2 1.3 1.4 1.5 1.6 1.7 Serum Triglyceride Levels 13 Log(Serum Triglyceride Levels) from Cord Blood of 282 Babies 35 30 count 25 20 15 10 5 0 -1.9 -1.7 -1.5 -1.3 -1.1 -0.9 -0.7 -0.5 -0.3 log(Serum Triglyceride) Levels -0.1 0.1 0.3 0.5 14 Definition of the Geometric Mean The geometric mean of a sample of n values is determined by multiplying all the values together and taking the nth root (for only two values this is the more familiar square root). 15 Geometric Mean • A common example of when the geometric mean is the correct choice average is when averaging growth rates. • Another Method: Take log of each value, find arithmetic mean and anti-log the result. Exp( (log(0.15) + … + log(1.66) )/40) = 0.467 Serum Triglyceride Levels from Cord Blood of 282 Babies Median=0.460 80 70 Geometric Mean=0.467 Mean=0.506 60 Count 50 40 30 20 10 0 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 1.1 1.2 1.3 1.4 1.5 1.6 1.7 Serum Triglyceride Levels 17 Why measures of variability are important Production of Aspirin • New production process of 100 mg tabs • Random sample from process – 96 97 100 101 101 mgs - mean 99 mg • Random sample from old process – 88 93 100 104 110 mgs - mean 99 mg • Same means but new is better because less variable 18 Definition of Range The range of a sample of values is the largest value minus the smallest value. • New process the range is 101-96=5 • Old process the range is 110-88=22 • Range is simple ….. BUT – Only uses min and max – Gets larger as sample size increases 19 Definition of Inter-quartile Range The inter-quartile range of a sample of values is the difference between the upper and lower quartiles. The lower quartile is the value which is greater than ¼ of the sample and less than ¾ of the sample. Conversely, the upper quartile is the value which is greater than ¾ of the sample and less than ¼ of the sample. 20 Ordered Blood Glucose Values 1/4 of 40 = 10 3/4 of 40 = 30 2.2 3.6 3.8 4.2 4.7 2.9 3.6 3.9 4.3 4.7 3.3 3.6 4.0 4.4 4.8 3.3 3.6 4.0 4.4 4.9 3.3 3.7 4.0 4.4 4.9 3.4 3.7 4.1 4.5 5.0 3.4 3.8 4.1 4.6 5.1 3.4 3.8 4.1 4.7 6.0 21 Inter-Quartile Range Inter-quartile range 7 6 Upper quartile Lower quartile 5 Count 4 3 2 1 0 2 3 4 5 6 Blood glucose (mmol/litre) 22 Standard deviation • Neither measure uses the numerical values - only relative magnitudes • A measure accounting for the values is the standard deviation • Consider the aspirin data from the new process 96 97 100 101 101 (mean 99 mg) • Determine deviations from mean -3 -2 1 2 2 • Square , add, average and square-root 9 4 1 4 4 5 4.4 2.098 23 Measures of scatter/dispersion – ‘how variable the data are’ • Range – smallest to biggest value – increases with sample size • Standard deviation – measure of variation around the mean – affected by skewness and outliers • Variance = square of standard deviation • Interquartile range (IQR) – from 25th centile to 75th centile 24 Plotting Data • Histograms • Stem and Leaf Plots 6 1 2 3 4 4 2 6 4 6 3 3 1 1 Blood glucose (mmol/litre) Stem Leaf 60 0 58 56 54 52 50 00 48 000 46 0000 44 0000 42 00 40 000000 38 0000 36 000000 34 000 32 000 30 28 0 26 24 22 0 ----+----+----+----+ Multiply Stem.Leaf by 10**-1 Box Plots 5 4 3 2 25 Mean and standard deviation • Best description if distribution reasonably symmetric (and single mode) • Give full description if data have Normal distribution 26 .4 Mean 3, s.d. 1 Mean 5, s.d. 1 .3 .2 Mean 5, s.d. 2 .1 0 0 1 2 3 4 5 x 6 7 8 9 10 27 Properties of Normal distribution • Symmetric distribution – mean, median and mode equal • Completely specified by mean and standard deviation • 95% of distribution contained within mean 1.96 standard deviations • 68% within mean 1 standard deviation 28 Continuous data, not Normally distributed • If symmetric use mean and standard deviation • If skewed use median and IQR Unless • Positively skewed, but log transformation creates symmetric distribution – use geometric mean 29 Nominal categorical data • Mode. • % in each category, especially when binary. Wheeze in last 12 months Frequency (n) % No 1945 75.2 Yes 642 24.8 2587 100.0 Total 30 Ordinal categorical data • Median and IQR if enough separate values. • Otherwise as for nominal. 