COST-EFFECTIVENESS ADVERTISING CLAIMS POLICY GUIDANCE UNDER REVIEW AT FDA: AGENCY IS ALSO LOOKING INTO ENDURING CME MATERIALS AND TIMELY AD SUBMISSIONS

Cost-effectiveness claims are catching more attention at FDA, and the agency has established an internal task force as the first step towards developing a guidance policy for that genre of advertising. FDA's Acting Director of the Division of Drug Marketing, Advertising and Communications Lucy Rose told a Sept. 8 conference in Washington, D.C. that the task force is "looking at bringing in an expert...to help us grow in our knowledge about what cost- effectiveness is and what outcome measurements are. We want you to know that we are doing our best to get guidance out to you as soon as possible." FDA met with a committee of the Pharmaceutical Manufacturers Association recently about the issue of cost effectiveness claims. The FDA task force will "involve" drug companies in the process to "find out what you [drug companies] know that we don't know," Rose declared. "We'd like to get the guidance out to you as quickly as we can," the FDAer stated. The conference was an annual session on marketing and promotion practices sponsored by the Food & Drug Law Institute. Norman Drezin, the regulatory counsel in FDA's drug ad area, also highlighted the agency's current interest in cost- effectiveness claims during a presentation to the FDLI meeting. "One of the issues that comes to use more and more and is becoming a very major issue is cost effectiveness and quality of life claims," Drezin reported. Stressing that FDA still does not feel comfortable with the issue, Drezin said: "We are working hard at getting a handle on how that should best be addressed. We have spoken to several people in the industry. We are all ears. We are examining it very carefully. It doesn't appear at the present time that anyone has a real finite way of looking at it, but we are working very hard at it." FDA has already questioned one "cost-effective" claim in advertising for the Berlex quinidine sulfate product, Quinagulate Dura-Tabs. An April 2 warning letter to the firm objects to a cost-effective comparison of the Berlex product to a competitive product from A.H. Robins. "Berlex's promotional labeling also claims that Quinagulate is 'cost-effective' compared to Quinidex," FDA observed. "However, mere reference to average wholesale price information is inadequate to support such claims," the April letter says. The agency further contended that the Berlex reference to cost-effectiveness "may be misleading, because dosing of these products may vary, given the differences in the amounts of quinidine base per tablet of Quinagulate compared to Quinidex." The agency has taken the position in the past that cost effectiveness claims will require the same type of clinical trial support that is now expected for other types of ad claims. Two years ago, former FDA ad division staffer Lou Morris told a Capitol Hill seminar on cost effectiveness studies that the standard two trial rule would apply to cost effectiveness claims. Morris noted, however, that the state of the art in economic studies lags behind clinical trials, making the definition of "well-controlled trials" more difficult in the cost effectiveness area ("The Pink Sheet" Sept. 16, 1991, T&G-8). During Q&A at the FDLI meeting, Drezin noted that the agency finds a cost comparison claims easier to judge. Comparative price claims should contain some "substantiation [as to] where are these prices coming from, a point in time and an industry-recognized source," Drezin said. The FDA lawyer noted that the reference to price should relate to the price of the product itself. "We've had issues being raised in which people have tried to make claims about retail prices," Drezin said, questioning: "how they do that I don't know, because retail prices are all over the place." FDAers from the drug ad group warned the FDLI meeting about two other areas under current scrutiny: enduring CME materials; and compliance with requirements to submit promotional materials to the agency when they first go into use. As part of the continuing effort to develop a final CME guidance, FDA is considering a separate document on enduring materials, such as textbooks. FDA Policy Development and Coordination Staff Director David Adams reported that in response to comments on the CME guidance issued in November last year, the agency sees "the need for [a] separate written policy guidance on enduring materials that really address three scenarios; company preparation [of materials], company dissemination of materials and company dissemination of textbooks." Adams observed that "continuing medical education (CME) addresses all scientific and educational activities but does not include educational materials and visuals." As an example, Adams noted that "the issue of sole-sponsored supplements is a sensitive one. We intend to provide more specific guidance on this issue and we intend to have further dialogue on the issue not just with drug company personnel but medical professionals, journal editors as well as the publishing community." Adams concluded that "FDA is concerned about sole- sponsored supplements. This area is as good a candidate as any for regulatory action as any other." Drezin warned the FDLI group about slack compliances with the requirements for submitting ad and promotional materials for prescription drugs. "The issue is that promotional material is supposed to be filed when it is initially used," Drezin explained. "A publication [is supposed to be submitted] when it is initially published and promotional labeling when it is initially disseminated." "We have raised this issue several times," Drezin pointed out. He specifically pointed to a guidance letter issued in early August reminding manufacturers of the submission requirement and Form FDA-2253. That letter noted that "recently" FDA "has become aware of several instances in which promotional labeling and advertising were not filed or were not timely filed." Drezin pointed out that the agency cited failure to submit the materials in two recent warning letters to Upjohn on a Glynase campaign and to Roxane on Marinol. In a June 22 letter to Roxane, for example, FDA pointed out the failure to submit ad material. "It appears that Roxane is also in violation for failing to comply with the filing requirements set forth in 21 CFR 314.81(b)(3). The FDA has no record that the Marinol journal ad was submitted to the agency under cover of FDA Form 2253." As part of the corrective actions requested of Roxane, FDA asked for "documentation that submissions" had been filed appropriately for the journal ads. "Any promotional labeling or advertising currently in use that have not previously been filed should be submitted immediately." The agency further asked for a "statement of corrective action to assure that, in the future, all required submissions will be filed, in a timely manner." "We have spoken about [the submission requirement] several times, including today," Drezin observed. "We have the feeling that adequate notice has now been provided. Everybody should be aware of it. If you haven't yet, you may want to go back and take a look at your internal procedures to make sure that you are complying with it." Drezin warned: "It is time that something will happen." Rose alerted the FDLI group to some of the "red flags" that draw FDA attention to ad campaigns. For example, she said that "sales reps must target the correct physicians. If we have reason to believe that representatives are calling on an entire group of specialists for which the product is not indicated it is obviously going to create a red flag for us." Lastly, Rose said that "sales reps should not mislead or discuss unapproved uses with physicians. It is important that companies send clear signals to their sales people." Rose also advised marketers to make sure that "materials for your sales reps" are "not ambiguous and they clearly define the areas that your products are indicated. Make certain that they don't make implied claims that your sales reps are going to leave behind that can get your company in trouble."