Bioequivalence and Bioavailability Forum

To pool or not to pool [Software]

posted by Helmut  – Vienna, Austria, 2014-06-30 22:51 (3948 d 09:44 ago) – Posting: # 13177
Views: 27,093

Hi Zan,

❝ […] If there is a significant treatment*Group effect, is the overall (all subject) ratio (CI90%) still valid, or we have to adopt the ratio (CI90%) from separate groups?

If you pool groups you’ll end up with common estimates of between- and within-subject variances. If groups are different in their responses to the treatments you will not get pooled unbiased esti­mates. AFAIK, there is not corrective method. Theoretically – if you would know (!) the correlations between intra-/inter-subject variances, take the group sizes into account,  – maybe some fancy weighting is possible. But: Estimates of these effects are not accessible in a simple 2×2 cross-over. Too many questions asked to poor little data.

❝ Regarding FDA's requirement below (equiva­lence be demonstrated in one of the groups), do we have a link to the source of the letter? I am hoping to keep it as a reference for study files.

Nope. I have seen similar wordings in confidential letters (and Detlew as well). Most phrases were identical to the letter. Copy/paste at the FDA?

❝ ❝ If the Treatment-by-Group term is not significant (p ≥0.1) this term can be dropped from the model, proceeding to Group Model II.

At least a similar quote in this post. I’m not in the office; will check tomorrow whether the signi­fi­cance level (0.05 different to FDA’s 0.1) is not a typo.

Do you have any good reasons to walk this dirty road at all? Multi-site study or the like? A split due to logistic reasons is very (very) common in BE. I have limited experience with the FDA, but in 30+ years I have neither seen a single BE study in Europe including group term(s) nor heard of any as­ses­sor asking for one. All trouble I experienced came from MENA-countries & Gulf states.

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


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

Complete thread:

• Phoenix WNL to handle 2x2 crossover study with multip group zan 2014-06-27 23:29 
  • Phoenix WNL to handle 2x2 crossover study with multip group ElMaestro 2014-06-28 23:23
  • Group effect commonly not relevant Helmut 2014-06-30 16:55
    • Group effect in 2x2 BE study zan 2014-06-30 19:18
      • Group effect in 2x2 BE study ElMaestro 2014-06-30 20:36
      • To pool or not to poolHelmut 2014-06-30 20:51
        • To pool or not to pool zan 2014-06-30 21:02
          • To pool or not to pool Helmut 2014-06-30 21:38
            • To pool or not to pool zan 2014-06-30 21:46
              • To pool or not to pool Helmut 2014-06-30 22:22
                • To pool or not to pool zan 2014-07-01 01:15
                  • Partial vs. sequential tests in WNL Helmut 2014-07-01 12:26
                    • Partial vs. sequential tests in WNL zan 2014-07-01 18:03
                      • Loosing patience Helmut 2014-07-01 18:23
            • To pool or not to pool ElMaestro 2014-06-30 22:11
              • To pool or not to pool zan 2014-07-01 01:18
              • To pool or not to pool zan 2014-07-02 19:56
                • To pool or not to pool ElMaestro 2014-07-03 00:17
                  • To pool or not to pool zan 2014-07-03 00:36
                • sequence- / period effect #666 Helmut 2014-07-03 10:05
    • Group effect commonly not relevant AngusMcLean 2014-07-06 16:19
      • Group effect commonly not relevant Helmut 2014-07-06 20:32
        • Group effect commonly not relevant AngusMcLean 2014-07-06 22:52
          • Group effect commonly not relevant Helmut 2014-07-06 23:57
            • PHX: Parameter mapping AngusMcLean 2014-07-07 15:04
              • PHX: Parameter mapping Helmut 2014-07-07 15:45
                • PHX: Parameter mapping Shuanghe 2014-07-07 17:35
                  • Great hint! Helmut 2014-07-07 17:54
                  • PHX: Parameter mapping AngusMcLean 2014-07-07 20:49
                • PHX: Parameter mapping AngusMcLean 2014-07-07 18:46