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Medical Statistics
  Masterclass


Fastbleep Academic Masterclass #4
          University Place
           31 May 2011
About us



         James Giles             Richard Salisbury
      MB PhD Student            F1 & MRes Graduate
  PAL & Fastbleep Director        Cochrane Author
Love stats, hated contextless      Bioscience geek
Medical Statistics Pt 1
1. Use of statistics
2. Statistical errors
3. Common statistical tests
1. Use of statistics

What is your question?
What do you want to do?
Descriptive statistics
• Averages - mean/median/mode
• Frequency
• Range (measures of spread)

• Box-and-whisker plot
• Bar chart
• Pie chart
Scales of measurement

Nominal


Ordinal


Numerical
Scales of measurement

Nominal     Name: red, blue, green


Ordinal


Numerical
Scales of measurement

Nominal     Name: red, blue, green


Ordinal     Order: tumour stage


Numerical
Scales of measurement

Nominal      Name: red, blue, green


Ordinal       Order: tumour stage


Numerical       Continuous: height
            Discrete: number of teeth
Nominal Variable
Description: Frequency/proportion
 Illustration: Bar chart/pie chart
Averages


Mean
Median - middle number
Mode - most frequent
Distributions
Distributions
Distributions
Distributions
Distributions
Averages


Mean - numerical & unskewed
Median - ordinal & skewed
Mode - nominal & bimodal
Measures of spread


Standard deviation (sd)
Standard error of the mean (SEM)
Measures of spread
Standard deviation (sd)
mean distance from the mean
Measures of spread


Standard deviation (sd)
Standard error of the mean (SEM)
Measures of spread
Standard error (SEM)
estimate of spread of your sample mean
from a true population mean
SEM = sd/   n                                        20




                         Neutrophil Count / 105/ml
                                                     15


                                                     10


                                                     5


                                                     0
                                                          A ac   C ad   B bc   D bd
feltron.com
Medical Statistics Pt 1
Analytical statistics
 Compare - difference, higher/lower

  Relate - correlation, regression,
             agreement
Comparisons
1) One variable against a constant

2) One variable across 2 dependant groups

3) One variable across 2 independent groups

4) One variable across pairs
Comparsion
      one variable against a constant

Is Hb level in heavy smokers higher than the
   average of 14?

Variable: Hb level
Constant: 14
Groups
              2 types of groups

• Dependent: one group a subset of the other




• Independent: different sets
Comparison
            Example: one variable across 2
            dependent(overlapping) groups
  Is serum PTH higher in severe renal failure than the average value in
  renal failure patients?
Variable: serum PTH
Groups: severe renal failure patients, all renal failure patients

      Is mortality rate in neck of femur fracture higher in case of
         cardiorespiratory co morbidity than average?
Variable: mortality rate
Groups: patients with neck of femur fracture and co morbidity,
  all patients with neck of femur fracture
Comparison
       Examples: One variable across 2
     independent(non-overlaping) groups
Is Trop T higher in patients with STE-ACS than NSTE-ACS?
Variable: Trop T
Groups: STE-ACS and NSTE-ACS

Is success rate to control variceal haemorrhage higher in
    SCLEROTHERAPY than BALLOON TAMPONADE?
Variable: success rate
Groups: sclerotherapy and balloon tamponade
Comparison
  Examples (pairs):

Pairs = repeated measurements:

t wo measurements of a variable on one patient at
   different time points
Comparison
   Is the PEF higher after Salbutamol nebuliser in asthma
   patients?
Variable: PEF
Pairs: prior and after nebuliser


Is the second-day serum lactate level higher than the
    third-day lactate level following antibiotic therapy in
    sepsis?
Variable: lactate level
Pairs: second and third day
Relation
    Association

Prediction/regression

     Agreement
Association
Association = correlation of t wo variables

         if one variable changes

        the other changes as well
   (in the same or opposite direction)

     No association = independence

            NOT CAUSATION
Association
Association = correlation of t wo variables

         if one variable changes

        the other changes as well
   (in the same or opposite direction)

