Bioequivalence and Bioavailability Forum • Validation?

Validation? [Software]

posted by Helmut – Vienna, Austria, 2015-12-30 17:02 (3334 d 12:19 ago) – Posting: # 15783
Views: 17,810

Hi G.C.,

❝ […] for most of the cases we are validating our methods and software tools based on regulatory's guideline data.

Not a particularly good idea. What’s written in GLs is not necessarily correct. F.i. the CV_intra in Canada’s BE guidance example data set was wrong for decades. Not only the value, but also the formula. See this presentation about validation of software.

❝ The same we are doing for this ED50 calculation. We tried many tools but none of them match exactly or come too closer to guideline data result.

❝

❝ You have written that model is wrong, which model are you talking ? Is it mentioned in guideline ? OR any other ?

Since the FDA reported only E_max and ED₅₀ on p.29 I used the simple model $$E=(E_\text{max}\times D)/(E_{50}+D)\tag{1}$$ The GL mentions on p.4 also the baseline model
$$E=E_0+(E_\text{max}\times D)/(E_{50}+D)\tag{2}$$ Let’s compare them (fitting mean data)

Emax ED50 E0 AIC (1) 1.139 -39.764 – 47.85 (2) 1.183 -39.523 -0.449 49.85

Since the AIC of the simple model is lower than the one of the baseline model, $\small{(1)}$ is the winner. Selection based on the minimum AIC is the easiest approach in comparing models. Alternatively you could run an F-test.

❝ You have compared the results and there is difference also, our question is also the same if values are different compare to guideline than is it acceptable to use that tool ?

Which tool? I cannot imagine that you will be able to find any software which comes even close to the FDA’s results. Not by any chance the software vendor went out of business. In the same guidance the FDA asked for data submitted on a diskette without specifying details. 8", 5¼", 3½"? If you want to be fully compliant, visit the next waste disposal site and search for a floppy drive. You could also ask the FDA for a copy of the famous P-Pharm software.

❝ Finally do you have any preference for software to use for this calculation ?

Phoenix/NLME. In R: nls/nlme/lme4, though it is not that easy to guess suitable starting values and specify weighting schemes.

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Complete thread:

Emax and ED50: NLME gcpatel126 2015-12-09 18:08 [Software]
- Emax and ED50: NLME Helmut 2015-12-10 02:09
  - Emax and ED50: NLME gcpatel126 2015-12-10 17:34
    - Emax and ED50: NLME SDavis 2015-12-15 11:50
      - Emax and ED50: NLME gcpatel126 2015-12-29 15:49
        
        Emax and ED50: NLME Helmut 2015-12-29 17:46
        
        Emax and ED50: NLME gcpatel126 2015-12-29 18:04
        
        Emax and ED50: NLME Helmut 2015-12-29 19:36
        
        Emax and ED50: NLME gcpatel126 2015-12-30 14:43
        
        Emax and ED50: NLME Helmut 2015-12-30 14:56
        
        Emax and ED50: NLME gcpatel126 2015-12-30 15:19
        
        Validation?Helmut 2015-12-30 16:02
        
        Validation? gcpatel126 2015-12-30 17:47
        
        Validation? Helmut 2015-12-30 21:15
        
        Validation? gcpatel126 2015-12-31 07:06
        
        Validation? gcpatel126 2016-01-11 14:54
        
        EOD Helmut 2016-01-11 22:13