Draft monograph: Petrelintide — submissions
The 15 submissions received, published in full with declared interests and secretariat responses.
§2Submissions and responses
15 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.
The document should not describe uses outside the approved indication
This submission concerns Petrelintide and makes one point.
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 monograph should state what the compound costs
The respondent read Petrelintide in draft. The point applies to it and to the series generally.
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 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.
The analytical section assumes a reference standard that is not generally available
The respondent read the draft monograph on Petrelintide and puts one point to the secretariat.
The draft describes identity and content determinations that require a reference standard of assigned content. For this compound no such standard is in general circulation, and a laboratory following the section as written cannot perform the determination described.
The respondent, employed by a contract analytical laboratory, proposes that the monograph state explicitly where a reference standard is unavailable and what a determination performed without one can still establish.
The secretariat accepts this submission. The section described an ideal case and did not say so.
The analytical section now states whether a reference standard is in general circulation for this compound and, where it is not, states which determinations remain possible and which become qualitative. A content figure obtained without a reference standard is recorded as an estimate against a stated assumption rather than as a determination.
The document is unreadable without specialist training
The respondent submits on Petrelintide. The point would apply equally to any document in the series.
The respondent states that the draft is written for a reader who already understands certainty grading, and that the people most affected by the subject matter will not reach the assessment at all.
The respondent proposes a plain-language summary at the head of every document, written to the same standard of accuracy as the document itself and not as a promotional abstract.
This submission is made in the same spirit as submission 001 and on a different aspect of the draft.
The secretariat accepts this submission in part. A plain-language summary is added. The proposal that it replace the technical abstract is declined, because the abstract is the part of the document other assessors read and cite.
Every document now opens with a plain-language summary of not more than 150 words, placed above the technical abstract and carrying the same certainty language, so that the two cannot diverge.
Trials are described as terminated where they completed as planned
The respondent notes that Petrelintide is frequently supplied in combination while this draft assesses it alone, and submits in that context.
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 respondent endorses the general approach taken in submission 003 and asks that it be extended to the matter identified here.
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.
Point estimates are given without an interval
The respondent has read the draft covering Petrelintide and makes one submission.
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.
Anti-drug antibody data are omitted
This submission concerns Petrelintide and a convention used across the Institute’s output.
The respondent states that immunogenicity is measured in the development programmes of peptide therapeutics and that the monograph does not report it, leaving a reader unable to judge whether loss of effect over time has an immunological explanation.
The respondent proposes that anti-drug antibody incidence and its relation to effect be reported for every compound in the series.
The secretariat accepts this submission in part. Immunogenicity is reported where a contributing trial reported it. The proposal to report it for every compound is declined because for many compounds in the series no such data exist and a uniformly empty row is not informative.
Anti-drug antibody incidence and any reported association with loss of effect are now reported where measured, and recorded as not measured where the contributing trials did not assess them.
A purity figure from a certificate is quoted as though it were a content figure
This is a submission on Petrelintide.
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.
What happens to weight after the compound is stopped is not in the assessed outcomes
The respondent’s interest in the draft for Petrelintide is in what a person starting the compound would want to have been told.
Several trials in the evidence base ran a withdrawal period and reported what happened. That evidence is the single most useful thing a person considering the compound could be told, and it appears in the monograph only as a sentence in the discussion.
The respondent proposes that post-withdrawal trajectory be an assessed outcome in its own right for every compound where a withdrawal period was studied, with its own certainty rating.
The respondent supports submission 003 so far as it goes and adds the matter set out here.
The secretariat accepts this submission. The evidence exists, it is directly relevant, and it was not being assessed.
Post-withdrawal trajectory is now an assessed outcome wherever a withdrawal period was studied, rated on the same scale as the others. Where no withdrawal period was studied the outcome is recorded as not assessed.
The preclinical section is extensive and the clinical section is not
This submission concerns the draft on Petrelintide. The respondent’s work is with satiation-directed compounds and the observation arises from that.
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 respondent read submission 007 after drafting this one and has not altered it, the two points being distinct.
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 compound is supplied under names the monograph does not list
Having read the draft under consultation, which concerns Petrelintide, the respondent submits as follows.
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.
The absence of a rare harm in the trial set is presented as reassurance
This is a submission on the draft monograph for Petrelintide, made from a clinical rather than an analytical standpoint.
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 respondent has read submission 008 above and makes this submission independently of it.
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.
Regulatory status is stated without naming the jurisdiction
The respondent submits on Petrelintide, on a matter that is not specific to this draft but is visible in it.
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.
Storage and reconstitution guidance is given without stating what it rests on
The respondent submits on the draft monograph for Petrelintide. The amylin class sits at an earlier stage of evidence than the incretin class, and a document about it should be readable as such.
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.
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.
Declared interests should appear on the document rather than on a separate page
Having read the draft on Petrelintide, the respondent submits on a single matter.
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.
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.