Sept. 5, 2017 – An FDA-proposed study to determine whether healthcare professionals (HCPs) and consumers can utilize disclosures to correctly frame efficacy claims in prescription drug promotion raises First Amendment concerns about communication and requires fixes to the study construct, according to August comments on the June 14 proposal.

“Disclosure is an important topic that should be properly researched, particularly in light of First Amendment considerations and the potential for disclosures to enable a broader range of manufacturer communications,” states a comment from the Pharmaceutical Research and Manufacturers of America (PhRMA).

“At the same time, it is a challenging topic to study reliably. It is not clear from the general description of the Agency’s proposed study whether it will yield useful information to evaluate whether disclosures provide appropriate contextual information in certain communications, whether such disclosures can be made more effective, and where the disclosures are necessary to ensure communications are truthful and non-misleading,” the PhRMA comment continues.

PhRMA asserts that any study of the efficacy of disclosures “must be carefully designed to fully evaluate the role of disclosures as a less restrictive alternative to restricting speech.”

The FDA’s notice of the study states that the proposed research “will examine the effectiveness of clear and conspicuous disclosures in prescription drug promotion…. The purpose of our study is to determine how useful disclosures regarding prescription drug information are when presented prominently and adjacent to claims.”

The agency states that to address this research question, “we have designed a set of studies that cover both consumers and HCPs, as well as three different types of claims: Scope of treatment, ease of use, and statistical significance.” It clarifies that the scope of treatment claim can be thought of as a disease-awareness claim; the ease of use claim is a simple claim of easy drug administration that omits specific important details that contribute to a more difficult drug administration than suggested; and the statistical significance claim is one in which the disclosure reveals that the presented analyses were not statistically significant, and thus must be viewed with considerable caution.

According to Eli Lilly and Co., FDA advertising regulations “regard sponsor product claims or representations either not appearing on the approved labeling or not supported by labeling’s ‘substantial evidence’ requirement bar as being per se misleading, and thus prohibited.”

The comment states that “as such, this interpretation has chilled sponsor advertising claims or statements, even when they are consistent with approved uses, for important information such as: discussing a drug’s long-term efficacy or time-of-onset; the patient preferences, disease experiences, or adherence to a therapeutic; a sponsor’s elaboration of pivotal clinical trial information (e.g., trial data which formed the basis of FDA approving the drug) like secondary endpoints and biomarkers; or, showing component scores for a composite physician administered evaluation score.”

The Lilly comment also states that the agency “has enforced against and objected to sponsor ads which contain such claims, even when accompanied by prominent, clear sponsor disclosures attempting to prevent potential misleading of the audience.”

As proposed by the FDA, each study participant will view three different mock promotional print pieces for different prescription drug products. For each of the three promotional pieces, “they will be randomized to see an ad with a weak disclosure, a strong disclosure, or no disclosure. We will manipulate the strength of disclosure by including additional concluding information (strong) or not (weak) in the disclosure statement. In all cases, disclosures will be adjacent to claims and written in font clear enough to be detected.”

Novartis suggests in its comment that the study include electronic advertisements in addition to print advertisements “to account for and reflect changes in consumer consumption of media, including the increase of electronic promotion and advertising of products by sponsors.” Novartis also states that if the study ad will have 1 of 3 levels of disclosure; “i.e., strong, week, or none, we propose that you consider having the following 3 strength factors:

• Additional concluding information makes it strong.
• Less additional information makes it weak.
• No additional information makes it none.”

The agency explained that both consumers and HCPs will be recruited from Internet panels. LEO Pharma Inc. recommends in its comment that the FDA “select study participants that represent a variety of demographics, including, gender, race, ethnicity, socio-economic status, etc., such that the study population is a comprehensive representation of the U.S. population.” PhRMA recommends that the consumer study be limited to disease sufferers, “Because the most useful information regarding the efficacy of disclosures to frame information in prescription drug promotion would arise in the context of patients suffering from the disease at issue.”

The FDA proposed study will include self-reported questionnaires and small eye-tracking studies “to determine what parts of each promotional piece consumers and HCPs actually viewed. Specifically, we will be able to determine whether they looked at the disclosure statement at all, and we can obtain a rough idea of how long they looked at it.”

Regarding the eye-tracking studies, Novartis commented that “oftentimes making disclosures stronger also means making them longer. Using eye tracking results that show the viewer is spending more time looking at a disclosure may only be reflective of there being more to read, not that the content/format is more or less effective.” PhRMA suggested that the agency increase the number of subjects in each group to ensure “more robust data.”

PhRMA called on the FDA to resolve these and other study design issues in order to enhance the quality, utility, and clarity of the information to be collected.