Draft monograph: GHRP-2 — submissions
The 7 submissions received, published in full with declared interests and secretariat responses.
§2Submissions and responses
7 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.
A rise in insulin-like growth factor 1 is reported in the position of a clinical outcome
The respondent’s comment on the draft for GHRP-2 arises from the anti-doping literature, in which this class is well represented and clinically it is not.
The assessed-outcome table carries a change in a circulating hormone concentration. That is a pharmacodynamic response and it is what the compound is expected to do; it is not an outcome in the sense the rest of the table uses the word, and printing it in the same column invites the reader to treat it as one.
The respondent proposes that biomarker responses be reported in the pharmacology section and excluded from the assessed-outcome table unless a validation link to a clinical outcome has been demonstrated.
The secretariat accepts this submission. A pharmacodynamic response placed in an outcome table is a category error and the series should not make it.
Biomarker responses now appear in §2 and are excluded from the assessed-outcome table unless the surrogate relationship has been validated, in which case the validation evidence is cited beside it.
The absence of paediatric evidence is not stated where a reader would look for it
This submission concerns the draft on GHRP-2 and is made from an endocrine standpoint.
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.
The respondent has read submission 001 and puts a further matter to the secretariat.
The secretariat accepts this submission. An unstated absence is indistinguishable from an unread section.
The population table now carries a paediatric row in every monograph, and where evidence exists the trials are named.
Trials are described as terminated where they completed as planned
Having read the draft monograph on GHRP-2, the respondent puts one point to the committee.
The respondent states that the draft uses the word terminated for trials stopped at pre-specified interim analyses, for trials stopped for futility and for trials closed for commercial reasons, and that these are three different facts.
The respondent proposes that the status vocabulary be fixed and defined in the glossary.
The secretariat accepts this submission in part. The vocabulary is fixed and defined. The proposal to distinguish commercial closure from futility in every case is accepted only where the Institute holds a document stating the reason.
Trial status now uses a fixed vocabulary defined in the glossary, and where the reason for stopping is not evidenced by a document the Institute holds, the status is recorded as stopped with the reason not established rather than assigned.
The document should not describe uses outside the approved indication
The respondent notes that GHRP-2 is supplied for indications that no trial in the draft addresses, and submits in that context.
The submission is made on behalf of a marketing-authorisation holder. It states that the draft describes uses of the compound that fall outside the approved indication, that such uses are not supported by the sponsor, and that describing them may be read as legitimising them.
The sponsor asks that the sections concerned be removed, or in the alternative that they carry a prominent statement that the sponsor does not support such use.
The secretariat does not accept this submission. The Institute records what is supplied and what is used, because a reader encountering a compound outside a regulated route is the reader most in need of an assessment of the evidence for it.
The sections remain. Every such section already states the regulatory status of the use described and states that the evidence for it is assessed separately from the evidence for the approved indication. The submission is published in full and identified as an industry submission.
The compound is supplied under names the monograph does not list
The respondent has read the draft covering GHRP-2 and makes one 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.
References should carry a persistent identifier for every cited source
The respondent read the draft on GHRP-2 and has confined this submission to a single matter.
Several references in the draft carry a journal, a year and a volume but no persistent identifier. The respondent states that retrieval of such a reference is materially slower and that identifiers should be supplied throughout.
The respondent asks in the alternative that where an identifier exists but is not carried, the omission be explained rather than left as a gap the reader must interpret.
The respondent’s submission overlaps with submission 004 and was prepared without sight of it.
The secretariat accepts the second limb of this submission and declines the first. Identifiers are supplied wherever the Institute holds one. Where the Institute does not hold an identifier it will not supply one, because a reconstructed identifier that resolves to the wrong record is a worse defect than an absent one.
Every reference without a persistent identifier now carries an explicit statement that the identifier is not held by the Institute, so that its absence is a recorded fact rather than an apparent oversight.
Open-label extension data are presented alongside randomised data without distinction
The respondent submits on the draft monograph for GHRP-2. Growth-hormone-axis compounds are supplied widely and studied narrowly, and a document about one should make that asymmetry visible.
Long-term figures in the clinical section come from open-label extensions in which every participant received the active compound and those who did not tolerate it had already withdrawn. They are printed in the same table as randomised comparisons and in the same typeface.
The respondent proposes that extension data be presented in a separate table, or at minimum in a separately labelled block, and that the surviving-population problem be stated once where it arises.
This submission should be read alongside submission 006, which arises on the same draft.
The secretariat accepts this submission. An extension estimate answers a different question from a randomised one and should not be read as though it answered the same one.
Extension data now appear in a separate table headed as uncontrolled follow-up, with a standing note on differential withdrawal.
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.