Panel · Use case · Medical Affairs

Real-World Evidence Divergence.

LiveDivergence Review

Map where specialists disagree on how far real-world evidence can substitute for a randomized trial, and what would settle it.

QuestionHow far can real-world evidence substitute for a randomized trial?

DisciplinesReal-world evidence, regulatory, HEOR, evidence

ReaderEvidence and regulatory leads

Not askedA study design

DepthStandard, four seats

Real-World Evidence Divergence is a ready-made use case for Medical Affairs. It ships under the Divergence Review template.

For evidence generation leads. You get each seat's answer to the same question, where the positions diverge, whether each split is evidence, assumption or value, the cruxes and what would settle it. Claims are cited or marked as gaps.

Add it to your library to reuse from New → From template. Edit the saved copy in your library on the service form.

The decision

How far can real-world evidence substitute for a randomized trial in supporting a label expansion?

Who is at the table

Studies that emulate trials with database analyses agree with the trials in some cases and not in others. The seats may read that record differently.

Seat	What it is asked	What it works from
Global Real-World Evidence Lead	What the available data can show and which biases remain.^{1Wang, S. V., Schneeweiss, S. and the RCT-DUPLICATE Initiative. Emulation of Randomized Clinical Trials With Nonrandomized Database Analyses: Results of 32 Clinical Trials. JAMA, 2023;329(16):1376–1385.}	The RCT-DUPLICATE emulations and the data sources catalogue.
Regulatory Strategist	Whether an agency would accept real-world evidence for this label change.^{2U.S. Food and Drug Administration. Considerations for the Use of Real-World Data and Real-World Evidence to Support Regulatory Decision-Making for Drug and Biological Products. August 2023.,3European Medicines Agency. Reflection paper on use of real-world data in non-interventional studies to generate real-world evidence. Final, EMA/99865/2025.}	FDA and EMA guidance on real-world evidence.
HEOR Evidence Lead	Whether payers will rely on it.	The NICE framework.
Global Value & Evidence Lead	How the evidence would be graded and what would lower its certainty.^{1Wang, S. V., Schneeweiss, S. and the RCT-DUPLICATE Initiative. Emulation of Randomized Clinical Trials With Nonrandomized Database Analyses: Results of 32 Clinical Trials. JAMA, 2023;329(16):1376–1385.}	Evidence grading methods.

What the review does

Agreement depends on design. In the RCT-DUPLICATE project, database studies agreed most closely with trials when the emulation closely matched the trial design. The review shows which seat gives that more weight.^{1Wang, S. V., Schneeweiss, S. and the RCT-DUPLICATE Initiative. Emulation of Randomized Clinical Trials With Nonrandomized Database Analyses: Results of 32 Clinical Trials. JAMA, 2023;329(16):1376–1385.}

Regulators put the burden on the applicant. EMA’s reflection paper asks the applicant to justify that the data are appropriate. The review shows who sees that bar as reachable.^{3European Medicines Agency. Reflection paper on use of real-world data in non-interventional studies to generate real-world evidence. Final, EMA/99865/2025.}

What would settle it. An emulation of a completed trial in the same disease using the proposed data, with a pre-specified agreement criterion.

Recommended length

Standard

Four disciplines will read this question differently. Standard depth types each divergence as evidence, assumption or value in about four pages.

You can pick another length on the form. The other two stay available.

Assumptions the review checks

The review states the assumptions each position relies on, and says what each gap limits. Examples for this question:

The proposed data capture the outcome and the confounders.
The label change is of a kind for which emulations have agreed with trials.
The agency will review the evidence on its merits.

Standards, guidance and sources

Frame

Wang, Schneeweiss et al., RCT-DUPLICATE, JAMA, 2023.^{1Wang, S. V., Schneeweiss, S. and the RCT-DUPLICATE Initiative. Emulation of Randomized Clinical Trials With Nonrandomized Database Analyses: Results of 32 Clinical Trials. JAMA, 2023;329(16):1376–1385.}
FDA, real-world evidence guidance for drugs and biologics.^{2U.S. Food and Drug Administration. Considerations for the Use of Real-World Data and Real-World Evidence to Support Regulatory Decision-Making for Drug and Biological Products. August 2023.}
EMA, reflection paper on real-world data in non-interventional studies, 2025.^{3European Medicines Agency. Reflection paper on use of real-world data in non-interventional studies to generate real-world evidence. Final, EMA/99865/2025.}

The decision practice behind the memo itself is on the template page.

What gets flagged

Any claim of agreement drawn from slides or commentary and not the paper, any design that cannot define a comparator, and any assumption that emulations in claims data apply to registries.

What arrives

The question as put
The shape of the disagreement
Each position, in its own terms
Where they diverge
Why they diverge: evidence, assumption or value
The cruxes
What would settle it

What it will not do

It does not force a consensus, and it is a deliberation of AI specialists and not a vote of human experts. The decision stays with you.

It does not design the study or predict an agency decision.

It does not force a consensus. A report that closes every gap would be the wrong output.

It is not a vote of human experts. Every seat is an AI specialist, and the report says so.

It does not name a winner. It says what would settle the question and leaves the decision to you.

References

[1] Wang, S. V., Schneeweiss, S. and the RCT-DUPLICATE Initiative. Emulation of Randomized Clinical Trials With Nonrandomized Database Analyses: Results of 32 Clinical Trials. JAMA, 2023;329(16):1376–1385. Known from search results and secondary summaries; not read in full.
[2] U.S. Food and Drug Administration. Considerations for the Use of Real-World Data and Real-World Evidence to Support Regulatory Decision-Making for Drug and Biological Products. August 2023. Title and date as known; not read in full.
[3] European Medicines Agency. Reflection paper on use of real-world data in non-interventional studies to generate real-world evidence. Final, EMA/99865/2025. Status as given in EMA’s listing; not read in full.

Links checked 9 October 2026

These are the sources the template drew on. None of their authors or issuers has reviewed it.

About the Panel service

Each panelist answers in their own voice, then the discussion is drawn together. You get the question and who was in the room, every position in full, what they agreed on, where they split, and what follows. Disagreements are written down rather than smoothed into a consensus nobody actually holds, because the split is usually the part you needed.

To edit a saved template, open New → Panel → From template, or the library rail on the service form.