1 Basic Biostatistic Applica tion in Research of Anesth esia Chan Wei-Hung MD Department of Anesthesiol ogy National Taiwan Un iversity
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Basic Biostatistic Application in Research of Anesthesia
Chan Wei-Hung MD
Department of Anesthesiology National Taiwan University
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How to Conduct a Study?
Experimental study: best for cause-effect relationship determination
Observational study: only associations are made; not cause-effect relationship Retrospective Prospective
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Experimental Study (Clinical Trial)
Patients are assigned into different groups, receiving different intervention in each group.
Random, blind, well-controlled (control over other confounding factors) design is key to success.
Power of measurement and cause-and-effect determination are also vital to success.
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Observational Study
Descriptive study (case report/series): no comparison is made
Case-control study: patients with an outcome (case) are analyzed along with patients without the outcome (control). ESPECIALLY PRONE TO SAMPLE SELECTION BIAS!
Cohort study: patients with an exposure are analyzed along with patients without the exposure.
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Case Control Study
Parturient
C-section NSD
WithEpidural
WithEpidural
WithoutEpidural
WithoutEpidural
outcome
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Clinical Trial
Parturient
Epidural
Random Grouping
Analgesics Normal Saline
C/S C/S NSDNSD
Random, blind, well-controlled
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Attention for Observational Study
Since the cause-effect relationship can not be established in this kind of study, if you want to do such a study, please notice that:
The sample size should be big. Documentation should be complete.
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Random Assignment
Simple random sampling with a random numbers chart
Number of patients can be balanced within a block of frame of patients (restricted randomization).
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Restricted Randomization
Group A: 20 patients
Group B: 20 patients
Frame size: 10 patients
No. of A and B are balanced within every 10 patients.
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p, α and β Error
p value: the probability that one will wrongly conclude that there is a difference between groups.
Type I error: also called α error, false-positive error. p value
Type II error: also called β error, false-negative error
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Type II Error (β Error)
False-negative error ( p>0.05 in the presence of difference)
When p>0.05, it is difficult to determine between lack of true difference or inability to detect the difference.
Most common problems: insufficient sample size, bias in selection, confounding factors
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Statistical Power
The ability to detect an effect when it is present.
Equal to 1 – false negative error (1-β)
A statistical power around 80% (β<0.2) for a reasonable effect
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How to Increase the Power?
1. Increase the size number
2. Reduce variation between measurements
3. The effect of intervention should be stronger
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Determination of Sample Size
In a t-test
N = 2 [(Zα- Zβ) * SD
Mean 1 – Mean 2]
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SD: 正常值 ( 對照組 ) 的標準差Mean 1 – Mean 2: 預估偵測到的差別值Zα: 預估的 α 所得的 Z 值 (p=0.05 時 , Zα=1.96)Zβ: 預估的 β 所得的 Z 值 (β=0.90-1.280;
β=0.80-0.825; β=0.70-0.525)
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Example in Size Number Determination
Onset of two muscle relaxants will be compared. You wish to detect a difference of 10 sec. The standard variation of the onset time is about 5 sec (according to the literature). You desire a p=0.05 and a statistical power of 80%. The sample size of each group would be how many ?
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Example in Size Number Determination
2 x [(1.96+0.825)x5/10]2 =3.87; about 4 in each group
If you want to detect a difference of 5 sec:
2 x [(1.96+0.825)x5/5]2 =15.5; about 16 in each group
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Noncentrality Parameter (φ)
You can also determine the sample size by computing φ and look up the table.
Φ=δ/σ
(the difference of effects / standard deviation of population)
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Critical Reviews of the Results
When you want to say there is an effect of intervention give us the p value (chance of false-positive error)
When you want to say there is no effect of intervention give us the power (chance of not to make a false-negative error)
Epidural Analgesia Enhances Functional Exercise Capacity and Health-related Quality of Life After Colonic Surgery
Anesthesiology 2002, 97: 540-549
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Determining the Test (I)
What kind of variables are they?
1. Numerical variable
2. Ordinal variable
3. Categorical variable (Nominal)
How many groups are there? T-test ANOVA
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Determining the Test (II)
Are they “normal distribution”?
Parametric vs. nonparametric methods.
T-test Mann-Whitney U test
ANOVA Kruskal-Wallis test
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Determining the Test (III)
Measurements are taken from the same patient for more than one time (before and after treatment); you should use Paired t-test Repeat-measures ANOVA
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Determining the Test (IV)
Common data are analyzed when they are completed (all the measurements are finished); but there are some studies that data input are still ongoing (5-year analysis for two treatment for lung cancer); basically for this kind of “unfinished studies”.
There is a tendency to use this method in anesthesia research (esp. PCA studies).
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An Example for Survival Analysis
Patients received meperidine or hydromorphone in the POR.
The time to start IVPCA is compared.
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Trick for Study Design
Thorough examination of past similar studies (sample size, statistical methods, items of measurements --- you can apply them to save you from brain drainage and avoid fatal errors!)
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Central Belief
Biostatistics is not a hindrance but an aid for data analysis.
As long as you have an idea for study, biostatistics should not be the excuse that you cannot finish the study.
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Paired t-test
When the two groups of data are obtained from the same subject (repeated measurements from a subject under different conditions), paired t-test should be used.
The differences between groups are of interest.
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Wilcoxon Signed Rank Test
In a repeated measurement, the differences are usually not “normally distributed”.
A Wilcoxon signed rank test should be used in the case.
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Screening Test Evaluation
The effectiveness of diagnostic or prognostic tests is assessed.
Sensitivity and specificity are explored in such studies.
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Sensitivity and Specificity
Disease Positive Disease Negative
Test Positive A B
Test Negative C D
Sensitivity =
Specificity =
A/(A+C)
False-negative = 1- sensitivity
False-positive = 1 - specificity
D/(B+D)
Sensitivity Specificity False-negative
False-positive
Palm print grade>0 1.00 0.57 0 26
Mallampati >1 0.41 0.80 13 12
Mallampati >2 0.50 0.98 21 1
TMD <6 cm 0.14 0.9 19 6
Head extension<35° 0.50 0.70 11 18
BMI > 27 0.23 0.97 17 2
DM > 10 yrs 0.91 0.67 2 20
DM type 0.45 0.51 12 30
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