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Unanswered questions

Questions with no answer at all. Not questions with no accepted answer — those are elsewhere.

741 questions · page 31 of 31

25 votes0 answers33k views
What has VendorInvestigate published on SSA lots in the last year?

Conditions: VendorInvestigate · SSA. I would like to know the limits of what can be inferred from this. What I am trying to avoid is over-reading a single result,…

vendor-investigate
vendor-investigate

VendorInvestigate, an independent vendor review and verification service. Use this tag for questions about its verification criteria, what a…

41 questions
batch-testing
batch-testing

Testing at the batch or lot level: sampling plans, how many vials from a lot need testing to say anything about the lot, and the difference…

865 questions
vendor-comparison
vendor-comparison

Side-by-side comparison of suppliers on measurable axes - independently confirmed purity and content, lead time, cold-chain handling,…

351 questions
asked by lucia_marchetti 18k · 2.3 years ago
27 votes0 answers31k views
What does REDEFINE-1 tell me about vomiting at the 5 mg dose?

Concretely: REDEFINE-1 · vomiting · 5 mg. I would like to know the limits of what can be inferred from this. What I am trying to avoid is over-reading a single…

clinical-trials
clinical-trials

Reading the primary literature properly: estimands, intention-to-treat versus per-protocol, confidence intervals, absolute versus relative…

913 questions
gi-side-effects
gi-side-effects

The gastrointestinal cluster as a whole - nausea, vomiting, diarrhoea, constipation, reflux, early satiety - with trial incidence rates, dropout…

416 questions
titration
titration

Stepwise dose increases over weeks, why the label schedules exist at all, and what tolerability-driven deviation from a schedule looks like in…

444 questions
asked by t_oyelaran 41k · 2.3 years ago
21 votes0 answers12k views
What does the mechanism of liraglutide predict that SURMOUNT-4 did not test?

The particulars: liraglutide · SURMOUNT-4. I would like the mechanism, because I want to be able to reason about the cases nobody has written about. I have tried to…

glp1-mechanism
glp1-mechanism

Receptor-level pharmacology: GLP-1R as a class B GPCR, cAMP and PKA signalling, biased agonism, internalisation and resensitisation, and the…

175 questions
clinical-trials
clinical-trials

Reading the primary literature properly: estimands, intention-to-treat versus per-protocol, confidence intervals, absolute versus relative…

913 questions
gip-receptor
gip-receptor

GIP receptor pharmacology, and the still-unsettled question of whether agonism or antagonism at GIPR is the metabolically useful direction.…

83 questions
liraglutide
liraglutide

A once-daily GLP-1 receptor agonist and the compound that established the class. Still relevant for its shorter half-life, its paediatric and…

14 questions
sleep-apnea
sleep-apnea

Obstructive sleep apnoea and the apnoea-hypopnoea index response to weight loss, including the SURMOUNT-OSA dataset and the question of whether…

14 questions
asked by RP_C18 85k · 2.3 years ago
19 votes0 answers24k views
What is the arithmetic to convert 50 mg in 1.5 mL into units on a U-100 scale?

The specifics, since they change the answer: 50 mg · 1.5 mL. I would rather understand the derivation than memorise the outcome. Two people I asked gave two answers…

dosing-math
dosing-math

The arithmetic itself: milligrams to millilitres to insulin units, concentration after reconstitution, dose per draw, and vial-days per vial. Show…

811 questions
insulin-syringe
insulin-syringe

U-100 and U-40 insulin syringes as measuring instruments. A U-100 syringe is graduated in insulin units where 100 units equals 1 mL, so one unit…

268 questions
reconstitution
reconstitution

Taking a lyophilised vial to a solution of known concentration: choice of diluent, volume selection, how to add liquid without shearing the cake,…

330 questions
asked by label_claim 11k · 2.3 years ago
12 votes0 answers5.8k views
Why do two papers on REDEFINE-1 report different headline figures?

I have the full paper rather than the abstract, and the supplementary appendix. I suspect the usual explanation for this is wrong, or at least incomplete. I am aware…

clinical-trials
clinical-trials

Reading the primary literature properly: estimands, intention-to-treat versus per-protocol, confidence intervals, absolute versus relative…

913 questions
dosing-math
dosing-math

The arithmetic itself: milligrams to millilitres to insulin units, concentration after reconstitution, dose per draw, and vial-days per vial. Show…

811 questions
semaglutide
semaglutide

A GLP-1 receptor agonist with a fatty-acid-acylated backbone and a roughly one-week half-life, marketed for type 2 diabetes and for weight…

360 questions
glucagon-receptor
glucagon-receptor

Glucagon receptor agonism as a deliberate component of dual and tri-agonists: what it adds in energy expenditure and hepatic fat mobilisation, and…

14 questions
asked by threadlock7 14k · 2.3 years ago
29 votes0 answers27k views
What did the placebo arm of SURMOUNT-5 report for dizziness?

