Bioequivalence and Bioavailability Forum

Reference scaled BE - EMA [RSABE / ABEL]

posted by Helmut  – Vienna, Austria, 2010-04-27 16:58 (5481 d 01:56 ago) – Posting: # 5249
Views: 36,467

Dear Dave & all,

THX again for the update!

<nitpicking>

What do you think about the switching condition theta_s (aka regulatory constant k)?

</nitpicking>

EMA did not give details of the calculation and (for simplicity?) used k=0.760. Actually it's based on the regulatory standardized variation sigma₀ (i.e., the limit for HVDs/HVDPs). For CV_WR=30% we get sigma₀=sqrt[ln(0.3²+1)]=0.293560379... and theta_s=k=ln(1.25)/sigma₀=0.760128298... Backcalculating from 0.760 one would get a limit for HVDs/HVDPs of 30.005%.
This explains small discrepancies between tables of Tóthfalusi et al. (2009), EMA (2010), and exact values.

        Tóthfalusi      EMA GL         exact
CV (%)   L     U      L      U       L      U
 30     80.0 125.0   80.00 125.00   80.00 125.00
 35     77.2 129.5   77.23 129.48   77.23 129.49
 40     74.6 134.0   74.62 134.02   74.61 134.02
 45     72.2 138.6   72.15 138.59   72.15 138.60
 50     69.8 143.2   69.84 143.19   69.83 143.20
 55     67.7 147.8   like CV 50 %   67.65 147.81
 60     65.6 152.4   like CV 50 %   65.61 152.42

In other words, what value would you use? 0.760 because stated as such in the guideline, or the exact value based on CV_WR 30%? It's similar to the limit for NTIDs: L=0.9 and U=1/L=1.1... (not 1.1111).

@Dave: For Method A – Direct Expansion of BE limits (outdated in the EU soon, but still applicable in other countries) the limits are L=0.75 and U=1/L=1.3 (not 1.33 as in cell Y10).

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна! 
Helmut Schütz


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Science Quotes

Complete thread:

• Reference scaled BE - FDA (and FARTSSIE update) ddubins 2010-04-26 20:28 [RSABE / ABEL] 
  • Reference scaled ABE - FDA d_labes 2010-04-27 08:58
    • Reference scaled ABE - FDA ElMaestro 2010-04-27 13:39
      • Factor 2 is unbiased d_labes 2010-04-27 14:30
      • Biased bonus from MoM d_labes 2010-05-04 12:10
        • Biased bonus from MoM ElMaestro 2010-05-04 12:54
          • Mixed MoM d_labes 2010-05-04 14:40
            • Mixed MoM ElMaestro 2010-05-04 15:08
              • R and G, CSH and UN d_labes 2010-05-05 10:42
                • A sailor gets confused ElMaestro 2010-05-05 11:49
                  • Confused V/Z matratzen and tips d_labes 2010-05-05 14:49
                    • superb post! ElMaestro 2010-05-05 21:32
                      • Gambling with UN d_labes 2010-05-06 11:00
            • Mixed MoM yjlee168 2010-05-05 09:12
  • Reference scaled BE - FDA (and FARTSSIE update) KR 2010-04-27 13:14
  • Reference scaled BE - EMAHelmut 2010-04-27 14:58
    • Reference scaled BE - EMA ddubins 2010-04-27 17:52
      • Partial replicate design and FDA ABE code d_labes 2010-04-28 09:47
      • Reference scaled BE - EMA Helmut 2010-04-28 14:46
      • Switching - null sWR d_labes 2010-05-04 14:04
  • The unknown x d_labes 2010-05-06 13:26
    • The unknown x jdetlor 2010-09-28 17:22
      • Unknown x corrected? d_labes 2010-10-01 12:14
        • Unknown x corrected? Qilex 2016-09-21 12:25
          • Official unknown x d_labes 2016-09-21 13:22