Draft monograph: Sermorelin — submissions
The 9 submissions received, published in full with declared interests and secretariat responses.
§2Submissions and responses
9 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.
Adverse event frequencies are given without the denominator or the exposure period
The respondent has read the draft covering Sermorelin and makes one submission.
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 secretariat accepts this submission. A frequency detached from its denominator is a number without a quantity.
Every reported frequency now carries the number of participants, the number of events and the exposure period, and comparator-arm figures are reported alongside rather than in a separate table.
The monograph should reproduce the approved labelling rather than paraphrase it
The respondent read the draft on Sermorelin and has confined this submission to a single matter.
The submission is made on behalf of the marketing-authorisation holder. It states that the draft paraphrases the approved indication, the posology and the contraindications, and that any paraphrase risks diverging from the authorised text.
The sponsor asks that the authorised wording be reproduced verbatim in each case, and offers the current summary of product characteristics as the source.
The secretariat accepts this submission in part. The authorised indication and the contraindications are reproduced verbatim and attributed. The posology is not, because the monograph reports what the trials administered as well as what the labelling authorises, and the two are frequently different.
The approved indication and contraindications are now reproduced verbatim from the named authorisation with its version and date, and the posology section reports the labelled schedule and the schedules studied side by side, with the source of each stated.
Local reactions are omitted from the adverse-event table because the trials reported them separately
The draft on Sermorelin was read from the standpoint of a clinician asked about the compound by people already taking it.
Injection-site reactions are reported in the source trials in a table of their own and do not appear in the systemic adverse-event table the monograph reproduces. The result is that the most common adverse experience of a subcutaneously administered compound is absent from the monograph’s adverse-event section.
The respondent proposes that local reactions be carried in the same table as systemic events, with the reporting convention of the source trial recorded in a footnote.
The secretariat accepts this submission. The omission arose from following the source tables and it produced a misleading total.
Local reactions are now carried in the adverse-event table wherever the source trials report them, footnoted with the convention each trial used.
The compound is supplied under names the monograph does not list
The respondent has read Sermorelin in draft and makes a single submission.
The respondent states that the compound is supplied under several trade names, research codes and transliterations, and that a reader holding a label bearing one of them will not find the monograph.
A list of names observed in supply, with the source of each observation, accompanied the submission.
The secretariat accepts this submission. A monograph a reader cannot find is not serving the reader.
The synonym list is extended to include every name the Institute can evidence from a document it holds, each recorded with its source. Names asserted without a supporting document are not added, and the distinction is stated at the head of the list.
Declared interests should appear on the document rather than on a separate page
Having read the draft monograph on Sermorelin, the respondent puts one point to the committee.
The draft links to a central conflicts register. The respondent argues that a reader assessing whether to rely on a particular document should not have to leave it to find out who assessed it and what they declared.
The respondent proposes that the interests of every named contributor to a document be printed on that document.
The secretariat notes this submission and records that the draft already provides for it, which the respondent could reasonably have missed because the provision sits in an appendix.
Every document carries the declared interests of its named contributors in its front matter, and the central register exists so that a reader can see a person across all documents rather than one at a time. No amendment arises; the provision has been moved from the appendix into the body of the methodology document so that it is findable.
Regulatory status is stated without naming the jurisdiction
The respondent submits on the draft monograph for Sermorelin. Growth-hormone-axis compounds are supplied widely and studied narrowly, and a document about one should make that asymmetry visible.
The draft states that the compound is approved, or not approved, without saying by whom. The respondent, employed by a health-technology assessment body, states that approval status differs between jurisdictions for several compounds in the series and that an unqualified statement will be wrong somewhere.
The respondent proposes that every status statement name the authority and carry the date on which the status was checked.
The secretariat accepts this submission. An unattributed status statement is a claim the Institute cannot support.
Every regulatory status statement now names the authority, states the date on which the status was verified, and is recorded per jurisdiction rather than as a single global assertion.
The supply section does not record that endotoxin is not determined
The respondent’s comment on the draft for Sermorelin arises from the anti-doping literature, in which this class is well represented and clinically it is not.
The compound is supplied as a lyophilisate intended for reconstitution and injection. The supply section lists the determinations that certificates carry and does not state that endotoxin is not among them, which is the determination whose absence has the most direct consequence for that presentation.
The respondent proposes an explicit line in §8 for every compound supplied in an injectable presentation, stating whether endotoxin is determined and, where it is not, what that means.
The secretariat accepts this submission. The omission was an artefact of listing what is present rather than what is absent.
Section 8 now carries an explicit endotoxin line for every compound supplied in an injectable presentation, and states plainly that an undetermined attribute is undetermined rather than acceptable.
Guidance on lyophilised storage is missing
The respondent notes that Sermorelin is supplied for indications that no trial in the draft addresses, and submits in that context.
The respondent asks that the monograph state storage conditions for lyophilised material as well as for reconstituted solution, since the two differ and the former governs the longer part of the shelf life.
The respondent states that the omission is the more consequential because lyophilised material is what is generally received.
The respondent endorses the general approach taken in submission 006 and asks that it be extended to the matter identified here.
The secretariat notes this submission. The draft addresses lyophilised storage, in the presentation section rather than in the section on in-use handling, which is where the respondent looked.
No amendment to content arises. The two storage statements have been brought together under a single heading so that a reader looking for either finds both.
The monograph should not describe how the compound is supplied outside a regulated route
This submission concerns Sermorelin and makes one point.
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.
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
Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.