Conditions: SURMOUNT-5 · dizziness. The figures are clear enough; the question is what they mean and what they do not. I can supply the numbers if the specifics…

clinical-trials
clinical-trials

Reading the primary literature properly: estimands, intention-to-treat versus per-protocol, confidence intervals, absolute versus relative…

913 questions
gi-side-effects
gi-side-effects

The gastrointestinal cluster as a whole - nausea, vomiting, diarrhoea, constipation, reflux, early satiety - with trial incidence rates, dropout…

416 questions
nausea
nausea

The dominant tolerability signal in every trial of the class: incidence, timing relative to a dose step, duration, and the distinction between…

346 questions
asked by micron22 36k · 2.3 years ago
40 votes0 answers20k views
Can I reconstitute survodutide at 20 mg/mL and still measure a small dose accurately?

The case in front of me: survodutide · 20 mg/mL. I want to decide this in advance so that I am not deciding it under pressure later. Assume I will follow the plan I…

diluent-volume
diluent-volume

Choosing how much diluent to add, which is really a question about what you want your measurement resolution to be. Larger volumes buy you…

308 questions
insulin-syringe
insulin-syringe

U-100 and U-40 insulin syringes as measuring instruments. A U-100 syringe is graduated in insulin units where 100 units equals 1 mL, so one unit…

268 questions
dosing-math
dosing-math

The arithmetic itself: milligrams to millilitres to insulin units, concentration after reconstitution, dose per draw, and vial-days per vial. Show…

811 questions
asked by u100_marks 38k · 2.3 years ago
40 votes0 answers61k views
Is a 98.4% result from VendorInvestigate comparable to 97.6% from Medutest?

The case in front of me: 98.4% · VendorInvestigate · 97.6% · Medutest. These are treated as interchangeable and I do not think they are. If both are acceptable I…

purity
purity

Purity as chromatographic area per cent - the fraction of detected material that is your target peak. It says nothing about how much material is…

788 questions
batch-testing
batch-testing

Testing at the batch or lot level: sampling plans, how many vials from a lot need testing to say anything about the lot, and the difference…

865 questions
reference-standard
reference-standard

Certified reference materials and in-house standards: traceability, the certificate of the standard itself, system suitability, and why every…

179 questions
asked by dmitri_savchuk 17k · 2.3 years ago
5 votes0 answers7.5k views
How should a twenty-person split be structured so a later dispute is resolvable?

I am comparing three suppliers on documentation rather than on price. I am trying to do this correctly the first time rather than learn it by getting it wrong. I have…

group-buy
group-buy

Pooled purchasing: how the economics work, what trust structure a pool needs, splitting a single tested lot, and the failure modes when the…

41 questions
payment-privacy
payment-privacy

Payment mechanics and their privacy properties: why suppliers ask for stablecoin transfers, what an on-chain transfer reveals, confirmation…

31 questions
vendor-vetting
vendor-vetting

Evaluating a supplier on evidence rather than reputation: testing history across batches, whether certificates are batch-specific, how failures…

436 questions
asked by loss_on_drying 47k · 2.3 years ago
26 votes0 answers35k views
Is a GLP-1 receptor agonist at 1 mg/mL stable enough for eight weeks of multi-withdrawal use?

Numbers first: a GLP-1 receptor agonist · 1 mg/mL · eight weeks. I would rather be corrected now than propagate something wrong. I am specifically not interested in a…

peptide-stability
peptide-stability

The chemistry of peptide degradation: deamidation, oxidation, hydrolysis, aggregation and fibrillation, and how temperature, pH, ionic strength,…

832 questions
bacteriostatic-water
bacteriostatic-water

Water for injection containing roughly 0.9 per cent benzyl alcohol as a bacteriostatic agent. It suppresses growth in a multiple-withdrawal vial;…

112 questions
shelf-life
shelf-life

How long a preparation remains within specification: labelled expiry for a sealed lyophilised vial, beyond-use dating after reconstitution, and…

301 questions
endotoxin
endotoxin

Bacterial endotoxin: LAL and kinetic chromogenic methods, how an endotoxin limit is derived from a dose, why endotoxin survives autoclaving, and…

14 questions
asked by Dr_Ravi_Selvarajah 42k · 2.3 years ago
19 votes0 answers11k views
What does a method section on a QST report change about how I read it?

