Draft scoping review: melanocortin receptor agonists — submissions
The 11 submissions received, published in full with declared interests and secretariat responses.
§2Submissions and responses
11 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.
Studies not published in English were excluded without assessment
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.
Patient-reported outcomes are collected by the trials and not reported by the review
The respondent, a trustee of a patient organisation, 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 choice of effect measure is not justified and changes the appearance of the result
The draft reports relative effects for benefits and absolute effects for harms. The respondent states that the combination flatters the intervention and that the choice should be justified or made uniform.
The respondent proposes that both relative and absolute effects be reported for every outcome.
The secretariat accepts this submission in part. Both measures are reported for every outcome where the baseline risk needed for the absolute effect can be stated. Where it cannot, the relative effect is reported alone with the reason.
Every outcome now reports the relative effect and, where an assumed baseline risk can be stated and sourced, the corresponding absolute effect, with the baseline risk and its source given in the same row.
An indirect comparison is presented without an assessment of transitivity
The draft compares two interventions through a common comparator. The respondent states that the trials contributing to each side differ in background therapy and in baseline severity, and that the resulting estimate assumes a similarity the draft does not test.
The respondent proposes that transitivity be assessed explicitly and reported before any indirect estimate is presented.
The secretariat accepts this submission. An indirect estimate presented without a transitivity assessment invites a reader to treat an assumption as a result.
Transitivity is now assessed against a stated list of effect modifiers and reported before any indirect estimate, and where the assessment fails the contrast is reported as unestimable with the reason rather than estimated with a caveat.
References should carry a persistent identifier for every cited source
Several references in the draft carry a journal, a year and a volume but no persistent identifier. The respondent, who works in a library setting, 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.
Baseline imbalance in a small contributing trial is not remarked on
The respondent identifies a small contributing trial with a baseline difference in the outcome variable, and states that the difference is large enough to account for a share of the reported effect.
The respondent asks that the trial be excluded or that the imbalance be addressed.
The secretariat notes this submission. The imbalance is recorded in the risk-of-bias assessment for that trial, in the domain concerning the randomisation process, where the respondent may not have looked.
No amendment arises. The judgement and the supporting figures are already reported at domain level for that study, and a sensitivity analysis omitting it is reported in the results, which does not change the direction of the estimate.
Analytical surveys are treated as evidence about suppliers when they establish only what was in a sample
Several included surveys purchased material anonymously and analysed it. The respondent states that where the chain from a named supplier to the analysed vial cannot be documented, the result describes a sample and not a supplier.
The respondent proposes that provenance be an explicit eligibility dimension, with surveys reported separately according to whether it could be established.
The secretariat accepts this submission. Moderate certainty evidence from the included surveys supports statements about material circulating in a market; it does not support statements about any named supplier's output.
Provenance is now assessed for every included survey and reported as a study characteristic, surveys without establishable provenance are reported separately rather than pooled with those that have it, and no supplier-level inference is drawn from a sample-level result.
The document should state what a reader ought to do
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.
The conclusion is stated more strongly than the certainty rating supports
The draft rates the anchor outcome at low certainty and then states in the conclusion that the intervention is effective. The respondent states that the two sentences cannot both be true as written.
The respondent proposes that conclusion language be tied mechanically to the certainty rating, so that a low rating cannot produce an unqualified claim.
The secretariat accepts this submission. The mismatch is the failure mode the certainty framework exists to prevent.
Conclusion wording is now drawn from a fixed set of formulations tied to the certainty rating, so that a low certainty rating produces a statement that the evidence may suggest an effect and that the estimate is likely to change with further research.
The search date is not on the face of the document
The draft carries a publication date and a review date but not the date on which the evidence was last searched. Those are three different dates and only the third tells a reader how current the assessment is. A document published in one quarter may rest on a search run two quarters earlier, and nothing on the page allows that gap to be measured.
The respondent proposes that the search date be printed adjacent to every certainty rating rather than in the methods section, on the ground that a reader who acts on a rating is unlikely to have read the methods section first.
The secretariat accepts this submission. The distinction between publication, review and search dates is real and the draft did not make it visible where it mattered.
The search date is now printed adjacent to every certainty rating and is carried in the document metadata, so that the interval between the search and the reading is visible without reference to the methods section.
Statistical heterogeneity is treated as though it measured clinical heterogeneity
The draft reports a heterogeneity statistic and proceeds to pool where it is low. The respondent states that a low statistic in a small set of trials is uninformative, and that clinical and methodological similarity should be assessed before any statistic is consulted.
The respondent proposes that the decision to pool be justified on clinical grounds first and that the statistic be reported as a description rather than used as a threshold.
The secretariat accepts this submission in part. The decision to pool is now made on clinical and methodological grounds and stated as such. The statistic continues to be reported, because readers expect it and its absence would be read as concealment.
The decision to pool is now justified in prose against the population, intervention, comparator and outcome before any statistic is presented, and the heterogeneity statistic is reported with its confidence interval and a note of the number of contributing studies.
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.