Sample Size Calculation

Sample Size Determination
Why it is important?
• Integral part of quantitative research.
• Ensuring validity, accuracy, reliability,
scientific and ethical integrity of research.
Considerations in sample size calculation
Three main concepts to be considered:

• Estimation (depends on several components).
• Justification (in the light of budgetary or biological
considerations)
• Adjustments (accounting for potential dropouts or
effect of covariates)
I-Scientific Reasons
• In a trial with negative results and a sufficient
sample size, the result is concrete (treatment has no
effect-no difference).
• In a trial with negative results and insufficient

power (insufficient sample size), may
mistakenly conclude that the treatment under
study made no difference (false conclusion).
II-Ethical Reasons
• Undersized study can expose subjects to potentially
harmful treatments without the capability to advance
knowledge.
• Oversized study has the potential to expose an
unnecessarily large number of subjects to potentially
harmful treatments.
III-Economic Reasons
• Undersized study is a waste of resources due to its

inability to yield a meaningful useful results.
• Oversized study potential of statistically significant
result with doubtful clinical significance leading to waste of
resources.
Factors Influencing Sample Size
Calculations
• The objective (precision, power analysis)
• Details of intervention and control trial.
• The outcomes
• Possible covariates to control (confounders).
Calculations
The research design: Research subjects
– Simple RCT-Cluster RCT - Target population
– Equivalence - Inclusion-exclusion
criteria
– Non-randomized - Baseline risk
intervention study - Compliance rate
– Observational study - Drop-out rate
– Prevalence study
– Sensitivity and specificity
– Paired comparison
– Repeated-measures study
Calculations
Parameters
a- Desired level of significance
b- Desired power
c- One or two-tails
d- Possible ranges or variations in expected outcome.
e- The smallest difference:
– Smallest clinically important difference
f- Justification of previous data:
– Published data, Previous work
– Review of records and experts opinion
g- Software or formula being used:
Statistical Terms
• P-value: Probability of obtaining an effect as extreme or
more extreme than what is observed by chance.
• Significance level of a test: Cut-off point for the p-
value (conventionally it is 5% or 0.05).
• Power of a test: Correctly reject the null hypothesis
when there is indeed a real difference or association
(typically set at least 80%).
• Effect size of clinical importance.
Effect size
• The numerical value summarizing the difference of interest
(effect size)
• Effect size is a simple way of quantifying the difference
between two groups
• Effect sizes facilitate the decision whether a clinically
relevant effect is found, helps determining the sample size for
future studies, and facilitates comparison between scientific
studies.
• The effect size of the population can be known by dividing the
two population mean differences by their standard deviation.
Approach in calculating the sample
size
1. Specify your hypothesis.
2. Specify the significance level ().
3. Specify an effect size.
4. Obtain historical values (previous research).
5. Specify a power ().
6. Use appropriate formula to calculate sample size.
Components of sample size
calculations
• Acceptable level of type I and type II errors
• Appropriate statistical power
• Effect size
• Significance
• Estimated measurement of variability
• Design effect in survey
Z and Z for calculating the sample size
Significance Z () critical value* Power Z () power

level **
0.01(99%) 2.576 0.08 0.842

2.326
0.02(98%) 2.326 0.85 1.036

1.645
0.05 (95%) 1.960 0.90 1.282

1.282
0.10 (90%) 1.645 0.95 1.645
*One tail
**Two tails
Sample size for comparative studies
(dichotomous outcomes)
n
Z P * (1  P *)  Z Pe(1  Pe)  Pc (1  Pc ) 
2
 2
P*  ( Pe  Pc ) / 2
=Pe -Pc
Pe= experimental
Pc= control Power=0.842
Significance=1.960
An investigator hypothesizes that caffeine is better than
aminophylline in terms of reducing apnea of prematurity.
Previous studies have reported an efficacy of 40% for
aminophylline. To detect a 5 % difference between them with
power of 80% and two tailed test of 5% significance level,
what sample size would be needed?
n
Z P * (1  P * )  Z Pe (1  Pe )  Pc (1  Pc )  2
2
P*  ( Pe  Pc ) / 2
N= {1.960√ [0.375(1-0.375)] +0.840√ [0.35 (1-0.35) + 0.4(1-

