Every letter we have printed
Page 55 of 77 of this archive, newest first.
On “Six words a verification badge would need to mean anything” — Analytics, 1 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. Ravensworth, York
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 “Six words a verification badge would need to mean anything” — Analytics, 1 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 Real behaviour is surely more complicated: a supplier might publish a poor result on a batch it has withdrawn, or publish everything for a period to establish credibility and then stop.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.
— E. Marchetti, Bologna
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 “Six words a verification badge would need to mean anything” — Analytics, 1 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. Devaney, Ballarat, VIC
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 “The one randomised trial that combined an incretin with supervised exercise” — Patient Notes, 1 Oct 2024
As a DXA technologist of twenty-two years I would add one thing to your precision section: the largest source of error in practice is not the machine, it is positioning. A patient scanned with their arms two centimetres further from their trunk will report different regional values. We are trained to a protocol and the protocol is not always followed.
— D. Sakamoto, Kobe
We should have said this and did not. It also argues for what you presumably practise: same device, same technologist, same protocol, and a note in the record when any of those changes.
On “How much water: the question with no single right answer” — Explainers, 29 Sep 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.
— L. Marulanda, Medellín
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 “How much water: the question with no single right answer” — Explainers, 29 Sep 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?
— P. Vuković, Split
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 “How much water: the question with no single right answer” — Explainers, 29 Sep 2024
You spend a page on the four-line calculation and then publish a reconstitution table anyway. Are you not providing exactly the pre-computed number you warned against?
— R. Mothibi, Gaborone
A fair catch, and the reason the table carries the note it does. It is indexed by both vial mass and diluent volume precisely so that it cannot be read as a single fixed answer, and it is preceded by the derivation. If we thought a reader would take one figure from it and carry that figure across a change of vial, we would remove it.
On “How much water: the question with no single right answer” — Explainers, 29 Sep 2024
A quibble on your dead-space figure. You give two to seven microlitres for insulin-type needles, which is right for fixed-needle syringes, but the detachable pen needle plus syringe hub combinations sold in this market are considerably worse and you should say so.
— R. Sundaresan, Coimbatore
Accepted and amended. The figure we gave applies to integrated fixed-needle insulin syringes; detachable arrangements on a luer fitting can retain an order of magnitude more, which at small injection volumes is a substantial loss. The table now distinguishes them.
On “How much water: the question with no single right answer” — Explainers, 29 Sep 2024
You recommend writing the concentration on the vial. I would add: write it on the box as well. My vial label came off in the fridge and I lost the only record of what diluent volume I had used.
— T. Brannon, Boise, ID
On “The named comparison we promised two years ago” — The Ledger, 28 Sep 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.
— V. Petrosyan, Yerevan
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 “The named comparison we promised two years ago” — The Ledger, 28 Sep 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.
— E. Thistlethwaite, Sheffield
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 “The named comparison we promised two years ago” — The Ledger, 28 Sep 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.
— H. Nakagawa, Fukuoka
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 “The named comparison we promised two years ago” — The Ledger, 28 Sep 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.
— A. Salcedo, Bilbao
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 named comparison we promised two years ago” — The Ledger, 28 Sep 2024
You note that no service offers sterility testing and that it takes fourteen days. Worth saying more plainly: a purity certificate and a sterility assurance are not merely different tests, they are different disciplines with different facilities, and no amount of chromatography will ever bear on it.
— E. Adamou, Nicosia
Correct and worth the emphasis. We have said it in the certificates piece and should say it here too: nothing any of these four services sells addresses sterility, endotoxin or container closure integrity, and no combination of their reports adds up to one.
On “Custody, condition and the temperature nobody logged” — Analytics, 27 Sep 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.
— K. Rautio, Tampere
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 “Why a result on one vial says less than the trade needs it to” — Analytics, 26 Sep 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.
— C. Tremonti, Palermo
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 “Why a result on one vial says less than the trade needs it to” — Analytics, 26 Sep 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.
