Escalating every six weeks instead of four: what I observed over eight months

Escalating every six weeks instead of four: what I observed over eight months Writing it up because I had to work it out twice and would rather nobody else did.

Asking about escalating every six weeks instead directly, because I have read four threads on it and each answered a slightly different question.

The version I want answered is the narrow one: given the method stated below, is the result within what anyone else has seen? I am not asking what it means yet.

Method, numbers and the two assumptions I am aware of making are below. If the assumptions are wrong that is more useful to me than agreement.

Picking up the opening post: that is the part I would want checked first.

Two things can be true about escalating every six weeks instead at once: the mechanism is plausible and the evidence for the size of the effect is thin. Most of the argument here is people defending the first against attacks on the second.

The confident answers on escalating every six weeks instead and the well-sourced answers are not the same answers, which is the most useful thing I have learned reading this category.

How the published trials escalated: they used specific step sizes and intervals. The STEP programme used a particular cadence; the SURPASS and SURMOUNT programmes used slightly different ones. Reading them side by side shows the variation is real but small.

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.

Adding the measurement that post #5 says would settle it.

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.

Filing this under things that are true until someone shows me otherwise.

The question underneath escalating every six weeks instead is usually "how would I tell?" rather than "what is true?", and that one has a method attached to it.

Write down what you would expect to see under each hypothesis before you collect anything. If they predict the same observation, collecting it will not help.

Small correction to my own earlier position on escalating every six weeks instead. I had the units the wrong way round, which changes the conclusion by an order of magnitude and therefore changes it entirely.

If you are stepping up mainly because the schedule says so rather than because the current dose has stopped doing what you wanted, that is worth noticing before rather than afterwards.

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.

I would put moderate confidence on the mainstream reading of escalating every six weeks instead and no more. That is not scepticism for its own sake; it is where the sourcing actually stops.

On escalating every six weeks instead: the maintained page in the documentation commons covers the general case with citations and a review date, which is more reliable than any reply here including this one.

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.

Happy to be the one who is wrong here if it settles the question.