fixed swr [RSABE / ABEL]

posted by Helmut Homepage – Vienna, Austria, 2013-03-28 23:34 (2967 d 20:12 ago) – Posting: # 10306
Views: 18,188

Hi Martin!

» What do you think about a kind of adaptive group-sequential design with one interim analysis (i.e. estimate CV) allowing to make a decision regarding average BE or scaled BE in the final analysis? This may solve the problem.

Nope. Actually the methods are (hidden) sequential.
Most clear in the FDA’s guidance:

Determine sWR, the within-subject standard deviation (SD) of the re­fe­rence pro­duct, for the pharmacokinetic (PK) parameters AUC and Cmax.

  1. If sWR < 0.294,1,2 use the two one-sided tests procedure to determine bio­equi­valence (BE) for the individual PK parameter(s)
  2. If sWR ≥ 0.294,2 use the reference-scaled procedure to determine BE for the in­di­vidual PK parameter(s)
However, once scaling is justified (sWR ≥ 0.294), the extent of scaling is still data-driven (dependent on sWR from the study). IMHO the problem would only vanish if regulators publish a fixed value of sW for each reference which has to be used independent from the findings in the study.

  1. sWR 0.294 ~ CVWR 0.300469…
  2. We see the worst inflation at CVWR 0.3. Maybe it would be better to use ABE if sWR 0.294 and RSABE if sWR > 0.294.

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Helmut Schütz

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