What the FDA told the Makers of Ditropan XL

Well, it seems Ditropan XL even had this seasoned critic snookered. When I reviewed their website, I pointed out areas of inconsistency. But the FDA, with access to the unpublished clinical trials, took an even stronger view.

On April 2, 1999, the FDA wrote to the Regulatory Affairs Director at Alza Corporation and charged that their promotional literature violated the Federal Food, Drug and Cosmetic Act for "Omission of Material Facts" and "Overstatement of Efficacy", and demanded immediate discontinuation of the offending literature.

In reaching their conclusions, FDA relied on information that is not available to the general public [Clinical Trial C-95-031]. Alza had said "Clinical studies show that people taking once-a-day Ditropan XL were able to reduce the number of wetting accidents by up to 90%".

But, as the FDA reminded Alza, the only people involved in this unpublished study of time-release medication were people who were already shown to be responsive to the plain version of Ditropan! FDA thinks that constitutes a "omission of material facts". In fact, according to the same FDA letter, Alza also failed to mention that patients who received a placebo had a 51% reduction in wetting accidents. This represents an improvement of only 34% better symptom reduction than a sugar pill.

In addition, the FDA accused Alza of "overstatement of efficacy" for saying "Help take control…Simply, Confidently", "Once-a-day confidence", and "…you may be able to go where you want to go and do what you want --- without the constant worry of finding a bathroom". FDA says these statements are "misleading because they suggest that Ditropan XL is more effective in treating overactive bladder than has been demonstrated." In fact, says the FDA, patients still had "1.5, 4.8, and 2.9 leaks per week" in the trials. "Therefore," they wrote, "these claims suggest a level of efficacy that is not supported by substantial evidence."

The weighted average of these FDA-cited studies is about 3.0 leaks per week. But there is a further discrepancy which is yet unresolved. The FDA letter appears to based on the current version of the Ditropan XL website and literature. But the December 1998 website and the "Edition 12/98" version of Alza's "000008465-0" labeling report show leakage reductions of "15.8, 17.6, and 14.5" respectively, for a weighted average remaining of about 5.1 leaks per week -- almost twice as bad as the 3.0 leaks that the FDA already said did not substantiate their claims. Which Alza version are we to believe? The 12/98 labeling was distributed with the "Take Control" ad campaign this spring.

Alza was order to discontinue the use of such materials and "all similarly violative promotional materials", and to inform the FDA of remedial actions by April 16, 1999.

[FDA notification letters are available under the Freedom of Information Act on the FDA's website: http://www.fda.gov, but only in Acrobat reader ("pdf") format.]