BAYER "DEAR DOCTOR" LETTER PUBLIC AIRING OBVIATES CORRECTIVE ACTION, FDA SAYS; DDMAC DISSUADES HMR FROM USING REPRINT COMPARING CARDIZEM CD AND DILACOR XR

Bayer will not be required to take corrective action concerning its distribution of a letter to physicians intended to counter recent negative publicity concerning calcium channel blockers, FDA's Division of Drug Marketing, Advertising & Communications told the company.

In an April 2 letter to Bayer, DDMAC states that "we have concluded that sufficient public discussion about Bayer's involvement in the Kaplan letter has occurred, such that DDMAC will not pursue its request that Bayer engage in a corrective campaign." DDMAC previously suggested to the company that Bayer "correct any false impressions that the Kaplan letter may have left in the minds of those who received it."

Bayer disseminated an August 1995 letter to physicians signed by Norman Kaplan, MD, University of Texas Southwestern Medical Center at Dallas, that countered the Psaty et al. study finding that calcium channel blockers may be associated with higher heart attack rate than beta blockers and diuretics. Public Citizen's Health Research Group called for an FDA investigation of the letter after Kaplan informed the group that he agreed to author the letter with the understanding that the letter would disclose that Bayer paid for the distribution ("The Pink Sheet" Sept. 25, 1995, T&G-1).

DDMAC says it "maintains its position that the Kaplan letter is labeling" and "is misleading because Bayer failed to disclose that it sponsored, disseminated, and had input into the contents of the letter."

In a Sept. 29, 1995 letter to the agency, Bayer maintained that the Kaplan letter "further balanced the understanding of medical issues among practicing physicians" and that the letter should not be considered promotional. Bayer acknowledges that the company retained the public relations firm Chandler & Chicco to contact Kaplan regarding the formulation of a letter on the Psaty study and the use of calcium channel blockers in hypertension.

Bayer explained to DDMAC that "because Dr. Kaplan was on vacation," he related "in a phone conversation the content of a draft `Dear Doctor' letter to Mr. Chicco who prepared it in typed form." Kaplan was then sent a copy of the letter for his comments and approval.

The company continues that it received the final text from Kaplan and "forwarded it to Carrafiello, Diehl & Associates" which "prepared Dr. Kaplan's text on [University of Texas] letterhead with Dr. Kaplan's signature." The letter was then forwarded to a mailing house that used an American Medical Association mailing list of primary care physicians, cardiologists and nephrologists, Bayer said.

Bayer also submitted to DDMAC records of grants or honoraria provided to Kaplan in the last two years. The company provided an unrestricted educational grant to the University of Texas to fund hypertension research by Kaplan and speaker fees to the physician. In addition, Bayer purchased 10,000 books entitled Management of Hypertension, authored by Kaplan, from the publisher in 1995.

In a Dec. 14 letter to DDMAC, Bayer told FDA that distribution of the Kaplan letter was a "singular event" and that the company had no intention to further distribute the letter.

Bayer maintained that no corrective action is necessary because the letter was not promotional and because Bayer's involvement "has already been well-publicized in the lay and professional media," and would be published in the Journal of the American Medical Association. The Feb. 21 issue of JAMA contained an exchange of letters from Kaplan, Bayer, Psaty and HRG regarding the issue.

In January, FDA's Cardiovascular & Renal Drugs Advisory Committee recommended inclusion of the Psaty data in immediate-release nifedipine products such as Bayer's Adalat and Pfizer's Procardia but not in other calcium channel blockers or the extended-release nifedipine products Adalat CC and Procardia XL ("The Pink Sheet" Jan. 29 p. 4).

Bayer recently began running Adalat CC cost comparison direct-to-consumer print ads precleared by FDA. Upon DDMAC advice, the company changed its price comparisons with Procardia XL from AWP to retail prices, which had the effect of allowing Bayer to claim a 28% rather than a 25% difference in price between the two brands.

