It’s All About “Substantial Evidence” for DDMAC

August 14, 2007

In two previous posts (here and here), we reported on a trend in Warning Letters issued by FDA’s Division of Drug Marketing, Advertising, and Communications (“DDMAC”) that focuses on ensuring that promotional pieces contain substantial evidence to support advertising claims and proper presentations of safety data.  In an August 10, 2007 article published by the Washington Legal Foundation, and titled “Recent Warning Letters for Ads Reflect FDA’s Fixation on ‘Substantial Evidence,’” former FDA Associate Chief Counsel Arnold I. Friede drives home the point that to avoid problems with DDMAC, companies need to pay attention to providing substantial evidence to support all advertising claims, and in particular comparative claims.  Mr. Friede comments that:

The recent DDMAC compliance correspondence should be studied closely by companies and practitioners to provide a first hand sense of how FDA applies the “substantial evidence” standard to specific advertising and promotional claims for prescription drugs. But the overall message is simple relatively straightforward: If you want to avoid problems with DDMAC, insure that claims in prescription drug advertising and promotion are supported by “substantial evidence,” no matter how competent and reliable the supporting evidence might otherwise be to the company and to leading experts in the field. To put it bluntly, DDMAC doesn’t really care.  What DDMAC cares about is like “location,” “location,” “location” in the real estate purchase context. It’s about “substantial evidence,” “substantial evidence,” “substantial evidence”.

So whether we like it or not, or whether we think it is unconstitutional or violates the [Administrative Procedure Act] or is otherwise illegal or not, for those who seek to avoid an unpleasant compliance confrontation with DDMAC, “substantial evidence” should be the watchword.

As if to reinforce this conclusion, on August 13, 2007, DDMAC posted a Warning Letter issued to Pfizer on July 16, 2007 concerning certain promotional materials for GEODON (ziprisadone mesylate) Injection.  GEODON is approved for the treatment of acute agitation in schizophrenic patients for whom treatment with ziprasidone is appropriate and who need intramuscular antipsychotic medication for rapid control of the agitation, and includes a black box warning concerning increased mortality in elderly patients with dementia-related psychosis.

DDMAC’s Warning Letter objects to Pfizer’s omission of important risk information (e.g., the failure to communicate certain warnings and precautions associated with Geodon) and to an unsubstantiated superiority claim.  Specifically, with respect Pfizer’s claim that there are “[p]roven advantages over haloperidol [intramuscular] ―twice the improvement as measured on the [Brief Psychiatric Rating Scale],” DDMAC comments that:

This presentation is misleading because it implies that Geodon for Injection is more effective than haloperidol [intramuscular] when this has not been demonstrated by substantial evidence or substantial clinical experience. The single study cited for this claim was an open-label study, which is not an appropriate study design to evaluate subjective endpoints, such as those measured by the Brief Psychiatric Rating Scale anchored version (BPRS), because of the potential for evaluator bias. In fact, FDA is not aware of any substantial evidence to support this claim. If you have data, please submit them to FDA for review. Of interest, in the clinical trials submitted to the NDA for Geodon for Injection, the BPRS was not used and there were no active comparators.

Certainly “substantial evidence” is the DDMAC watchword for now and for the foreseeable future. 

Indeed, as we were drafting this post, DDMAC updated its Warning Letter webpage with a yet another Warning Letter objecting to ubsubstantiated superiority claims.  The letter, issued to Novartis last week, cites certain statements in promotional materials for EXELON (rivastigmine tartrate) Capsules and Oral Solution that are misleading “because, on the basis of an inadequate study, it suggests that Exelon is superior to donepezil [(ARICEPT)] in patients with mild-to-moderate Alzheimer’s Disease who have not responded to donepezil.”

Categories: Enforcement