FDA makes significant qualitative changes in its final guidance on quantitative information in drug advertising

Regulatory background

• The FDA’s Center for Drug Evaluation and Research’s (CDER) Office of Prescription Drug Promotion (OPDP) regulates pharmaceutical advertising in the U.S., including direct-to-consumer advertising. In general, OPDP is concerned with ensuring that advertisements are truthful, non-misleading, include important information about a product’s benefits and risks, and that information is presented in ways that make the advertisement comprehensible to its intended audience.
• The FDA regulates prescription drug advertising under 21 CFR 202.1, Prescription drug advertisements. The regulation includes a bevy of requirements for each advertisement, as well as specific exemptions from the rule. While the Federal Food, Drug and Cosmetic (FD&C) Act does not specifically define the term “advertisement,” the regulation does contain illustrative examples including “advertisements in published journals, magazines, other periodicals, and newspapers, and advertisements broadcast through media such as radio, television, and telephone communication systems,” as well as things like brochures, booklets and other types of printed materials.
• Because drug advertisements take many forms, the OPDP has long conducted research on drug advertisements and promotions to discern which factors may play a role. For example, in April 2024, the FDA announced its intent to conduct a study of “quantitative claims in direct-to-consumer prescription drug advertising” to better understand the role that quantitative claims have on consumer understanding.
• The notice specifically made mention of a 2018 draft guidance document, Presenting Quantitative Efficacy and Risk Information in Direct-to-Consumer Promotional Labeling and Advertisements, and noted that “it is not fully understood how consumers will interpret specific quantitative claims.” FDA explained that “while some types of quantitative information are well-studied (e.g., relative frequencies), many questions remain on how best to communicate certain quantitative information about prescription drugs. For example, we do not have sufficient information about how consumers interpret different claims describing medians,” it wrote. Its study aimed to study consumers’ “interpretation of specific quantitative claims.”
• This area of research is especially important for certain therapeutic areas like cancer, where OPDP staff have noted that patients “have access to a large amount of quantitative information about prescription oncology drugs from consumer and healthcare professional webpages.” However, not all information is equally useful, and some may be misunderstood (or simply not understood) by its intended audience.

An overview of FDA’s 2018 draft guidance

• Despite FDA’s admission that there are gaps in the regulator’s understanding of quantitative information, its 2018 draft guidance does offer some important advice to life sciences companies about FDA’s expectations for the presentation of quantitative information in drug advertising.
• The guidance document describes – as the name implies – how companies can best present quantitative information about their products in promotional materials, including advertising. The overall goal of the guidance is to make the presentation of these materials “more consumer-friendly,” according to the FDA. As noted in the guidance, “Firms generally have flexibility with respect to the presentation of efficacy and risk information about their products so long as the presentation is not false or misleading and complies with other applicable statutory and regulatory requirements. When firms develop DTC promotional materials, they should consider how to best convey information about a drug’s efficacy and risks so the audience understands it. This includes consideration of whether to provide efficacy and risk information by using words, numbers, or visual aids, or a combination of these elements.”
• The guidance also notes that FDA had observed an increase in the use of quantitative presentations about drug risks and efficacy, which was potentially to the benefit of consumers of that advertising since it avoided the use of qualitative statements like rare, common or most that were imprecise.
• Because quantitative efficacy or risk information “may offer more precision that qualitative information,” FDA has some recommendations for how advertisers can provide this information. For example, FDA recommended that sponsors make use of absolute frequencies or percentages, and avoid the use of relative frequencies. If companies insist on using relative frequencies, those data should be contextualized alongside the “corresponding absolute probability measures.” (e.g., “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.)
• The guidance also made recommendations about formatting quantitative information. For example, FDA states that information should be presented in the “same numerical format throughout a promotional labeling piece or advertisement;” to use the same denominator (and ones that are in multiples of 10), and to express probabilities using whole numbers to the extent that doing so is accurate.
• Visual aids are also addressed, with FDA recommending the inclusion of graphs, tables and “icon arrays” to help illustrate the information and put data points into context. However, FDA does note that not all visual aids are “equally effective in conveying all types of information,” and that companies need to be aware of over- or under-stating important information.
• The draft guidance received relatively light feedback from industry. There were six comments submitted by the health care industry, including comments from the industry group PhRMA, the biopharmaceutical company Bayer and the Blue Cross Blue Shield Association. Comments were generally positive, although some offered suggestions based on situational or modality-specific concerns.
• FDA seemed poised to release a final version of the guidance earlier this year, but the document lingered after a review by the White House’s Office of Information and Regulatory Affairs (OIRA), which cleared the document for release on March 2, 2023 “without change,” meaning as-written by the FDA. Following the release of FDA’s Quantitative Claims proposed survey in April 2023, AgencyIQ speculated that perhaps the delay of the guidance and could be attributable to internal debate about whether to first obtain the results of that research, or to publish the guidance first.

