Q（Question）

Regarding principle ③, which refers to 'materials that have undergone review by a third party for appropriateness (such as peer review of academic papers),' given the history of peer review being used as a blanket endorsement and scientific standards being interpreted loosely, is it correct to understand that even peer-reviewed materials must meet the requirement of being 'subject to objective evaluation and verification by third parties'?

A（MHLW answer）

That understanding is correct. 'Peer review of academic papers' and 'evaluation materials or review reports used in marketing approval reviews' are cited as examples on the premise that they are subject to objective evaluation and verification by third parties; providing information that cannot be said to be subject to such objective evaluation and verification is not permissible.

So what (meaning): Peer review status alone does not satisfy the scientific evidence requirement. Even peer-reviewed papers must be objectively evaluable and verifiable by third parties; papers with opaque methodology or irreproducible findings do not qualify.

So why (rationale): In response to the historical pattern of peer review being treated as automatic validation, the Guidelines clarify that peer review is merely an example of third-party evaluability — the substantive requirement is objective verifiability.

Commentary — background, application, practical notes

Peer review is widely recognized as a mechanism to ensure the quality of scientific evidence, but its operation has real limitations. Cases have accumulated in which peer review did not guarantee substantive scientific validity — including situations where reviewers had conflicts of interest, where trial methods were not disclosed in sufficient detail for independent verification, and where subsequently retracted papers continued to be cited in promotional materials. Against this backdrop, this Q&A clarifies that peer review is merely 'an example of what it means for third-party evaluation to be possible,' not a sufficient condition in itself.

Scenarios that tend to be problematic include case series reports involving small numbers of patients or single-institution studies funded by the pharmaceutical company that appear in peer-reviewed journals. Even with peer-reviewed publication, if the study is not pre-registered, independent replication of the data is not possible, and research transparency has not been ensured, the requirements of principle ③ cannot be considered satisfied.

There are three practical verification points: (1) whether the trial was prospectively registered (e.g., in ClinicalTrials.gov or an equivalent registry); (2) whether the research methods are described in sufficient detail to allow replication under equivalent conditions; and (3) whether conflicts of interest among authors, the peer-reviewed journal, and the publisher are appropriately managed and disclosed. Papers that do not satisfy these criteria are not eligible for use in materials regardless of whether they have undergone peer review.