In mid-May 2010, the U.S. Food and Drug Administration (FDA) launched an educational outreach program designed to inform healthcare professionals of the role they may play in monitoring and reporting misleading prescription drug promotion. At the helm of the Agency’s “Bad Ad Program” is the Division of Drug Marketing, Advertising, and Communication (DDMAC). Housed in the Agency’s Center for Drug Evaluation and Research, the group is responsible for ensuring truthful advertising and promotion of prescription drugs. Its mission is to “protect the public health by assuring prescription drug information is truthful, balanced and accurately communicated. This is accomplished through a comprehensive surveillance, enforcement and education program, and by fostering better communication of labeling and promotional information to both healthcare professionals and consumers.” The Bad Ad Program enlists healthcare professionals to assist in DDMAC’s on-going surveillance efforts by describing how healthcare professionals can be involved in helping FDA ensure that prescription drug advertising and promotion is truthful and not misleading.

In announcing the program, FDA plainly states it is seeking to educate healthcare professionals on what constitutes misleading prescription drug promotion in order to move beyond traditional surveillance activities – consisting primarily of reviewing materials submitted to the Agency at the time of first use, attending major medical conferences, and evaluating third-party complaints – to monitor drug promotion occurring directly as it occurs with healthcare professionals. Specifically, FDA cited its inability to monitor drug promotion in physicians’ offices, at local dinner programs, and during promotional speaker training sessions as a limitation to its traditional surveillance activities.

As stated in a “Dear Colleague” letter issued by the Agency in conjunction with its press release regarding the program, the dual purposes of the Bad Ad Program are to inform healthcare professionals of the steps FDA is taking to prevent misleading promotion of prescription drugs by drug companies and to request the healthcare professionals’ assistance in identifying and reporting the misleading promotion of prescription drugs by drug companies. The educational outreach program has three phases: First, to educate and inform healthcare professionals about the role they can play in surveillance of prescription drug promotions. DDMAC in the first phase will attend certain major medical conferences and partner with specific medical societies to distribute information regarding the program and speak to attendees about how to recognize misleading prescription drug promotion and how to report potential violations to the Agency. As part of the initial phase of educational rollout, beginning in May 2010, DDMAC will exhibit at major medical conferences to encourage healthcare professionals to visit and learn more about recognizing and reporting misleading drug promotions. FDA is also offering to provide in-service training for large medical groups or hospitals to support the program. The subsequent phases will increase the sphere of the Agency’s collaborative efforts as well as update the materials distributed to educate healthcare professionals based on feedback to the initial materials used during the primary phase.

The preliminary guidance offered to healthcare professionals to identify potential misleading drug promotion includes a pamphlet briefly summarizing that “prescription drug advertising must: be accurate, balance the risk and benefit information, be consistent with the prescribing information approved by FDA, and only include information that is supported by strong evidence from clinical studies.” Armed with this background and training, DDMAC is asking for healthcare professionals’ insights into sales representative presentations, speaker program presentations, broadcast advertisements, and all written or printed prescription drug promotional materials, specifying that the most common violations observed in drug promotion include “omitting or downplaying risks, overstating the effectiveness, promoting off-label, or unapproved, uses, and misleading drug comparisons.” However, FDA does point out that the Bad Ad Program is not intended to reach promotion not regulated by FDA, which the Agency specifically enumerates in materials as over-the-counter drugs, dietary supplements, and medical devices.

Under the program, healthcare professionals can report misleading drug promotion via E-mail or toll-free number. While reports can be made anonymously, FDA encourages the healthcare professionals to include contact information for follow-up communication, if necessary. The Agency requests the information, including evidence such as actual promotional materials or documentation of oral statements made by drug company representatives, be provided to help stop misleading promotion. After DDMAC receives a report, it will evaluate the information to determine whether it warrants regulatory action. Specifically, the information provided by the healthcare professional will be forwarded to the Regulatory Review Officer in DDMAC responsible for the class of drugs to which the report pertains. The reviewer will be responsible for evaluating the report to determine whether it can serve as the basis for an enforcement action. Where FDA finds the reported drug promotion to be in violation, the Agency stated it will “move forward with a risk-based enforcement strategy.” Tools DDMAC may use include an untitled letter, warning letter, or referral for criminal investigation. Where the report does not meet the minimum criteria for regulatory action, the Agency will use the report to inform its on-going surveillance activities.

