Draft monograph: Melanotan-II — submissions
The 4 submissions received, published in full with declared interests and secretariat responses.
§2Submissions and responses
4 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
The respondent submits on the draft monograph for Melanotan-II. This class has a documented adverse-effect profile and a document about it should carry that profile with the prominence the evidence supports.
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.
Adverse event frequencies are given without the denominator or the exposure period
This submission concerns the draft on Melanotan-II. The respondent works in pharmacovigilance and reads documents of this kind for what they would let a reporter recognise.
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 preclinical section is extensive and the clinical section is not
The respondent’s comment on the draft for Melanotan-II arises from the regulatory history of the class.
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 notes that submission 002 has already been made and confines this submission to a matter not covered by it.
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.
Trials are described as terminated where they completed as planned
The respondent notes that Melanotan-II is supplied for indications for which it has never been assessed, 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.
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.