Protocols and protocol deviations:
key points
i)
The trial protocol
The trial
protocol is a document which is prepared before the trial is run to record why
the trial is needed, how it will be run and how it will be analysed. Although largely an administrative document,
there are various components which are of a scientific nature. E.g., some problems of multiple testing are
overcome by recording beforehand which analyses will be performed.
ii)
Protocol deviation
In
practice most trials are not run wholly in accordance with the protocol. Some patients randomized to one treatment
receive the other treatment, others might drop out of the trial
altogether. Comparing the groups that do
complete the trial according to the protocol can be flawed, as the groups may no
longer be comparable.
iii)
Intention to treat analysis
This is
a way of analysing trials when there have been deviations from the protocol. The treatment groups are compared as
randomized, so the comparison is unbiased.
However, you may not be comparing groups that are constructed in the way
you like. In many trials this can be
rationalised by noting that the deviation from protocol merely represent the
vagaries of real clinical practice, and therefore represent a useful comparison
of the intention to use the different treatments.