Profiles with no measurable concentrations [Outliers]

posted by ElMaestro  – Denmark, 2011-10-06 19:45 (4261 d 01:57 ago) – Posting: # 7437
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Dear all,

I have a lot of sympathy for Dr_Dan's post here:
Do we really want to try to conclude a lot about product performances when this happens? Or should we rather stop for a second and start thinking and focus on trial performance instead?

If a subject's PK is just a row of BLQ's then something very basic, whatever it is, went badly wrong (yeah right, he/she could be a supergiga-metaboliser. Not). For me personally, I would not think primarily of product failure (as in a tablet with zero API) - I think other reasons come more realistically to mind, but that's just me and it is said with reference to the rather strict GMP and release criteria in EU.

I know I am going to extremes here but considering eg. ICH E6 2.2 ('Before a trial is initiated, foreseeable risks and inconveniences should be weighed against the anticipated benefit for the individual trial subject and society. A trial should be initiated and continued only if the anticipated benefits justify the risks.') or 2.5 ('Clinical trials should be scientifically sound, and described in a clear, detailed protocol.'), if a trial has a subset subjects having just BLQ's would lead me to think the following:
  1. The trial's outcome itself might be dubious, regardless of product performance.
  2. I want to know why it happened.
  3. I want to know how to prevent it from happening again cf. the quotes above, otherwise there may be a potential element of futility in future trials, and regulators -notably FDA imho- can have a very big problem with that.
I do acknowledge that a reason for mishaps cannot always be identified. But there is no excuse for not trying very very hard, mefinks.

Pass or fail!

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