Two days ago, we examined the number of enforcement actions by DDMAC and yesterday we looked at what tripped regulatory wires to result in a Notice of Violation (NOV) letter. Today, we're going to look Warning Letters and examine some of the salient issues.
- August – A journal ad for a product claimed efficacy percentage rates by stating the most favorable result for the product and ignoring placebo results when the difference between the placebo and the treatment results was actually a much smaller effect. That was one strike – an overstatement of efficacy. There was also a failure to fully disclose risk. Even though the manufacturer included information from the Warnings and Precautions section, they did not include the Drug Interactions information.
- Another Warning Letter went out in August for multiple violations involving professional visual aids. Here DDMAC found that the promotional materials talked about a possibly improved outcome if the product were combined with a procedure, in spite of the fact that this was not part of the PI. In addition, the material presented information about 52 week use, even though the product was indicated for short-term, non-maintenance use. While the material did state that the product was not for maintenance, the information was contained on the reverse side the aid, not on the side where the indication was being stated. Further, by truncating the risk information considerably, particularly by failing to spell out the whole effect against which there was warning. Then, by using before and after pictures that were not considered a typical response, DDMAC felt there as an overstatement of efficacy. And lastly, the manufacturer used an unapproved PI.
- August was a busy month. A professional direct mailer was cited by DDMAC for recommending use for the product for which the drug had not been evaluated, for minimizing risk and presenting unsubstantiated superiority claims. With respect to the first, the subject matter of the mailer regarded treatment for a specific pain condition for which the product had not been evaluated, though it had been approved for something not too far off in the way of pain. The product was an NSAID, after all. But as well, the printed material stated that the onset of the product was faster than other products – which would be difficult to say if the product was not approved for the indication, resulting in the unsubstantiated superiority claim. Perhaps of equal interest is that the company was cited for an omission and minimization of risk information because omitted was highly specific language about the potentially fatal risks associated with use of COX-2 selective and nonselective NSAIDS.
- September – Two Web pages were cited in about a product for failing to include any information about the risks of the product. And apparently it was not the first time. Enough said.
- Two Video News Releases (VNRs) – regarding a product with abuse potential and which has a boxed warning were the subject of a Warning Letter for failing to include risk information. Here, while risk information was included, the aspects of the potentially fatal risks were not while at the same time, there were representations in the pieces about the products innovative technology. In other words, higher praise, lowered risk.
- November – A quadruple whammy went to one manufacturer for a brochure that was found to omit risk information, make unsubstantiated superiority claims, overstate efficacy and to broaden the indication. First of all, in spite of the fact that there were several classes of patients for whom there were precautions against use, there was no risk information in the brochure, even though the brochure was aimed at patients (though in fairness, the brochure was intended for people already on the drug). The superiority claim was pretty obvious.
- A Patient Profile Card was found to omit and minimze risks and to overstate the efficacy of a product. The overstatement resulted from a claim that a certain percentage of patients saw a response when treated, but the references that supported the claim showed that this was in a subgroup analysis where the patients studied were the most likely to benefit, thus the response might not be seen as typical. There were a host of other patient claims, such as patients getting the energy to perform tasks they didn't before – something not in the label. With respect to the risk information, while there was such information included, the potential fatal events and other highly important risk information.
It should go without saying, but the inclusion of risk information is essential and is not a new requirement. But especially where risk information includes potentially fatal risks, omitting it is bound to catch DDMAC's attention. When there is a boxed warning, the conveyance of risk information is especially important, even though execution in a promotional piece may be very challenging. And, as learned in yesterday's NOV letter review, you cannot put that information anywhere other than in proximity to the place where you are making clear the indication and your claim.
Also, one can see from the multiple violations contained in a single piece, or continued or on-going violations, or minimizing risk when the risk includes potentially fatal incidents, or any combination thereof, tends to result in a Warning Letter, as opposed to an NOV.