Every letter we have printed
Page 54 of 77 of this archive, newest first.
On “The GLP-1 receptor is not a switch, and retatrutide is not a key” — Pharmacology, 14 Oct 2024
The claim that nothing at baseline predicts response is too strong. Surely baseline BMI, sex and diabetes status shift the expected outcome — the trials stratify on exactly those variables.
— P. Hollingsworth, Norwich
They shift the mean, which is why the trials stratify. They barely narrow the distribution around it, which is the claim we made. Both statements are in the responder analyses and we should have distinguished them more carefully in the paragraph you are objecting to.
On “The GLP-1 receptor is not a switch, and retatrutide is not a key” — Pharmacology, 14 Oct 2024
I have read three separate articles this month describing cagrilintide as a GLP-1 agonist and one describing tirzepatide as "semaglutide with an extra bit". Thank you for the glossary. Please run it again.
— F. Okonjo, Asaba
On “Is survodutide better than retatrutide, or differently balanced?” — Pharmacology, 13 Oct 2024
A small thing: you write "class B GPCR" and then "secretin-like receptor" as though these were different classifications. They are the same family under two naming conventions, and the piece would be clearer if it said so.
— L. Dziedzic, Wrocław
Fair, and now stated in the text.
On “Is survodutide better than retatrutide, or differently balanced?” — Pharmacology, 13 Oct 2024
I have been on treatment for fourteen months and stopped losing weight at month eleven. Your piece says this is energy balance rather than receptor desensitisation. I would find that easier to accept if anybody had explained it to me at the start rather than after I had spent two months assuming the drug had stopped working.
— E. Beauchamp, Ottawa, ON
That is a fair criticism of the field rather than of this article, and we take the point about timing. The plateau is predictable and predicted; it is very rarely mentioned before it happens.
On “What a split-sample exercise can establish, and what it cannot” — The Ledger, 12 Oct 2024
On the archive point: a public record of submissions by vendor would be gamed within a month. Vendors would submit under the names of resellers, or through intermediaries, and the archive would show a distribution as selected as the current one but with a veneer of completeness.
— T. Nkemelu, Port Harcourt
Probably true in part, and it is the strongest argument against our proposal. Our answer is that gaming requires effort and leaves traces, which the present arrangement does not, and that a partially gamed record is more informative than no record. We would not claim more than that.
On “What a split-sample exercise can establish, and what it cannot” — The Ledger, 12 Oct 2024
VendorInvestigate does not measure anything and you have grouped it with three laboratories under the heading independent testing. That is exactly the conflation your article says the market makes.
— L. Nyoni, Harare
A fair hit. The tag under which this coverage sits predates the distinction we now draw, and we have added the distinction to the second paragraph and to the table. The department name will follow at the next reorganisation of the site.
On “A part per million, in context” — Laboratory Notebook, 12 Oct 2024
I have spent a week trying to reconcile a certificate’s stated mass of 4113.6 with a figure of 4111.1 I calculated from the sequence, and had convinced myself something was wrong with the vial. It was the isotope convention. Thank you, and also: how is this not stated on every certificate in existence?
— J. Wenninger, Graz
We wish we knew. It is the single most common source of spurious discrepancies reaching this desk, it costs nothing to state, and we have now asked all twenty companies in the dossier programme to add it. Three have.
On “The badge economy, and what it is actually certifying” — Analytics, 11 Oct 2024
VendorInvestigate does not measure anything and you have grouped it with three laboratories under the heading independent testing. That is exactly the conflation your article says the market makes.
— S. Bergqvist, Malmö
A fair hit. The tag under which this coverage sits predates the distinction we now draw, and we have added the distinction to the second paragraph and to the table. The department name will follow at the next reorganisation of the site.
On “The badge economy, and what it is actually certifying” — Analytics, 11 Oct 2024
On the archive point: a public record of submissions by vendor would be gamed within a month. Vendors would submit under the names of resellers, or through intermediaries, and the archive would show a distribution as selected as the current one but with a veneer of completeness.
