“I’m Looking Through You” and “You Won’t See Me,” both songs from The Beatles’ 1965 Rubber Soul album, came to mind when we read the Food and Drug Administration’s recently issued document, “Presenting Quantitative Efficacy and Risk Information in Direct-to-Consumer (DTC) Promotional Labeling and Advertisements Guidance for Industry.”¹ This guidance covers DTC promotional labeling and advertisements for prescription human drug and biological products and prescription animal drugs and DTC promotional labeling for over-the-counter animal drugs (medical devices and OTC human drugs are not included). The agency explained that quantitative efficacy and risk information “refers to information that numerically addresses the likelihood or magnitude of a drug’s efficacy or risks.”

Transparency and balanced information are some common themes in the document.

The agency issued a draft guidance in 2018; this finalizes the draft. FDA will accept comments from interested parties.

In this Bulletin, we summarize the new guidance (and some, but not all, of the examples provided) and offer our own observations.

Highlights of the New Guidance

• The guidance covers:
  • providing quantitative efficacy or risk information for the control group, when applicable;
  • presenting probability information in terms of absolute frequencies, percentages, and relative frequencies;
  • formatting quantitative efficacy or risk information; and
  • using visual aids to illustrate quantitative efficacy or risk information.

• FDA said that quantitative information may help consumers better evaluate the drug’s benefits and risks because:

consumers differ in their interpretations of qualitative descriptors (e.g., rare, common, most) and how the context in which qualitative terms are presented can affect how consumers understand them. Quantitative efficacy or risk information may offer more precision than qualitative information; therefore, consumers can use quantitative efficacy and risk information to form more accurate perceptions about the drug.

• The agency recommends companies should consider the amount of space or time available in a media forum to ensure any quantitative efficacy or risk information presented is understandable.

Quantitative Efficacy or Risk Information From the Control Group

• If a company uses a study that includes a control group, the quantitative efficacy or risk information should provide quantitative information from both the treatment group and the relevant control group.
  • Including quantitative benefit or risk measures observed in the control group may help consumers better understand the drug’s benefits and risks, resulting in a more informed decision.
  • Promotional communications that include control group information should accurately describe the comparator used in the control group.

FDA Example

In a clinical trial of 173 participants, 68% of patients who were treated with FDA Drug X plus a sulfonylurea experienced a reduction in blood glucose levels, while 33% of patients treated with a sulfonylurea alone experienced a reduction in blood glucose levels.

The firm is developing a social media web page for Drug X and includes a presentation that 68% of patients treated with Drug X plus a sulfonylurea experienced a reduction in blood glucose levels.

To improve consumers’ ability to comprehend the drug’s effect on blood glucose levels, the firm should also include that 33% of patients treated with a sulfonylurea alone experienced a reduction in blood glucose levels.>

Probability Presentations

• A company should present quantitative efficacy or risk probabilities information in terms of absolute frequencies (e.g., 57 out of 100) or percentages (e.g., 57%).

FDA Example

A firm is developing a magazine advertisement and includes a presentation showing that in clinical trials, most patients experienced a response after 12 weeks of treatment with Drug X.

The firm wants to add numeric values to the presentation to help consumers understand this information.

To communicate this information in a manner that will facilitate consumer comprehension, the firm presents the information as an absolute frequency: In a clinical trial, 78 out of 100 patients experienced a response after 12 weeks of treatment with Drug X, compared to 20 out of 100 patients on placebo.

• FDA said that, based on its research, consumers do not understand relative frequencies (e.g., 33% reduction in symptoms; 3 times as likely to experience a side effect) in health communications.

• The agency cautions that, if a company decides to provide information in a relative frequencies format, it should offer context to help improve consumers’ ability to accurately understand the efficacy or risk information.
  • Firms should include the corresponding absolute probability measures in presentations of relative frequency measures.
  • A company should present the absolute probability measure prominently and in direct conjunction with the relative frequency measure.

FDA Example

A firm is developing a DTC television advertisement for Drug X, which is indicated to reduce the risk of stroke. In a clinical trial, the following absolute risk reductions were observed: 1% of patients treated with Drug X had a stroke, compared to 2% of patients in the control group. This represents a 50% relative reduction in risk of stroke.

