Q（Question）

When a physician or pharmacist requests information on a peer-reviewed original research article and that article contains information on off-label drugs or dosages not approved domestically, may the peer-reviewed article be provided?

A（MHLW answer）

There is no objection to providing the article in accordance with the conditions of the Guidelines, provided that it is clearly communicated that the article contains information on efficacy, dosage, etc. not covered by domestic approval.

Items requiring particular attention: (5), (7)

So what (meaning): Peer-reviewed articles containing off-label information may be provided, but disclosure that they include unapproved indication/dosage content is mandatory. Non-arbitrary article selection (provision (5)) and inclusion of negative articles are also required.

So why (rationale): Peer-reviewed articles are high-reliability documents that have undergone scientific scrutiny, but compliance with provision (5) on non-arbitrary selection is required to prevent companies from cherry-picking only favorable publications.

Commentary — background, application, practical notes

Peer-reviewed original research articles are primary sources that have passed editorial board scientific review — one of the document types that physicians most rely on to support clinical decision-making. As enumerated in Q1 as a benchmark for scientific grounding, peer-reviewed articles carry high evidentiary reliability. However, the risk of 'cherry picking' — where a company selectively provides articles that support a particular use while concealing contradictory publications — is inherent, and Q12 specifically requires compliance with provision (5) prohibiting arbitrary selection.

A typical scenario involves a physician requesting 'the latest evidence on efficacy at this dosage,' prompting the company to search and compile relevant peer-reviewed articles. In doing so, the company must include both articles supporting efficacy and those reporting negative results, and must explicitly communicate — verbally or in writing before provision — that the articles contain information on domestically unapproved indications or dosages. It is also desirable to be in a position to explain the selection criteria, demonstrating that no intentional filtering toward favorable outcomes was applied.

A common misunderstanding is the belief that 'providing only the articles the physician asked for is inherently non-arbitrary.' When a physician specifies a particular article by name, the concern does not arise. But when the physician makes a broad request such as 'I want to understand the evidence base for this dosing,' and the company selects which articles to provide, the selection process must be free of arbitrary bias. Additionally, in situations where a sales representative provides oral explanation alongside the literature, care must be taken to ensure that the explanation does not merge with promotional sales activity in a way that violates the separation requirement.