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Dear all,
I need to know on the following.
1. What is the significance/importance of BLINDING in a
Bioequivalence [or
comparative Bioequivalence] study ?
Anyway one of them is the Reference product, the profile of which is
known.
Secondly, these Investigational Products [reference and test] are not
being
evaluated in studies like these for any indication / therapeutic
benefit /
adverse drug reactions. So there is no determination of the level of
significance of effectiveness / ineffectiveness [of the test] in
comparison
to a comparator product [reference].
2. For submission to which countries is this Blinding study a
requirement ?
3. How would the Sponsor send the Investigational Products in a blinded
manner to the Investigator [Site] ?
Or who is authorised to blind the formulations at the site in case these
are not sent by the sponsor in a blinded manner ? [Since the
Investigator
cannot do so]
4. Are QA [Quality Assurance] personnel at the Investigation Site
allowed
to have access at the time of blinding [by a pharmacist or any other
authorised person other than Investigator] in case the procedure of
blinding is done at the site.
Could anybody just explain.
Warm regards,
Prasanna Gudi
Research Associate & Pharmacist
Clinigene, Bangalore, India
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Prasanna
I suppose blinding is done even in BE studies where the outcome is a
matter
of pure data just to ensure that no extra source of bias has crept
in. What
sources you may ask... Well there are accidental and there are
deliberate
ones...
Accidental ones are quite difficult to imagine as long as the
randomisation
really has distributed the two outwardly indistinguishable treatments
evenly...so eliminating bias due to dose order for example. It also
ensures
that the blinding continues right through the sample-handling, assay and
data-handling phases, where other bias could easily be introduced.
Deliberate ones are quite easy to imagine if an unscrupulous
manufacturer or
clinical site had an interest in say, dosing the standard formulation
in a
more uniform fashion in relation to food in order to widen the
variance in
the standard treatment and keeping it narrower in the case of the new
formulation. That would make the new formulation look better. There are
subtle ways of ensuring that the standard would have more
variation...differences in posture of the volunteers or amount they
exercise
being obvious ones.
One aspect of this question I would like to ask the forum is if
anyone has
measured the effect of putting the standard formulation inside a gelatin
capsule. One that dissolves easily, that is. There seems to be a great
emphasis on this in regulatory procedures for Phase 2 studies in
particular, as though it makes a large difference in t max for
example, but
to my mind that is unlikely as the gelatin dissolves so rapidly,
almost in
the mouth. Sure, there are some old references to some capsules
apparently
compacting in the stomach and sealing off the contents but that must
be very
rare... If it does occur, could it be due to some circumstance that we
could avoid? If so, it would make it easier to blind reference
compounds in
Phase 2 , proof of concept studies especially.
Would such an effect be eliminated by giving treatments WITH food ?
I would
expect that to would reduce the effect of the gelatin to an
insignificant
proportion of the variation ...and patients prefer to take their
capsules
with food in the first place..While volunteers are more prepared to
fast.
Of course if we did that we might find that we should be doing
volunteer BE
studies in the fed state and not the fasting. Obviously that would
introduce
more variation in both groups, but on the other hand it would more
accurately reflect actual clinical conditions...
Thanks in anticipation of some useful input..
Andrew Sutton
Guildford Clinical Pharmacology Ltd.
The Technology Centre, Occam Road
Guildford, Surrey, UK. GU2 7YG
Tel: +44 (0)1483 455375. Direct: 688303
Mobile +44 (0) 7770 820 145 (To 5pm EST)
URL: www.gcpl.co.uk
Registered in England & Wales
Registration No. 2934719
Registered Office: 8 Baker Street, London W1U 3LL
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The following message was posted to: PharmPK
Dear all,
Is it possible to do BE(Bioequivalance) blinded study,
If yes, can anyone can explain.
Regards,
Dr.Sridhar
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The following message was posted to: PharmPK
Dear All,
I would like to share some of experiences in conducting a BE study under
blinding conditions, even though it is still a debatable issue.
To my Knowledge, only Canadian regulatory requires/suggests a BE study
to be done under blinding condition (Ref: Conduct and analysis of BA and
BE studies-Part A. Health Canada). The entire objective is to keep the
bias to the minimum level possible.
We can try to blind it to certain extent, like by keeping the
Investigator and other study personnel who are going to be directly
involved in the study, away from all the drug related activities such as
receipt of IPs, dispensing etc. These responsibilities should be
assigned only to select few people, who won't be involved in those
specific activities. Also we can prepare a code just like that for a
clinical trial and should be broken only in case of any emergency. All
these things has to be captured in the protocol and if possible as an
SOP.
So, ideally speaking this cannot be a perfect blind, since we cannot
expect the test product to be identical to that of the reference.
Hope, this is of some use.
Regards
Dr. M. Joseph
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The following message was posted to: PharmPK
Dear Dr Sridar
As Joseph says, it is possible to blind the study right up to the last
opaque sachet that contains the final tablet...
....but as you are implying, the volunteer will sense a different
shape, size
and taste even if the tablet is sucked out of the sachet without
showing it
to the attending physician or nurse, so I would like to find out if
we can
put both into a gelatin capsule that would maintain the blind right down
into the volunteer's stomach... If the capsule does have a significant
effect then why wouldn't it balance out when applied to both doses?
Andrew Sutton,
Guildford Clinical Pharmacology Ltd.
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