Draft monograph: CagriSema (cagrilintide with semaglutide) — submissions
The 5 submissions received, published in full with declared interests and secretariat responses.
§2Submissions and responses
5 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 purity figure from a certificate is quoted as though it were a content figure
Having read the draft monograph on CagriSema (cagrilintide with semaglutide), the respondent puts one point to the committee.
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.
Evidence for one member of the class is presented as evidence for this compound
The respondent submits on the draft monograph for CagriSema (cagrilintide with semaglutide). A document about a combination has to keep separate what is known about the combination from what is known about each component.
The draft supports a statement about this compound with a citation to a trial of a different compound in the same class. The respondent states that a class-level inference is a judgement that should be labelled as one rather than presented as direct evidence.
The respondent proposes that any class-level extrapolation be flagged at the point of use and excluded from the certainty rating for the compound itself.
The secretariat accepts this submission. Moderate certainty evidence supports several class-level statements in this area, but a class-level statement is not evidence about a particular member of the class.
Class-level inferences are now labelled at the point of use, are excluded from the certainty rating for the compound, and are reported in a separate subsection stating which compound the underlying evidence concerns.
A sortable table implies a comparison the underlying data do not support
This submission concerns the draft on CagriSema (cagrilintide with semaglutide). The respondent’s interest is in whether the evidence cited was generated with the combination or with its parts.
The draft presents a sortable table whose columns are drawn from sources of differing quality. The respondent states that sorting on such a column produces an ordering that looks like a ranking and is not one.
The respondent proposes that sorting be disabled on any column whose values are not commensurable.
This submission is made in the same spirit as submission 002 and on a different aspect of the draft.
The secretariat notes this submission and records that the point is correct in principle.
No amendment arises here because every sortable table in the document set already carries a standing statement above it that the ordering is not a ranking and that the values in each column are commensurable only where the column header says so. The proposal to disable sorting was considered and not adopted, because a reader who cannot sort a table generally sorts it elsewhere and without the statement.
The monograph should not describe how the compound is supplied outside a regulated route
The respondent has read the draft covering CagriSema (cagrilintide with semaglutide) and makes one submission.
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 respondent’s submission overlaps with submission 003 and was prepared without sight of it.
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 absence of a rare harm in the trial set is presented as reassurance
The respondent read the draft on CagriSema (cagrilintide with semaglutide) and has confined this submission to one matter.
The draft states that a specific serious event was not observed in the contributing trials. The respondent states that trials of the size conducted here could not have detected an event at the frequency in question, and that reporting the absence without that arithmetic converts an uninformative result into a reassuring one.
The respondent proposes that the detectable frequency be stated wherever the absence of an event is reported.
The secretariat accepts this submission. The Institute's own framework treats an absent event in an underpowered set as uninformative, and the draft departed from it.
Wherever the monograph reports that an event was not observed, it now states the total exposure and the frequency the contributing trials could have detected, so that the absence is read as the limit of the evidence rather than as a finding.
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.