Confirming the opening post from a second method, which matters more than confirming it from a second person. What I would want before treating micro-titration as settled: the method, the sample, and whether anyone tried to find the opposite result. Two of the three are usually missing.
Micro-titration: a disputed topic, argued properly Writing it up because I had to work it out twice and would rather nobody else did.
Two things I would like separated before anyone answers on micro-titration, because they get bundled and then argued about as one thing.
The first is descriptive: what has actually been observed, by whom, and how. The second is causal: why. I am asking about the first only.
Confirming the opening post from a second method, which matters more than confirming it from a second person.
What I would want before treating micro-titration as settled: the method, the sample, and whether anyone tried to find the opposite result. Two of the three are usually missing.
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.
I am not the right person to answer the follow-up to this.
Post #4 is the version of this I will quote in future. One addition.
Taking micro-titration seriously for a moment rather than deflecting: the honest position is that the community has observations and no controlled comparison, and those two things support very different sentences.
The starting dose in most of these programmes is a tolerance step and produces little effect by design. Judging the compound at the starting dose is judging the wrong thing.
Small correction to my own earlier position on micro-titration. I had the units the wrong way round, which changes the conclusion by an order of magnitude and therefore changes it entirely.
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.
I looked this up rather than remembered it, which is the right order.
Micro-titration: the concept of increments smaller than the labelled steps. It has no evidence base from trials but is described by some people. The downside is that very small increments are hard to measure accurately with a syringe.
The honest answer is that it depends, and here is what it depends on.
Distinguishing three things in the micro-titration discussion that keep getting used interchangeably: the observation, the proposed mechanism, and the recommendation that gets attached to both.
Where I part company with post #12, and it is a narrow parting.
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.
Take the reasoning and check the arithmetic; I do not always get it right.
Adding a null result on micro-titration. I looked, carefully, and found nothing, and null results deserve posting precisely because they never are.
Confirming post #14 from a second method, which matters more than confirming it from a second person.
A titration plan written down in advance is easier to stick to and easier to abandon deliberately. An improvised one becomes a series of decisions made on the worst day of each week.
The variance between people here is larger than the effect being discussed.
Where the micro-titration reasoning breaks down for me is the step from the group result to the individual case. That step is almost never argued for.
Micro-titration looks different depending on whether you are reading the primary literature or the summaries of it, and the difference is not in our favour.
Answering the question post #16 raises rather than the one it answers.
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.
Post #17 put the caveat in the right place and I want to underline it.
I would keep micro-titration and the decision it usually gets used for separate in this thread. They are related and they are not the same question, and merging them is why the last one went badly.
Building on post #21 rather than restating it.
The practical version of micro-titration is three sentences long. The rigorous version is three pages and reaches the same conclusion with the conditions attached.
That reframing is the whole thing. The facts I already had.
I read post #26 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 has held every time I have looked, which is not the same as always.
An honest declaration on micro-titration: I have a prior here and it is strong enough that you should weight what I say downward. Stating it rather than hiding it.
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.