This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1.
Post #120 answers the question as asked. The question underneath it is different.
Where I have landed on steady state, having got it wrong once in public: the direction is clear, the magnitude is not, and anyone quoting a precise magnitude has borrowed it from somewhere that did not measure it.
I read post #118 twice before replying, because I had assumed the opposite.
Worth separating steady state as a question about the compound from steady state as a question about the documentation. They get answered by different people and only one of them is answerable here.
Concentration and dose get conflated constantly in this subcategory. Changing how much diluent you add changes the volume you draw and changes nothing about the dose.
There is no published evidence about slower escalation because nobody studied it. That means the trials support not going faster and are silent on going slower, which is a different claim from "slower is fine".
The four-week escalation interval is a convention from the pivotal trials, not a pharmacological constant. The pharmacological argument is that with a week-long half-life, four weeks approaches steady state and you can assess the dose fairly. That is an argument for not going faster. It is not an argument against going slower.
Thank you — that answers what I came here to find out.
Steady state has a well-known answer and a correct answer, and the interesting work is establishing that they are the same. Nobody has done that here yet.
Good question, well framed, and I would like to see it answered properly.
Picking up post #129: that is the part I would want checked first.
Escalating before steady state means you are judging a dose you have not yet fully experienced. That is the whole argument against compressing the schedule and it is a good one.
The step people skip is the one I have spelled out.
Steady state looks different depending on whether you are reading the primary literature or the summaries of it, and the difference is not in our favour.
Steady state means the plasma concentration is stable from dose to dose. That happens around 4 to 5 half-lives. Before that, the concentration is rising with each dose. Escalating before steady state means escalating on incomplete information about the dose you are on.
This follows post #134 rather than contradicting it.
Small methodological point on steady state: repeating a measurement is cheap and resolves most of what is being argued about here at no cost to anyone.
I read post #134 twice before replying, because I had assumed the opposite.
Concentration and dose get conflated constantly in this subcategory. Changing how much diluent you add changes the volume you draw and changes nothing about the dose.
That is all I can say without guessing.
Two questions I would want answered before drawing anything from the steady state data above: how were the cases selected, and what happened to the ones that dropped out.
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