Draft monograph: LL-37 — submissions
The 6 submissions received, published in full with declared interests and secretariat responses.
§2Submissions and responses
6 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.
Quantitative claims are reproduced without the method that produced them
Several figures in the draft are quoted from sources that determined them by different methods. A figure obtained by one determination and a figure obtained by another are not comparable, and the draft places them in the same sentence without distinguishing them.
The respondent, an analytical chemist, proposes that every quantitative claim carry the method that produced it at the point of use rather than in the reference.
The secretariat accepts this submission. Placing two figures side by side is an implicit claim that they are the same kind of quantity, and in the cases identified they were not.
Every quantitative claim now carries the determination that produced it at the point of use, and figures obtained by non-comparable methods are no longer presented in the same row or sentence.
Guidance on lyophilised storage is missing
The respondent asks that the monograph state storage conditions for lyophilised material as well as for reconstituted solution, since the two differ and the former governs the longer part of the shelf life.
The respondent states that the omission is the more consequential because lyophilised material is what is generally received.
The secretariat notes this submission. The draft addresses lyophilised storage, in the presentation section rather than in the section on in-use handling, which is where the respondent looked.
No amendment to content arises. The two storage statements have been brought together under a single heading so that a reader looking for either finds both.
Trials are described as terminated where they completed as planned
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 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.
Evidence for one member of the class is presented as evidence for this compound
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.
The same concept is given three different names in one document
The draft refers to the same quantity as a response rate, a responder proportion and a categorical outcome in different sections. The respondent, who works in health-technology assessment, states that a reader cannot tell whether the three refer to one thing or to three.
The respondent proposes that the glossary term be used at every occurrence and that the glossary entry be linked at first use in each section rather than only at first use in the document.
The secretariat accepts this submission. The variation was stylistic and its cost to the reader exceeds any benefit.
A single term is now used throughout for each defined concept, and the glossary entry is linked at first use within each section rather than once per document.
The analytical section assumes a reference standard that is not generally available
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.
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.