— T. Oyelowo, Abeokuta
Probably true in part, and it is the strongest argument against our proposal. Our answer is that gaming requires effort and leaves traces, which the present arrangement does not, and that a partially gamed record is more informative than no record. We would not claim more than that.
On “The badge economy, and what it is actually certifying” — Analytics, 11 Oct 2024
As a buyer I found the section on who chose the vial genuinely clarifying and slightly deflating. I have been treating vendor-published reports as equivalent to my own submissions for two years, and on your account they are not equivalent by an amount that cannot be measured.
— J. Vasilenko, Chisinau
That is the correct reading, and the unmeasurable part is the honest part. We would add only that vendor-published reports are not worthless — a vendor willing to commission testing at all is behaving better than one that will not — they are simply weaker in a specific way.
On “What a split-sample exercise can establish, and what it cannot” — The Supply Chain, 9 Oct 2024
Your suggestion that laboratories publish the fact of a submission while keeping the result confidential is the first proposal I have read in this area that a laboratory could actually implement without breaching a client obligation. I have raised it internally.
— N. Villaseñor, Guadalajara
We would be glad to report the outcome either way, including if the answer is no and the reason is commercial. The proposal is only useful if somebody adopts it, and a published refusal is more informative than silence.
On “What a split-sample exercise can establish, and what it cannot” — The Supply Chain, 9 Oct 2024
You disclose that two of these services advertise with you and then spend four thousand words on structural criticism of the sector they operate in. I cannot decide whether that is admirable independence or an elaborate way of appearing independent. Probably the former. I wanted to say that I noticed the question.
— N. Zangwill, Manchester
So do we, every time this department writes about the sector. The only answers we have are procedural: the disclosure, the standards desk edit, the consulting prohibition on the writer, and the practice of printing objections like yours unedited.
On “What a split-sample exercise can establish, and what it cannot” — The Supply Chain, 9 Oct 2024
As a buyer I found the section on who chose the vial genuinely clarifying and slightly deflating. I have been treating vendor-published reports as equivalent to my own submissions for two years, and on your account they are not equivalent by an amount that cannot be measured.
— P. Havlíček, Brno
That is the correct reading, and the unmeasurable part is the honest part. We would add only that vendor-published reports are not worthless — a vendor willing to commission testing at all is behaving better than one that will not — they are simply weaker in a specific way.
On “Reading a barrel in the wrong increments” — Explainers, 8 Oct 2024
As a practice nurse I would add the ten-second hold to your list of things people skip. I watch patients withdraw immediately and then wonder about the wet patch on their skin. It is the most visible underdose there is and almost nobody connects the two.
— C. Aguirre, Rosario
Well observed, and now in the priming section and the sidebar. The wet skin is exactly the useful feedback signal — unlike most of the errors in this file, this one announces itself, and the announcement is being misread.
On “Reading a barrel in the wrong increments” — Explainers, 8 Oct 2024
The section on in-use stability is unhelpfully agnostic. Everyone in this market uses a figure of around thirty days refrigerated. Surely you can say whether that is roughly right rather than declining to comment.
— G. Rasmussen, Odense
We can say where it comes from, which is the in-use period established for licensed pen presentations of specific formulations in specific containers. Whether it transfers to a different peptide reconstituted in a different diluent in a different vial is not something the stability literature permits anyone to assert. Declining to guess is not agnosticism; it is the difference between a study and a convention.
On “Reading a barrel in the wrong increments” — Explainers, 8 Oct 2024
I have accumulated about eighteen months of used needles in a plastic tub because I did not know where to take them and assumed I would be asked questions. Your paragraph on this is the first time I have seen the situation described rather than lectured about.
— E. Nkomo, Polokwane
Collection services are not interested in what was in the syringe. A pharmacy or local authority sharps point will take a rigid sealed container without inquiry, and the barrier you describe is built entirely of anticipated judgement. We would rather say that plainly than add to the lecturing.
On “Reading a barrel in the wrong increments” — Explainers, 8 Oct 2024
Your rotation advice says site does not affect absorption in this class, and then says to rotate anyway. If absorption is unaffected, why bother?