31 Discrete quantitative data • As for continuous data if many values, as for ordinal data if fewer. Difference Between Standard Deviation & Standard Error 33 Measure of Variability of the Sample Mean • Range, inter-quartile range and standard deviation relate to population (sample) not mean. • To understand the difference carry out a sampling experiment using the Ritchie Index values 34 Values of the Ritchie Index (Measure of Joint Stiffness) in 50 Untreated Patients 14 9 8 9 1 20 3 3 2 4 2 3 6 1 2 11 16 24 16 21 19 22 33 12 12 12 19 10 33 2 19 40 1 20 1 2 4 7 9 4 9 6 14 8 27 10 27 7 24 21 Mean = (14+…+21)/50 = 12.18 35 Location = Central Tendency 16 Mode - not necessarily central (categgorical data) 14 Median - only uses relative magnitudes 12 Arithmetic Mean - outlier prone 10 8 6 4 2 0 36 0-5 6 - 10 11 - 15 16 - 20 21 - 25 26 - 30 31 - 35 36 - 40 Values of the Ritchie Index Sampling Experiment • Take a random sample (10) from the 50 values • Determine the mean of the 10 values • Repeat 50 times • These means show variation - HOW LARGE IS IT ? 37 Variations in Samples 16 Mean=12.18 14 12 10 8 6 4 2 0 0-5 6 - 10 11 - 15 16 - 20 21 - 25 26 - 30 31 - 35 36 - 40 Values of the Ritchie Index Mean=10.00 16 14 14 12 12 10 10 8 8 6 6 4 4 2 2 0 0-5 6 - 10 11 - 15 16 - 20 21 - 25 26 - 30 31 - 35 36 - 40 Values of the Ritchie Index 16 14 12 0 0-5 6 - 10 11 - 15 16 - 20 21 - 25 26 - 30 31 - 35 36 - 40 Values of the Ritchie Index 16 Mean=12.60 14 10 8 8 6 6 4 4 2 2 0 -38 5 6 - 10 11 - 15 16 - 20 21 - 25 26 - 30 31 - 35 36 - 40 Values of the Ritchie Index Mean=11.50 12 10 0 Mean=13.40 16 0 0-5 6 - 10 11 - 15 16 - 20 21 - 25 26 - 30 31 - 35 36 - 40 Values of the Ritchie Index Ritchie Values Original values (mean - 12.18 ; sd - 9.69) 30 25 20 15 10 5 0 39 0-5 6 - 10 11 - 15 16 - 20 21 - 25 26 - 30 31 - 35 36 - 40 Values of the Ritchie Index Ritchie Values Sampling Experiment – Sample Means 30 25 Original values (mean - 12.18 ; sd - 9.69) Sample means (mean - 12.21 ; sd - 2.97) 20 15 10 5 0 40 0-5 6 - 10 11 - 15 16 - 20 21 - 25 26 - 30 31 - 35 36 - 40 Values of the Ritchie Index Definition of the Standard Error The standard deviation of the sampling distribution of the mean is called the standard error of the mean. 41 Increasing Sample Size 40 n=10 40 35 35 30 30 Sample means (mean - 12.21 ; sd - 2.97) 25 Sample means (mean - 12.37 ; sd - 2.43) 25 20 20 15 15 10 10 5 5 0 n=15 0 0-5 6 - 10 11 - 15 16 - 20 21 - 25 26 - 30 31 - 35 36 - 40 Values of the Ritchie Index 0-5 6 - 10 11 - 15 16 - 20 21 - 25 26 - 30 31 - 35 36 - 40 Values of the Ritchie Index • Increased precision (smaller standard error) • Less skewness 42 Standard error of the mean as a function of the sample size 10 Standard Error of the Mean 9 sd 8 7 se / 6 5 n 4 3 2 1 0 0 10 20 Sample Size 43 30 40 1000 1500 2000 2500 3000 0 500 Frequency Population of Gene Lengths n=20,290 0 44 5000 10000 Gene Length (# of nucleotides) 15000 150 100 0 50 Frequency 200 250 300 Samples of size : n=100 0 45 5000 10000 Gene Length (# of nucleotides) 15000 Practical Confusion • A mean is often reported in medical papers as 12.18 1.37 what is 1.37 ? sd or se ? 46 Thanks! 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