RE: What are the best studies to combine?

From: Mark Sale - Next Level Solutions mark@nextlevelsolns.com Subject: RE: [NMusers] What are the best studies to combine? Date: Thu, 30 Mar 2006 13:22:18 -0700 IMHO, this is a perfectly fine combination, with (of course) a few caveots. First, one must always have a set of objectives in mind when selecting data and a modeling approach. If you are interested in defining differences between HV and patients, or IV and SC then clearly these data will be helpful. If you have no interest in the SC absorption, and you have enough data (enough individuals, rich enough) in the HV IV study, then don't include the SC etc, etc. But, it sounds like your interest might include KA for SC administration, and if you have inadequate data in the patient population alone, then might consider adding the HV with SC. If you have inadequate data to define the distribution/elimination in the patient data and HV SC data, you might consider adding the IV (which will likely better define the distribution, possibly the elimination). Caveot #2, you MUST ALWAYS, at least consider that these different populations are different in important ways. Might be safe (please note might) to assume that the 2 HV populations are the same (especially if the entry criteria/demographics, formulation, assay method etc) are the same. But, I'd suggest you are obligated to test whethe the patient population is different, in pretty much every parameter (clearance, KA, lag time, volume - maybe even K12/K21). Probably should consider even whether the structural model (# of compartments) is different - although if found to be, it may be just as likely that sampling scheme difference results in the appearance of structural differences. Finally, you should also consider whether the interindividual or (especially) residual error is different. So, yes, by all means combine data if the objectives of the analysis warrant it. But, consider all the possible (biologically plausible) ways that the different populations might be different - and test the ones you can test. Not sure what you mean by estimate of KA, given observation prior to dosing - is this an endogenous compound? But, in general, yes it should be OK. Mark Sale MD Next Level Solutions, LLC www.NextLevelSolns.com