Non-responders, and the honest state of the evidence about them
A catalogue of open questions, with an assessment of how likely each is to be resolved.
Salomé Adeyemi
Page 9 of 13 of this archive, newest first.
Archive — page 9
243 piecesWhat the trials counted as intolerance
We set out the questions that distinguish a symptom to manage from a dose to change.
What the new Spain guidance says about stopping
The evidence base is thin and the document says so, which is to its credit.
A supply gap is a pharmacological event
One omitted dose is a labelling question. Four omitted doses is a clinical one. The two are routinely conflated.
What the new Germany guidance says about stopping
The evidence base is thin and the document says so, which is to its credit.
Reading a barrel in the wrong increments
Almost every case involves a change — a new vial, a new syringe size, a new supplier — carried forward with an old number.
A few hundred participants carry the whole body-composition argument
What was pre-specified, what was exploratory, and what was calculated afterwards by people who did not run the trial.
Escalating onto a rising curve
We work the arithmetic out in full, because it is arithmetic and it is short.
What the new Japan guidance says about stopping
The evidence base is thin and the document says so, which is to its credit.
The one randomised trial that combined an incretin with supervised exercise
One randomised trial has combined a GLP-1 receptor agonist with supervised exercise. Its result is the single most useful piece of evidence in this area.
What the new Nigeria guidance says about stopping
The evidence base is thin and the document says so, which is to its credit.
What STEP 4 and SURMOUNT-4 actually established
A plateau at an intermediate dose and a plateau at the maximum dose look identical from the outside and mean different things.
Do you need the top of the ladder?
The dose-response curve in this class flattens near its top. That has direct consequences for whether the final rung is worth climbing.
Target dose, effective dose, and the distance between them
The dose-response curve in this class flattens near its top. That has direct consequences for whether the final rung is worth climbing.
What the new Singapore guidance says about stopping
The evidence base is thin and the document says so, which is to its credit.
Errors ranked by how much dose they move
The most dangerous errors are the ones that leave no trace: nothing looks wrong, the mark is in the same place, and the dose is wrong by an order of magnitude.
Six tells, in order of how quickly they can be checked
A blank certificate with the numbers left editable is an ordinary internal document. Its circulation as a finished record is the problem.
A schedule that bends does not break
Nausea and gastric delay attenuate over weeks at an unchanged dose. That single physiological fact is the entire justification for holding.
The limits of mechanism: why receptor data will not tell you who responds
The mechanism is well described. The variance is not.
The area postrema, and the anatomy of an unwanted effect
A single drug producing both constipation and diarrhoea looks contradictory until the motility data is read properly.