— J. Costanzo, Naples
Because rotation protects tissue rather than controlling absorption. Repeated injection into one small area produces lipohypertrophy, and absorption from lipohypertrophic tissue is blunted and erratic for any injected depot. Rotation prevents the condition that would make site matter. The advice is consistent; we should have made the causal order clearer.
On “Reading a barrel in the wrong increments” — Explainers, 8 Oct 2024
I gave myself a tenth of my intended dose for five weeks. I had been using insulin syringes, ran out, and used the 1 mL syringes that came with the vials, which are marked in millilitres. I did not notice because the plunger was in roughly the same place. Nobody warned me these were different scales.
— P. Sarkissian, Beirut
This is the error we rank first for magnitude and we are grateful for the account, because it happened exactly as the mechanism predicts: a substitution that produced no visible signal. The one structural defence is to buy syringes deliberately and keep to a single type rather than using whatever arrives in the parcel.
On “A tested vial is evidence about a vial” — The Ledger, 7 Oct 2024
Your suggestion that laboratories publish the fact of a submission while keeping the result confidential is the first proposal I have read in this area that a laboratory could actually implement without breaching a client obligation. I have raised it internally.
— R. Sundaresan, Coimbatore
We would be glad to report the outcome either way, including if the answer is no and the reason is commercial. The proposal is only useful if somebody adopts it, and a published refusal is more informative than silence.
On “A tested vial is evidence about a vial” — The Ledger, 7 Oct 2024
You disclose that two of these services advertise with you and then spend four thousand words on structural criticism of the sector they operate in. I cannot decide whether that is admirable independence or an elaborate way of appearing independent. Probably the former. I wanted to say that I noticed the question.
— R. Mothibi, Gaborone
So do we, every time this department writes about the sector. The only answers we have are procedural: the disclosure, the standards desk edit, the consulting prohibition on the writer, and the practice of printing objections like yours unedited.
On “A tested vial is evidence about a vial” — The Ledger, 7 Oct 2024
I submitted a vial to one of these services last year, got a result three points below what the vendor advertised, and did not know what to do with it. Your article explains why: I had one measurement on one vial, no method comparison, and no way to know if my vial was representative. I still do not know what to do with it, but I understand the shape of not knowing.
— P. Vuković, Split
That is a better summary of this article’s practical content than our own closing paragraphs. The one thing we would add is that your result is worth publishing wherever you can, because buyer-submitted results are the scarcest and most informative category in the entire corpus.
On “A tested vial is evidence about a vial” — The Ledger, 7 Oct 2024
I run analytical services and I object to the framing of your blind comparison. You bought our cheapest tier, published the number it produced alongside a competitor’s most thorough package, and called the result a spread. It is not a spread. It is three different products, priced accordingly, and your own table says so two columns to the right of the headline figure.
— L. Marulanda, Medellín
This is the objection we thought was most likely and we think it is partly right. The comparison is of standard products at standard prices, which is what buyers actually purchase, and we said so. But the presentation invites the reading you object to, and the figure caption now states the tier alongside each result rather than leaving it to the method columns.
On “The certificate is silent on contamination, and it never claimed otherwise” — Laboratory Notebook, 7 Oct 2024
Why did you submit only two vials for sterility testing when the whole article argues that the sample size is the problem? Two is worse than twenty by exactly the argument you make.
— B. Tejeda, Santo Domingo
Because we could not afford twenty, and because the two results are reported as what they are: two vials, each destroyed, telling us nothing about their batches. The purpose was to establish that the test is commercially available to a private purchaser and what it costs, not to characterise anything. We should have said that in the article rather than in this reply.
On “Sending the same vial twice, under two names” — The Ledger, 6 Oct 2024
You disclose that two of these services advertise with you and then spend four thousand words on structural criticism of the sector they operate in. I cannot decide whether that is admirable independence or an elaborate way of appearing independent. Probably the former. I wanted to say that I noticed the question.
— K. Rautio, Tampere
So do we, every time this department writes about the sector. The only answers we have are procedural: the disclosure, the standards desk edit, the consulting prohibition on the writer, and the practice of printing objections like yours unedited.
