3+3 dose level groups versus individualized dose titration:
Which approach maximizes the prospect for clinical benefit (a core principle for ethical clinical research) – arguably, in my view, the reason most patients take part.
Which approach best protects the study participants from harm?
Are there preferred methods to find the recommended dose (or range of doses) for different classes of study drugs?
What language is needed to inform participants about possible side effects and the potential for benefit for the competing methods in dose finding studies? For example, should the consent document explain that there’s a risk of receiving sub-clinical doses of the study drug in the 3+3 design - if you are assigned to an early dose level groups?
Should the consent explain (in plain language of course) absorption, distribution, metabolism, and excretion (ADME), and how ADME can vary among individuals, and how this can influence both the risk and the potential for meaningful activity of the drug?