Draft monograph: Ipamorelin — submissions
The 10 submissions received, published in full with declared interests and secretariat responses.
§2Submissions and responses
10 submissions were received. Each is published in full below with its declared interest, the secretariat response and the disposition. The Institute publishes submissions it did not accept in the same form as those it did.
Point estimates are given without an interval
The respondent submits on the draft monograph for Ipamorelin. Growth-hormone-axis compounds are supplied widely and studied narrowly, and a document about one should make that asymmetry visible.
Several estimates in the draft appear as single figures. The respondent states that a point estimate without an interval invites a precision the underlying data do not support, and that the effect is worst where the estimate is drawn from a small contributing set.
The respondent proposes that no point estimate appear anywhere in the document set without its interval, including in summary tables and in the abstract.
The secretariat accepts this submission in part. Intervals are added wherever the source reports one. The proposal is declined for figures the source published without an interval, because the Institute will not compute an interval a source did not report.
Every estimate now carries its interval where the source reported one, and where it did not, the estimate is annotated as reported without an interval rather than left to appear as a precise figure.
Registered trials that never reported are absent from the monograph
The respondent has read Ipamorelin and submits on a matter of presentation.
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.
The secretariat accepts this submission. A trial list built from publications reproduces publication bias in the shape of the document.
The trial list now includes every registered trial the Institute identified, with its reporting status stated, and the monograph reports the proportion of registered trials for which no result has been posted or published.
Storage and reconstitution guidance is given without stating what it rests on
The respondent submits on Ipamorelin.
The draft states storage conditions and a period of use after reconstitution. The respondent asks what evidence supports the period, and states that in the absence of a stability study on this presentation the figure is a convention rather than a finding.
The respondent proposes that any in-use period be accompanied by the stability evidence that produced it, or removed.
Submission 002 raises an adjacent matter. The respondent regards the two as separable and addresses only this one.
The secretariat accepts this submission in part. The period is retained where a stability study on a comparable presentation exists and is cited. Where no such study exists the figure is removed rather than annotated, because an annotated figure is still a figure a reader will use.
In-use periods now appear only where supported by a cited stability determination on a stated presentation, and elsewhere the monograph records that no in-use stability evidence was identified for this presentation.
The interaction section lists mechanisms rather than interactions
This submission concerns Ipamorelin and a convention used across the Institute’s output.
The section describes pathways by which an interaction could occur. It does not say which interactions have been observed, in what setting, or with what consequence. A reader dispensing alongside other therapy cannot act on a mechanism.
The respondent proposes that observed interactions be separated from theoretical ones, and that the theoretical ones be labelled as such.
The secretariat accepts the separation and declines to expand the section beyond the evidence.
The interaction section is now divided into interactions reported in clinical use and interactions predicted from mechanism, with the second labelled as prediction. Where neither exists the section says so in one line rather than being padded.
The monograph should not describe how the compound is supplied outside a regulated route
The respondent notes that Ipamorelin is supplied for indications that no trial in the draft addresses, and submits in that context.
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.
The secretariat notes this submission and records the concern as a real one that the draft had already considered.
No amendment arises. The monograph describes what is supplied and names no supplier, price or route of acquisition, and it carries the standing statement that the Institute assesses evidence and does not recommend use. Describing a presentation a reader may already hold is the condition of being useful to that reader.
Two factual descriptions of the sponsor's programme are inaccurate
The respondent has read the draft covering Ipamorelin and makes one submission.
The submission is made on behalf of the marketing-authorisation holder and is confined to two matters of fact. The draft describes a trial as terminated where the sponsor closed it at a pre-specified interim analysis, and gives a dose in a unit that does not match the approved labelling.
Supporting documentation, comprising the published trial report and the current summary of product characteristics, accompanied the submission. No view is expressed on the certainty ratings, which the sponsor considers a matter for the assessment committee.
The respondent notes submission 002 above and does not repeat the ground it covers.
The secretariat accepts this submission. Both points are matters of fact, both were checkable against documents the Institute holds, and both were wrong in the draft.
The trial status now reads as completed at a pre-specified interim analysis, with the analysis identified, and the dose is stated in the unit used in the approved labelling. The submission is identified as an industry submission on its face in accordance with the conflicts policy.
The search date is not on the face of the document
Having read the draft monograph on Ipamorelin, the respondent puts one point to the committee.
The draft carries a publication date and a review date but not the date on which the evidence was last searched. Those are three different dates and only the third tells a reader how current the assessment is. A document published in one quarter may rest on a search run two quarters earlier, and nothing on the page allows that gap to be measured.
The respondent proposes that the search date be printed adjacent to every certainty rating rather than in the methods section, on the ground that a reader who acts on a rating is unlikely to have read the methods section first.
The secretariat accepts this submission. The distinction between publication, review and search dates is real and the draft did not make it visible where it mattered.
The search date is now printed adjacent to every certainty rating and is carried in the document metadata, so that the interval between the search and the reading is visible without reference to the methods section.
The preclinical section is extensive and the clinical section is not
This submission concerns the draft on Ipamorelin. The respondent works in an endocrine service in which compounds of this class are assessed.
The draft summarises a large animal literature and a small or absent human literature. The respondent states that the resulting document reads as though a great deal is known, when what is known concerns rodents.
The respondent proposes that the preclinical section be reduced to a statement of what has been observed in animals and that the detail be removed entirely.
The secretariat accepts this submission in part. The section is shortened and given a standing statement. The proposal to remove the detail is declined, because a reader encountering claims derived from that literature needs to be able to see what it actually contains.
The preclinical section is reduced in length, placed after the clinical assessment rather than before it, and opens with a standing statement that an effect observed in an animal model is not a clinical outcome and does not support a certainty rating.
The indication table mixes approved indications with uses for which the compound is merely supplied
The respondent’s comment on the draft for Ipamorelin arises from the anti-doping literature, in which this class is well represented and clinically it is not.
The indication table lists indications in a single sequence. Some are approved by a competent authority, some are the subject of trials that have not reported, and some are uses observed in supply with no trial evidence at all.
The respondent states that the three categories should not share a table without being distinguished in it.
This submission should be read alongside submission 004, which arises on the same draft.
The secretariat accepts this submission. A shared table is an implicit claim of comparable standing.
The indication table now carries a status column with three values, approved, under investigation and supplied without trial evidence, and the value is stated for every row. Rows in the third category also state that no certainty rating is assigned because there is no evidence base to rate.
A purity figure from a certificate is quoted as though it were a content figure
The respondent read the draft on Ipamorelin and has confined this submission to a single matter.
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 secretariat accepts this submission. The conflation is the error the Institute most often corrects in supply documentation, and it appeared in an Institute draft.
Purity and content are now reported in separate rows with separate definitions, and the monograph states that a purity figure sets no bound on content and that a content figure requires a determination against a standard of assigned content.
References cited on this page
References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.
- International Organization for Standardization. ISO/IEC 17025:2017 General Requirements for the Competence of Testing and Calibration Laboratories. ISO/IEC Standard 2017;3rd edition. identifier not held by the Institute
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