On “Sending the same vial twice, under two names” — The Ledger, 6 Oct 2024
Your suggestion that laboratories publish the fact of a submission while keeping the result confidential is the first proposal I have read in this area that a laboratory could actually implement without breaching a client obligation. I have raised it internally.
— M. Ferrari, Trieste
We would be glad to report the outcome either way, including if the answer is no and the reason is commercial. The proposal is only useful if somebody adopts it, and a published refusal is more informative than silence.
On “Sending the same vial twice, under two names” — The Ledger, 6 Oct 2024
Your selection-effect model assumes a supplier publishes results above a fixed threshold. Real behaviour is surely more complicated: a supplier might publish a poor result on a batch it has withdrawn, or publish everything for a period to establish credibility and then stop. The arithmetic is fine and the behavioural assumption is a cartoon.
— C. Wilcoxson, Des Moines, IA
Agreed, and the figure caption now says illustrative arithmetic rather than model. The point survives the simplification, which is that a small amount of selection produces a large apparent effect, but we should not have dressed a demonstration as an estimate.
On “Sending the same vial twice, under two names” — The Ledger, 6 Oct 2024
As a buyer I found the section on who chose the vial genuinely clarifying and slightly deflating. I have been treating vendor-published reports as equivalent to my own submissions for two years, and on your account they are not equivalent by an amount that cannot be measured.
— H. Barreto, Recife
That is the correct reading, and the unmeasurable part is the honest part. We would add only that vendor-published reports are not worthless — a vendor willing to commission testing at all is behaving better than one that will not — they are simply weaker in a specific way.
On “A few hundred participants carry the whole body-composition argument” — Patient Notes, 6 Oct 2024
Three vendors have now sent me marketing material claiming their product preserves lean mass during GLP-1 treatment, two of them citing your publication as a source for the underlying composition figures. You may want to know that.
— L. Kowalski, Gdańsk
We did not, and we are grateful. Quoting our reporting of a substudy alongside an unevidenced product claim is a misuse of it, and the standards desk has written to all three.
On “A few hundred participants carry the whole body-composition argument” — Patient Notes, 6 Oct 2024
I have read your protein tables twice and I still cannot work out what I should eat. I appreciate that this is the honest position but it is not a useful one for a person in a supermarket.
— B. Osei-Bonsu, Kumasi
It is a fair complaint about a real limitation. What we can say is that the defensible range is narrower than the disagreement suggests, that the denominator matters more than the ratio, and that a clinician or dietitian can convert a range into a number for your body in a way that a magazine cannot.
On “What we would need to randomise to answer this properly” — Clinical Trials, 5 Oct 2024
My mother is eighty-one and on a low dose for her diabetes. Her weight is down nine kilograms and she now struggles to get out of a low chair, which she did not eighteen months ago. Nobody has measured anything. I do not know whether this is the drug, the weight loss, or being eighty-one, and neither does anybody I have asked.
— M. Tsvangirai, Bulawayo
That is the situation the missing endpoint produces, and we are sorry to have no better answer. A chair-stand time takes thirty seconds to measure and would at least establish a baseline against which the next six months could be judged. It is worth asking for by name.
On “What we would need to randomise to answer this properly” — Clinical Trials, 5 Oct 2024
The soft-tissue artefact point in your bone section is underplayed. In a patient losing twenty per cent of body mass the change in overlying tissue is well outside the range the calibration was validated over, and the published analyses do not report a sensitivity analysis for it. That is not a caveat, it is a gap.
— Y. Sasaki, Sapporo
We accept the escalation and have strengthened the wording. The absence of any published sensitivity analysis is, as you say, the more damaging observation.
On “The dose that got you here and the dose that keeps you here” — Patient Notes, 3 Oct 2024
You say no dose-equivalence data exists between agents in this class. During the shortage my pharmacy substituted one for another on the basis of a conversion table they had printed from somewhere. Where would such a table have come from?
— R. Hollenbeck, Spokane, WA
Almost certainly from cross-trial comparison of weight-loss percentages, which is not an equivalence basis. There is no head-to-head dose-titration study permitting conversion between these agents, and STEP 8 — the only head-to-head weight trial we know of — compared two agents at their own licensed doses rather than establishing equivalence between them.
