Loss in power [Regulatives / Guidelines]

posted by Helmut Homepage – Vienna, Austria, 2017-05-14 19:22 (2619 d 10:33 ago) – Posting: # 17352
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Hi mittyri,

continuing the evaluation of the data sets of this post.
Background: Some studies are quite dated (the oldest performed in October 1992!). In those days a pre-specified acceptance range of 75.00–133.33% (or even 70.00–142.86%) was acceptable for Cmax. However, I evaluated all data sets for the common 80.00–125.00%. This explains why more than the expected 20% failed (no, I didn’t screw up the design ;-)). If ever possible I tried to avoid equal group sizes but kept one as large as possible. Didn’t succeed sometimes. Working in a CRO, the sponsor is always right…
All data sets were evaluated by model 3 for pooled data (like in the reports – I never cared about groups) and by model 1 to get the p value of the Group-by-Treatment interaction.Here the results:

86 studies, 60 analytes, data sets: 85 (AUC), 86 (Cmax).
Evaluated by model 1 (all effects fixed); p (G×T) <0.1:
AUC :   8.24% ( 7/85)
Cmax:  12.79% (11/86)

Summary of passing results.

AUC : model 2 (pooled)                           :  84.62% (66/78)
      model 2 (pooled without pre-test)          :  84.71% (72/85)
              loss (compared to pooled model 3)  :   1.18% ( 1/85)
      model 3 (largest group)                    :  85.71% ( 6/ 7)
      model 2 (pooled) or model 3 (largest group):  84.71% (72/85)
              loss (compared to pooled model 3)  :   1.18% ( 1/85)
      model 3 (pooled)                           :  85.88% (73/85)
              CV (range)                         :  21.36% (4.59–61.73%)

Cmax: model 2 (pooled)                           :  62.67% (47/75)
      model 2 (pooled without pre-test)          :  63.95% (55/86)
              loss (compared to pooled model 3)  :   0.00% ( 0/86)
      model 3 (largest group)                    :  27.27% ( 3/11)
      model 2 (pooled) or model 3 (largest group):  58.14% (50/86)
              loss (compared to pooled model 3)  :   5.81% ( 5/86)
      model 3 (pooled)                           :  63.95% (55/86)
              CV (range)                         :  27.88% (6.82–76.99%)

The loss in power if we follow the FDA’s procedure (compared to the pooled model 3) is lower than I expected. Surprise. A possible explanation is that studies were usually powered for Cmax. Therefore, already the largest groups passed AUC.
On another note: If we apply model 2 without a pre-test (maybe the best way to go for regulators insisting in a group-term) the loss in power compared to the pooled model 3 is negligible. Reasonable, since we lost only few residual degrees of freedom:
pooled model 3: DF=n1+n2–2
pooled model 2: DF=n1+n2-(Ngroups–1)–2

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