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Planning for
the number of participants involves obtaining a realistic number
of patients as well as considering whether or not this number
can be reached in a given time period. Recruiting patients for
a mucositis study can be especially difficult, as patients are
often overwhelmed with the treatment in general. Battling cancer
is mentally, emotionally, and physically draining. In addition,
following treatment regimens alone can be overwhelming enough
for patient to refuse any involvement in clinical trials. Hence,
it is important to realistically consider the sites that will
be involved and the number of patients that can be recruited from
each site.
In regards
to randomization, patients in cycle 1 who develop mouth and throat
pain with redness (WHO grade 1) will be randomized into 2 groups:
one receiving the active rinse (A) and the other a placebo rinse
(B). The same group of subjects will then be evaluated during
the 2nd cycle. A crossover is done if and when pain and redness
develops during this cycle. Hence, if the patients develop mouth
pain during their 2nd cycle, group A will receive the placebo
instead of the active rinse while group B will be given the rinse
instead of the placebo. This allows a fair assessment of whether
or not the drug decreases throat and mouth pain. Subsequent crossovers
are done with each cycle.
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9.1: The Crossover Design
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The advantage of using a crossover
design in mucositis-related studies is the reduction
in variability, which enables the use of a smaller sample. As
mentioned earlier, recruiting patients for mucositis within a
given time frame may be challenging. Crossover studies allow the
same patient to evaluate both the drug and the placebo. However,
an important assumption is made when using this method: that the
effects of the drug used in the first cycle will not affect the
outcome of the second cycle. In this case the assumption is valid
because this is a palliative rinse for throat and mouth pain that
does not have curative or long-term effects in regards to the
development of mucositis. Hypothetically, the rinse provides a
barrier that has been shown to last only for 3 days. In addition,
the cycles are repeated every 5 weeks, giving the patients ample
time to recover and proceed with additional cycles.
The
most challenging aspect of using crossover studies is developing
a placebo that tastes and feels like the drug, especially for
drugs delivered as a swish and swallow by mouth. Patients are
keen on tastes, consistencies of the rinse, and how it feels after
swallowing. Developing an identical placebo with the same flavor,
aftertaste, and consistency may be difficult. However, patients
undergoing cancer chemotherapy often complain of altered taste,
which can affect their perception. These patients may be less
suspicious or concerned because their baseline ability to taste
is affected during chemotherapy.
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