Statistical Methods in Medical Research 4ed

2 We shall be interested in the mean lead time for the whole group of cases,
including those in whom the disease is not detected. This is called the
programme lead time, and is equal to (1 b) L, where b is the proportion
of false negatives (i.e. cases missed).
3 To estimate m, use may be made of the relation (19.4),
P ˆ Im,
19.12 Disease screening 709
where P is the prevalence of presymptomatic disease (which can be estimated
from the results of the screen, allowing for the false negatives), and I is the
incidence of symptomatic disease (which might be estimated from a control
series).
4 The estimation of s 2 , which is needed for the calculation of L, is more
troublesome than that of m, and may require a further assumption about
the functional form of the distribution of y.
The discussion so far has been in terms of a single screening occasion. In
practice, it will be preferable to consider a series of screening occasions, so that
each individual who develops the disease at some time has a reasonable chance of
being screened whilst the disease is presymptomatic (see Walter & Day, 1983;
Day & Walter, 1984).
It has been assumed above that all cases detectable by screening would, if
undetected and therefore untreated, progress to symptomatic disease. This is not
always the case and the sojourn time may be subdivided into two stages.
Presymptomatic disease in the first stage may not progress to the second stage,
and may even regress, whilst those who progress to the second stage would
progress to symptomatic disease. This situation is considered by Brookmeyer
and Day (1987).
A comprehensive review of modelling the disease-screening process is given
by Stevenson (1998).
The effectiveness of a screening programme may be assessed by a randomized
controlled trial in which individuals are randomized to either a screening group
or a control group. The considerations discussed in Chapter 18 would apply and
there are also special considerations. The primary analysis would be of the endpoint
that it is the aim of screening to modify, often mortality. The analysis
would follow the intent-to-treatÐthat is, intent-to-screenÐapproach, for the
reasons discussed in §18.6. The data from such a trial offer the opportunity for
secondary analyses concerned with modelling the natural history of the disease.
The timing of the outcome is also important, as follow-up continues for several
years; in the stop-screen design, follow-up continues for several years after the
screening regimen has been completed and any effect of screening would be
expected to decline towards the end of the follow-up period.
Randomized controlled trials of screening are usually large studies continuing
over several years and are infrequently conducted. If screening is available