Statistical Methods in Medical Research 4ed

The scope of statistics 3
and questions about the aetiology of disease can be tackled by carefully
designed epidemiological surveys (Chapter 19). Secondly, the methods of
statistical inference provide a largely objective means of drawing conclusions
from the data about the issues under research. Both these developments, of
planning and inference, owe much to the work of R.A. (later Sir Ronald)
Fisher (1890±1962), whose influence is apparent throughout modern statistical
practice.
Almost all the techniques described in this book can be used in a wide variety
of branches of medical research, and indeed frequently in the non-medical
sciences also. To set the scene it may be useful to mention four quite different
investigations in which statistical methods played an essential part.
1 MacKie et al. (1992) studied the trend in the incidence of primary cutaneous
malignant melanoma in Scotland during the period 1979±89. In assessing
trends of this sort it is important to take account of such factors as changes
in standards of diagnosis and in definition of disease categories, changes in the
pattern of referrals of patients in and out of the area under study, and changes
in the age structure of the population. The study group was set up with these
points in mind, and dealt with almost 4000 patients. The investigators found
that the annual incidence rate increased during the period from 3 4to71 per
100 000 for men, and from 6 6to104 for women. These findings suggest that
the disease, which is known to be affected by high levels of ultraviolet radiation,
may be becoming more common even in areas where these levels are
relatively low.
2 Women who have had a pregnancy with a neural tube defect (NTD) are
known to be at higher than average risk of having a similar occurrence in a
future pregnancy. During the early 1980s two studies were published suggesting
that vitamin supplementation around the time of conception might
reduce this risk. In one study, women who agreed to participate were given
a mixture of vitamins including folic acid, and they showed a much lower
incidence of NTD in their subsequent pregnancies than women who were
already pregnant or who declined to participate. It was possible, however,
that some systematic difference in the characteristics of those who participated
and those who did not might explain the results. The second study
attempted to overcome this ambiguity by allocating women randomly to
receive folic acid supplementation or a placebo, but it was too small to give
clear-cut results. The Medical Research Council (MRC) Vitamin Study
Research Group (1991) reported a much larger randomized trial, in which
the separate effects could be studied of both folic acid and other vitamins.
The outcome was clear. Of 593 women receiving folic acid and becoming
pregnant, sixhad NTD; of 602 not receiving folic acid, 21 had NTD. No
effect of other vitamins was apparent. Statistical methods confirmed the
immediate impression that the contrast between the folic acid and control