— G. Thorbjørnsen, Tromsø
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 “Why a result on one vial says less than the trade needs it to” — Analytics, 26 Sep 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.
— E. Sørheim, Stavanger
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 “Why the bone question is harder than the muscle question” — Clinical Trials, 25 Sep 2024
I train four times a week, eat a hundred and sixty grams of protein and my appendicular lean mass has fallen by 1.8 kg over ten months while every lift has gone up. Your section on mass against function was the first thing I have read that made that seem normal rather than a failure.
— Q. Delacroix, Montréal, QC
On “Why the bone question is harder than the muscle question” — Clinical Trials, 25 Sep 2024
Your piece treats the one-quarter rule as discredited and then quotes fractions of one third and two fifths from the substudies as though those were more solid. They are group means from a hundred and forty people. Physician, heal thyself.
— P. Sandoval, Albuquerque, NM
A fair hit, and we have amended the paragraph to carry the same caveat in both places. The distinction we should have drawn is that the substudy figures are at least attached to a stated population and a stated instrument, which the textbook rule is not. Neither is a constant.
On “Why the bone question is harder than the muscle question” — Clinical Trials, 25 Sep 2024
I am sixty-eight, I have lost nineteen kilograms over fourteen months, and my consultant has twice told me my lean mass is fine on the basis of a handheld bioimpedance device in the clinic corridor. Having read your piece on what that device measures, I am no longer sure what I have been reassured about.
— T. Aoyama, Nagoya
Nor are we. A handheld device measures impedance across the upper body and infers the rest, and the inference is least reliable exactly where you sit: older, substantial weight change, changing hydration. That is not a criticism of your consultant’s judgement, which may be sound on other grounds, but the device is not the evidence for it.
On “Why the bone question is harder than the muscle question” — Clinical Trials, 25 Sep 2024
Small correction to your table: the S-LiTE exercise prescription was two supervised group sessions and two individual sessions weekly, not two sessions in total. The distinction matters because "add some exercise" is not what was tested.
— S. Weatherall, Newcastle, NSW
Correct, and that is precisely the point we were trying to make and then undermined in our own table. Amended.
On “Why the bone question is harder than the muscle question” — Clinical Trials, 25 Sep 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.
— T. Blakemore, Hull
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 “Reproducibility, measured rather than assumed” — The Supply Chain, 25 Sep 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.
— H. Baptiste, Fort-de-France
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 “Reproducibility, measured rather than assumed” — The Supply Chain, 25 Sep 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.
— R. Hollenbeck, Spokane, WA
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 “Reproducibility, measured rather than assumed” — The Supply Chain, 25 Sep 2024
You note that no service offers sterility testing and that it takes fourteen days. Worth saying more plainly: a purity certificate and a sterility assurance are not merely different tests, they are different disciplines with different facilities, and no amount of chromatography will ever bear on it.
— T. Elorriaga, San Sebastián
Correct and worth the emphasis. We have said it in the certificates piece and should say it here too: nothing any of these four services sells addresses sterility, endotoxin or container closure integrity, and no combination of their reports adds up to one.
On “Reproducibility, measured rather than assumed” — The Supply Chain, 25 Sep 2024
The price table is the most useful thing you have published this year and also the thing most likely to be quoted out of context by somebody selling a comparison service. You might consider a note.
— N. Halvorsen, Trondheim
There is one, and we have strengthened it. The figures are what this publication was invoiced at list rates and are not quotations a reader should expect; volume submitters pay materially less.
On “Reproducibility, measured rather than assumed” — The Supply Chain, 25 Sep 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 “Accumulation, trough, and the exposure curve nobody draws for patients” — Explainers, 24 Sep 2024
I found the section on the area postrema genuinely clarifying. I had assumed nausea was a stomach problem and had been treating it as one, unsuccessfully, for four months.
— E. Sørheim, Stavanger
On “Why people actually stop, in the order they actually stop” — The Ledger, 23 Sep 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.
