On September 13, 2019, FDA’s Office of Prescription Drug Promotion (OPDP) issued a Warning Letter stating that a professional email made false or misleading claims and representations about the risks and effectiveness associated with the use of a drug for treating insomnia. Eleven days later, OPDP sent an Untitled Letter alleging that a direct-to-consumer patient testimonial video montage posted on YouTube.com presented false or misleading claims and representations about the risks associated with a drug for high cholesterol.
The Warning Letter concerned a drug that is a controlled substance and contains a Boxed Warning, and the Untitled Letter involves a drug to treat high cholesterol that has a number of serious risks. As such, these letters appear to follow the agency mandate to concentrate on promotional violations that raise serious risks and significant public health concerns.
Warning Letter Allegations
- The professional email made numerous claims regarding the benefits of the drug, but completely omitted one of the Warnings and Precautions. The email also presented some risk information regarding serious risks, but omitted certain material information pertaining to those risks from the Warnings and Precautions section of the approved labeling.
- The email included a section on the abuse potential of sleep medications and a chart indicating that the relative likelihood of abuse of the subject drug was considerably lower than a number of other sleep aids, including over-the-counter products. OPDP concluded that the claims were misleading, because they minimized the risks of abuse and dependence associated with the use of the subject drug, and suggested that this controlled substance is superior in safety to other prescription and over-the-counter drug products. In addition, the cited reference relies on an algorithm that lacks actual abuse data in human subjects and has not been validated. Moreover, the misleading impression is compounded by the fact that the email fails to disclose the drug is a schedule IV controlled substance.
- The email claimed that the drug was the “only marketed medication for Insomnia that helps with all three important components of sleep: Difficulty falling asleep; Difficulty staying asleep; Early morning awakening.” OPDP determined that this statement was false, because there are other marketed medications indicated for all three of these components of sleep.
- The email also made statements about the use of the drug in treating insomnia, but failed to include material information from the Indications and Usage section of the approved labeling (limitations to the Indication).
- It is unusual for OPDP to send a Warning Letter for one email communication. However, the “Prior Communications” section of the Warning Letter clarifies that OPDP sent an Untitled Letter in 2014 to a previous sponsor of the same product regarding a professional sales aid that omitted important risk information, contained unsubstantiated superiority claims, and omitted material facts. OPDP was concerned that the current sponsor “is continuing to promote this product in a similarly violative manner.”
Untitled Letter Allegations
- The video posted on YouTube included three patient testimonials. Each patient described how they switched statins numerous times due to side effects and, how after taking the subject drug, they experienced a reduction in side effects or no side effects at all. OPDP concluded that the presentation misleadingly suggested that the drug was safer than its competitors. Although the testimonials may be an accurate reflection of these patients’ own personal experiences with the drug, they do not adequately support the suggestion that other patients switching to the drug will experience a similar reduction in side effects compared to other statins, or no side effects at all. FDA was not aware of any data to support this suggestion. OPDP stated that the suggestion about the drug’s side effects was especially concerning given that the drug is associated with serious risks, several of which are the same as those associated with other statins.
- OPDP also determined that the video was misleading, because it failed to present risk information for the drug with a prominence and readability reasonably comparable with the presentation of information relating to benefits of the drug. Specifically, the benefit claims were presented prominently as part of the patient testimonials (encompassing the majority of the screen), while the risk information was presented as scrolling text relegated to the bottom of the video during the patient testimonials. The patient testimonials also competed for the viewers’ attention, making it difficult for them to adequately comprehend the risk information. OPDP concluded that the overall effect of disclosing risk information in this manner undermined the communication of risk information and, thereby, misleadingly minimized the risks associated with the use of the drug.
- When evaluating “Prior Communications” that might elevate an Untitled Letter to a Warning Letter, OPDP will not only consider prior communications to the same firm, they will also consider letters to a prior sponsor of the drug, particularly if the cited violations are similar. Successor owners of a drug product must recognize this fact, including during product acquisition due diligence.
- When presenting risk information, it is important to not only include all Warnings and Precautions, but to also provide information from the Warnings and Precautions that is material to those risks. Including a reference to the approved labeling for a full list of Warnings and Precautions will not mitigate the omission of risk.
- Comparative safety claims (e.g., likelihood of abuse) should be based on head-to-head data in human subjects. Algorithms that lack abuse data in human subjects and which are not validated are not sufficient. Similarly, comparative claims based on patient testimonials alone will be considered misleading. A disclaimer that “Individual results may vary” will not mitigate a misleading presentation.
- As we constantly remind clients, companies are responsible for patient testimonials (and doctor endorsements), which must be representative and typical of an on-label experience of the product.
- Sponsors of controlled substances are reminded to disclose that the drug is a controlled substance (and the classification) in promotional materials.
- It is important to include complete Indications and Usage information, including any limitations to the Indication, particularly if the limitations of use are part of the Indications itself.
- Information relating to risk should be presented with a prominence and readability reasonably comparable to the presentation of information relating to benefits. In addition, the consumer must not be distracted and should be allowed to take in the information in a reasonable manner.
- Sponsors of drugs with serious risks (e.g., drugs with Boxed Warnings, controlled substances, drugs with Risk Evaluation Mitigation Strategy programs) and drugs that treat diseases that raise significant public health concerns should be particularly careful with how they promote their products.