The specifics, since they change the answer: method section · QST. I have the document in front of me and I can read the numbers. What I cannot do is interpret them.…

coa
coa

Certificates of analysis: what fields a useful one carries, how to tell a real analytical report from a marketing document, batch and lot…

749 questions
batch-testing
batch-testing

Testing at the batch or lot level: sampling plans, how many vials from a lot need testing to say anything about the lot, and the difference…

865 questions
vendor-vetting
vendor-vetting

Evaluating a supplier on evidence rather than reputation: testing history across batches, whether certificates are batch-specific, how failures…

436 questions
asked by cap_the_luer 15k · 2.3 years ago
21 votes0 answers16k views
How do I tell reflux from an energy deficit on 800 kcal a day?

For reference: reflux · 800 kcal. Something has gone wrong and I would like to know how badly before I decide what to do. Nothing else in the setup changed, which is…

fatigue
fatigue

Tiredness on treatment: how much is energy deficit, how much is dehydration or electrolyte drift, how much is genuinely drug-attributable, and…

38 questions
nutrition
nutrition

Eating on a suppressed appetite: hitting nutritional targets inside a small energy budget, micronutrient risk, meal structure, and what the trial…

92 questions
electrolytes
electrolytes

Sodium, potassium and magnesium during reduced intake and GI losses: what the symptoms of a shortfall look like, when a panel is worth drawing,…

36 questions
asked by nkem_obiora 46k · 2.3 years ago
18 votes0 answers10k views
Would you re-test dulaglutide after two weeks at minus 80 °C, or accept the original certificate?

Stated plainly: dulaglutide · two weeks · minus 80 °C. I am trying to build something sustainable rather than something thorough that I will abandon. I have already…

batch-testing
batch-testing

Testing at the batch or lot level: sampling plans, how many vials from a lot need testing to say anything about the lot, and the difference…

865 questions
peptide-stability
peptide-stability

The chemistry of peptide degradation: deamidation, oxidation, hydrolysis, aggregation and fibrillation, and how temperature, pH, ionic strength,…

832 questions
coa
coa

Certificates of analysis: what fields a useful one carries, how to tell a real analytical report from a marketing document, batch and lot…

749 questions
asked by plunger_stop 18k · 2.4 years ago
37 votes0 answers55k views
Does JEEP issue lot-specific documentation, or a batch certificate?

I have the report as a PDF with the chromatogram on page two, so I can quote specifics. I can parse the result. I am less sure what it licenses me to conclude. I have…

batch-testing
batch-testing

Testing at the batch or lot level: sampling plans, how many vials from a lot need testing to say anything about the lot, and the difference…

865 questions
coa
coa

Certificates of analysis: what fields a useful one carries, how to tell a real analytical report from a marketing document, batch and lot…

749 questions
vendor-vetting
vendor-vetting

Evaluating a supplier on evidence rather than reputation: testing history across batches, whether certificates are batch-specific, how failures…

436 questions
asked by nils_karlberg 13k · 2.4 years ago
36 votes0 answers53k views
Does holding at 40 mg for twelve weeks before escalating reduce constipation?

Conditions: 40 mg · twelve weeks · constipation. I want to know whether this is a real physical effect or an artefact of how it is measured. What prompted the…

titration
titration

Stepwise dose increases over weeks, why the label schedules exist at all, and what tolerability-driven deviation from a schedule looks like in…

444 questions
nausea
nausea

The dominant tolerability signal in every trial of the class: incidence, timing relative to a dose step, duration, and the distinction between…

346 questions
dose-escalation
dose-escalation

The decision to move up a step: what evidence supports a four-week interval, what happens when you compress it, and how trial protocols handled…

88 questions
asked by linnea_wahlberg 14k · 2.4 years ago
27 votes0 answers35k views
Does holding at 20 mg for two weeks before escalating reduce constipation?

