McNeil, Whitehall object to FDA studies of alcohol warnings for OTC analgesics.

ALCOHOL WARNING ON ANALGESICS: McNEIL QUESTIONS RATIONALE, METHODS OF FDA STUDY to examine consumer comprehension of several possible versions of the label warning in Sept. 29 comments to FDA on the agency's Feb. 27 proposed revisions to OTC product labeling. McNeil points out the agency "routinely issues rules containing warnings for OTC drug products without consumer surveys," and questions "why FDA deems it necessary to conduct consumer research on this issue."

The Tylenol marketer also argues that "conducting a consumer study on a labeling issue which has been publicly reviewed and voted upon by two advisory committees and which has already been implemented by the agency in the context of several NDA approvals seems entirely unnecessary." FDA's Nonprescription Drugs Advisory Committee reviewed and recommended alcohol warnings for acetaminophen and later aspirin and other nonsteroidal anti-inflammatory analgesics at two meetings in 1993. FDA has required the alcohol warning on subsequent NDAed new analgesic products including the Rx-to-OTC switches of the NSAIDs naproxen sodium (Aleve) and ketoprofen (Orudis and Actron).

Under its broad initiative to review and change the way OTCs are labeled, FDA identified two targets for consumer comprehension studies in a May 23 Federal Register notice: product statements of identity and analgesic alcohol warnings ("The Tan Sheet" June 2, p. 8). As proposed, the two consumer surveys would involve a total of 480 test subjects. The agency extended the comment period on the studies from July 22 to Sept. 30 ("The Tan Sheet" Aug. 4, In Brief).

"All OTC analgesic products should be labeled now with an alcohol warning," McNeil declares. The J&J subsidiary is one of the few to place alcohol warnings on it analgesic products voluntarily; the company says all of its adult acetaminophen drug products carry the warning.

McNeil also questions the timing of the label comprehension study in its comments. "The need for conducting Study D at this late point in time is highly suspect and questionable. If needed, this study should have been conducted several years ago and should not be utilized now as a means to delay a long overdue rule," the firm says.

Whitehall-Robins disagrees. The Advil marketer reiterates in Sept. 30 comments its "long-standing" objection to FDA's plans to require alcohol warning statements in all OTC analgesic labeling. While Whitehall's acetaminophen-based products carry the alcohol warning, the company has not adopted the voluntary label warning on its Advil brand of ibuprofen.

McNeil also provided FDA with a series of questions about the design and methodology of the proposed consumer survey. McNeil notes the protocol calls for data collection in locations with diverse populations that will generally represent the population of OTC drug users. "What controls are in place to ensure that the sample will represent the population of OTC analgesic users? What data source is being utilized to determine if the profile of the study matches the profile of analgesic users," McNeil asks. Another issue, the company says, is: "How do we know if the sample contains `at risk' respondents?" McNeil observes that a question at the bottom of the survey form "briefly asks" about "drinking behavior"; however, the firm questions, "what constitutes an `at risk' respondent?"

Regarding the 18 different warning statements that will be presented to consumer study subjects, McNeil argues "the wording being examined (`generally' versus `usually' versus `frequently') in part of the warnings statements is very similar." McNeil says in its experience respondents are "unlikely to truly differentiate between these similar words." The company also criticizes the length of the questionnaire, noting respondents will be asked 72 questions about the warnings -- four questions about each -- which, after the "significant amount of `mental gymnastics,'" may lead to fatigue and, probably, "confusion and lack of objectivity."

In its comments, Whitehall points to several potential problems with the study design and methodology. "The research objective is not clear in that the study protocol does not reflect how the results are to be evaluated," the firm says, adding it has identified "several methodological areas of concern in the study design."

"We suggest that the study design undergo substantial modification prior to implementation in order to provide more meaningful data," Whitehall advises. "Additionally, we question its timing prior to FDA's establishment through the regulatory process of the need for such warnings on a drug-by-drug basis."

The Nonprescription Drug Manufacturers Association, in Oct. 6 comments on the entire FDA OTC labeling proposal, objects on "both procedural and substantive grounds" to the agency conducting further labeling research. In its objection, NDMA includes the alcohol warning studies along with two larger FDA studies on labeling comprehension that received approval from the Office of Management & Budget in July.

"As a procedural matter, it makes little sense to conduct research after issuing the notice of proposed rulemaking," NDMA declares, adding "the agency should not embark on a path that could lead to additional label redesign and implementation later." As a "matter of substance, there is simply no point to the research," NDMA states, citing data developed in connection with Rx-to-OTC switch applications and available literature on readability. "Additional research would be redundant," the association maintains.

"Moreover, there are significant design problems with the proposed surveys, as discussed in detailed comments from NDMA to OMB, which could yield misleading results," the trade association says. NDMA outlines a number of "procedural, methodological flaws" in FDA's OTC labeling studies in a June 13 letter to OMB ("The Tan Sheet" June 23, p. 5). NDMA made many other suggestions as well to the agency regarding the proposed rule.