— J. Wenninger, Graz
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 “Why people actually stop, in the order they actually stop” — The Ledger, 23 Sep 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?
— P. Ekundayo, Akure
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 “Why people actually stop, in the order they actually stop” — The Ledger, 23 Sep 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.
— L. Fontaine, Brussels
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 “What “LC-MS: conforms” tells a reader, which is almost nothing” — Laboratory Notebook, 23 Sep 2024
On your point about D-amino acids: chiral amino-acid analysis after hydrolysis is not exotic and several contract laboratories offer it. The obstacle is that hydrolysis itself racemises a few per cent of most residues, so the method has a blank problem, and interpreting a low-level D content is genuinely difficult rather than merely expensive.
— N. Ó Broin, Sligo
An important qualification and we are glad to have it. The article implied the barrier was commercial when a substantial part of it is methodological. Recorded, and the section has been rewritten accordingly.
On “What “LC-MS: conforms” tells a reader, which is almost nothing” — Laboratory Notebook, 23 Sep 2024
You state that fourteen of twenty suppliers report an MS identity test. Does that count reports supplied to you on request, or only what appears on the certificate a customer receives?
— F. Duquesne, Lyon
The former, which the table note now says explicitly. The count for what appears on a customer-facing certificate is lower in at least four cases, and we should have separated the two columns rather than merging them.
On “What “LC-MS: conforms” tells a reader, which is almost nothing” — Laboratory Notebook, 23 Sep 2024
I would add one omission to your six lines: the date and nature of the last calibration. A parts-per-million figure from an instrument last calibrated a fortnight ago is a different claim from one calibrated that morning with an internal standard.
— S. Nortje, Stellenbosch
Agreed, and it may be the best suggestion we have received on this subject. It is now a seventh line in the version of the list we send to suppliers, with the note that internal calibration should be stated where it was used.
On “What “LC-MS: conforms” tells a reader, which is almost nothing” — Laboratory Notebook, 23 Sep 2024
Your article says a matching mass does not confirm a sequence, which is correct, and then rather implies that vendors are trading on the ambiguity. I run analytical services and I would put it differently: we report what we measured, in the words our clients ask for. If the Journal wants the word confirmed retired, write to the buyers, not to us.
— T. Kirchner, Hamburg
That is a fair reallocation of the criticism and we accept it. The word is chosen by whoever commissions the report, and laboratories are answering the question they were paid to answer. Our complaint is with the practice, not with the analysts, and the article should have located it more precisely.
On “How far back does this document actually reach?” — The Supply Chain, 22 Sep 2024
I have a certificate with an expiry date twenty-four months from manufacture and no stability data behind it, which your article says is a claim the documentation cannot support. The supplier tells me it is industry standard. Is it?
— P. Sarkissian, Beirut
Twenty-four months is a common default and “industry standard” is an accurate description of the practice rather than a justification of the claim. The distinction we would press is between an expiry date, which asserts shelf life, and a retest date, which asserts only a review interval. The second is defensible without stability data. The first is not.
On “Why a 0.036-dalton difference is the hardest number in peptide identity” — Analytics, 22 Sep 2024
You give the glutamine-to-lysine difference as 0.036 daltons and say it needs an orbital trap. In practice you also need the two species to be chromatographically separated or present in a sensible ratio, because at one per cent of the parent intensity the minor peak sits on the shoulder of the isotope envelope regardless of resolving power.
— D. Ferreira-Lopes, Porto
Yes, and this is the more useful statement of the problem. Resolving power is necessary and not sufficient; dynamic range and separation matter as much. We have added a sentence to the table note.
On “The advice is mostly reasonable. The certainty is not earned.” — Patient Notes, 22 Sep 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.
— R. Whitlam, Adelaide, SA
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 advice is mostly reasonable. The certainty is not earned.” — Patient Notes, 22 Sep 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.
— C. Rautenbach, Pretoria
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.