On “The dose that got you here and the dose that keeps you here” — Patient Notes, 3 Oct 2024
As a prescriber I would push back on your framing of the maintenance gap. We are not practising without evidence; we are practising on pharmacological inference, which is what clinicians do in every field where the trial has not been run. Calling it unevidenced makes reasonable practice sound reckless.
— H. Baptiste, Fort-de-France
A fair objection and we have adjusted the wording. Our intention was to locate the absence with the people who could have funded the trial rather than with the clinicians managing without it, and on rereading the original paragraph did not achieve that.
On “The dose that got you here and the dose that keeps you here” — Patient Notes, 3 Oct 2024
I lost access for eleven weeks during the shortage, restarted at the dose I had been on because nobody told me otherwise, and spent a fortnight unable to keep food down. I had been on that dose for seven months without difficulty. Reading your resumption section was the first time anybody explained it.
— N. Halvorsen, Trondheim
It is entirely predictable from the label and the pharmacokinetics, and the failure to communicate it during the shortage period was systemic rather than individual. We are sorry it reached you this way and we are glad it reached you.
On “The dose that got you here and the dose that keeps you here” — Patient Notes, 3 Oct 2024
Your piece describes tapering as pharmacologically pointless and then spends three paragraphs making a case for it. Pick one.
— T. Elorriaga, San Sebastián
Both, we think, and deliberately. There is no pharmacological rationale, because there is no withdrawal syndrome and a week-long half-life produces its own decline. There is a behavioural rationale, which is different in kind and untested. Our objection is to tapers advocated in pharmacological language, not to the practice.
On “The dose that got you here and the dose that keeps you here” — Patient Notes, 3 Oct 2024
I stopped eight months ago after reaching a weight I was happy with, and I have regained four of the twenty-two kilograms I lost. Every article I read told me to expect two-thirds back. I am not complaining, but I would like to know whether I am unusual or whether the two-thirds figure was always a mean concealing an enormous range.
— T. Oyelowo, Abeokuta
The second. The published interquartile ranges around those means are wide, and outcomes like yours are well within them. The trials were not designed to explain why some people hold weight after cessation and others do not, and nothing measured at randomisation predicts it usefully. You are not an anomaly; you are part of a distribution nobody quotes.
On “Side effects, cost, supply, target: four reasons with four trajectories” — The Ledger, 2 Oct 2024
The claim that stopping does not leave you worse off than baseline is a group-level claim about trial arms. Individuals can and do overshoot. Your phrasing invites readers to conclude otherwise.
— J. Prendergast, Wollongong, NSW
Correct, and the distinction matters. We have added a clause: no arm overshot at a group level, which is not the same as no participant overshooting. The trials do not report individual overshoot rates and we have not found them published anywhere.
On “Side effects, cost, supply, target: four reasons with four trajectories” — The Ledger, 2 Oct 2024
I take this for kidney disease, not for weight. Every piece of writing I encounter about stopping is about the weight coming back. It has taken me a year to find anybody willing to say plainly that the renal benefit accrued over years of treatment and nobody has tested what happens if I stop.
— E. Marchbank, Perth, WA
On “Six words a verification badge would need to mean anything” — Analytics, 1 Oct 2024
VendorInvestigate does not measure anything and you have grouped it with three laboratories under the heading independent testing. That is exactly the conflation your article says the market makes.
— L. Dziedzic, Wrocław
A fair hit. The tag under which this coverage sits predates the distinction we now draw, and we have added the distinction to the second paragraph and to the table. The department name will follow at the next reorganisation of the site.
On “Six words a verification badge would need to mean anything” — Analytics, 1 Oct 2024
On the archive point: a public record of submissions by vendor would be gamed within a month. Vendors would submit under the names of resellers, or through intermediaries, and the archive would show a distribution as selected as the current one but with a veneer of completeness.
— E. Beauchamp, Ottawa, ON
Probably true in part, and it is the strongest argument against our proposal. Our answer is that gaming requires effort and leaves traces, which the present arrangement does not, and that a partially gamed record is more informative than no record. We would not claim more than that.