     No association = independence

            NOT CAUSATION
Association
                    Two variables
Examples
1. Is serum GENTAMICIN level dependent on serum
    CREATININE?
Variables: serum Gentamicin, serum Creatinine

2. Is THROMBOLYTIC THERAPY related to the number of in-
   hospital DEATHS in stroke?
Variables: thrombolytic therapy, number of deaths
Prediction/regression
                A Formula

   Knowing the value of one variable(s)



Calculating the value of the other variable
Prediction/regression
   Usage: To describe the relationship

               Y = aX + b

               Y= aX2 + b

            Z = aX + bY + c

           Z = a X2 + bY3 + c

    Framingham CHD Risk Calculator
Prediction/regression
    the predicted and predictor (s)

                   Examples:
The TIMI risk score to predict odds of death in STEMI
 The APACHE III system to predict mortality in ICU
The IMPACT models to predict 6-month disability in
            severe traumatic brain injury
Medical Statistics Pt 1
2. Statistical error

What do my findings mean?

How likely are my findings to
          be true?
Types of error

Two types:
  Type I ( ) error
  Type II ( ) error
Hypothesis synthesis
Research question/objective

And the answer to three questions:
  What are the variables?

  What are the groups/pairs?

  What is the statistical analysis?
Example 1
• Objective: to assess the effect of oral glucocorticoid on
  serum IL-8 in COPD patients
• Variable: serum IL-8
• Groups/Pairs: prior and following glucocorticoid oral
  therapy
• Statistical analysis: comparison
• Alternative hypothesis: there is a difference bet ween
  serum IL-8 prior and after glucocorticoid therapy
• Null hypothesis: there is no difference bet ween serum
  IL-8 prior and after glucocorticoid therapy
Example 2
• Objective: to assess whether or not high levels of serum
  Neuron Specific Endolase (NSE) is associated with CT
  abnormality in head injury
• Variable: serum NSE
• Groups: patients with CT abnormality, patients with no CT
  abnormality
• Statistical analysis: comparison
• Alternative hypothesis: there is a difference bet ween
  serum NSE levels in head-injury patients with and without
  CT abnormality
• Null hypothesis: there is no difference bet ween serum NSE
  levels in head-injury patients with and without CT
  abnormality
Example 3
• Objective: to describe the relationship of
  ISS and ED length of stay
• Variables: ISS and ED length of stay
• Groups/pairs: NIL
• Statistical analysis: regression
• Alternate hypothesis: the coefficient is
  not zero.
Sample vs. Population

Population = everyone

Sample = in your study
Probability of error
          is the following question:

How certain are we that what is observed in the
      sample can be inferred on the actual
                  population?
Belonje et al.
              (Circulation. 2010;121:245-251.)




Increased Erythropoietin level is associated
  with increased mortality in 605 heart
  failure patients ( p < 0.05).

Question: how true is this in the population
 of all heart failure patients?
Bloom et al.
           (Aliment Pharmacol Ther. 2004 Apr 15;19(8):871-8.)




No difference in colitis activity of 48
  ulcerative colitis patients who receive
  Tinzaparin with 52 patients who receive
  placebo (p = 0.84)

Question: How true is this in the population
 of all ulcerative colitis patients?
Type I error or
Definition:
When the null hypothesis is rejected in the
  sample but is true in the population
Rejecting null hypothesis, when it is true
False positive result

         Sample              Population
       difference          no difference
       association         no association
Type II error or
Definition:
When the null hypothesis is true in the
  sample but is false in the population
Accepting null hypothesis, when it is false
False negative result

          Sample            Population
      no difference         difference
      no association        association
Population

 Sample
                   +                -
 outcome

     +                            c
                   a
reject null                  type 1 error

    -              b
                                    d
accept null   type 2 error
Belonje et al.
                 (Circulation. 2010;121:245-251.)

Increased Erythropoietin level is associated with
  increased mortality in 605 heart failure
  patients ( p < 0.05).

