Draft monograph: GHK-Cu — 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.
What happens when the compound is stopped is not addressed
Having read the draft monograph on GHK-Cu, the respondent puts one point to the committee.
The draft assesses the effect of the compound while it is being taken. The respondent, who declares having used a compound in the class under prescription, states that the question a person actually faces is what happens afterwards, and that the monograph is silent on it.
The respondent proposes that the trajectory after discontinuation be an assessed outcome wherever any contributing trial measured it, and a recorded evidence gap wherever none did.
The secretariat accepts this submission. The omission was one of framing rather than of evidence, and the framing followed the trials rather than the decision.
Discontinuation trajectory is now an assessed outcome in every monograph where a contributing trial measured it, and a recorded evidence gap in every monograph where none did, so that its absence is visible rather than silent.
The certainty rating for the principal assessed outcome cannot be traced to the contributing trials
This submission concerns the draft on GHK-Cu. The respondent’s interest is in whether a reader can tell which of the cited work was done in animals, in cell culture, or in people.
The draft states a certainty rating for the principal assessed outcome and lists the contributing trials, but does not state which domain drove the downgrade. A reader who disagrees with the rating cannot tell whether the disagreement concerns risk of bias, imprecision, indirectness or inconsistency.
The respondent proposes that each rating carry its downgrade reasons explicitly, in the same row as the rating, so that a reader can accept the evidence assessment while disputing a single domain judgement.
The secretariat accepts this submission. A rating without its reasoning is an assertion, and the draft asserted rather than showed.
Each assessed outcome now carries its downgrade domains in the summary-of-findings row, with a short statement of the judgement made in each, so that the rating can be checked domain by domain against the contributing trials.
A superseded version should remain reachable from the version that replaced it
This submission addresses the draft on GHK-Cu from the standpoint of a reader who meets the compound in supply material before meeting it in a journal.
The respondent states that the draft supersedes an earlier document and that a reader who cited the earlier version has no way to reach it from the new one, which makes it impossible to see what changed.
The respondent asks that every version carry a link both to what it supersedes and to what supersedes it.
Submission 001 concerns the same document. The respondent’s point is a different one.
The secretariat notes this submission. The corrections and versioning policy already requires bidirectional version links and every superseded document is retained at its own address.
No amendment arises. The requirement is stated in the corrections and versioning policy and the amendment log of this document links to the version it replaced. The respondent is correct that the link was absent from the draft page furnished for consultation, which was a defect of the consultation copy and not of the policy.
The document should not describe uses outside the approved indication
The respondent notes that the draft on GHK-Cu carries no controlled human trial, and submits with that in view.
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.
This submission is made by a respondent with a different professional interest in the outcome from the one behind submission 002.
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 monograph should not describe how the compound is supplied outside a regulated route
The respondent submits on the draft monograph for GHK-Cu. Repair peptides are where the distance between the preclinical literature and the clinical literature is widest, and a monograph earns its place by measuring that distance.
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.
The monograph should state what the compound costs
The respondent read the draft on GHK-Cu and has confined this submission to one matter.
The respondent states that a reader deciding whether to pursue treatment needs to know what it costs, and that omitting price makes the assessment less useful than it could be.
The respondent proposes that a price range be recorded for each compound with the source and date.
The respondent read submission 003 after drafting this one and has not altered it, the two points being distinct.
The secretariat does not accept this submission. Price varies by jurisdiction, payer, presentation and date to a degree that no single figure could survive, and a stale price is worse than no price.
No price is recorded. The monograph records the presentations available and the regulatory status in each jurisdiction, which are the facts the Institute can verify and maintain. The submission remains published in full.
Nothing is said about impaired renal or hepatic clearance
The draft on GHK-Cu was read against the sources cited in it, and this submission arises from that comparison.
The pharmacokinetic section gives clearance and half-life in healthy volunteers or in the trial population. It does not say whether either has been characterised in impaired renal or hepatic function, which is the question a clinician reaches the section with.
The respondent proposes that the pharmacokinetic section state, for each compound, whether a dedicated study in impaired function exists, and where none does, say so rather than leaving the field out.
The secretariat accepts this submission. A missing row and an absent study look the same on the page and are not the same thing.
The pharmacokinetic table now carries renal and hepatic rows in every monograph, populated with the study where one exists and with an explicit statement of absence where none does.
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.