While FDA’s ability to peer into the healthcare professionals’ offices is limited, FDA reliance on healthcare professionals to report misleading prescription drug promotion in enforcing the advertising and promotion rules is not new. In fact, FDA has used these interactions as the basis for several enforcement actions. FDA has previously written untitled and warning letters based on interactions between company sales representatives and healthcare professionals that occur in the office. For example:

• In a December 2008 untitled letter, DDMAC cited oral statements made by a sales representative to a healthcare professional regarding Seroquel, at which time the product was approved for schizophrenia. Specifically, the sales representative called upon the physician in his office, where the sales representative proactively initiated a product discussion by stating Seroquel was approved for the treatment of major depressive disorder. The statement prompted the called-upon physician to request that AstraZeneca provide written information supporting the statement that the product was approved for such use. AstraZeneca subsequently mailed the physician information regarding the use of Seroquel in major depressive disorder, including summaries of several clinical trials. While the subsequent mailing acknowledged the product was not approved for treatment of major depressive disorder, DDMAC deemed that the oral statements and the mailing both suggested a use for Seroquel that had not been approved by the FDA, and misbranded the product in violation of the Federal Food, Drug, and Cosmetic Act and implementing regulations.
• DDMAC also cited Celgene for sales representative promotion of its product, Thalomid, which was approved at the time only for use in the acute treatment of the cutaneous manifestations of moderate to severe erythema nodosum leprosum (ENL) and as maintenance therapy for prevention and suppression of the cutaneous manifestations of ENL recurrences. The Agency wrote the product was being presented to physicians for use to treat various cancers, for cancer patient weight loss, and to enhance a feeling of general well-being in those patients. In the April 2000 warning letter, FDA highlighted two different circumstances in which sales representatives interacted directly with healthcare professionals, relying on oral statements reported to the Agency. In the first case, DDMAC wrote regarding a Chicago-area Celgene sales representative who promoted the use of Thalomid to a physician in multiple myeloma patients supported by a copy of a press release. The sales representative made oral statements specifically asking whether the healthcare professional would “consider using thalidomide in a patient with myeloma who did not achieve an adequate response with other agents, because of thalidomide’s anti-angiogenesis potential?” In the second case, the Agency described a sales representative in the northeastern U.S. who promoted the product as “good for weight loss,” “as an appetite stimulant,” and a “great drug for feelings of general well-being” for cancer patients. In the latter situation, when probed by an oncologist attending the lunch sales presentation regarding the status of FDA-approval for these uses, the sales representative acknowledged the product was not approved for these uses, stating, “No, but do you want some material anyway?”
• DDMAC followed up on reports from multiple healthcare professionals regarding the promotion of Xopenex by a Sepracor sales representative in Dallas for an unapproved dosing regimen. The approved dosing regimen for Xopenex at the time was “0.63 mg or 1.25 mg three times a day (every 6 to 8 hours).” However, DDMAC determined the sales representative had orally promoted use of the product “every 4 hours, similarly to albuterol” on several occasions. The Agency issued an untitled letter stating, “Sepracor’s oral statements promoting an unapproved dosage regimen are false and misleading. The dosage regimen being promoted is more frequent than that recommended in the Xopenex approved product labeling.”

While enforcement actions based on healthcare professional reports of misleading promotion has occurred, it is relatively uncommon compared to traditional surveillance mechanisms. Based on new Bad Ad Program, it appears the Agency intends to increase enforcement in this area.

Gary C. Messplay and Colleen Heisey are partners in the Washington, D.C. office of Hunton & Williams LLP in the firm’s Food and Drug Practice. Mr. Messplay can be reached at [email protected]. Ms. Heisey can be reached at [email protected].