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Statistical formulae for calculating

some 95% confidence intervals

95% confidence interval = effect size 1.96 standard error of the effect size

Single-arm phase II trial

Counting people (single proportion)
Number of responses to treatment = 28
Number of subjects (N) = 50
Observed proportion (P) = 28/50 = 0.56 (or 56%)

Standard error of the true proportion (SE) = [P (1 P)]/N =

(0.56 0.44)/50 = 0.07

95% CI = P 1.96 SE = 0.56 1.96 0.07 = 0.42 to 0.70 ( or 42 to 70%)
For small trials (e.g. N < 30) exact methods provide a more accurate 95%
confidence interval (Geigy Scientific Tables. Introduction to Statistics, Statistics
Tables and Mathematical Formulae, 8th edn. Ciba Geigy, 1982).

Taking measurements on people (single mean value)

Mean value (x) = 34 mm (VAS score)
Standard deviation (s) = 18 mm
Number of subjects (N) = 40

s
Standard error (SE) = = 18/ 40 = 2.8 mm
n
95% CI = mean 1.96 SE = 34 1.96 2.8 = 34 5.5 = 28 to 40 mm
For small trials (N < 30), a different multiplier to 1.96 is used. It comes from
the t-distribution, and gets larger as the sample size gets smaller

The multiplier of 1.96 is associated with a two-sided confidence interval.

For a one-sided limit a value of 1.645 could be used, but only the lower
or upper limit is needed, depending on whether the proportion or mean

A Concise Guide to Clinical Trials Allan Hackshaw

2009 Allan Hackshaw. ISBN: 978-1-405-16774-1

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Statistical formulae for 95% CI

associated with the new therapy should be greater or smaller than standard
treatments to indicate improvement.

Randomised phase II or III trial with two groups

Counting people (risk difference or relative risk)
Example is serological flu (Box 7.1)
P1 = r1 /N1 = 41/927 = 0.044
P2 = r2 /N2 = 80/911 = 0.088

For risk difference

Observed risk difference = P1 P2 = 0.044 (4.4%)

{[P1 (1 P1 )]/N1 + [P2 (1 P2 )]/N2 } = 0.01155

Standard error (SE) =

95% CI = difference 1.96 SE = 0.044 1.96 0.01155

= 0.066 to 0.021 = 6.6% to 2.1%

For relative risk (RR)

Observed RR = P1 P2 = 0.5
Take natural logarithm (base e) = loge (0.5) = 0.693
Standard error of the log RR (SE) =

(1/r1 + 1/r2 1/N1 1/N2 ) = 0.186

95% CI for the log RR = log RR 1.96 SE

= 0.693 1.96 0.186 = 1.058 to 0.328
Transform back (take exponential) = 0.35 to 0.72 (i.e. e1.058 to e0.328 )
(e is the natural number 2.71828)
Converted to a percentage change in risk, 95% CI is 28 to 65% reduction in risk

Taking measurements on people (difference between

two mean values)
Example is the Atkins diet (Box 7.4)
Change in weight loss at three months
Atkins diet:
Conventional diet:

N1 = 33 Mean1 = 6.8 kg
N2 = 30 Mean2 = 2.7 kg

SD1 = 5.0 kg
SD2 = 3.7 kg

Difference between the two means = Mean1 Mean2 = 6.8 (2.7) = 4.1 kg

Standard error of the mean difference (SE) = (SD12 /N1 + SD22 /N2 )

= (5.02 /33 + 3.72 /30) = 1.1

95% CI = mean difference 1.96 SE
= 4.1 1.96 1.1 = 6.3 to 1.9 kg

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Statistical formulae for 95% CI

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1.96 is used when each trial group has at least say 30 subjects. For smaller studies, a larger multiplier and the t-distribution are used, and there is a different
formulae depending on whether the standard deviations are similar between
the groups.

Time-to-event data (hazard ratio)

A statistical package should be used to estimate 95% CIs because the calculation for the standard error is not simple. However, if only the median and
number of events in each treatment group are available, there is a simple
method to obtain an approximate estimate of the CI, but only after assuming
that the distribution of the time-to-event measure has an exponential distribution (i.e. the event rate is constant over time).
Example is early vs late radiotherapy in treating lung cancer (Spiro et al.,
J Clin Oncol 2006; 24: 38233830), and the outcome is time to death:
Early radiotherapy:
Median survival M1 = 13.7 months Number of deaths = E1 = 135
Late radiotherapy:
Median survival M2 = 15.1 months Number of deaths = E2 = 136
Hazard ratio (early vs late) HR = M2/M1 = 15.1/13.7 = 1.10

Standard error of the log hazard ratio (SE) = (1/ E1 + 1/ E2)

= (1/135 + 1/136) = 0.1215

95% CI for the log HR = loge HR 1.96 SE
= log(1.10) 1.96 0.1215 = 0.143 to 0.333
Transform back (take exponential) = 0.87 to 1.40 (i.e. e0.143 to e0.333 )
These are close, but not identical, to the results calculated using the raw data:
HR = 1.16, 95% CI 0.91 to 1.47