Draft synthesis: Completeness of certificates of analysis in… — submissions
The 8 submissions received, published in full with declared interests and secretariat responses.
§2Submissions and responses
8 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.
A funnel plot is presented for a set too small to interpret 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.
A sponsor trial meeting the eligibility criteria was excluded
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 document is unreadable without specialist training
The respondent, a trustee of a patient organisation, states that the draft is written for a reader who already understands certainty grading, and that the people most affected by the subject matter will not reach the assessment at all.
The respondent proposes a plain-language summary at the head of every document, written to the same standard of accuracy as the document itself and not as a promotional abstract.
The secretariat accepts this submission in part. A plain-language summary is added. The proposal that it replace the technical abstract is declined, because the abstract is the part of the document other assessors read and cite.
Every document now opens with a plain-language summary of not more than 150 words, placed above the technical abstract and carrying the same certainty language, so that the two cannot diverge.
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.
The review protocol is described but its registration record is not linked
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.
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.
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.
Risk-of-bias judgements are reported as an overall rating without the domains
The draft reports a single overall risk-of-bias judgement per study. The respondent states that the overall judgement conceals which domain drove it, and that a reader assessing whether the concern applies to their question needs the domain.
The respondent proposes a domain-level table with the supporting quotation for each judgement.
The secretariat accepts this submission. The overall judgement is a summary of the domains and publishing only the summary makes it uncheckable.
Risk of bias is now reported at domain level for every included study, with the text on which each judgement was based quoted and referenced, and the overall judgement derived from the domains rather than asserted alongside them.
The review does not say when it will be updated or what would trigger an update
The respondent states that a synthesis in a field where trials report frequently is out of date from the day it is published, and that a reader has no way to know whether the version in front of them is current.
The respondent proposes a stated trigger for an update as well as a scheduled review date.
The secretariat accepts this submission. A review date alone tells a reader when the document will be looked at, not whether it should already have been.
Every synthesis now records a scheduled review date and a stated update trigger, being the reporting of a trial that would materially change the contributing evidence, and the registered trials capable of triggering an update are listed by name.
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.