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To prove the bioequivalency of the highly variable solid oral dosage forms,
replicate designs are recommended to reduce the Number of subjects while
achieving the required power of study (0.8),it is highly acclaimed
scientifically ( you may be minimizing the type 2 error) and on ethical
grounds also.
I would like to know about the FDA's stance and Has anybody submitted some
studies in replicate designs? if so what was FDA's response.
I would like to know the opinion from experts in this field about the
Pros and Cons of replicate designs to 2 way crossover designs.
regards.
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I have recently had some communication from the FDA as regards the
replicate design for bioequivalence.
In terms of the pros and cons. The biggest pros are with this design that
the subject-specific treatment means are assumed to follow a bivariate
distribution across subjects with the variances of these subject-specific
means (referred to as the between- subject variances) are not necessarily
assumed to be equal for the two treatments, T and R. Also, the
within-subject variances associated with T and R are not necessarily
assumed to be equal and can be estimated separately.
Also, the replicate design is necessary for the assessment of individual
bioequivalence.
The following is the FDA guidance on statistical approaches to establishing
bioequivalence and should help you further.
(See attached file: STATIS~1.PDF) - [Not attached - db]
Kind regards,
Alun Bedding
Clinical Pharmacology Statistician
Eli Lilly
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[I have resent the message with the URL for the attachment - db]
I have recently had some communication from the FDA as regards the
replicate design for bioequivalence.
In terms of the pros and cons. The biggest pros are with this design that
the subject-specific treatment means are assumed to follow a bivariate
distribution across subjects with the variances of these subject-specific
means (referred to as the between- subject variances) are not necessarily
assumed to be equal for the two treatments, T and R. Also, the
within-subject variances associated with T and R are not necessarily
assumed to be equal and can be estimated separately.
Also, the replicate design is necessary for the assessment of individual
bioequivalence.
The following is the FDA guidance on statistical approaches to establishing
bioequivalence and should help you further.
(See attached URL below)
http://www.fda.gov/cder/guidance/3616fnl.pdf
Kind regards,
Alun Bedding
Clinical Pharmacology Statistician
Eli Lilly
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)