Much like how Ray Charles lamented in 1967, the pharmaceutical industry is saying, “Here we go again, she’s back in town again,” as the Food and Drug Administration issued its second Notice of Violation in a month.1 Last week, FDA’s Office of Prescription Drug Promotion issued an NOV to a pharmaceutical company regarding misleading claims made on its branded website intended for healthcare professionals.2 The company’s website was brought to the agency’s attention through its Bad Ad Program. FDA found that the company’s product efficacy webpage contained false and misleading claims about the benefits of its product, overstating the product’s efficacy and misrepresenting study conclusions. This Bulletin will highlight FDA’s criticism of the website and offer our observations.
Highlights
- FDA emphasized that it found the misleading efficacy claims “particularly concerning” because the relevant disease, a type of lung cancer, is “an incurable condition with a 5-year survival rate of less than 10% . . . lung cancer is a serious public health concern and treatment for this condition involves serious risks. Lung cancer is by far the leading cause of cancer death in the United States, accounting for about 1 in 5 of all cancer deaths.”
- Each of FDA’s comments in the NOV refer to a “Clinical Data” section of the product’s efficacy webpage. This section had several claims that FDA felt were not properly supported by the cited studies.
- Certain efficacy conclusions cited a study that was not designed to demonstrate the stated conclusions, which drew from a composite of efficacy endpoints, one of which was not included in the cited study. FDA noted that “it is misleading to include in promotional materials representations or suggestions that rely on a study or studies whose design is not capable of supporting such representations or suggestions.”
- The “Clinical Data” section also contained claims regarding survival, which FDA found to be “misleading because they are based on the results of a trial that is not capable of producing interpretable OS [overall survival] and PFS [progression-free survival] results.”
- FDA acknowledged that the company put “descriptive analysis” and a disclaimer that “single-arm trials do not adequately characterize time-to-event endpoints such as OS/PFS. Thus, these data from [the study] cannot be interpreted as having OS/PFS benefit,” under the survival-related claims. However, the agency said that the representations were nonetheless misleading, because the product’s efficacy claims were made based on a study that did not support the representations, and the disclosure could not correct the study’s limitations.
- FDA had similar concerns with the “Clinical Data” section’s duration of response (“DOR”)-related representations, where one DOR claim appeared to be inconsistent with other DOR-related conclusions. FDA was unable to verify or identify any data that supported the DOR claim.
- FDA found that certain conclusions based on a post-hoc analysis were misleading, as they implied that the post-hoc analysis established certain effects of the drug, thereby overstating the efficacy conclusions. This section too had a disclaimer, in all caps, denoting the limitations of the conclusions from the post-hoc analysis, but the agency found this to be inadequate to mitigate the overall misleading impression of the claims.
AGG Observations
- A company should be careful when stating conclusions from its studies, limiting claims to what each study can support. OPDP reviews the supporting materials, not only the promotional piece itself.
- Adding disclaimers (such as what a certain study design is able to support or instructing the reader to use caution when interpreting the study results) may help, but not eliminate, risk if the overall impression is misleading.
- This NOV came through the Bad Ad Program, where a healthcare provider can provide OPDP with perceived unlawful promotion. Scrutiny can come from many areas.
- FDA focused this NOV only on one section of a promotional page. The company must now locate each promotional item with these claims, or similar claims, and revise them. Companies use core messaging and claims across many promotional pieces, disseminated to different audiences and in different forms. Where there is smoke, there may be fire. So, a company should ensure all materials are reviewed internally to maximize regulatory compliance. Otherwise, noncompliance can be costly and very disruptive.
- After nearly six months without issuing an NOV, OPDP has issued two within a month. Does this portend a trend? We are not prognosticators, but this might lead companies to start humming Ray Charles, singing, “Here we go again, [FDA is] back in town again.”
[1] See our Bulletin covering the prior Notice of Violation, available here: https://www.agg.com/news-insights/publications/cant-hardly-wait-opdp-issues-a-notice-of-violation-where-risk-information-was-not-provided-adequately/.
[2] The Notice of Violation is available here: https://www.fda.gov/media/180633/download?attachment.