Bayer also added price balancing information indicating that "the cost of these products may vary depending on where you live and your pharmacy's pricing policy." At FDA's suggestion, the company added the statement that "when switching brands of drugs, additional costs may be incurred for office visits or monitoring." A disclaimer was added to the advertisement at the request of DDMAC stating that "price comparisons are not intended to compare effectiveness."

The FDA ad division has been asking sponsors to submit DTC ads for preclearance on a voluntary basis and reported 486 individual consultations for DTC promotions in 1995 in its recent budget justifications. In fiscal 1995, DDMAC issued a total of 624 advisory letters and held 46 advisory conferences but issued no warning letters, demonstrating a preference for working with industry to avoid enforcement actions ("The Pink Sheet" March 25, T&G-1).

In mid-April, DDMAC told Hoechst Marion Roussel that dissemination of an abstract reprint comparing Cardizem CD to Rhone-Poulenc Rorer's Dilacor XR would not meet FDA standards because the article did not describe the design of the study and comparison measures. HMR had requested review of the reprint in accordance with a court order that requires the company to preclear promotional materials that make comparisons to Dilacor XR.

DDMAC pointed out to the company that the article, which found that a 32% failure rate occurred when patients were switched from one diltiazem product to the other, was based on a literature review of dose-ranging trials. "Promotional materials are false and misleading if they contain representations or suggestions that a drug's safety or effectiveness is comparable or superior to that of another drug when it has not been demonstrated by substantial evidence," DDMAC told the company. "Due to the vague and ambiguous nature of the reprint, and in the absence of further information, DDMAC would consider the dissemination of this reprint to be misleading and violative," the agency said.

DDMAC suggestions led to a revision by Pfizer of its Cardura journal ads to read "JNC V includes," rather than "recommends," selective alpha1 blockers as initial monotherapy. In a Feb. 8 letter, DDMAC agreed that "alpha1 blockers as initial therapy is consistent" with the Joint National Committee on Detection, Evaluation & Treatment of High Blood Pressure-V report. However, the division emphasized that "JNC-V concluded that because diuretics and beta blockers have been shown to reduce morbidity and mortality, only they are recommended as first-choice agents."

In response to DDMAC comments, Merck altered its DTC ads for Fosamax so that the headline reads "If you have osteoporosis, now there's hope. Now there's Fosamax." The original headline of "Osteoporosis. Now there's new hope," suggested that Fosamax is indicated for prevention when it is only approved for treatment, DDMAC maintained.

In a February letter to the company, DDMAC also took issue with a statement in Fosamax patient materials calling it the "first treatment available that's proven to rebuild bone." DDMAC pointed out that Fosamax "is not the first treatment proven to rebuild bone."

The division also objected to the statement that "by strengthening bone, Fosamax reduces the risk of fracture," because it "implies that Fosamax is indicated to reduce the risk of fracture." DDMAC asked for revision of a section called "What are the results of treatment?" to include the statement that "while studies were not designed to detect fracture risk, predefined analyses support that Fosamax reduced vertebral fracture risk."

NeXstar had to discontinue its "Coming Soon" journal ads for its liposomal Kaposi's sarcoma therapy DaunoXome following a January letter from DDMAC. The division requested discontinuation of the journal ad after it became aware that DaunoXome labeling would include a boxed warning concerning severe myelosupression. "Sponsors may not use a `coming soon' ad for pre-approval promotion of drugs whose labeling contains or is likely to contain a boxed warning," DDMAC said. DaunoXome was approved in April ("The Pink Sheet" April 15, p. 11).

DDMAC advised NeXstar competitor Sequus regarding a telephone marketing campaign for its liposomal doxorubicin product Doxil, which was approved in December. The ad division concluded in a January letter that the telephone campaign to oncologists constitutes broadcast advertisement and therefore would require a statement of the major side effects and contraindications of the drug.

"This would have to be an integral part of the telephone message, not as a separate piece or mailing," DDMAC noted. DDMAC also said a brief summary of the side effects and contraindications would have to be faxed or mailed to the oncologists within two business days.