Null hypothesis: no association bet ween
 Erythropoietin and mortality

Result: reject null hypothesis - positive finding
Reality


Test outcome   +              -


     +                       = 0.04


     -
Belonje et al.
          (Circulation. 2010;121:245-251.)


                     p < 0.05

       Probability of type I error < 0.05

 Probability of no association in the population
                      <0.05

Probability of no association bet ween increased
 erythropoietin and mortality in all heart failure
                  patients < 0.05
Medical Statistics Pt 1
Medical Statistics Pt 1
Medical Statistics Pt 1
Medical Statistics Pt 1
Bloom et al.
              (Aliment Pharmacol Ther. 2004 Apr 15;19(8):871-8.)




No difference in colitis activity of 48 ulcerative
  colitis patients who receive tinzaparin with
  52 patients who receive placebo (p = 0.84)

• Null hypothesis: no effect for tinzaparin

                                                                   Probability
of

• Result: true null hypothesis                                     Type
II
error
?
Reality


Test outcome   +               -


     +                        = 0.84


     -         =?
Bloom et al.
         (Aliment Pharmacol Ther. 2004 Apr 15;19(8):871-8.)




Power calculation: 42 subjects in each group
(treatment and placebo)

Sample size: 48 patients in treatment group
              52 patients in placebo group

              Large enough sample
Bloom et al.
          (Aliment Pharmacol Ther. 2004 Apr 15;19(8):871-8.)




      Low probability of type II error

 High probability of true null hypothesis in
                the population

High probability of no effect for tinzaparin
       in all ulcerative colitis patients
Medical Statistics Pt 1
Reality
Faecal Occult
 Blood Test         +              -

     +             20             180         200

     -             10          1820           1830

                   30          2000           2030

      Sensitivity = 1 - beta = 1 - (10/30) = 0.66

         Probability you’ll detect a real cancer
Reality
Faecal Occult
 Blood Test        +              -

     +            20             180        200

     -            10          1820          1830

                  30          2000          2030

    Specificity = 1 - alpha = 1 - (180/2000) = 0.91

     Probability you’ll reassure a healthy person
Reality
Faecal Occult
 Blood Test        +              -

     +            20             180        200

     -            10          1820          1830

                  30          2000          2030

      Positive predictive value = 20/200 = 0.1

     Probability a positive result means cancer
Reality
Faecal Occult
 Blood Test        +              -

