Bioequivalence and Bioavailability Forum

RSABE ⇒ ABEL [General Statistics]

posted by Helmut – Vienna, Austria, 2017-03-03 14:34 (3051 d 01:54 ago) – Posting: # 17126
Views: 20,792

Hi VStus,

❝ I have limited data about partial replicate trial (2x3x3) with RSABE, which I want to use to assess the feasibility of same study under EMA regulation (assuming that EU has the same Reference product as US).

❝ Reported parameters:

❝ Number of subjects (observations per treatment arm)

❝ Swr estimated using PROC GLM

❝ Point Estimate (%) from RSABE-approach

❝ […]

❝ Is it feasible to try calculation of 90% CIs?

Yes.

❝ Can I apply the formula below?

❝ 90% CI = log(Point_Estimate) +/- Swr * qt(0.05, df))*100,

No (see this post). Let’s compare the EMA’s Q&A dataset II (n = 24; n₁ = n₂ = n₃ = 8), evaluated by the FDA’s RSABE (PE = 1.022644, s_wR = 0.11397298) with results of the EMA’s methods: PE 102.26%; 90% CI: Methods A/B 97.32–107.46%, Method C 97.05–107.76%.

n <- c(8, 8, 8) pe <- 1.022644 swR <- 0.11397298 CI <- exp(log(pe) + c(-1, +1)*qt(1-0.05, 2*sum(n)-3)*sqrt(1/6*swR^2*sum(1/n))) names(CI) <- c("lower", "upper") round(100*CI, 2) # lower upper # 97.49 107.28

Alternatively:

library(PowerTOST) round(100*CI.BE(pe=pe, CV=se2CV(swR), n=n, design="2x3x3"), 2) # lower upper # 97.49 107.28

Pretty close but in this case (s_wR <0.294) the FDA requires a mixed-effects model for ABE, where s²_wR = 0.013246498 (PE 102.26%, 90% CI 97.05–107.76%). Hence, we have to take that into account.

library(PowerTOST) n <- c(8, 8, 8) pe <- 1.022644 s2wR <- 0.013246498 round(100*CI.BE(pe=pe, CV=mse2CV(s2wR), n=n, design="2x3x3", robust=TRUE), 2) # lower upper # 97.32 107.46

Or the hard way:

CI <- exp(log(pe) + c(-1, +1)*qt(1-0.05, sum(n)-3)*sqrt(1/6*s2wR*sum(1/n))) names(CI) <- c("lower", "upper") round(100*CI, 2) # lower upper # 97.32 107.46

Bingo!

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Helmut Schütz

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Complete thread:

Confidence Interval for Transformed data Unbalanced study usfda_emea 2007-03-06 14:39
- CI for Transformed data Unbalanced study Helmut 2007-03-06 16:46
  - CI for Transformed data Unbalanced study drshiv 2007-03-06 18:49
  - CI for Transformed data Unbalanced study usfda_emea 2007-03-07 06:21
    - CI for Transformed data Unbalanced study Helmut 2007-03-07 12:04
      - CI for Transformed data Unbalanced study usfda_emea 2007-03-07 12:34
      - CI for Transformed data Unbalanced study Ohlbe 2014-07-30 15:04
        
        LSM limbo Helmut 2014-07-31 02:54
        
        LSM limbo Ohlbe 2014-07-31 09:47
        90% CI limbo VStus 2017-03-01 14:07
        
        RSABE ⇒ ABELHelmut 2017-03-03 13:34
        
        RSABE ⇒ ABEL VStus 2017-03-03 15:31
        
        s2wR != mse, FDA != EMA d_labes 2017-03-04 14:49
        
        s2wR != mse, FDA != EMA ElMaestro 2017-03-04 19:13
        
        s2wR from ISC in FDA approach d_labes 2017-03-05 12:18
        
        s2wR from ISC in FDA approach ElMaestro 2017-03-05 13:50
        
        s2wR != mse, FDA != EMA VStus 2017-03-04 21:41
        
        s2wR != mse, FDA != EMA Helmut 2017-03-06 13:40

RSABE ⇒ ABEL [General Sta­tis­tics]

Complete thread:

RSABE ⇒ ABEL [General Statistics]