The firm wants to include this information in the DTC television advertisement to communicate this information in the DTC television advertisement in a manner that will facilitate consumer comprehension, the firm presents the absolute risk percentages in direct conjunction with the 50% relative risk reduction information and with equal prominence: In a clinical trial, Drug X reduced the risk of stroke by 50% (1% of patients treated with Drug X had a stroke, compared to 2% of patients in the control group).

Formatting Quantitative Efficacy or Risk Information

• FDA recommends the following formatting:
  • Present the information in the same numerical format throughout a promotional communication.
    • E.g., if providing two probabilities about two efficacy outcomes, include both probabilities as absolute frequencies or provide both probabilities as percentages.
  • If characterizing efficacy or risk information quantitatively and consistently throughout a piece, do not alternate between qualitative descriptors and quantitative information to describe similar information.
  • Describe frequencies with the same denominator when providing more than one absolute frequency.
  • Use denominators that are multiples of 10.
  • Provide probabilities using whole numbers where the probabilities in that manner accurately reflect the numerical value provided.
  • If a whole number is not appropriate, express the value as is (e.g., as a decimal — do not round up or down to the nearest whole number).
  • Do not minimize risk information.
  • Do not highlight promotional communications — avoid presentations that focus on low probability or insignificance of a serious risk occurring.

FDA Example

A firm is developing a consumer brochure for Drug X and is considering whether to describe quantitative information about moderate symptom relief in patients treated with Drug X and treated with placebo in terms of absolute frequencies (9 out of 10 and 3 out of 10, respectively) or as percentages (90% and 30%, respectively).

Although either probability measure would be appropriate to describe these outcomes, to help consumers process the information, the firm should provide the outcomes for both the treatment and placebo groups in the same format (i.e., both outcomes as absolute frequencies or both outcomes as percentages): In patients treated with Drug X, 9 out of 10 patients experienced moderate symptom relief, compared to 3 out of 10 patients who received placebo. Alternatively: In patients treated with Drug X, 90% of patients experienced moderate symptom relief, compared to 30% of patients who received placebo.

Visual Aids

• FDA advises a company to use a visual aid design that best communicates the quantitative efficacy or risk information, specifically offering the following recommendations.
  • Consider the purpose of the communication.
  • A bar graph might be appropriate for visually depicting comparisons between probabilities, while a line graph is more useful for illustrating trends.
  • Explain the purpose of the visual aid clearly and accurately and what is shown (e.g., a title, header, or caption (written or oral depending on the media) and identify the visual aid’s variables, scales, and axes (when applicable)).
  • Include visual representations of both the numerator and denominator of ratios or frequencies (e.g., an icon array, graph, or other visual aid depicting an absolute frequency should represent the people who experienced the effect (numerator) and the total people studied (denominator)).
  • If possible, provide the denominator as a multiple of 10 in the display.

FDA Example

Drug X is used to treat a serious condition. Infection is a risk associated with the use of Drug X.

The firm intends to include a visual aid on Drug X’s consumer website to communicate information from Drug X’s FDA-approved labeling about the percentage of patients who experienced a mild to moderate infection and those who experienced a severe to life-threatening infection after treatment with Drug X compared to patients treated with placebo.

The firm prepares a bar graph to present this information because it facilitates the comprehension of visual comparisons between probabilities. As illustrated below, the firm includes a title that describes what the bar graph portrays, labels the scales and variables, does not truncate the y axis, and ensures that the values graphically displayed are proportionate to the quantities being described.

AGG Observations

• An FDA guidance document is not legally binding on FDA or companies. However, the guidance represents the agency’s current thinking, so it is advisable to review the guidance and see how it might apply to a product’s current and potential messaging.

• If we start from the premise that FDA wants promotional messaging to be truthful and not misleading, many common recommendation themes are transparency, balance, prominence, user-friendly language and symbols or icons, and clarity (not an exhaustive list). The bottom line is to tell a truthful story.

• Industry can benefit from the examples provided by FDA (we did not include each example) to better understand the agency’s intent and objectives.

• While OTC human drugs and medical devices are not included in the guidance, and promotional rules among FDA-regulated industries can differ, companies in these spaces should review the document to see how they might learn potential best practices and how to improve their DTC promotional communications.

• Following the guidance, a company can hope not to see FDA (“you won’t see me”), and the agency won’t look through it (“I’m looking through you”).

[1] See https://www.fda.gov/media/169803/download.