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Statistical Methods in Medical Research 4ed

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The 95% confidence limits for m1 m2 are<br />

19 0 …2 110†…10 04†<br />

ˆ 19 0 21 2<br />

ˆ 2 2 and 40 2:<br />

The range of likely values for m 1<br />

m 2 is large. If the experimenter feels dissatisfied with<br />

this range of uncerta<strong>in</strong>ty, the easiest remedy is to repeat the experiment with more<br />

observations. Higher values of n1 and n2 will tend to decrease the standard error of<br />

x1 x2 and hence <strong>in</strong>crease the precision of the comparison.<br />

It might be tempt<strong>in</strong>g to apply the unpaired method to paired data. This<br />

would be <strong>in</strong>correct because systematic differences between pairs would not be<br />

elim<strong>in</strong>ated but would form part of the variance used <strong>in</strong> the denom<strong>in</strong>ator of the t<br />

statistic. Thus, us<strong>in</strong>g the unpaired method for paired data would lead to a less<br />

sensitive analysis except <strong>in</strong> cases where the pair<strong>in</strong>g proved <strong>in</strong>effective.<br />

Unequal variances<br />

In other situations it may be either clear that the variances differ considerably or<br />

prudent to assume that they may do so. One possible approach, <strong>in</strong> the first case,<br />

is to work with a transformed scale of measurement (§10 8). If the means, as well<br />

as the variances, differ, it may be possible to f<strong>in</strong>d a transformed scale, such as the<br />

logarithm of the orig<strong>in</strong>al measurement, on which the means differ but the<br />

variances are similar. On the other hand, if the orig<strong>in</strong>al means are not too<br />

different, it will usually be difficult to f<strong>in</strong>d a transformation that substantially<br />

reduces the disparity between the variances.<br />

In these situations the ma<strong>in</strong> defect <strong>in</strong> the methods based on the t distribution<br />

is the use of a pooled estimate of variance. It is better to estimate the standard<br />

error of the difference between the two means as<br />

s<br />

SE…x1 x2† ˆ<br />

s 2 1<br />

n1<br />

‡ s2 2<br />

n2<br />

A significance test of the null hypothesis may be based on the statistic<br />

d ˆ x1 x2<br />

s ,<br />

s 2 1<br />

n1<br />

4.3 Comparison of two means 109<br />

‡ s2 2<br />

n2<br />

which is approximately a standardized normal deviate if n1 and n2 are reasonably<br />

large. Similarly, approximate 100 (1 a)% confidence limits are given by<br />

x1 x2 zaSE…x1 x2†,<br />

where za is the appropriate standardized normal deviate correspond<strong>in</strong>g to the<br />

two-sided probability a.<br />

:

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