Now the FDA has at last published the final guidance on quantitative efficacy and risk information

• As expected based on the number of industry comments, the guidance, published on June 27, 2023, is highly similar to the prior draft version. While most of the changes that have been made to the guidance are generally clarifying in nature, there is at least one major addition that is likely to affect a significant number of companies related to the presentation of information about the control group in the study from which a quantitative data point was obtained.
• This change occurs in a new section (Section III.A, Page 3-4) on providing quantitative efficacy or risk information for the control group, when applicable. FDA notes that, “When a study includes a control group, firms that provide quantitative efficacy or risk information about a drug in DTC promotional communications should provide quantitative information from both the treatment group and the relevant control group.” The agency justifies this approach by pointing to research showing that such information “plays an important role in evaluating a drug’s benefits and risks,” and “improves consumers’ ability to process and comprehend the drug’s benefits and risks and can lead to more informed decision making.”
• By way of example, if a company claims that a trial showed that 68% of patients treated with Drug X experienced a reduction in blood glucose levels, they should also note the reduction experienced by patients treated with the standard of care or placebo.
• Another key change is that firms “should present the absolute probability measure prominently and in direct conjunction with the relative frequency measure.” This sentence was previously not in the guidance, but the specific wording – “in direct conjunction” – makes clear that FDA isn’t interested in information being presented in such a way as to detract from consumers’ ability to directly compare data.

Other changes of note:

• The final guidance document eliminates a sentence that stated the recommendations of the guidance applied to promotional materials “regardless of the medium in which they are presented (e.g., print, electronic, audiovisual, broadcast).” This seems to imply that FDA may recognize that certain communication mediums are more conducive to communicating quantitative information in full form than others. Instead, there’s a new paragraph that notes 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.”
• FDA now also advises companies to “avoid presentations that focus attention on the low probability of a serious risk occurring, that characterize the probability of that risk occurring as insignificant, or that otherwise suggest that the risk is not important based on its probability of occurring.” (Section III.C.) In other words: Don’t minimize important risks with claims like, “only 2% of patients experienced bleeding that required hospitalization.”
• There are several new footnotes, such as one indicating that the recommendations of the guidance are intended for “firms that include quantitative efficacy or risk information in DTC promotional communications for their drugs.” Such firms, the footnote explains, may include “manufacturers, packers, and distributors of prescription drugs,” including their representatives.

Analysis

• Despite the relatively small quantity of changes, some are nevertheless quite important. FDA’s insistence that drug advertisements control information about the control group when making quantitative claims is a significant new point, and is likely to affect a substantial amount of drug promotion in the U.S. that make efficacy- or safety-based claims. It’s worth noting that this new section in the guidance is listed before all other recommendations and is entirely new – not simply a revision.
• We also found it interesting that FDA wants sponsors to avoid subjective words in their promotions, like “only,” when referring to risk. Companies should probably review their promotions for similar words (e.g., “just”) to avoid FDA scrutiny.
• However, there’s perhaps an upside to this requirement. Many of OPDP’s Warning Letters and Untitled Letters to companies for advertising-related issues explicitly allege that the company minimized the presentation of critical risk information. By following the advice of this guidance with respect to the two points above, companies could greatly reduce their risk of incurring such a warning from regulators by ensuring proper contextualization and avoiding risk-minimizing language.
• What about that OPDP research on quantitative claims, anyways? We still find it odd that the FDA held onto this guidance for nearly four months after it was cleared by the White House for review, and we can’t help but wonder why. To be clear: This is highly unusual and not standard practice for the FDA to not publish guidance when it has gone to the trouble of developing it and obtaining White House clearance to publish it. Most cleared documents are released within days – not held for months. We’re also curious about OPDP’s recently-announced research on this same topic, and wonder if we’ll see yet another update to this guidance document in the future based on the results of that research.
• The FDA is having a remarkably busy year for advertising and promotion policy. In addition to this final guidance document, it has also released a new proposed rule on Patient Medication Information that would establish a new type of patient-friendly labeling. FDA is also planning to release a new, revised or final draft by the end of the year on Prescription Drug-Use Related Software (PDURS), which is a type of software application “disseminated by or on behalf of drug sponsors for use with one or more of their prescription drug products” that is regulated more like drug labeling. Finally, the agency plans to release new guidance pertaining to the labeling of interchangeable biosimilar biological products by September 30, 2023. [ Read our preview of FDA’s drug labeling and promotion activities here.]

To contact the editor of this analysis, please email Alec Gaffney ( agaffney@agencyiq.com)

Key Documents and Dates

• Presenting Quantitative Efficacy and Risk Information in Direct-to-Consumer (DTC) Promotional Labeling and Advertisements