In the new final guidance, FDA cemented its October 2018 recommendations for DTC promotional labeling and advertising, citing research showing the use of quantitative information, rather than qualitative terms (e.g., "most," "rare," or "common"), may allow consumers to form more accurate and precise perceptions of the information presented. In keeping with the draft, FDA suggests that companies should:

• ensure consistency in presentation, for example in numeric formats (e.g., absolute frequencies versus percentages) and in expression of quantitative versus qualitative descriptions of risk or efficacy information;

• use consistent denominators that are easy for consumers to understand (e.g., 31 out of 100 compared to 50 out of 100, rather than 1/3 compared to 1/2);

• express probabilities as whole numbers to the extent possible, and when inappropriate, use decimals as opposed to rounding up or down;

• select appropriate visual depictions of data (e.g., bar charts for comparisons, line charts for time series) and label them clearly (e.g., axes, numerator and denominator of ratios or frequencies);

• include quantitative information for the relevant control group as well as the treatment group; and

• in presenting information on probability of efficacy or risk, highlight absolute frequencies, which are better understood by consumers rather than depictions of relative frequencies (e.g., 33% reduction in symptoms; 3 times as likely to experience a side effect), which may require additional context. For example, when presenting information stating that in clinical trials most patients experienced a response after 12 weeks of treatment with Drug X, the firm can add numerical values to help consumers understand the presentation by stating, "In a clinical trial, 78 out of 100 patients experienced a response after 12 weeks of treatment with Drug X."

Further, the final version of the guidance – compared to the draft – adds the following:

• a recommendation that “firms should consider the amount of space or time available and any other factors specific to the media type in which their presentation will appear when determining how to present quantitative efficacy or risk information in their DTC promotional communications so that consumers have an opportunity to attend to and understand it.”

• notes about the importance of prominence of probability/frequency measures.

• an example recommending avoiding the qualifier “only.”

• advice to consider illustrating a denominator as a multiple of 10 in a display.

The “Quantitative Efficacy or Risk Information from the Control Group” section was also moved from the end of the draft guidance to the beginning of the final guidance, which may reflect OPDP’s heightened prioritization of DTC promotional communications providing quantitative information from both the treatment group and the relevant control group.

Next steps

OPDP’s latest final guidance comes on the heels of the agency’s proposed rule “Medication Guides: Patient Medication Information,” which would significantly alter FDA’s prescription drug product labeling regulations to require that Rx drug and biological product applicants create a new type of Medication Guide, called the “Patient Medication Information” (PMI); we summarized that proposed rule online here. Among other issues, the proposed rule emphasized that the PMI should not be false or misleading, nor promotional in tone.

These regulatory documents were published within weeks of each other, following several years without new guidance from OPDP. This latest guidance also comes on the heels of the OPDP’s first enforcement letter of 2023, which was just issued in June. Thus, it is fair to ask whether FDA’s prescription drug promotion office will become more active. OPDP may be completing its research into which claims may mislead consumers and into how health care providers (HCPs) interpret those claims, and now moving into a new phase where it will use that research to inform its regulatory positions.

Moving forward, one significant question for the pharmaceutical industry is whether OPDP’s evolving regulatory paradigms may result in heightened enforcement action against promotional materials that the agency deems false or misleading. In the past, pharmaceutical and biotechnology manufacturers have struggled to translate approved instructions for HCPs into patient-friendly language for patient brochures, DTC advertising, and direct-to-patient communication, and accordingly, they will want to closely assess guidance and OPDP statements as the Office crafts new rules that medicinal product sponsors must follow.