"FAIR BALANCE" IN COMPARATIVE DRUG ADS REQUIRES MENTIONING ADVANTAGES OF COMPETITORS's DRUG AS WELL AS PROMOTED PRODUCT, FDA's BANKS TELLS RAPS MEETING

The concept of "fair balance" as applied to comparative drug ads requires that promotions include disadvantages as well as advantages of the promoted product, FDA Prescription Drug Advertising & Labeling Division Assistant Director David Banks told a Sept. 27 meeting of the Regulatory Affairs Professionals Society. Promotions featuring "partial comparison claims" -- which focus on certain aspects of a product's safety or efficacy relative to a competing drug -- should exhibit fair balance, Banks maintained. Noting that "fair balance" usually is applied to an ad's reference to a product's risks as well as benefits, Banks said FDA will "demand fair balance in terms of competing products' advantages." The principle is being expanded because the agency sees an "increasing incidence of promotional claims" of superiority based on a product's sole advantage over a competing drug, Banks noted. Although "there are relatively few cases where one drug is superior in every regard to a competing product," current advertisements lead "to that conclusion," he said. This requirement "is not going to be . . . very palatable" to the industry, Banks acknowledged, but it is a requisite to "the prescriber's ability to make an informed decision." The FDAer described a "continuum" of comparative claims that distinguishes, for example, "first-choice" from "first-line" claims. "First-line" or "first-step" therapy claims, if not expressly prohibited by FDA, can be made in approved labeling, Banks said. Such a claim denotes that the product is one among many indicated for first-line use; however, if the claim implies superiority to other first-line products, "then it is no longer a first-line overall claim but rather a claim of superiority." Such claims, Banks said, require documentation. FDA plans to issue "a paper" in the "relatively near future" that will explain in greater detail its regulatory concepts regarding pharmaceutical promotions, Banks said. Claims of overall superiority should be "based on an overall assessment of risk-to-benefit ratio . . . that involves efficacy from adequate and well-controlled studies and safety in terms of both common and uncommon but severe side effects," Banks explained. Such claims should be made with regard to comparable products and should contain fair balance regarding the competing product's benefits. "First-choice" or "drug of choice" claims are the strongest that can be made, he continued. Such a claim has "a special connotation for the medical and related communities; it is a claim that the drug is clearly superior to competing products." Banks said FDA permits first-choice claims "only on the basis of indisputable clinical evidence and universal utilization of a drug by the medical community. The drug must be head and shoulders above competing products." FDA believes "there are relatively few cases where drugs of choice are actively marketed because, if it's the drug of choice, it has already been accepted by the medical community to such an extent that there's relatively little need to market a product," Banks said. However, the agency is "seeing more and more efforts" to market products as drugs of choice even when, "from our perspective [they are] clearly not drugs of choice." The agency recently objected to ads for Bristol-Myers' Buspar as "the first choice for chronic anxiety" and Boehringer Ingelheim's Alupent as "the first choice for asthma" ("The Pink Sheet" Sept. 26, T&G-5). A step below the "drug of choice" claim on the agency's continuum is the "near drug of choice" claim. Such promotions refer to "a drug of choice," indicating that the product is one among a category of appropriate therapies. Banks said sponsors making such claims should possess data to document general superiority. FDA considers the phrase "a logical drug of choice" equivalent to a first-line claim. However, Banks cautioned that the use of all comparative claims will be reviewed by the agency in the context of the overall promotion. In other words, FDA may demand data to support a drug of choice claim for an ad containing what is normally considered a first-line claim if the ad presents a series of advantages that imply overall superiority. Lower on the continuum are "most-prescribed" claims. These statements should not claim superiority based on greater use rates, Banks said. Most-prescribed claims "should specify the time period of the comparison," and the claims should be discontinued over time as product use declines, he said. "Prescriber preference" claims require documentation in the form of surveys on which the claim is based; the amount of information needed decreases if a third-party conducted the survey. Further down the continuum, Banks noted, are comparability statements -- those claiming similarity to a competing product. Ads making a comparability claim require "some basis for that claim" but "a relatively low level of data." On the other hand, he cautioned, comparability claims should not be based on "active control trials that do not show a difference." At the bottom of the continuum are noncomparative claims -- those citing the promoted product's attributes. Obviously, such claims require no comparative data, Banks said. However, open-ended comparative claims do; ads that imply the promoted drug is the only product with the attribute must be supported by comparative data. The regulatory policy has been updated in response to "an increasing incidence of what we consider to be inadequately supported comparative claims," Banks said. The policy embraces a "pragmatic perspective," in which "what matters is patient response." Under the new policy, advertising "standards for quality of data are not fundamentally different from those for drug approval," he stated. FDA will require "data from adequate and well-controlled studies" that demonstrate the superiority of one product over another, Banks explained. The agency "cannot operate on the basis of theory, testimony, or scientifically derived data that has no known correlation to patient response," he said. Comparative claims "should be on the basis of head-to-head adequate and well-controlled studies," he continued. "In most cases it is not valid to compare data from" unrelated studies with different patient populations, different "rating instruments," and different modalities for monitoring patients. The industry should generate more comparative ads to address infrequent, but severe side effects, Banks maintained. The industry "does a relatively good job of comparing relatively frequent side effects," but it does not often "compare infrequent but severe side effects." For example, if a hypnotic causes a severe side effect in one in 10,000 patients, "that can be a significant aspect of overall risk to benefit," he said. Yet "we see relatively little [advertising] addressing this problem."