Bioequivalence and Bioavailability Forum

Hey, hey wait another moment.... [General Sta­tis­tics]

posted by d_labes  – Berlin, Germany, 2018-06-28 21:48 (2299 d 16:28 ago) – Posting: # 18991
Views: 13,923
(edited on 2018-06-28 23:33)

Dear Helmut, dear other Disku-Tanten,

❝ You want to get both T1 and T2 approved.

T1 = R ∧ T2 = R: ⇒ 95% CI

Clearly needs an adjustment because of the simultaneous tests and both T1 and T2 will be marketed.

I'm not quite sure if you are right here.
Consider the analogy with the "simultaneous" tests of AUC and Cmax.
I haven't seen any alpha correction for that case .
The IUT (intersection union test) principle protects us.
But can be very conservative.

IMHO we don't need an alpha correction for your case above, if we combine the tests with 'and'.

If we combine with 'or', e.g. any of the test products T1 or T2 is choosen for further development or for approval, than we have to split the familywise level of alpha = 0.05 and the two individual null hypotheses have to be tested at a comparisonwise type I error which is a fraction of alpha, e.g. according to the Bonferroni procedure. Means 95% CIs instead of 90% CIs in case of T1, T2 and R.

Reference (wording of my post partly copied from that Reference):
Hauschke D., Steinijans V.W., Pigeot I.
Bioequivalence Studies in Drug Development: Methods and Applications.
New York: Wiley; 2007.
Chapter 7 Designs with more than two formulations / 7.4 Multiplicity

Seems a case for sims if we don't trust in the Reference. Isn't it?
Eventually we can miss-use power.2TOST() if we consider for simplicity two simultaneous test of AUC_T1R and AUC_T2R as the two metrics, which are usually interpreted as two different metrics, e.g. AUC and Cmax, respectively.
Then of course the question of the correlation parameter rho arises. How to choose?

Complete thread:

• Decision of confidence interval of three period BE study libaiyi 2018-06-26 12:00 
  • Two tests and one reference Helmut 2018-06-26 13:13
    • Two tests and one reference Brus 2020-08-31 09:58
      • Two tests and one reference ElMaestro 2020-08-31 10:23
      • Two regions: No α adjustment Helmut 2020-08-31 10:26
        • Two regions: No α adjustment Brus 2020-08-31 11:09
          • Two regions: different populations Helmut 2020-08-31 11:26
  • Decision of confidence interval of three period BE study ElMaestro 2018-06-26 22:20
    • Any of two tests and one reference Helmut 2018-06-27 00:33
      • Any of two tests and one reference libaiyi 2018-06-27 08:25
      • Hey wait a moment.... ElMaestro 2018-06-27 08:29
        • Hey wait a moment.... Helmut 2018-06-27 11:45
          • Pilot or pivotal ? Ohlbe 2018-06-27 12:14
            • Pilot or pivotal ? ElMaestro 2018-06-27 13:01
              • Pilot or pivotal ? Ohlbe 2018-06-27 14:13
                • Pilot or pivotal ? ElMaestro 2018-06-27 14:48
                  • Pilot or pivotal ? Ohlbe 2018-06-27 15:43
                    • Pilot or pivotal ? ElMaestro 2018-06-27 22:13
            • Pilot or pivotal ? jag009 2018-06-29 20:53
              • Pilot or pivotal ? ElMaestro 2018-06-29 22:11
                • Pilot or pivotal ? jag009 2018-07-03 17:38
          • Hey, hey wait another moment....d_labes 2018-06-28 19:48
            • Hey, hey wait another moment.... Helmut 2018-07-03 17:22
              • Old belives die hard d_labes 2018-07-04 13:28