     +            20             180         200

     -            10          1820          1830

                  30          2000          2030


   Negative predictive value = 1820/1830 = 0.995

     Probability a negative result means all clear
Medical Statistics Pt 1

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Medical Statistics Pt 1

  • 1. Medical Statistics Masterclass Fastbleep Academic Masterclass #4 University Place 31 May 2011
  • 2. About us James Giles Richard Salisbury MB PhD Student F1 & MRes Graduate PAL & Fastbleep Director Cochrane Author Love stats, hated contextless Bioscience geek
  • 4. 1. Use of statistics 2. Statistical errors 3. Common statistical tests
  • 5. 1. Use of statistics What is your question? What do you want to do?
  • 6. Descriptive statistics • Averages - mean/median/mode • Frequency • Range (measures of spread) • Box-and-whisker plot • Bar chart • Pie chart
  • 8. Scales of measurement Nominal Name: red, blue, green Ordinal Numerical
  • 9. Scales of measurement Nominal Name: red, blue, green Ordinal Order: tumour stage Numerical
  • 10. Scales of measurement Nominal Name: red, blue, green Ordinal Order: tumour stage Numerical Continuous: height Discrete: number of teeth
  • 11. Nominal Variable Description: Frequency/proportion Illustration: Bar chart/pie chart
  • 12. Averages Mean Median - middle number Mode - most frequent
  • 18. Averages Mean - numerical & unskewed Median - ordinal & skewed Mode - nominal & bimodal
  • 19. Measures of spread Standard deviation (sd) Standard error of the mean (SEM)
  • 20. Measures of spread Standard deviation (sd) mean distance from the mean
  • 21. Measures of spread Standard deviation (sd) Standard error of the mean (SEM)
  • 22. Measures of spread Standard error (SEM) estimate of spread of your sample mean from a true population mean SEM = sd/ n 20 Neutrophil Count / 105/ml 15 10 5 0 A ac C ad B bc D bd
  • 25. Analytical statistics Compare - difference, higher/lower Relate - correlation, regression, agreement
  • 26. Comparisons 1) One variable against a constant 2) One variable across 2 dependant groups 3) One variable across 2 independent groups 4) One variable across pairs
  • 27. Comparsion one variable against a constant Is Hb level in heavy smokers higher than the average of 14? Variable: Hb level Constant: 14
  • 28. Groups 2 types of groups • Dependent: one group a subset of the other • Independent: different sets
  • 29. Comparison Example: one variable across 2 dependent(overlapping) groups Is serum PTH higher in severe renal failure than the average value in renal failure patients? Variable: serum PTH Groups: severe renal failure patients, all renal failure patients Is mortality rate in neck of femur fracture higher in case of cardiorespiratory co morbidity than average? Variable: mortality rate Groups: patients with neck of femur fracture and co morbidity, all patients with neck of femur fracture
  • 30. Comparison Examples: One variable across 2 independent(non-overlaping) groups Is Trop T higher in patients with STE-ACS than NSTE-ACS? Variable: Trop T Groups: STE-ACS and NSTE-ACS Is success rate to control variceal haemorrhage higher in SCLEROTHERAPY than BALLOON TAMPONADE? Variable: success rate Groups: sclerotherapy and balloon tamponade
  • 31. Comparison Examples (pairs): Pairs = repeated measurements: t wo measurements of a variable on one patient at different time points
  • 32. Comparison Is the PEF higher after Salbutamol nebuliser in asthma patients? Variable: PEF Pairs: prior and after nebuliser Is the second-day serum lactate level higher than the third-day lactate level following antibiotic therapy in sepsis? Variable: lactate level Pairs: second and third day
  • 33. Relation Association Prediction/regression Agreement
  • 34. Association Association = correlation of t wo variables if one variable changes the other changes as well (in the same or opposite direction) No association = independence NOT CAUSATION
  • 35. Association Association = correlation of t wo variables if one variable changes the other changes as well (in the same or opposite direction) No association = independence NOT CAUSATION
  • 36. Association Two variables Examples 1. Is serum GENTAMICIN level dependent on serum CREATININE? Variables: serum Gentamicin, serum Creatinine 2. Is THROMBOLYTIC THERAPY related to the number of in- hospital DEATHS in stroke? Variables: thrombolytic therapy, number of deaths
  • 37. Prediction/regression A Formula Knowing the value of one variable(s) Calculating the value of the other variable
  • 38. Prediction/regression Usage: To describe the relationship Y = aX + b Y= aX2 + b Z = aX + bY + c Z = a X2 + bY3 + c Framingham CHD Risk Calculator
  • 39. Prediction/regression the predicted and predictor (s) Examples: The TIMI risk score to predict odds of death in STEMI The APACHE III system to predict mortality in ICU The IMPACT models to predict 6-month disability in severe traumatic brain injury
