Bioequivalence and Bioavailability Forum

Dear all,

we are collecting data for a publication about the annoying ‘Group-by-Treatment interaction’ (for some thoughts see this article).
Below what we have so far in a small meta-analysis of multi-group studies:

To make a long story short: As expected, significant Group-by-Treatment interactions were detected at approximately the level of the test (0.1). Hence, based on our observations in well-controlled studies likely they are mere ‘statistical artifacts’, i.e., false positives. The Kol­mo­go­rov–Smirnov tests were not significant, accepting the expected standard uniform distribution of \(\small{p(G\times T)}\).

Any type of comparative BA study (BE, food-effect, DDI, dose-proportionality) is welcome.
Of course,  data will be treated strictly confidential and not published . The preferred data format is CSV (though xls(x), ODS, SAS XPT or Phoenix project files would serve as well).

Columns (any order is fine):

1. Company or individual (text)
   
2. Study code (text)
   
3. Analyte (text) if you don’t want to give this information, use not spec. X, where X is an integer 1 … number of analytes
   
4. Design (2x2x2, 3x6x3, 3x3, 4x4, 2x2x4, 2x2x3, 2x3x3)
   Simple crossover, 6-sequence 3-period Williams’ design, 3-period Latin Squares, 4-sequence 4-period Williams’ design or 4-period Latin Squares, 2-sequence 4-period full replicate, 2-sequence 3-period full replicate, partial replicate; no parallel design
   
5. Drug (integer) 1 … number of analytes
   
6. Subject (integer or text) min(n) … max(n); missings due to dropouts not a problem
   
7. Group or Site (integer) 1 … number of groups / sites
   
8. Sequence (character or integer), e.g., TR, RT or AB, BA or 1, 2 (simple crossover), e.g., TRTR, RTRT or TRT, RTR (full re­pli­cate designs), TRR, RTR, RRR (partial re­pli­cate design), ABC, BCA, CAB (Latin Squares), ABC, ACB, BAC, BCA, CAB, CBA (Williams’ design)
   Essentially any kind of coding is possible, as long as it is unambiguous.
   
9. Treatment (character) mandatory T or R (not A or B)
   
10. Period (integer) 1 … number of periods
    
11. AUC (numeric); for single dose AUC_0–t or AUC_0–72, for multiple dose AUC_0–τ.
    Missing values should be coded with NA (preferred) or Missing.
    
12. C_max (numeric)

Optional columns:

• Interval (integer) days separating groups; only if equal across groups
  
• Sex (character) f or m

If you want to participate, please send data to [email protected].
No cherry-picking, otherwise we will fall into the trap of selection bias and the outcome will be useless. Hence, if you decide to provide data, please do so irrespective of whether you ‘detected’ a significant Group-by-Treatment interaction or not.
We are primarily working on 2×2×2 crossover designs. How­ever, if you have data of replicate designs, fine as well. In Higher-Order crossover designs indicate which of the treatments is the test and the reference.
If possible, give the analyte. Once we have enough data sets, we will perform sub-group analyses.

So far we have only data of one multi-site study. If you could share some data, great.

THX in advance!