## Steampunk [RSABE / ABEL]

Hi Nastia,

» » The problem starts already here. How reliable is Oodendijk’s result? Is it the only one?

»

» The reliability of someone else's data - that is the question (especially when one of the authors says "waouf"

» » The crucial point is what we consider a

»

» As far as we (and the Agency) proclaim 25% to be clinically not relevant there is no difference in the rate of the harm for the customer's health independently from the a- or b- approach. For the b-approach he'll just receive not worser drug or doesn't receive it at all.

Here you err. In (a) all is good. In (b) everything is in a flux; the applicant and agency agree only that the acceptable risk may be either 20% or 25%.

We are dealing with

» » Try the function

» I try:

»

» As CI is shifted to the right …

Skewed to the right because the variance follows a \(\small{\chi^2}\)-distribution.

» … does it mean that for these initial conditions the probability of the conclusion of HV is higher?

Yes (for

» (By the way shouldn't we lower the degrees of freedom for the CV of the reference drug? 3*40-3 should correspond to the common CV of the Test and Reference, shouldn't it?)

Oops,

» » The problem starts already here. How reliable is Oodendijk’s result? Is it the only one?

»

» The reliability of someone else's data - that is the question (especially when one of the authors says "waouf"

*Willard Oodendij*k twittered and*Nemo Macron*said “waouf”.» » The crucial point is what we consider a

*“clinically not relevant \(\small{\Delta}\)”*»

» As far as we (and the Agency) proclaim 25% to be clinically not relevant there is no difference in the rate of the harm for the customer's health independently from the a- or b- approach. For the b-approach he'll just receive not worser drug or doesn't receive it at all.

Here you err. In (a) all is good. In (b) everything is in a flux; the applicant and agency agree only that the acceptable risk may be either 20% or 25%.

We are dealing with

*average*BE. Classifying HVD(P)s based on CV_{wR}is fine in principle. However, once we make this classification*post hoc*(based on \(\small{\widehat{CV_\textrm{wR}}}\)), troubles start. Hence, I don’t like* the reference-scaling methods and (b) as well.» » Try the function

`CVCL()`

in `PowerTOST`

.» I try:

»

`library(PowerTOST)`

» `CVCL(CV = 0.3, df = 3*40-4, side ="2-sided")`

» ` lower CL upper CL`

» `0.2646219 0.3466708`

» As CI is shifted to the right …

Skewed to the right because the variance follows a \(\small{\chi^2}\)-distribution.

» … does it mean that for these initial conditions the probability of the conclusion of HV is higher?

Yes (for

*any*condition).» (By the way shouldn't we lower the degrees of freedom for the CV of the reference drug? 3*40-3 should correspond to the common CV of the Test and Reference, shouldn't it?)

Oops,

*one more*degree of freedom! In the 2-sequence 4-period replicate design we have df = 3n – 4 for the pooled CV_{w}. Following the EMA’s model for the estimation of CV_{wR}we have one factor (the treatment)*less*in the model and therefore, df = 3n – 3:`library(PowerTOST)`

CVCL(CV = 0.3, df = 3*40-3, side = "2-sided")

lower CL upper CL

0.2647549 0.3464397

- Not for an initiate like you but others:
- Such a study is not bijective like when assessed for ABE. Whereas in ABE we could reverse the procedure (if T ≈ R also R ≈ T), this is highly unlikely here (only if CV
_{wR}≡ CV_{wT}).

- In ABE every application has to follow the same rules and \(\small{\Delta}\) is known. Here every study
*sets*its own rule. The BE-limits and hence, \(\small{\Delta}\) are random variables. Without access to the study report patients and physicians don’t know the risk.

- Such a study is not bijective like when assessed for ABE. Whereas in ABE we could reverse the procedure (if T ≈ R also R ≈ T), this is highly unlikely here (only if CV

—

Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮

Science Quotes

*Dif-tor heh smusma*🖖Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮

Science Quotes

### Complete thread:

- Inflated type I error with fixed widened limits? Helmut 2020-11-25 10:50 [RSABE / ABEL]
- Inflated type I error with fixed widened limits? d_labes 2020-11-25 15:07
- Inflated type I error with fixed widened limits? Helmut 2020-11-26 00:09
- Inflated type I error with fixed widened limits d_labes 2020-11-26 15:38
- Inflated type I error: Not nice Helmut 2020-11-26 17:14
- Power of the GCC framework and power of PowerTOST d_labes 2020-11-28 11:20
- Sample sizes (ignoring the inflated TIE) Helmut 2020-11-29 11:21

- Power of the GCC framework and power of PowerTOST d_labes 2020-11-28 11:20

- Inflated type I error: Not nice Helmut 2020-11-26 17:14

- Inflated type I error with fixed widened limits d_labes 2020-11-26 15:38

- Inflated type I error with fixed widened limits? Helmut 2020-11-26 00:09
- Inflated type I error with fixed widened limits? wienui 2020-11-29 14:03
- Inflated type I error with fixed widened limits d_labes 2020-11-29 17:51
- Inflated type I error with fixed widened limits Helmut 2020-11-30 00:14
- Inflated type I error with fixed widened limits wienui 2020-11-30 03:30
- Houston, we have a problem! Helmut 2020-11-30 14:42
- Paradox of tolerance Astea 2020-12-01 23:34
- Οὐτοπεία ∨ Εὐτοπεία Helmut 2020-12-02 01:37
- Uchronia Astea 2020-12-02 09:46
- SteampunkHelmut 2020-12-02 11:34
- Dieselpunk Astea 2020-12-02 15:28
- Dieselpunk Helmut 2020-12-02 16:18

- Steampunk? OT d_labes 2020-12-02 19:30
- Steampunk? OT Astea 2020-12-02 19:58

- Dieselpunk Astea 2020-12-02 15:28

- SteampunkHelmut 2020-12-02 11:34

- Uchronia Astea 2020-12-02 09:46

- Οὐτοπεία ∨ Εὐτοπεία Helmut 2020-12-02 01:37

- Paradox of tolerance Astea 2020-12-01 23:34
- PowerTOST 1.5-2.9000 on GitHub Helmut 2020-12-23 12:18

- Houston, we have a problem! Helmut 2020-11-30 14:42

- Inflated type I error with fixed widened limits wienui 2020-11-30 03:30

- Inflated type I error with fixed widened limits Helmut 2020-11-30 00:14

- Inflated type I error with fixed widened limits d_labes 2020-11-29 17:51

- Inflated type I error with fixed widened limits? d_labes 2020-11-25 15:07