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Hello,
I have a relatively simple question that I hope the group can help me
with. When designing a clinical drug-drug interaction study, what
are the specific reasons for choosing each of the following designs,
one-sequence crossover, randomized crossover, or parallel design.
Thank you,
Bonnie
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Bonnie,
Hope you are well.
I am just copying the following lines from the guidance. http://
www.fda.gov/cder/guidance/2635fnl.htm
............................ The selection of one of these or another
study design depends on a number of factors for both the substrate
and interacting drug, including (1) acute or chronic use of the
substrate and/or interacting drug; (2) safety considerations,
including whether a drug is likely to be an NTR (narrow therapeutic
range) or non-NTR drug; (3) pharmacokinetic and pharmacodynamic
characteristics of the substrate and interacting drugs; and (4) the
need to assess induction as well as
inhibition. ...........................
Look at the link for complete details. It illustrates different
scenario under which one design might be useful than other.
Hope it helps.
Pravin
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The following message was posted to: PharmPK
Hi Pravin,
Thanks for your reply. I have looked at the guidance document but I
just had a few more specific questions. Are there any other reasons for
using a parallel design besides half life? I know duration of
induction/inhibition may also play a role, however in this situation I
believe that a one-sequence crossover can also be used. Also, from my
experience one sequence crossovers appear to be used fairly commonly and
are also relatively easy to conduct. Are there any disadvantages to
using this design when looking at PK endpoints only?
Thanks,
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Dear Forum,
It seems to me that when the risk of a carryover effect is suitably
remote,
the main disadvantage of a crossover design from a purely PK
viewpoint is
the narrower population because it has a greater tendency to be
biased by
including outliers. Theoretically it will also be marginally less
representative of the intended clinical population, although healthy
volunteers are usually so unrepresentative anyway that this probably
makes
little real difference.
I think that a theoretical advantage to the crossover design as a
tool of
management is due to eliminating several sources of variation at
once. That
means a difference between two PK profiles in a crossover design more
likely
to be due to the formulation itself. However, I'm not sure that this
translates into a real practical aid to decision taking and anyway it is
minor compared with the greater reliability, lower costs ands faster
timelines. (It is always easier to recruit the first half of a
population
than the second half!).
If someone in the forum would be interested to do them I would like
to see
some calculations of the different size groups required, based on actual
data. I would reciprocate by calculating the differences in costs and
giving them to the forum.
Andrew Sutton
--
Andrew Sutton, MBBS, MD(London), FFA
Guildford Clinical Pharmacology Ltd.
The Technology Centre, Occam Road
Guildford, Surrey, UK. GU2 7YG
Tel: +44 (0)1483 455375. Direct: 688303
URL: www.gcpl.co.uk
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Dear Barbara
The other reason to use a parallel design is while assessing
different formulations (PK profile) in patients.
With regards
Vinay
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The following message was posted to: PharmPK
Bonnie,
You can also refer to J. Clin. Pharmacology 2003 (43) pg. 443-469
The Conduct of In Vitro and In Vivo Drug-Drug Interaction Studies: A
PhRMA
Perspective.
Rucha.
Rucha Sane
University of Cincinnati.
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