Statistical Methods in Medical Research 4ed

group could be assigned to a patient who dropped out. In the analysis, a broad
categorical response category should then include all patients with that score or
worse. Treatment groups are then compared by the Mann±Whitney test (§10.3).
Devices of this type may be useful, even unavoidable, if crucial responses are
missing, but they involve the sacrifice of information, and estimation may be
biased. The best solution is to avoid withdrawals as far as possible by careful
advance planning.
Compliance
The term compliance may imply adherence to all the protocol requirements. In
drug trials it usually refers more specifically to the ingestion of the drug at the
prescribed times and in the prescribed quantities.
The effects of non-compliance in the broad sense have been discussed throughout
this section. They are multifarious and difficult to quantify. Nevertheless,
attempts have been made to model non-compliance in some very simple situations,
which we describe below. The aim here is to estimate the effect of noncompliance
on treatment comparisons, and hence to go beyond an ITT approach
to the estimation of treatment effects.
The narrower sense of drug compliance is somewhat more amenable to
modelling, since the proportion of the scheduled amount of drug that was
actually taken can often be estimated by patient reports, counts of returned
tablets, serum concentrations, etc. Models for this situation are described
later.
A simple model for non-compliance is described by Sommer and Zeger
(1991) and attributed by them to Tarwotjo et al. (1987). It relates to a trial of
an active treatment against a control, with a binary outcome of success or failure.
Non-compliers may form part of each group, but are likely to form different
proportions and to be different in prognostic characteristics. The analysis concentrates
on the subgroup of compliers in the treatment group. The proportion
of successes in this subgroup is observed, and the aim of the analysis is to
estimate the proportion of successes that would have been observed in that
subgroup if those patients had received the control treatment. The key assumption
is that this proportion is the same (apart from random error) as the
proportion of successes observed in the control group. The calculations are
illustrated in Example 18.1.
Example 18.1
18.6 Protocol departures 609
Table 18.1 shows results from a trial of vitamin A supplementation to reduce mortality
over an 8-month period among preschool children in rural Indonesia, reported by
Tarwotjo et al. (1987) and discussed by Sommer and Zeger (1991).