Draft synthesis: Dual and triple incretin receptor agonists… — submissions
The 7 submissions received, published in full with declared interests and secretariat responses.
§2Submissions and responses
7 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.
Patient-reported outcomes are collected by the trials and not reported by the review
The respondent has read the draft synthesis on In adults with obesity, does a multi-receptor incretin agonist produce a larger reduction in body weight than a single glucagon-like peptide-1… and makes one submission.
The respondent states that several contributing trials measured quality of life and function and that the review reports neither, having selected outcomes on the basis of what could be pooled.
The respondent proposes that these outcomes be reported narratively where they cannot be pooled.
The secretariat accepts this submission in part. The outcomes are reported narratively. The proposal to pool them is declined because the instruments used are not comparable and pooling would produce a figure with no interpretation.
Patient-reported outcomes measured by any contributing trial are now reported narratively by instrument, with the instrument named and its minimum important difference stated where one is published, and the absence of a pooled estimate explained.
The timepoint at which each outcome was extracted was chosen after the data were seen
The respondent read the draft review of In adults with obesity, does a multi-receptor incretin agonist produce a larger reduction in body weight than a single glucagon-like peptide-1… and has confined this submission to a single matter.
The methods state that outcomes were extracted at the latest available timepoint. Several contributing trials report the same outcome at three timepoints, and taking the latest is a choice that can be made in the knowledge of what each shows.
The respondent proposes that the extraction timepoint be prespecified in the protocol, and that where it was not, the review report the estimate at every reported timepoint so that the choice is visible.
The secretariat accepts this submission. An extraction rule applied after the data are visible is a degree of freedom and should be recorded as one.
The extraction timepoint is now prespecified in the protocol for new reviews. Where a review predates the requirement, estimates are reported at every timepoint the contributing trials report.
The review question is drawn too broadly to be answerable
This is a submission on the draft review of In adults with obesity, does a multi-receptor incretin agonist produce a larger reduction in body weight than a single glucagon-like peptide-1…, made from a statistical standpoint.
The respondent states that the population as registered spans groups in which the intervention would be expected to behave differently, and that a single estimate across them is uninformative.
The respondent proposes that the question be split and the review re-registered.
The secretariat does not accept this submission. The breadth was registered before screening, the pre-specified subgroups address the variation the respondent identifies, and re-registering after the results are known would convert a pre-specified analysis into a post hoc one.
The question stands as registered. The point is recorded in the limitations, and the assessment committee has noted it for the protocol of the next version of this review, which will be registered before the search is run. The submission remains published in full.
The document should state what a reader ought to do
The respondent notes that the review question — In adults with obesity, does a multi-receptor incretin agonist produce a larger reduction in body weight than a single glucagon-like peptide-1… — is answerable only if the contributing trials measured the same thing, and submits with that in view.
The draft assesses evidence and stops. The respondent, a practising clinician, states that a reader arriving at the document with a decision to make is left to convert an assessment into an action without help, and proposes that each document close with a recommendation.
The respondent argues that other evidence bodies issue recommendations and that declining to do so transfers the difficult part of the work to the reader.
The secretariat does not accept this submission, and records that the point is a reasonable one rather than a misunderstanding.
The Institute assesses evidence and does not issue recommendations, because a recommendation embeds values and a resource context that the Institute does not hold and cannot state. That constitutional limit is published on the methodology page and is not varied by consultation. The submission remains published in full.
Studies not published in English were excluded without assessment
The respondent’s comment on the draft review of In adults with obesity, does a multi-receptor incretin agonist produce a larger reduction in body weight than a single glucagon-like peptide-1… arises from comparing the included set against the respondent’s own knowledge of the field.
The respondent states that a language restriction was applied at screening and that for some of the compounds in scope a substantial literature is published in other languages.
The respondent proposes that the restriction be removed and the review re-run.
The secretariat accepts this submission in part. The restriction is removed prospectively and the records already excluded on language grounds have been retrieved and screened on title and abstract in translation. The full re-run proposed is not undertaken, and the limitation is recorded rather than concealed.
Language restriction is removed from the protocol for the series, the records previously excluded on that ground are listed with their screening outcome, and the residual limitation is stated in the abstract of this review.
References should carry a persistent identifier for every cited source
The draft review of In adults with obesity, does a multi-receptor incretin agonist produce a larger reduction in body weight than a single glucagon-like peptide-1… was read against its registered protocol.
Several references in the draft carry a journal, a year and a volume but no persistent identifier. The respondent states that retrieval of such a reference is materially slower and that identifiers should be supplied throughout.
The respondent asks in the alternative that where an identifier exists but is not carried, the omission be explained rather than left as a gap the reader must interpret.
The secretariat accepts the second limb of this submission and declines the first. Identifiers are supplied wherever the Institute holds one. Where the Institute does not hold an identifier it will not supply one, because a reconstructed identifier that resolves to the wrong record is a worse defect than an absent one.
Every reference without a persistent identifier now carries an explicit statement that the identifier is not held by the Institute, so that its absence is a recorded fact rather than an apparent oversight.
A funnel plot is presented for a set too small to interpret it
The respondent submits on the draft synthesis addressing In adults with obesity, does a multi-receptor incretin agonist produce a larger reduction in body weight than a single glucagon-like peptide-1…. This submission concerns the methods rather than the conclusion, on the view that a conclusion is only as good as the search that produced it.
The draft includes a funnel plot for an outcome contributed by fewer than ten studies. The respondent states that asymmetry cannot be assessed reliably at that number and that presenting the plot invites a conclusion the data cannot support.
The respondent proposes that the plot be removed and replaced with a statement that publication bias could not be assessed.
The secretariat accepts this submission. Presenting an uninterpretable graphic is not a neutral act.
The funnel plot is removed for every outcome contributed by fewer than ten studies, and replaced by a statement that small-study effects could not be assessed at that number, together with the count of registered trials identified without posted results.
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.