Bioequivalence and Bioavailability Forum

Simulants of the world, unite! [🇷 for BE/BA]

posted by Helmut  – Vienna, Austria, 2011-01-21 15:05 (4842 d 22:02 ago) – Posting: # 6473
Views: 28,605

Ahoy ElMeastro!

❝ ❝ We can't incoporate a political constraint in an explicit statistical formula. The only way IMHO would be to go with Monte Carlo simulations.

❝

❝ I can't imagine this is really a big deal, because the chance that a PE is outside 0.8 - 1.25 while the CI still evaluates to BE must be next to nothing.

To quote from L. Tóthfalusi et al. (2009), p.739:

It is interesting to note the effect of the GMR constraint on the overall performance, notably on the producer risk of bioequivalence determinations. This effect depends on the comparative positions of the three criteria: the GMR constraint, the regulatory limit for SABE, and the estimated scaling variance. Depending on the relative magnitudes of these parameters, either SABE or the GMR restriction can become the dominant regulatory criterion. For instance, with a constraint of 0.80–1.25 on the GMR, when both the switching and scaling variations are 30%, then the combined criteria of SABE and the GMR restriction have, at moderately high within-subject variability (CV = 35%), almost the same proportion of regulatory approvals as SABE alone. In contrast, at substantially higher within-subject variability (CV = 60%), the proportion of approvals with the combined criteria is very similar to that with just the GMR constraint alone.

Have a look at Fig.2B of

Endrényi L and L Tóthfalusi
Regulatory conditions for the determination of bioequivalence of highly variable drugs
J Pharm Pharmaceut Sci 12 (1): 138-149 (2009)
online

The GMR constraint was 1.25, filled diamonds are the EMA's method (filled circles conventional ABE, open squares unconstrained SABE, open triangles PE 0.8-125 without CI = Canada C_max). Simulation: 10,000 studies, 3-period replicate, true GMR 1.0-1.6.
Due to the variability inherent to HVDs almost 40% pass at 1.25 and still ≈20% at 1.35.

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


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Science Quotes

Complete thread:

• Feature suggestion for bear and PowerTOST ElMaestro 2011-01-16 19:13 [🇷 for BE/BA] 
  • Sample size for widened scaled ABE limits d_labes 2011-01-17 13:19
    • 0.760 or... Helmut 2011-01-17 14:38
      • ... full precision is the question d_labes 2011-01-17 16:37
        • ... full precision is the question Helmut 2011-01-17 18:06
          • OT: Number of horns on a unicorn d_labes 2011-01-18 08:32
            • Goooogle Helmut 2011-01-18 11:44
    • Cadmium ElMaestro 2011-01-19 17:50
      • Never eaten Cadmium deliberately d_labes 2011-01-20 15:00
        • Never eaten Cadmium deliberately Helmut 2011-01-20 15:25
          • Call of duty for simulants d_labes 2011-01-20 16:15
            • Counterinuitive Helmut 2011-01-21 04:13
              • Counterintuitive d_labes 2011-01-21 08:36
                • Counterintuitive Helmut 2011-01-21 12:53
              • Counterinuitive, but ... d_labes 2011-01-21 12:12
                • Counterinuitive, but ... Helmut 2011-01-21 13:01
                  • Wow, Wow ... d_labes 2011-01-21 14:43
          • Never eaten Cadmium deliberately ElMaestro 2011-01-21 12:59
            • Simulants of the world, unite!Helmut 2011-01-21 14:05
              • Simulants of the world, unite! ElMaestro 2011-01-21 14:52
                • Hyslop, Howe, scaled ABE and that all d_labes 2011-01-21 15:28
                  • Hyslop, Howe, scaled ABE and that all ElMaestro 2011-01-21 15:45
                    • scABE and missings d_labes 2011-01-21 16:19
                • Intuition Helmut 2011-01-21 18:41
        • Never eaten Cadmium deliberately ElMaestro 2011-01-20 15:34
          • Use of Cadmium d_labes 2011-01-20 16:06
            • Use of Cadmium ElMaestro 2011-01-20 16:52
            • Use of Cadmium ElMaestro 2011-01-20 17:53