(2) Balance of efficacy and safety | JPMA Guide Commentary | Advertising Regulation in Japan (Promotional Material Review) and Artificial Intelligence

When Chapter 1, Section 1(2) states that materials must "balance efficacy and safety," it is not a call for fair-mindedness. It is a structural constraint on design — governing which items appear in which column, and even at what point size they are printed. The rule reaches this far: on the very same page where efficacy figures are displayed, safety information must be present, must be mandatory, and must be printed at a type size that is no smaller.

Measured against the foreword's three pillars, this provision carries pillar two: "implement balance in the layout." If "blocking misunderstanding" means never stating a falsehood, "implementing balance" means never permitting a page structure where only efficacy enters the eye. Even when every word is accurate, if placement and type size push safety information to a corner, the reader walks away with efficacy only — and that asymmetric reading risk is closed off by the physical design of the page itself.

01Why "balance" is an obligation, not a guideline

Materials for prescription drugs are written by the seller. There is a structural gravitational pull toward putting efficacy first. The Guide recognizes this pull and places a constraint on it — not as a stylistic norm saying "write with balance," but as a conditional obligation: if you show efficacy, you must show safety.

Detailed rule (a) is the core of this. "When clinical results present efficacy findings, safety findings must also be recorded." A clinical results section that shows only efficacy is not permitted. Efficacy and safety must appear together. The rule simultaneously activates, in the most concrete possible column, the foreword's idea of an asymmetric duty — safety-related information is disclosed even when it is unfavorable to the company.

Why call it asymmetric? Efficacy data is something the writer is eager to show. Safety data is sometimes something the writer would prefer not to highlight. Despite this asymmetry of incentive, the Guide does not allow safety to be omitted. By presupposing that asymmetric motivation and encoding "if there is efficacy, safety must accompany it" as a structural rule, omission is foreclosed at the design stage.

02Type size as a physical quantity — keeping the reader's first gaze from bypassing safety

Detailed rule (b) is one of the most concrete provisions in the entire Guide. "The safety entries shall be in a type size equal to or larger than the body text presenting the efficacy results." By specifying point size as a physical quantity, the rule closes the loopholes available through layout.

If the type is smaller, information may exist on the page but never be read. A precautions column packed with fine print loses the competition for the physician's attention against large numbers and readable graphs. Even when every word is accurate, a situation in which safety has been "included" but never "communicated" can arise. The Guide's reference to type size reflects an understanding of exactly that reading risk.

Detailed rule: how safety must be shown in the clinical results column

When efficacy results are presented in a clinical results column, the safety content must include the following: adverse event rates, event names, and case counts shown in comparison with the control drug or placebo; and for serious adverse reactions or those leading to discontinuation, the event names and case counts must be recorded. At no point may the entry conclude with a statement that "there were no serious adverse reactions" — there is a clear line between the factual statement that none occurred and the evaluative conclusion that the drug "is safe." The latter constitutes emphasis of safety, which the Guide prohibits.

At the top of the first page of clinical results, place a note — in a larger point size than the body text — that warnings, contraindications, and so on are on a specified page. Precisely because this is where the eye goes first for efficacy figures, the route to safety information is shown before anything else. The logic is the same as the type-size rule: the page design is engineered to place safety information in view first.

When safety text is set in a smaller size than the surrounding efficacy figures, it has been "included" but not "communicated." The type-size requirement of rule (b) is the minimum physical condition for honesty in layout.

03Disclosing unpublished data — the reach of Section 1(11)

Chapter 1, Section 1(11) takes the balance principle one step further. "Important safety-related information shall be thoroughly verified in-house, and shall be recorded even when the data are unpublished."

The reach of this provision is broad. As a rule, the data carried in product information materials are limited to peer-reviewed original papers or approval-review evaluation materials — the clinical results column is the clearest example of this gate. Yet for important safety information, the obligation to disclose arises even beyond that threshold. If unpublished safety data that the company already holds could affect a physician's prescribing decision, the fact that the data have not yet appeared in a journal is not a sufficient reason to withhold them.

This provision connects to the verifiability pillar as well. Information that has not been published cannot be checked from the outside. The Guide requires disclosure anyway because the asymmetric duty to disclose safety information is calibrated not to the existence of external evidence, but to whether the company is aware of the information. The writer is required to "thoroughly verify in-house" before making that judgment — because without the verification step, the disclosure obligation cannot function, and so the verification itself is made an obligation.

The duty to disclose unpublished data connects to both pillar one ("block misunderstanding") and pillar three ("verifiability"). Withholding safety information leaves the physician prescribing under a false sense of safety. When the writer holds information that has not appeared in a journal, failing to surface it can actively produce misunderstanding — not merely fail to prevent it. Section 1(11) closes that gap.

In closing

Sections 1(2) and 1(11) together implement what the word "balance" actually requires. The norm of "writing with balance" becomes, in detailed rule (a), a conditional obligation: "if you record efficacy, you must record safety." In detailed rule (b) it becomes a layout constraint: "the safety text must be set in type at least as large as the efficacy body text." Section 1(11) presses further: "even when the data are unpublished, important safety information must be disclosed."

