NTIDs # HVDs (or not?) [Design Issues]

posted by Helmut Homepage – Vienna, Austria, 2010-06-07 16:18 (5015 d 07:18 ago) – Posting: # 5453
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Dear Jo!

❝ Which is the most appropriate design for a narrow therapeutic index drug with very high intra-subject variability?

This is strange. NTIDs are generally not highly variable – otherwise they wouldn’t have ‘survived’ the MA in the first place.

❝ For example, we have an immunosuppressive agent with an intra-subject CV% > 45%.

Oops?! Can you give us the name of the drug?

❝ Using a standard two – way crossover design with acceptance interval tightened (90.00 – 111.11%), we will have a sample size of more than 300 subjects :-(.


❝ It is possible to use a replicate design in this situation?

If we are talking about immunosuppressants, we are talking about a study in patients, right? Steady state too. Likely parallel design – it’s unethical to interrupt treatment by a washout. The disease state may change between periods which will prevent a cross-over anyhow.
Even if you opt for a cross-over, a replicate design doesn’t help in the reducing the numbers of treat­ments applied (or in other words, the number of biosamples and study costs). If the 2×2 study size is 300, the size for a 4-period replicate is still 150, but expect more drop-outs and problems with the increased number of blood samples / subject.

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