Draft synthesis: Incretin receptor agonists in heart failure… — 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 axis of the forest plot exaggerates a small difference
The respondent has read the draft synthesis on In adults with heart failure with preserved ejection fraction and obesity, what is the effect of an incretin receptor agonist on symptoms and on… and makes one submission.
The plot is drawn on an axis spanning a narrow range, so an effect of no clinical consequence occupies most of the width of the figure. A reader who takes the visual impression rather than the number will overstate the finding.
The respondent proposes that a minimally important difference be marked on every forest plot where one has been established for the outcome.
The secretariat accepts the proposal where a minimally important difference exists and declines to invent one where it does not.
Forest plots now carry a marked minimally important difference wherever a published one exists for the outcome, with its source cited. Where none exists the figure says so beneath the axis.
A sponsor trial meeting the eligibility criteria was excluded
This submission addresses the draft synthesis on In adults with heart failure with preserved ejection fraction and obesity, what is the effect of an incretin receptor agonist on symptoms and on… from the standpoint of a reader who will use the summary and not the appendices.
The submission is made on behalf of the sponsor. It identifies a completed trial of the sponsor's compound that meets the stated eligibility criteria and does not appear in the included set, and supplies the trial report and the registry record.
The sponsor asks that the trial be included and the estimate recomputed. No view is expressed on the direction the recomputation should take.
The secretariat accepts this submission in part. The trial does meet the criteria and has been included. The recomputed estimate is materially unchanged, which the response states explicitly so that the outcome of the correction is on the record.
The trial is added to the included set, the estimate and the certainty rating have been recomputed, and the screening record now states why the trial was missed, which was a database indexing gap rather than a screening judgement. The submission is identified as an industry submission.
The review protocol is described but its registration record is not linked
The respondent notes that the review question — In adults with heart failure with preserved ejection fraction and obesity, what is the effect of an incretin receptor agonist on symptoms and on… — is answerable only if the contributing trials measured the same thing, and submits with that in view.
The respondent asks for the prospective registration record of the review protocol so that the registered outcomes can be compared with the reported ones.
The respondent states that without it the claim of prospective registration cannot be checked.
Submission 002 raises an adjacent matter. The respondent regards the two as separable and addresses only this one.
The secretariat accepts this submission in part. The protocol is published in full on the Institute site with its version history, which permits the comparison the respondent asks for. Where an external registration identifier is not held by the Institute, the review says so rather than supplying one.
Each synthesis now links its own protocol with the version in force at screening, and states explicitly where an external registration identifier is not held, so that the absence is a recorded fact.
Regulatory assessment documents were not searched
The respondent submits on the draft synthesis addressing In adults with heart failure with preserved ejection fraction and obesity, what is the effect of an incretin receptor agonist on symptoms and on…. 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 respondent states that regulatory assessment reports frequently contain analyses that never appear in journals, and that a search limited to bibliographic databases will miss them.
The respondent proposes that regulatory documents be searched for every review in the series.
The secretariat accepts this submission in part. Regulatory assessment documents are searched. The proposal that they be treated as equivalent to a full study report is declined, because the level of detail varies and is often insufficient for risk-of-bias assessment.
Published regulatory assessment documents are now searched as a named source, are reported as a distinct evidence class in the included-studies table, and contribute to the assessment while being excluded from pooled estimates where risk of bias could not be assessed from the document.
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.