All three provisions stem from the same recognition. Efficacy information is something the writer advances voluntarily. Safety information tends to matter most precisely in the situations where the writer would rather not surface it. Presupposing that asymmetric incentive, the Guide tilts consistently toward the safety side — from the physical design of the page to the threshold for disclosure. That is the design philosophy running through this cluster of provisions.

Case studies — the "it isn't written, so…" mindset, and how each lands

Layout directs the eye before language does. Efficacy numbers land first; safety information ends up in the margin — and no one has technically lied. The four levels below show where that design choice hits the provisions.

GRAY 1 — Straying from the spirit (untouched by the wording, but against the foreword's spirit)

The scheme: "We included one line: 'For safety details, refer to the package insert.' Nothing is false. Efficacy data are spelled out; nothing in the provision prohibits condensing the safety side. The reader can look it up."

Verdict: When efficacy results are presented, the provision requires that safety results be "stated" in the same material — not pointed toward. A cross-reference does not fulfil the layout obligation to place both on the same page. If readers have no real encounter with safety data in the same document, balance is nominal only. The fix is to include specific safety data in the same piece.

GRAY 2 — Exploiting the gap (deliberately working a loophole to invite misreading)

The scheme: "Safety section font matches efficacy at 10 pt — the provision doesn't set a size. But a large bar chart fills 70% of the page for efficacy, leaving the safety text in the remaining 30%. Both sections are 'stated.'"

Verdict: The provision requires that the safety information's type size be no smaller than the efficacy information's. Equal type can still be visually subordinated when a large efficacy figure dominates the page. The intent covers overall visual balance, not type size alone. The chart must be resized so safety information does not appear secondary in the layout.

GRAY 3 — Violating higher norms (arguably "not in the text," yet almost certainly out under the PMD Act, Fair Advertising Standards, and the JPMA Code)

The scheme: "We listed adverse-event types and rates. We also set an internal threshold: adverse events occurring in less than 0.5% of patients are omitted. That threshold is not specified anywhere in the guidelines, so we set it ourselves. We've stated safety information — balance is maintained."

Verdict: Omissions that create a discrepancy with the warnings and contraindications in the package insert violate the PMD Act's prohibition on exaggerated advertising and the Fair Advertising Standards. Rare adverse events can be severe; arbitrarily cutting them out distorts the safety profile. Adverse events recorded in the package insert cannot in principle be omitted.

BLACK — Breaching the explicit text (a plain violation of the provision itself)

The scheme: "We split efficacy data and safety information into two separate materials. The efficacy piece goes to every physician at the congress booth; the safety piece is available 'on request.' Each document individually satisfies the provision."

Verdict: The provision states: "When efficacy results are presented in clinical data, safety results shall also be stated." The obligation attaches to each act of presenting efficacy — distributing an efficacy-only document is a direct breach. Efficacy and safety must appear in the same material and be distributed in the same interaction.

Improper intent by implication — three scopes of "insinuating" without stating it

The balance requirement prevents physically removing safety information. However, choices of area, font, and placement can render one side practically unread while it technically remains present. The three levels below show how.

Implication 1 — Local: carried in a single word or sentence

How it is built: The entire adverse-event table is compressed into a single sentence — "For details see the Adverse Reactions section of the package insert" — while the efficacy results are presented as a full-size table in the body of the piece.

Intent that can be read: Safety information is formally present as a cross-reference instruction, yet effectively occupies zero space on the page. A prescriber reading the material cannot compare efficacy and safety side by side.

Verdict: "See package insert" satisfies a minimal existence check but fails the design requirement that safety information appear on the same page at equivalent prominence. Key adverse events and their frequencies must be stated as numbers in the body of the material, not delegated to a reference.

Implication 2 — Adjacent: read across neighboring clauses

How it is built: The upper two-thirds of a slide carry a full-colour bar chart of the primary efficacy endpoint. The lower third shows "Adverse events: nausea 3.2%, headache 1.8% (mild, transient)" in grey text. Both sections exist on the same page.

Intent that can be read: The eye is drawn to the coloured chart above; safety text in the lower zone is absorbed in passing. The area ratio is roughly 3:1 in favour of efficacy. The formal requirement for same-page disclosure is met while visual attention is engineered away from safety.

Verdict: The requirement calls for safety information of equivalent size and legibility, not merely equivalent location. The asymmetry of colour versus grey, large versus small, is designed to reduce the probability that safety data is actually read. Safety tables must match efficacy tables in font size and visual weight.

Implication 3 — Whole-context: arising from the document as a whole

How it is built: Across all eight pages of the product information summary, efficacy appears on every page as independent tables, graphs, and quotations. Adverse-event information is collected on the final page only; every preceding page carries a footnote directing readers to "see final page."

Intent that can be read: With each page turn the reader accumulates a favourable efficacy impression; safety is processed once, at the end, as a supplement. The structural centre of gravity across eight pages tilts decisively toward efficacy.

Verdict: Consolidating safety on the last page operates as a structural mechanism for deferring page-level safety obligations. The efficacy–safety balance must be maintained page by page; the architectural decision to "collect safety at the end" does not exempt each preceding page from the requirement.