Independent · non-commercial · publishes on a quarterly cycle|Current cycle 2026 Q3
Compound Evidence InstituteEvidence synthesis · established 2023Graded assessments of compounds, trials, methods and supply
Document set current to 30 July 2026
Public comment period · §2

Draft synthesis: Tirzepatide compared with semaglutide in… — submissions

The 7 submissions received, published in full with declared interests and secretariat responses.

Document identifier
CEI-CP-118/2
Series
Public comment period
Version
1.0
Published
16 Apr 2025
Last reviewed
16 Apr 2025
Next review
16 Apr 2026
Identifier
10.71829/cei.cp.118
Certainty
Not rated
Cycle
2025 Q1
Window
24 Jan 2025 – 25 Mar 2025
Status
Closed
Submissions
7

§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.

Dr Oswin Yorkstone, PhD (Pharmacology) Hospital microbiology and endotoxin testing service
DRAFT-TIRZEPATIDE-/004 received 30 Jan 2025

The search strategy as published cannot be re-run

The strategy is described in prose rather than reproduced as executed. The respondent, an information specialist, attempted to reconstruct it and obtained a different yield, which may reflect the reconstruction or the original.

The respondent proposes that the strategy be published line by line as run in each database, with the interface, the date and the number of records retrieved at each line.

Declared interest. Is an employee of a marketing-authorisation holder for a compound named in the draft. This submission is made on behalf of that company and is identified as an industry submission throughout.
Secretariat responseAccepted05 Apr 2025

The secretariat accepts this submission. A strategy that cannot be re-run cannot be checked, and a review whose search cannot be checked rests on an assertion.

The full line-by-line strategy for each database is now published with the interface, the run date and the yield at each line, and the total retrieved is reconciled against the screening flow.

Dr Kamila Ubertini, PharmD, BCPS Regulatory affairs, generic medicines sector
DRAFT-TIRZEPATIDE-/003 received 08 Feb 2025

Subgroup findings are reported that were not registered in the protocol

The draft reports differences between subgroups that do not appear in the registered protocol. The respondent states that unregistered subgroup analysis is hypothesis-generating and that the draft presents it in the same form as the pre-specified results.

The respondent proposes that unregistered analyses be removed.

Declared interest. Has used a compound in the class under assessment under prescription. Declared at the Institute's request; the Institute regards a lived-experience declaration as an interest and not as a disqualification.
Secretariat responseAccepted in part06 Apr 2025

The secretariat accepts this submission in part. The analyses are retained and relabelled rather than removed, because removing an analysis that was conducted leaves no record that it was.

Every subgroup analysis is now labelled as pre-specified or post hoc against the registered protocol, post hoc analyses are reported in a separate subsection without a certainty rating, and the protocol version against which the labelling was made is stated.

Dr Quintus Kettlewell, PharmD, MSc National medicines information service
DRAFT-TIRZEPATIDE-/006 received 27 Feb 2025

The review question is drawn too broadly to be answerable

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.

Declared interest. No financial interest. Has published a systematic review reaching a different conclusion from the draft, which the respondent declares as a non-financial interest.
Secretariat responseNot accepted01 Apr 2025

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.

Dr Ottoline Oppenheimer-Ade, MD, MPH Primary-care research network
DRAFT-TIRZEPATIDE-/007 received 01 Mar 2025

A sortable table implies a comparison the underlying data do not support

The draft presents a sortable table whose columns are drawn from sources of differing quality. The respondent states that sorting on such a column produces an ordering that looks like a ranking and is not one.

The respondent proposes that sorting be disabled on any column whose values are not commensurable.

Declared interest. Is a trustee of a patient organisation that has received a restricted educational grant from a manufacturer in the class under assessment.
Secretariat responseNoted, no amendment31 Mar 2025

The secretariat notes this submission and records that the point is correct in principle.

No amendment arises here because every sortable table in the document set already carries a standing statement above it that the ordering is not a ranking and that the values in each column are commensurable only where the column header says so. The proposal to disable sorting was considered and not adopted, because a reader who cannot sort a table generally sorts it elsewhere and without the statement.

Dr Theodora Ingelbrecht, MSc, CChem Academic sports-medicine and anti-doping laboratory
DRAFT-TIRZEPATIDE-/005 received 06 Mar 2025

Point estimates are given without an interval

Several estimates in the draft appear as single figures. The respondent states that a point estimate without an interval invites a precision the underlying data do not support, and that the effect is worst where the estimate is drawn from a small contributing set.

The respondent proposes that no point estimate appear anywhere in the document set without its interval, including in summary tables and in the abstract.

Declared interest. Employed by a national competent authority. This submission is made in a personal capacity and does not represent the position of that authority.
Secretariat responseAccepted in part16 Apr 2025

The secretariat accepts this submission in part. Intervals are added wherever the source reports one. The proposal is declined for figures the source published without an interval, because the Institute will not compute an interval a source did not report.

Every estimate now carries its interval where the source reported one, and where it did not, the estimate is annotated as reported without an interval rather than left to appear as a precise figure.

Dr Quentin Whitmarsh-Obi, MD, FRCS Academic peptide-chemistry group
DRAFT-TIRZEPATIDE-/001 received 14 Mar 2025

A superseded version should remain reachable from the version that replaced it

The respondent states that the draft supersedes an earlier document and that a reader who cited the earlier version has no way to reach it from the new one, which makes it impossible to see what changed.

The respondent asks that every version carry a link both to what it supersedes and to what supersedes it.

Declared interest. Has received consultancy fees from a supplier named in the Institute's supplier assessment set within the preceding two years.
Secretariat responseNoted, no amendment05 Apr 2025

The secretariat notes this submission. The corrections and versioning policy already requires bidirectional version links and every superseded document is retained at its own address.

No amendment arises. The requirement is stated in the corrections and versioning policy and the amendment log of this document links to the version it replaced. The respondent is correct that the link was absent from the draft page furnished for consultation, which was a defect of the consultation copy and not of the policy.

Dr Delphine Trelawney, MSc (Regulatory Affairs) Public-sector clinical trials unit
DRAFT-TIRZEPATIDE-/002 received 23 Mar 2025

Studies using different outcome definitions are pooled into one estimate

The contributing studies define the outcome in at least two ways, and the draft pools them. The respondent states that the resulting estimate is an average across definitions rather than an estimate of any one quantity.

The respondent proposes that studies be pooled only within a definition, and that the definitions be reported separately with their own certainty ratings.

Declared interest. Is a member of the Institute's external reviewer register but did not review the document under consultation.
Secretariat responseAccepted01 Apr 2025

The secretariat accepts this submission. Pooling across definitions produces a figure with no referent, and the draft did it without saying so.

Studies are now pooled only within an outcome definition, each definition is reported with its own estimate and certainty rating, and the summary of findings states which definition each row concerns.

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.

  1. 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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