  • 41. 2. Statistical error What do my findings mean? How likely are my findings to be true?
  • 42. Types of error Two types: Type I ( ) error Type II ( ) error
  • 43. Hypothesis synthesis Research question/objective And the answer to three questions: What are the variables? What are the groups/pairs? What is the statistical analysis?
  • 44. Example 1 • Objective: to assess the effect of oral glucocorticoid on serum IL-8 in COPD patients • Variable: serum IL-8 • Groups/Pairs: prior and following glucocorticoid oral therapy • Statistical analysis: comparison • Alternative hypothesis: there is a difference bet ween serum IL-8 prior and after glucocorticoid therapy • Null hypothesis: there is no difference bet ween serum IL-8 prior and after glucocorticoid therapy
  • 45. Example 2 • Objective: to assess whether or not high levels of serum Neuron Specific Endolase (NSE) is associated with CT abnormality in head injury • Variable: serum NSE • Groups: patients with CT abnormality, patients with no CT abnormality • Statistical analysis: comparison • Alternative hypothesis: there is a difference bet ween serum NSE levels in head-injury patients with and without CT abnormality • Null hypothesis: there is no difference bet ween serum NSE levels in head-injury patients with and without CT abnormality
  • 46. Example 3 • Objective: to describe the relationship of ISS and ED length of stay • Variables: ISS and ED length of stay • Groups/pairs: NIL • Statistical analysis: regression • Alternate hypothesis: the coefficient is not zero.
  • 47. Sample vs. Population Population = everyone Sample = in your study
  • 48. Probability of error is the following question: How certain are we that what is observed in the sample can be inferred on the actual population?
  • 49. Belonje et al. (Circulation. 2010;121:245-251.) Increased Erythropoietin level is associated with increased mortality in 605 heart failure patients ( p < 0.05). Question: how true is this in the population of all heart failure patients?
  • 50. Bloom et al. (Aliment Pharmacol Ther. 2004 Apr 15;19(8):871-8.) No difference in colitis activity of 48 ulcerative colitis patients who receive Tinzaparin with 52 patients who receive placebo (p = 0.84) Question: How true is this in the population of all ulcerative colitis patients?
  • 51. Type I error or Definition: When the null hypothesis is rejected in the sample but is true in the population Rejecting null hypothesis, when it is true False positive result Sample Population difference no difference association no association
  • 52. Type II error or Definition: When the null hypothesis is true in the sample but is false in the population Accepting null hypothesis, when it is false False negative result Sample Population no difference difference no association association
  • 53. Population Sample + - outcome + c a reject null type 1 error - b d accept null type 2 error
  • 54. Belonje et al. (Circulation. 2010;121:245-251.) Increased Erythropoietin level is associated with increased mortality in 605 heart failure patients ( p < 0.05). Null hypothesis: no association bet ween Erythropoietin and mortality Result: reject null hypothesis - positive finding
  • 55. Reality Test outcome + - + = 0.04 -
  • 56. Belonje et al. (Circulation. 2010;121:245-251.) p < 0.05 Probability of type I error < 0.05 Probability of no association in the population <0.05 Probability of no association bet ween increased erythropoietin and mortality in all heart failure patients < 0.05
  • 61. Bloom et al. (Aliment Pharmacol Ther. 2004 Apr 15;19(8):871-8.) No difference in colitis activity of 48 ulcerative colitis patients who receive tinzaparin with 52 patients who receive placebo (p = 0.84) • Null hypothesis: no effect for tinzaparin Probability
of
 • Result: true null hypothesis Type
II
error
?
  • 62. Reality Test outcome + - + = 0.84 - =?
  • 63. Bloom et al. (Aliment Pharmacol Ther. 2004 Apr 15;19(8):871-8.) Power calculation: 42 subjects in each group (treatment and placebo) Sample size: 48 patients in treatment group 52 patients in placebo group Large enough sample
  • 64. Bloom et al. (Aliment Pharmacol Ther. 2004 Apr 15;19(8):871-8.) Low probability of type II error High probability of true null hypothesis in the population High probability of no effect for tinzaparin in all ulcerative colitis patients
  • 66. Reality Faecal Occult Blood Test + - + 20 180 200 - 10 1820 1830 30 2000 2030 Sensitivity = 1 - beta = 1 - (10/30) = 0.66 Probability you’ll detect a real cancer
  • 67. Reality Faecal Occult Blood Test + - + 20 180 200 - 10 1820 1830 30 2000 2030 Specificity = 1 - alpha = 1 - (180/2000) = 0.91 Probability you’ll reassure a healthy person
  • 68. Reality Faecal Occult Blood Test + - + 20 180 200 - 10 1820 1830 30 2000 2030 Positive predictive value = 20/200 = 0.1 Probability a positive result means cancer
  • 69. Reality Faecal Occult Blood Test + - + 20 180 200 - 10 1820 1830 30 2000 2030 Negative predictive value = 1820/1830 = 0.995 Probability a negative result means all clear

Editor's Notes