Case Study Sanctura (trospium chloride)
Bad Ad Case Study Sanctura (trospium chloride) Facilitator Guide Approximate Time: 30 minutes Exercise prerequisite: Students should view the Bad Ad e-learning CME/CE course located on CD- ROM or at www.fda.gov/badad prior to completing this exercise. Student Materials: Before the exercise: Sanctura journal advertisement Prescribing Information (PI) for Sanctura After the exercise: Sanctura journal advertisement (journal ad), keyed with answers FDA untitled letter for Sanctura Student evaluation form Facilitator Materials: Facilitator guide (includes a detailed answer key for the case study) Facilitator instructions: 1. Distribute the Sanctura journal ad along with the PI for Sanctura. 2. Present the Background and Case Study Instructions shown below. 3. Allow students approximately 10 minutes to review the Sanctura journal ad. 4. Use the discussion questions in this guide to assist students in identifying prescription drug promotion regulatory issues of concern, including false or misleading statements. 5. After discussing the regulatory issues of concern, distribute the Sanctura journal ad, keyed with answers, along with the FDA untitled letter for Sanctura. 2
Background and case study instructions: This promotional piece is a health care professional journal advertisement for Sanctura. Sanctura is indicated for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency. Using the PI as a reference, identify the issues of concern in the advertisement. (Approximately 10 minutes) Discussion Questions: General 1. What are the key promotional messages for Sanctura in the journal ad? 2. Based on your knowledge and information from the PI, which claims, if any, do you think are false or misleading? Specific 3. Is there evidence to support the following claims in the journal ad? a. In a world where many OAB drugs are the same... ONE stands out. (page 1) b. SANCTURA stands alone. The unique quaternary structure makes all the difference. (page 2) (See Detailed Answer Key #1 Unsubstantiated Superiority) 4. Does the journal ad adequately communicate adverse events and other risks associated with Sanctura? (See Detailed Answer Key #2 Omission and Minimization of Risk) 5. Is there evidence to support the following claims made on page 2 of the journal ad? a. No known metabolic drug interactions b. A safe choice (See Detailed Answer Key #2 Omission and Minimization of Risk) 6. Is there evidence to support the following claims made on page 2 of the journal ad? a. Day 1 relief with sustained efficacy. b. Quality of life significantly improved. (See Detailed Answer Key #3 Overstatement of Efficacy) 3
Detailed Answer Key: 1. Unsubstantiated Superiority The journal ad includes the claim In a world where many OAB drugs are the same... ONE stands out coupled with the illustration of a large four-leaf clover surrounded by a golden halo, standing above numerous three-leaf clovers. This claim and presentation misleadingly suggests that Sanctura confers more therapeutic benefits than other therapies for OAB when this has not been demonstrated by substantial evidence or substantial clinical experience. The journal ad claims SANCTURA stands alone. The unique quaternary structure makes all the difference. This claim suggests that Sanctura is superior to other OAB therapies based on its clinical pharmacology. Although the intrinsic chemical structure (i.e., quaternary amine) of Sanctura is different from other OAB drugs, FDA was not aware of any studies demonstrating that the structure of Sanctura offered any distinct patient benefits or conveyed any clinically significant advantage, nor was FDA aware of any studies indicating that Sanctura was superior to other drugs for the treatment of OAB. 1 2. Omission and Minimization of Risk The journal ad fails to present risk information with a prominence and readability reasonably comparable to the presentation of efficacy claims for Sanctura. Throughout the journal ad, effectiveness claims are presented using large, bold, colorful text and graphics. In contrast, the risk information is presented at the bottom of the first page of the journal ad in a single block paragraph, in small black font, following a statement of the indication without any signal to indicate to the reader that this is important risk information. The journal ad includes the claim No known metabolic drug interactions. This claim is misleading because although it presents positive information concerning certain drug-drug interactions, it omits risk information associated with the concomitant use of Sanctura and other drugs. Although metabolic drug interactions between Sanctura and other medications are not expected, as stated in the PRECAUTIONS section of the PI, Sanctura is associated with risks related to drug interactions with other anticholinergic agents. The PI also recommends careful patient monitoring for patients receiving Sanctura concomitantly with drugs 1 When FDA reviews a promotional piece, it makes such judgments in light of the information available at that time. 4
eliminated by active tubular secretion (e.g., procainamide, pancuronium, morphine, vancomycin, metformin, and tenofovir). By not disclosing this risk information, the journal ad misleadingly suggests that Sanctura is safer than has been demonstrated. The journal ad fails to communicate pertinent risks such as common adverse events associated with Sanctura (e.g., dry mouth, constipation, and headache). By omitting these risks, the journal ad misleadingly suggests that Sanctura is safer than has been demonstrated. The omission of these risks is exacerbated by the claim in the ad that Sanctura is A safe choice, which further minimizes the risks associated with the use of Sanctura. 2. Overstatement of Efficacy The journal ad includes the claim Day 1 relief... This claim is misleading because it is not supported by substantial evidence or substantial clinical experience. The reference cited for this claim is a post-hoc analysis of efficacy data from one of the clinical studies (described in the CLINICAL STUDIES section of the PI) in which patients with overactive bladder were randomized to placebo or Sanctura. Although the approach used could potentially be acceptable if planned prospectively, the analysis of the data in this case was done retrospectively. This retrospective analysis does not soundly support the claim made. The journal ad claims Quality of life significantly improved This claim is misleading because it asserts that Sanctura significantly improves a patient s quality of life when this has not been demonstrated by substantial evidence or substantial clinical experience. In support of this claim, the journal ad references a study that is not adequately designed to support the claim. Among the reasons that this study is insufficient, the instrument used in the referenced study was the Incontinence Impact Questionnaire (IIQ), which measures the impact of overactive bladder on travel, physical activity, social relationships, and emotional health but not on other domains covered by the broad claim of quality of life such as non-healthrelated aspects of life including work productivity and financial stability. The referenced study also did not show a significant improvement on all of the IIQ subscales; specifically, the results demonstrated that Sanctura did not affect the physical activity subscale that reflects the impact of incontinence on patient perception of overall physical health, shopping activities, and ability to perform household chores. Moreover, the IIQ used in this study was not validated in men, and the IIQ scores in men did not improve in this study. Therefore, this reference cannot support the claim in the Ad that Sanctura will significantly improve patients' quality of life. 5
Outcome: The FDA untitled letter for Sanctura was issued on January 27, 2009. As a result, the manufacturer for Sanctura stopped using the journal ad. In addition, the manufacturer for Sanctura stopped using other promotional pieces for Sanctura that contained similar claims and presentations. 6