Draft monograph: DSIP — 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.
Regulatory status is stated without naming the jurisdiction
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.
Two factual descriptions of the sponsor's programme are inaccurate
The submission is made on behalf of the marketing-authorisation holder and is confined to two matters of fact. The draft describes a trial as terminated where the sponsor closed it at a pre-specified interim analysis, and gives a dose in a unit that does not match the approved labelling.
Supporting documentation, comprising the published trial report and the current summary of product characteristics, accompanied the submission. No view is expressed on the certainty ratings, which the sponsor considers a matter for the assessment committee.
The secretariat accepts this submission. Both points are matters of fact, both were checkable against documents the Institute holds, and both were wrong in the draft.
The trial status now reads as completed at a pre-specified interim analysis, with the analysis identified, and the dose is stated in the unit used in the approved labelling. The submission is identified as an industry submission on its face in accordance with the conflicts policy.
The absence of a rare harm in the trial set is presented as reassurance
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.
Mechanistic claims for a peptide fragment are carried without evidence that the fragment acts as described
The respondent states that the draft repeats a mechanistic account originating in supply documentation rather than in the primary literature, and that the account attributes activity to a fragment on the basis of the activity of the parent molecule.
The respondent proposes that any mechanistic claim be traceable to a primary source and removed where it is not.
The secretariat accepts this submission. A mechanism repeated from marketing material has no evidential status regardless of how widely it is repeated.
Mechanistic claims not traceable to a primary source are removed, and those retained carry their source and a statement of whether the underlying work was conducted in vitro, in animals or in humans.
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
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