The eighteenth month, and the conversation that should have happened in the third
What the trials measured was continuation against withdrawal. What patients want to know is continuation at a lower dose, and that study has largely not been done.
Explainers in 2025
Page 3 of 5 of this archive, newest first.
Gauge, pain and flow rate
Skin thickness at the standard injection sites is approximately two millimetres in adults and varies remarkably little with body mass. That single finding is why short…
How a correct calculation becomes a wrong dose
Almost every case involves a change — a new vial, a new syringe size, a new supplier — carried forward with an old number.
Retained gastric contents, and how a small finding became a large argument
A drug that delays gastric emptying complicates the assumption behind every fasting instruction in perioperative medicine. The professional bodies have moved twice on this…
Escalating onto a rising curve
What the published pharmacokinetics permit, what the labels state, and where the two diverge.
Electrospray, MALDI, and the choice that shapes every spectrum after it
The two ionisation techniques in general use produce different charge distributions, different adducts and different failure modes. Certificates almost never say which was…
Gauge, pain and flow rate
The insulin injection-technique literature is large, well conducted and directly transferable on questions of depth and tissue. We say where it stops transferring.
The eighteenth month, and the conversation that should have happened in the third
The dose-response curve in this class flattens near its top. That has direct consequences for whether the final rung is worth climbing.
Assay against a standard, or area per cent: two different questions
We asked the four independent testing services what standards they run against and what suitability criteria they apply. The answers are printed.
Four millimetres is enough, and the data says so
The insulin injection-technique literature is large, well conducted and directly transferable on questions of depth and tissue. We say where it stops transferring.
The tolerance was set by whoever wrote the certificate
The arithmetic of significant figures, applied to a document that routinely reports four of them.
Mapping a rotation that you will actually follow
A rotation scheme that is too complicated will not be followed. We describe the simple ones that are.
The figure of merit this trade chose, and the four it did not
A market that competes on one measurement will optimise that measurement. There are legitimate ways to raise a purity figure that involve no change to the product at all.
Holding a dose is a decision, not a failure
Every major phase 3 protocol in this class allowed escalation to be delayed for tolerability. Almost no product label explains the mechanics of doing so.
From milligrams in a vial to units in a barrel
A more concentrated reconstitution means smaller injection volumes, which means larger proportional errors from graduation, dead space and technique.
Diminishing returns, quantified
Where the curve flattens, what flattens with it, and what does not.
The impurity hiding underneath the parent peak
Where two methods disagree, the conservative convention is to report the lower figure. It is not universal, and whether a laboratory follows it belongs on the report.
Units, millilitres, milligrams: three scales on one small object
We work through the arithmetic in full, because it is short, and because the errors it prevents are order-of-magnitude errors.
Gallstones during rapid weight loss: drug, or weight loss?
A small number of serious gastrointestinal events occur in people taking these drugs. Distinguishing them from the expected effect profile is the most consequential…
What the trial protocols permitted, and what the labels omitted
The practice is near-universal, clinically sensible, and supported by observational data rather than randomised comparison. We say which is which.