Draft synthesis: Discontinued development programmes as… — submissions
The 3 submissions received, published in full with declared interests and secretariat responses.
§2Submissions and responses
3 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.
Doses differing several-fold are pooled without examining dose-response
The draft review of What can be concluded from a development programme that was discontinued, and how should the Institute record it? was read against its registered protocol.
Contributing trials administer doses that differ by a factor of several. The draft pools them and reports one estimate. The respondent states that where a dose-response relationship exists the pooled figure corresponds to no dose that anyone receives.
The respondent proposes that estimates be reported by dose and that dose-response be examined where the data allow.
The secretariat accepts this submission. A pooled estimate across doses is an estimate for an average dose that no protocol specifies.
Estimates are now reported by dose group, a dose-response examination is reported where three or more dose levels contribute, and the pooled across-dose estimate is removed rather than retained alongside.
A funnel plot is presented for a set too small to interpret it
This submission addresses the draft synthesis on What can be concluded from a development programme that was discontinued, and how should the Institute record it? from the standpoint of a reader who will use the summary and not the appendices.
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.
The comparator was given at a dose below the one in general use
Having read the draft synthesis on What can be concluded from a development programme that was discontinued, and how should the Institute record it?, the respondent puts one point to the committee.
Two contributing trials compare the intervention against an active comparator titrated to a dose lower than that reached in ordinary practice. Pooling them with trials using a full comparator dose produces an estimate that flatters the intervention.
The respondent proposes that comparator dose be tabulated in the included-studies table and that a sensitivity analysis restricted to full-dose comparators be reported.
The secretariat accepts this submission. Comparator dose is a condition of an effect estimate and was not being recorded.
Comparator dose is now a column in the included-studies table, and a sensitivity analysis restricted to comparators at the dose in general use is reported wherever the trials permit it.
References cited on this page
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- 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
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