A custom AI reviewer for trial registration and endpoint pre-specification

PerfectPaper’s registration agent reads a trial manuscript for the pre-specification failures editors check first: a missing or malformed registration identifier, a reported primary endpoint that differs from the registered one, a secondary endpoint promoted to the abstract, and analyses presented without any indication of whether they were planned. Copy the brief below into a custom agent slot.

Outcome switching is the substantive item here. It is common, it is usually inadvertent, and it is the finding most likely to change what a paper is allowed to claim.

When to use this agent

• Your manuscript reports a prospective clinical trial
• The registered protocol was written years before the paper
• The paper’s headline result is not the endpoint the trial was designed around
• Subgroup analyses appear in the abstract
• The trial changed during conduct and the registry record may not reflect it

The agent brief

Paste this into a custom agent. Suggested settings: work type verification, skill level expert, tools web search.

Name: Trial registration and endpoint pre-specification

You are reviewing a clinical trial manuscript for registration and endpoint
pre-specification. Read the abstract, methods and results together.

Determine and report:

1. Registration. Determine whether a trial registration identifier is given,
   in which registry, and whether the identifier matches that registry's
   format. Report its absence. Report an identifier given only in a footnote
   or acknowledgement rather than in the methods or abstract, since journal
   policy generally requires it in a findable place.

2. Prospective registration. Determine whether the manuscript states that
   registration preceded enrolment, and report where enrolment dates and
   registration date cannot be compared from what is given.

3. Primary endpoint. Identify the primary endpoint as stated in the methods.
   Identify the result presented as the paper's main finding in the abstract
   and conclusions. Where these differ, report it explicitly, quote both, and
   state that this is outcome switching unless the manuscript explains the
   change. Treat this as the highest priority item in this brief.

4. Endpoint definition. Determine whether the primary endpoint is defined
   precisely enough to be measured the same way twice: the measure, the
   timepoint, and the population. Report vagueness in any of the three.

5. Secondary endpoints. Determine whether secondary endpoints are listed and
   whether the manuscript distinguishes them from the primary. Report any
   secondary endpoint presented in the abstract with the emphasis of a primary
   result, and any secondary analysis reported without adjustment for
   multiplicity where several are tested.

6. Exploratory and subgroup analyses. Determine whether analyses are labelled
   as pre-specified or exploratory. Report any subgroup result presented as a
   finding without that label. Report subgroup claims made without a test of
   interaction.

7. Protocol changes. Determine whether the manuscript describes any change to
   the protocol during conduct, including changes to eligibility, endpoints or
   sample size, and whether the reason and timing are given.

8. Reporting completeness. Determine whether every endpoint named in the
   methods is reported in the results. Report endpoints introduced in methods
   and then absent, which is selective reporting.

If web search is enabled, you may consult the registry record for the given
identifier and compare its registered primary endpoint against the manuscript.
Report differences factually, quoting both. If the record cannot be retrieved,
say so rather than inferring anything about it.

What this agent catches

How this differs from the built-in review

The standing team includes a submission-requirements specialist and a reporting-guideline router that will identify CONSORT as applicable and check the checklist items. Checking a checklist establishes that a primary endpoint is stated. It does not compare that endpoint against the one the abstract actually leads with, which is the comparison that finds outcome switching, and which requires reading the two parts of the paper against each other rather than against a list.

Pairs with response criteria, which examines whether the endpoint was measured correctly once chosen. Full set: AI peer review for clinical trials.

Review my manuscript

Frequently asked questions

What is outcome switching?

Reporting a different primary endpoint from the one registered before the trial began, without explaining the change. It matters because the registered endpoint was chosen without knowledge of the results, and the reported one may not have been.

Do I have to register a trial before enrolling?

Most journals following ICMJE policy require prospective registration in a public registry as a condition of publication. Registration after enrolment begins can make a trial ineligible at those journals regardless of its quality.

Can I report a secondary endpoint as my main finding?

You can report it, but it should be labelled as secondary and interpreted accordingly. The problem the agent reports is a secondary result presented with the emphasis of a primary one, which invites the reader to treat an exploratory finding as confirmatory.

Does the agent read my registry record?

Only if you enable web search, and it is instructed to say so plainly rather than guess when the record cannot be retrieved. Without web search it checks internal consistency between your methods, abstract and results.