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Statistical Methods in Medical Research 4ed

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244 Experimental design<br />

The sum of squares of the 32 residuals <strong>in</strong> the body of the table is 13 7744, <strong>in</strong> agreement<br />

with the value found by subtraction <strong>in</strong> Table 9.3 apart from round<strong>in</strong>g errors. (These errors<br />

also account for the fact that the residuals as shown do not add exactly to zero along the<br />

rows and columns.) No particular pattern emerges from the table of residuals, nor does<br />

the distribution appear to be grossly non-normal. There are 16 negative values and 16<br />

positive values; the highest three <strong>in</strong> absolute value are positive (1 66, 1 33 and 1 22), which<br />

suggests mildly that the random error distribution may have slight positive skewness.<br />

If the l<strong>in</strong>ear model (9.1) is wrong, there is said to be an <strong>in</strong>teraction between the<br />

row and column effects. In the absence of an <strong>in</strong>teraction the expected differences<br />

between observations <strong>in</strong> different columns are the same for all rows (and the<br />

statement is true if we <strong>in</strong>terchange the words `columns' and `rows'). If there is an<br />

<strong>in</strong>teraction, the expected column differences vary from row to row (and, similarly,<br />

expected row differences vary from column to column). With one observation <strong>in</strong><br />

each row/column cell, the effect of an <strong>in</strong>teraction is <strong>in</strong>extricably mixed with the<br />

residual variation. Suppose, however, that we have more than one observation per<br />

cell. The variation between observations with<strong>in</strong> the same cell provides direct<br />

evidence about the random variance s 2 , and may therefore be used as a basis of<br />

comparison for the between-cells residual. This is illustrated <strong>in</strong> the next example.<br />

Example 9.2<br />

In Table 9.4 we show some hypothetical data related to the data of Table 9.3. There are<br />

three subjects and three treatments, and for each subject±treatment comb<strong>in</strong>ation three replicate<br />

observations are made. The mean of each group of three replicates will be seen to agree<br />

with the value shown <strong>in</strong> Table 9.3 for the same subject and treatment. Under each group of<br />

replicates is shown the total Tij and the sum of squares, Sij (as <strong>in</strong>dicated for T11 and S11).<br />

The Subjects and Treatments SSq are obta<strong>in</strong>ed straightforwardly, us<strong>in</strong>g the divisor 9<br />

for the sums of squares of row (or column) totals, s<strong>in</strong>ce there are n<strong>in</strong>e observations <strong>in</strong> each<br />

row (or column), and us<strong>in</strong>g a divisor 27 <strong>in</strong> the correction term. The Interaction SSq is<br />

obta<strong>in</strong>ed <strong>in</strong> a similar way to the Residual <strong>in</strong> Table 9.3, but us<strong>in</strong>g the totals Tij as the basis<br />

of calculation. Thus,<br />

Interaction SSq = SSq for differences between the n<strong>in</strong>e subject/treatment cells<br />

± Subjects SSq ± Treatment SSq,<br />

and the degrees of freedom are, correspond<strong>in</strong>gly, 8 2 2 ˆ 4. The Total SSq is obta<strong>in</strong>ed<br />

<strong>in</strong> the usual way and the Residual SSq follows by subtraction. The Residual SSq could<br />

have been obta<strong>in</strong>ed directly as the sum over the n<strong>in</strong>e cells of the sum of squares about the<br />

mean of each triplet, i.e. as<br />

…S11 T 2 11 =3†‡…S12 T 2 12 =3†‡...‡…S33 T 2 33 =3†:<br />

The F tests show the effects of subjects and treatments to be highly significant. The<br />

<strong>in</strong>teraction term is not significant at the 5% level, but the variance ratio (VR) is nevertheless<br />

rather high. It is due ma<strong>in</strong>ly to the mean value for subject 8 and treatment 4 be<strong>in</strong>g<br />

higher than expected.

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