OVERVIEW INTRODUCTION CONFIDENCE INTERVAL CONFIDENCE LEVEL CONFIDENCE LIMITS HOW TO SET? FACTORS – SET SIGNIFICANCE APPLICATIONS
INTRODUCTION Statistical parameter Descriptive statistics : Describe what is there in our data Inferential statistics : Make inferences from our data to more general conditions
Inferential statistics Data taken from a sample is used to estimate a population parameter Hypothesis testing (P-values) Point estimation (Confidence intervals)
POINT ESTIMATE Estimate obtained from a sample Inference about the population Point estimate is only as good as the sample it represents Random samples from the population - Point estimates likely to vary
ISSUE ??? Variation in sample statistics
SOLUTION Estimating a population parameter with a confidence interval
CONFIDENCE INTERVAL A range of values so constructed that there is a specified probability of including the true value of a parameter within it
CONFIDENCE LEVEL Probability of including the true value of a parameter within a confidence interval Percentage
CONFIDENCE LIMITS Two extreme measurements within which an observation lies End points of the confidence interval Larger confidence – W ider interval
A point estimate is a single number A confidence interval contains a certain set of possible values of the parameter Point Estimate Lower Confidence Limit Upper Confidence Limit Width of confidence interval
HOW TO SET
CONCEPTS NORMAL DISTRIBUTION CURVE MEAN ( µ ) STANDARD DEVIATION (SD) RELATIVE DEVIATE (Z)
NORMAL DISTRIBUTION CURVE
Perfect symmetry Smooth Bell shaped Mean (µ) Median Mode SD( σ ) - 1 Area - 1
RELATIVE DEVIATE (Z) Distance of a value (X) from mean value (µ) in units of standard deviation (SD) Standard normal variate
Z = x – µ SD
CONFIDENCE LIMITS From µ - Z(SD) To µ + Z(SD)
CONFIDENCE INTERVAL
FACTORS – TO SET CI Size of sample Variability of population Precision of values
SAMPLE SIZE Central Limit Theorem “Irrespective of the shape of the underlying distribution, sample mean & proportions will approximate normal distributions if the sample size is sufficiently large” Large sample – Narrow CI
SKEWED DISTRIBUTION
VARIABILITY OF POPULATION
POPULATION STATISTICS Repeated samples Different means Standard normal curve Bell shape Smooth Symmetrical
POPULATION STATISTICS
Population mean (µ) Standard error - Sampling (SD/√n) Z = x – µ SD/√n Confidence limits From µ - Z(SE) To µ + Z(SE)
95% 95% sample means are within 2 SD of population mean
95% Significance Observed value within 2 SD of true value
Confidence Interval and α Error Type I error Two groups Significant difference is detected Actual – No difference exists False Positive
Confidence level is usually set at 95% (1 – ) = 0.95
Margin of Error x
Margin of error Reduce the SD ( σ ↓) Increase the sample size (n ↑) Narrow confidence level (1 – ) ↓
P value 95% CI corresponds to hypothesis testing with P <0.05
SIGNIFICANCE If CI encloses no effect, difference is non significant
P value – Statistical significance Confidence Interval – Clinical significance
APPLICATIONS CLINICAL TRIALS
Margin of error Increase the sample size Reduce confidence level Dynamic relation Confidence intervals and sample size
Example Series of 5 trials Equal duration Different sample sizes To determine whether a novel hypolipidaemic agent is better than placebo in preventing stroke
Smallest trial 8 patients Largest trial 2000 patients ½ of the patients in each trial – New drug All trials - Relative risk reduction by 50%
Questions In each individual trial, how confident can we be regarding the relative risk reduction Which trials would lead you to recommend the treatment unequivocally to your patients
More confident - Larger trials CI - R ange within which the true effect of test drug might plausibly lie in the given trial data
Greater precision Narrow confidence intervals Large sample size
THERAPEUTIC DECISIONS Recommend for or against therapy ?
Minimally Important Treatment Effect S mallest amount of benefit that would justify therapy Points
Uppermost point of the bell curve Observed effect Point estimate Observed effect
Tails of the bell curve Boundaries of the 95% confidence interval Observed effect
Trial 1
Trial 2
CI overlaps the smallest treatment benefit Not Definitive Need narrower Confidence interval Larger sample size
Trial 3
Trial 4
CI overlaps the smallest treatment benefit Not Definitive Need narrower Confidence interval Larger sample size
Confidence intervals for extreme proportions Proportions with numerator – 0 Proportions approaching - 1 Proportions with numerators very close to the corresponding denominators
Example 20 people – Surgery None had serious complications Proportion 0/20 3/n – 3/20 15%
Proportions approaching - 1 Translate 100% into its complement
Example Study on a diagnostic test 100% sensitivity when the test is performed for 20 patients who have the disease. T est identified all 20 with the disease as positive – 100% No falsely negatives – 0%