I was looking at a couple of papers for journal club. The first looks at a
new treatment that requires once-daily dosing rather than multiple-daily
dosing. The belief is that superior compliance with once-daily dosing will
lead to as good as or better outcomes. Surprisingly, though, the paper
looked at a placebo as the comparison group rather than a multiple-daily
dosing alternative.
The second looks at as-needed dosing compared with regular dosing, and again
used a placebo as the control. It seems like a regular dosing of an active
drug is the more appropriate comparison.
But if the researchers need to start first by showing that the medication is
superior to placebo, I guess that is okay. But both papers then seem to
criticize other research that does what I consider the more relevant
comparison.
"On the other hand, once-daily BUD 200ug was found to be as effective as
twice-daily BUD 100 ug in adults with mild-to-moderate asthma, although this
study was not placebo controlled. In another study, which also lacked a
placebo group, once-daily BUD 800ug was less effective than twice-daily BUD
400ug for long-term management of PEF, asthma symptoms, and rescue
medication use." (Nuyak et al 2000)
"Juniper et al compared regular and as-needed usage and found regular usage
to be superior. In a more recent study in which a quality of life
questionnaire was used, the difference between as-needed and regular use
were statistically significant, but the authors did not find that the degree
of improvement with regular use was clinically significant compared with
as-needed use. In neither of those studies was a placebo comparison
included; thus we are not certain whether the as-needed use of intranasal
corticosteroids is better than placebo treatment." (Jen et al 2000)
I'm not sure why these studies need to be placebo controlled. Clearly they
can be blinded through the use of a placebo, but that defeats the purpose of
showing equivalent or better results because the regimen is easier to comply
with. I suspect that what the authors were really criticizing though is that
the research did not have a third arm: 1=once-daily, 2=twice-daily (positive
control), 3=placebo (negative control). Or alternately: 1=as-needed dosing,
2=regular dosing (positive control), 3=placebo (negative control).
So does it make sense to look at a placebo at all when the interest is in
whether once-daily dosing is as good as or better than multiple-daily dosing
or whether as-needed dosing is as good as or better than regular dosing?
There's both a pragmatic aspect and an ethical aspect to this question. I'm
more interested in the pragmatic aspect, but you are welcome to address
either or both aspects.
The two papers are:
Nuyak AS et al. Once-daily mometasone furoate dry powder inhaler in the
treatment of patients with persistent asthma. Ann Allergy Asthma Immunol
2000;84:417-424.
Jen A et al. As-needed use of fluticasone propionate nasal spray reduces
symptoms of seasonal allergic rhinitis. J Allergy Clin Immunol
2000;105(4)732-738.
Steve Simon, [log in to unmask], Standard Disclaimer.
STATS - Steve's Attempt to Teach Statistics: http://www.cmh.edu/stats
%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
|