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Good
results have been reported for improvement in constipation associated
with the spastic pelvic floor syndrome through the use of biofeedback
(Bleijenberg
and Kuijpers, 1987), but results for operative treatment of
slow colonic transit or the presence of rectocele are often mediocre.
As a consequence, laxatives remain a mainstay of treatment of
functional constipation and certainly of constipation associated
with medical illness.
Hence, knowledge
of the relative effectiveness of different laxative preparations
is clinically important. This applies not only to laxatives administered
orally but also to those given rectally as enemas or suppositories.
Trial design
of symptom management
While the gold
standard randomized controlled trial (RCT) has been widely used in laxative comparisons,
blinding to the preparations used is often difficult because of the widely differing
physical properties of various laxative preparations. For drug trials of symptom
control, in general, or constipation, in particular, many inherent issues must
be addressed including:
- Parallel
group or crossover
- Duration
of study period
- Value
of a placebo arm
- Length
of washout period
- Dose
flexibility and rescue medication
- Eligibility,
endpoints, and practical considerations
Parallel
group or crossover
Crossover
trials hold the benefit of requiring a smaller number of subjects
in order to establish a significant result, as the variability
is only within subjects rather than between them (Hills
and Armitage, 1979). The disadvantage is that the length of
the trial is at least doubled and this may, depending on the nature
of the population, greatly increase the dropout rate.
Duration
of study period
This is clearly
a function of the characteristics of both the intervention being
studied and the patient group involved. The latency of action
of stimulant laxatives is eight hours or more, and that of softening
agents around three days, so a trial of oral laxatives should
probably last at least a week. To avoid confusion by the inherent
natural variability in bowel habit and by carry-over effects of
previous laxative medication, longer trial periods of four to
eight weeks or more are common in studies in chronic constipation.
Desirable as such study durations might be, they are not necessarily
available in palliative care populations that suffer a rapidly
changing clinical picture and high attrition through disease progression.
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