0.4)]} 2 ⁄ 0.05 2
Sample size required per group is 876.
For correction of continuity and high degree of accuracy one
need to increase the sample size by 2/(Pe - Pc).
Then final sample size would be 896 per group.
Sample size calculations for comparative studies
(continuous outcome)
N  4 (Z  Z  )
2 2
2
D
= Standard deviation of the outcome variable
Z= confidence level=1.960
Z= Power= 0.842
D2 = the effect size
An investigator plans a randomized control trial of the effect
of salbutamol and ipratropium bromide on FEV 1 after 2 weeks
of treatment. Previous study has reported mean FEV 1 in
persons treated with asthma was 2 liters with a standard
deviation of 1 liter. If the investigator tries to detect a
difference of 10% between them, how many individual will
be required for the study?
N  4 (Z  Z  )
2 2
2
D
N= 4*1 2(1.960+0.842) 2 / 0.2 2
=785 person required.
Sample size for descriptive studies: continuous
variable
4 * Z S 2 2
N 2
W
Z=Confidence level=1.960
S= Standard deviation
W= Width of Confidence interval
Suppose an investigator wants to detect the mean
weight of newborns between 30-34 week of gestation
with 95% confidence interval not more than ±0.1 kg.
From the previous study the standard deviation has
been reported of 1 kg, then the sample size required
would be,
N = 4*1.96 2*1 2/0.2 2=384 newborns required.

Descriptive study: Dichotomous variable
4 * Z * P(1  P) 2
N 2
W
Z= Confidence level=1.960

W= width of C.I
P= pre study estimate of proportion
Let us consider that an investigator wish to determine
the incidence of nosocomial pneumonia (NP) in
neonatal intensive care with 95% confidence level.
He selected a confidence interval of ± 10 and the
mean incidence NP has been reported earlier is 20%.
Then the required sample size would be
N = 4*1.96 2*0.20(1-0.20)/ 0.20 2 = 62

Strategies For Maximizing Power and
Minimizing the Sample Size
• Use common outcomes.
• Use paired design (such as cross-over trial)
• Use continuous variables
General Rules of Thumb
1- Don’t forget multiplicity testing corrections
(Bonferroni)
2- Better to be conservative (assume two-sided).
3- Remember that sample size calculation gives you
the minimum required.
4- None RCTs require a much larger sample to allow
adjustment for confounders.
5- Equivalence studies need a larger sample size than
studies aimed to demonstrate a difference.
General Rules of Thumb
• For moderate to large effect size (0.5<effect

size<0.8), 30 subjects per group.
• For comparison between 3 or more groups,

to detect a moderate effect size of 0.5 with
80% power, require 14 subjects/group.
Rules of Thumb for Associations
• Multiple Regression
– Minimal requirement is a ratio of 5 subjects:1
independent variable. The desired ratio is 15:1
• Multiple Correlations
– For 5 or less predictors use n>50
– For 6 or more use 10 subjects per predictor
• Logistic Regression
– For stable models use 10-15 events per predictor
variable
• Large samples are needed in:

– Non-normal distribution
– Small effect size
– Substantial measurement error
– Stepwise regression is used
• For chi-square testing (2X2 table):
– Enough sample size so that no cell <5
– Overall sample size should be at least 20
For Factor analysis

– At least 50 participants/subjects per variable
– Minimum 300
• N=50 very poor
• N=100 poor
• N=200 fair
• N=300 good
• N=500 very good
Software for calculations
• nQuery Advisor 2000

• Power and Precision 1997
• Pass 2000
• UnifyPow 1998
• Epi-Info: descriptive studies
• OpenEPI: descriptive studies
Thank you

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Sample Size Determination

Three main concepts to be considered:

• In a trial with negative results and insufficient

• Undersized study is a waste of resources due to its

Significance Z () critical value* Power Z () power

0.01(99%) 2.576 0.08 0.842

0.02(98%) 2.326 0.85 1.036

0.05 (95%) 1.960 0.90 1.282

0.10 (90%) 1.645 0.95 1.645

N= {1.960√ [0.375(1-0.375)] +0.840√ [0.35 (1-0.35) + 0.4(1-

N = 41.96 21 2/0.2 2=384 newborns required.

Z= Confidence level=1.960

N = 41.96 20.20(1-0.20)/ 0.20 2 = 62

• For moderate to large effect size (0.5<effect

• For comparison between 3 or more groups,

• Large samples are needed in:

For Factor analysis

• nQuery Advisor 2000

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