Statistical Methods in Medical Research 4ed

The principle of masking the identity of a treatment may be extended to trials
in which two or more potentially active treatments are compared. The main
purpose here is to ensure that the measurement of the response variable is not
affected by a knowledge of the specific treatment administered. If the relevant
response is survival or death, this is almost certain to be recorded objectively and
accurately, and no bias is likely to occur. Any other measure of the progress of
disease, such as the reporting of symptoms by the patient, the eliciting of signs by
the doctor, the recording of major exacerbations of disease, or even the recording
of biomedical test measurements, may be influenced by knowledge of the treatment
received. This includes knowledge by the patient or by the physician or
other technical staff.
It is important, therefore, to arrange when possible for treatments to be
administered by some form of masking. (The term blinding is often used, but is
perhaps less appropriate, if only because of the ambiguity caused in trials for
conditions involving visual defects.) In a single-masked (or single-blind) trial, the
treatment identity is hidden from the patient. In the more common doublemasked
(or double-blind ) design, the identity is hidden from the physician in
charge and from any other staff involved with the assessment of response. In
some cases it may be necessary for the physician to be aware of the treatment
identity, particularly with a complex intervention, but possible for the assessments
of response to be completely masked.
Masking is achieved by ensuring that the relevant treatments are formulated
in the same way. If two drugs have to be administered in different ways, for
instance by tablet or capsule, it may be possible to use a double-dummy technique.
To compare drug A by tablet with drug B by capsule, the two groups
would receive
or
Active A tablets, plus placebo B capsules
Placebo A tablets, plus active B capsules.
18.5 Assessment of response 605
Once the treatment assignment for a patient has been decided, the tablets,
capsules, etc., should be packaged and given a label specific to that patient. An
alternative system is sometimes used, whereby a particular treatment is given a
code letter, such as A, and all packages containing that drug are labelled A. This
system has the defect that, if the identity of A becomes known or suspectedÐfor
instance, through the recognition of side-effectsÐthe code may be effectively
broken for all patients subsequently receiving that treatment.
The use of a placebo may be impracticable, either because a treatment causes
easily detectable side-effects, which cannot, or should not, be reproduced with a
placebo, or because the nature of the intervention cannot be simulated. The
latter situation would, for instance, normally arise in surgery, except perhaps for