What I am working with: 20 mg · two weeks · constipation. I keep seeing this stated as a fact with no explanation attached, and unexplained facts make me suspicious.…

titration
titration

Stepwise dose increases over weeks, why the label schedules exist at all, and what tolerability-driven deviation from a schedule looks like in…

444 questions
nausea
nausea

The dominant tolerability signal in every trial of the class: incidence, timing relative to a dose step, duration, and the distinction between…

346 questions
dose-escalation
dose-escalation

The decision to move up a step: what evidence supports a four-week interval, what happens when you compress it, and how trial protocols handled…

88 questions
asked by esben_lykke 15k · 2.4 years ago
27 votes0 answers39k views
Does ALT tell me anything about hepatic fat on cagrilintide?

Stated plainly: ALT · cagrilintide. I keep seeing this stated as a fact with no explanation attached, and unexplained facts make me suspicious. My background is…

liver-enzymes
liver-enzymes

ALT, AST, GGT and ALP: what they do and do not indicate about hepatic fat, why enzymes are a poor surrogate for histology, and where non-invasive…

50 questions
mash
mash

Metabolic dysfunction-associated steatohepatitis: histological endpoints, resolution without worsening fibrosis, fibrosis improvement by stage,…

51 questions
bloodwork
bloodwork

Laboratory monitoring: which panels are worth ordering, sensible intervals, reference-range versus optimal-range arguments, and how to read a…

284 questions
asked by kirsi_lahtinen 45k · 2.4 years ago
18 votes0 answers15k views
How do I get 20 units out of a vial reconstituted to 8 mg/mL without guessing?

Setup, so nobody has to ask: 20 units · 8 mg/mL. This is a procedural question rather than a theoretical one, and I would like the procedure rather than the theory.…

insulin-syringe
insulin-syringe

U-100 and U-40 insulin syringes as measuring instruments. A U-100 syringe is graduated in insulin units where 100 units equals 1 mL, so one unit…

268 questions
dosing-math
dosing-math

The arithmetic itself: milligrams to millilitres to insulin units, concentration after reconstitution, dose per draw, and vial-days per vial. Show…

811 questions
diluent-volume
diluent-volume

Choosing how much diluent to add, which is really a question about what you want your measurement resolution to be. Larger volumes buy you…

308 questions
asked by gel_pack_warm 13k · 2.4 years ago
39 votes0 answers51k views
Is there evidence that a slower ladder produces the same end result?

I am asking about the protocol logic rather than about my own case specifically. I would like to know whether this claim survives contact with evidence. If the answer…

titration
titration

Stepwise dose increases over weeks, why the label schedules exist at all, and what tolerability-driven deviation from a schedule looks like in…

444 questions
dose-escalation
dose-escalation

The decision to move up a step: what evidence supports a four-week interval, what happens when you compress it, and how trial protocols handled…

88 questions
clinical-trials
clinical-trials

Reading the primary literature properly: estimands, intention-to-treat versus per-protocol, confidence intervals, absolute versus relative…

913 questions
asked by swab_stopper 16k · 2.4 years ago
14 votes0 answers21k views
Would you accept 97.9% on retatrutide from GGPeps without a content assay?

Details up front: 97.9% · retatrutide · GGPeps. This is a planning question. I know what my options are; I do not know how to weigh them. What I want is the minimum…

purity
purity

Purity as chromatographic area per cent - the fraction of detected material that is your target peak. It says nothing about how much material is…

788 questions
content-assay
content-assay

Quantified content: how many milligrams of peptide are actually in the vial, measured against a calibrated reference standard. A separate test…

438 questions
vendor-vetting
vendor-vetting

Evaluating a supplier on evidence rather than reputation: testing history across batches, whether certificates are batch-specific, how failures…

436 questions
asked by bridget_nyathi 16k · 2.4 years ago
17 votes0 answers18k views
Is a titration interval of four weeks better supported than four weeks for dulaglutide?

What I have: four weeks · dulaglutide. I am asking for verification rather than opinion, ideally with something I can read myself. It is possible the evidence exists…

titration
titration

Stepwise dose increases over weeks, why the label schedules exist at all, and what tolerability-driven deviation from a schedule looks like in…

444 questions
dose-escalation
dose-escalation

The decision to move up a step: what evidence supports a four-week interval, what happens when you compress it, and how trial protocols handled…

88 questions
clinical-trials
clinical-trials

Reading the primary literature properly: estimands, intention-to-treat versus per-protocol, confidence intervals, absolute versus relative…

913 questions
thyroid
thyroid

Thyroid questions: the rodent C-cell findings behind the labelled warning, human calcitonin data, TSH drift during weight loss, and the…

14 questions
asked by juliette_farnese 12k · 2.4 years ago