Draft monograph: IGF-1 LR3 — submissions

The absence of paediatric evidence is not stated where a reader would look for it

The draft on IGF-1 LR3 was read from the standpoint of a clinician asked about the compound by people already taking it.

The population section describes the adult trial populations. Nothing states whether the compound has been studied in anyone under eighteen. For several compounds in this series it has not, and for one or two it has; the document does not let the reader tell which case applies.

The respondent proposes a standing row in the population table recording paediatric evidence as present, absent, or present in a named subpopulation only.

Registered trials that never reported are absent from the monograph

The respondent notes that IGF-1 LR3 is supplied for indications that no trial in the draft addresses, and submits in that context.

The respondent states that the trial list appears to be drawn from published reports, and that registered trials which completed without a report are therefore invisible. The proportion of a programme that never reported is itself a finding about the evidence base.

The respondent proposes that every registered trial of the compound be listed, with its reporting status, whether or not a report exists.

Adverse event frequencies are given without the denominator or the exposure period

Having read the draft monograph on IGF-1 LR3, the respondent puts one point to the committee.

The draft reports adverse event frequencies as percentages. The respondent states that a percentage without a denominator and without an exposure period cannot be compared with any other figure, including the corresponding figure in the comparator arm.

The respondent proposes that every frequency carry the number of participants and the exposure period over which it was observed.

The monograph should not describe how the compound is supplied outside a regulated route

The respondent read the draft on IGF-1 LR3 and has confined this submission to a single matter.

The respondent states that describing presentations observed in unregulated supply risks being read as a guide to obtaining them, and asks that the material be removed.

The respondent accepts that the information is accurate and objects to its presence rather than to its content.

Submission 002 concerns the same document. The respondent’s point is a different one.

The same concept is given three different names in one document

The respondent has read the draft covering IGF-1 LR3 and makes one submission.

The draft refers to the same quantity as a response rate, a responder proportion and a categorical outcome in different sections. The respondent, who works in health-technology assessment, states that a reader cannot tell whether the three refer to one thing or to three.

The respondent proposes that the glossary term be used at every occurrence and that the glossary entry be linked at first use in each section rather than only at first use in the document.

The respondent read submission 004 after drafting this one and has not altered it, the two points being distinct.

The analytical section is longer than the clinical assessment it accompanies

This submission concerns the draft on IGF-1 LR3. The respondent works in an endocrine service in which compounds of this class are assessed.

The respondent states that the analytical section occupies more of the monograph than the assessment of clinical effect, and that the proportions imply the Institute considers the analytical question the more important one.

The respondent proposes that the analytical material be moved to the standards series and referenced rather than reproduced.

The respondent supports submission 002 so far as it goes and adds the matter set out here.

A purity figure from a certificate is quoted as though it were a content figure

The respondent submits on the draft monograph for IGF-1 LR3. Growth-hormone-axis compounds are supplied widely and studied narrowly, and a document about one should make that asymmetry visible.

The draft quotes a purity percentage from supply documentation in a sentence about how much compound a vial contains. Chromatographic purity is a relative area within what was detected; it is not a mass fraction and it does not bound vial content.

The respondent, an analytical chemist, proposes that purity and content never appear in the same sentence without an explicit statement that they answer different questions.

The mechanism section is written with more confidence than the clinical section it precedes

This submission concerns the draft on IGF-1 LR3 and is made from an endocrine standpoint.

The pharmacology section states what the compound does at its receptor in the indicative mood and without hedging. The clinical section then reports that the effect has not been demonstrated in people. A reader who stops after the first section, as many will, takes away a claim the document goes on to withdraw.

The respondent does not propose that the pharmacology be hedged, which would be inaccurate, but that each pharmacology section close with a sentence stating which of the described actions has been shown to produce a clinical effect and which has not.

The monograph does not tell a reader that two vials of the same compound may not contain the same thing

The respondent’s comment on the draft for IGF-1 LR3 arises from the anti-doping literature, in which this class is well represented and clinically it is not.

The analytical section describes what a determination measures and the supply section describes what suppliers document. Neither says that the quantity of peptide in two vials bearing the same label may differ by more than the difference between two doses in the trial schedule.

The respondent proposes an explicit statement, in §8, that a purity figure describes the lot it was measured on and nothing else, and that the practical consequence is that a dose calculated from a label is an estimate.