Bioequivalence and Bioavailability Forum • Assumptions…

Assumptions… [Power / Sample Size]

posted by Helmut – Vienna, Austria, 2019-09-09 19:19 (1854 d 18:57 ago) – Posting: # 20562
Views: 6,960

¡Hola Rocco!

❝ When you run a FIM, you do not have two populations. You have a treatment and (perhaps) a control. So if you have a geometric CV, say, CV1 calculated from that one treatment sample in the FIM.

Correct, so far.

❝ It is not pooled variance, is it? There is only one sample…

Here you err. Although we have just one sample, we have two variances, between- (that’s obvious) and within-subjects (not so obvious). The fact that you administered the drug on one occasion does not mean the within-subject disappears. Administer the same drug the next day and you will get different concentrations. Hence, within-subject variance is always there, we can only not estimate it. We get only the total (or pooled) variance. Given, generally CV_b > CV_w but there are cases where it is the other way ’round. We simply don’t know.

❝ … there and then use it to design a parallel follow-up, do you need to assume that the CV of the other arm, call it CV2, is equal to CV1,…

Yes.

❝ … and then CVp = pooled(CV1,CV2) as input into sample size formula, eg, sampleNTOST?

Wait a minute. CV2 is unknown until we performed the parallel study. Therefore, simply plug in the one you found in the FIM study.

❝ […] I do not seem to understand what are the components of the pooled variance that go into the sample size computation.

See my previous post, esp. case #4. We have one variance, which is pooled from s²_w and s²_b. Maybe the terminology is confusing. Pooling does not mean that we have the individual components. We know only the result and there is is an infinite number of combinations which gives the same result. However, that’s not important. In planning the parallel design you need only the CV1 and have to assume that CV2=CV1.

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Complete thread:

Input for CV when small first-in-man has been run Rocco_M 2019-09-03 18:45 [Power / Sample Size]
- Geometric mean and CV Helmut 2019-09-05 14:05
  - Geometric mean and CV Rocco_M 2019-09-05 23:49
    - Geometric mean and CV Helmut 2019-09-06 00:15
      - Geometric mean and CV Rocco_M 2019-09-06 17:49
        
        Geometric mean and CV Helmut 2019-09-06 18:15
        
        Geometric mean and CV ElMaestro 2019-09-06 19:03
        
        Geometric mean and CV Helmut 2019-09-07 09:57
        
        Geometric mean and CV Rocco_M 2019-09-09 13:31
        
        Assumptions… Helmut 2019-09-09 14:09
        
        Assumptions… Rocco_M 2019-09-09 16:35
        
        Assumptions…Helmut 2019-09-09 17:19
        
        Assumptions… Rocco_M 2019-09-13 21:28
        
        t-test & Welch-test Helmut 2019-09-14 00:16
        
        sampleN.TOST and CI.BE Rocco_M 2019-09-17 22:02
        
        assumptions vs. realizations Helmut 2019-09-18 11:04