Who doesn't remember Hall and Oates' 1984 hit, "Out of Touch?"1 Perhaps, reviewers in the Food and Drug Administration's Office of Prescription Drug Promotion were humming this song when it recently issued an Untitled Letter to a pharmaceutical company for unlawfully promoting its topical treatment for plaque psoriasis in adults.2 OPDP found the promotions (a direct-to-consumer ("DTC") video (shown on a Lifetime TV program initially) and storyboard, and the product's healthcare professional-directed website) were out of touch with regulatory requirements, particularly regarding the presentation of risk information and overstatement of benefit for the dermatological product.
We will highlight some of OPDP's concerns in this Bulletin, as well as share our own observations.
Highlights of the Untitled Letter
- OPDP said the DTC video provided efficacy claims, but did not
provide important risk information about the drug (e.g., warning
and precaution for embryofetal risk).
- The patient in the video appeared to be of child-bearing age with two young children and suggested the product had worked for her (despite the aforementioned risk information in the FDA-approved label).
- OPDP noted that some information regarding embroyofetal risk was presented in the video; however, it found that it did "not mitigate the misleading impression created by the omission of material facts regarding the need for pregnancy testing and birth control from the video."
- The video did not include information about photosensitivity or
sunburn risks, and the promotion showed the patient outside, with
exposed shoulders and arms, touting the drug's benefits (there
were other safety risks not provided).
- OPDP wrote that the omission of these serious risks in the video misleadingly suggested that the product was safer than had been shown.
- OPDP said that the promotion failed to present the risk information prominently and "reasonably comparable" with the benefits. For example, the promotion provided certain risk information in text-only format and in small font at the bottom of the screen; however, the promotion described the product benefits prominently and on the screen in large print, verbally by the narrator in the audio portion of the video.
- The video included a physician spokesperson claiming the product was the "first and only" topical combination medicine for the indication, but OPDP said that was inaccurate. There were other FDA-approved topical plaque psoriasis combination drugs marketed before the product.
- The video included a patient spokesperson who suggested the product was clinically superior to, or more effective than, other treatments for plaque psoriasis when the company had not demonstrated this claim with data. These claims also suggested that the product worked in patients who failed to respond to other plaque psoriasis treatments, when this was not the case. OPDP acknowledged that the promotional claims about the product were "the personal experience of this patient," but this was insufficient to demonstrate that the product was superior to other commercially available plaque psoriasis drugs.
- Separately, OPDP stated concerns with the HCP-directed webpage
and claims about efficacy and mechanism of action, which the agency
concluded were based on inadequate data.
- The claims of "demonstrated synergy" and "superior efficacy," compared to the aggregated results of two monotherapies on the webpage, were based on data derived from post hoc analyses of a single phase 2 trial of limited sample size, which compared the product separately to its individual components and vehicle. The agency found these claims misleading because they suggested a much larger difference in efficacy between treatment arms than was actually demonstrated.
- Online communications and DTC promotion remain a high area of OPDP scrutiny. In addition, lack or minimization of risk information, as well as an overstatement of benefit, are on the top of the "don't do this" list at FDA.
- As we have noted in past Bulletins, a company is responsible for the statements and actions of its spokespeople (here, a doctor and patient). While the statements made might have been the individual's personal experience, they cannot run afoul of FDA's promotional requirement —certainly if they are not supported by sufficient data for claim substantiation.
- As noted, OPDP carefully reviews the presentation of risk
information. We know from a review of enforcement letters and OPDP
advisory comments, as well as our experience on clients'
Promotional Review Committees, this issue comes up constantly.
- In the Untitled Letter, the agency recognized the company provided risk information but, according to OPDP, did not offer enough (or omitted) material facts, or not as prominently and comparable to the possible messaging. If a company presents the "good" a certain way, it should describe the "bad" in a similar way.
- Comparative claims are always tricky. A company attempts to depict its product as better than the competitor with a graph or only a few sentences. It is difficult, however, to tell a full story in a few words. There is a risk that the comparison might be misleading for a number of reasons, including on what the basis the data is derived and shown.
- A company cannot rely on third-party programs, such as a TV show or a conference, to ensure the promotion is compliant with FDA requirements, particularly if the company intends to use the material for its own purposes. As we often note to clients, if the company wants the benefits of specific messaging, it must assume the risks of that messaging.
- To be compliant, don't ignore FDA. It is not clear in the Untitled Letter what specific concerns the agency raised previously (it is redacted), but it did note:
OPDP expressed similar concerns that [company] appears to be promoting [product] without presenting the serious risks and efficacy of the drug in a truthful and non-misleading manner, despite concerns previously expressed by OPDP. A company can respectfully disagree with OPDP, but it would be well advised to implement as many changes when OPDP provides free advice on ways to minimize risk.
- The Untitled Letter focused on the presentation of risk and claims about efficacy. There were no allegations of promoting unapproved uses, but the agency used the "truthful, not misleading" phrase used by courts and FDA concerning First Amendment issues and off-label discussions.
- A company should review this Untitled Letter (and other FDA letters, as well as our past Bulletins) to make sure its promotional messaging is not out of touch with OPDP requirements and expectations.
1. This song selection is a nod to the (junior) co-author, whose father likes the duo.
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