July 23, 2012 –Michael Sauers, team leader (DTC1) at the FDA’s Office of Prescription Drug Promotion (OPDP), held a workshop at the DIA 2012 Annual Meeting that walked attendees through actual examples of where promotional materials for pharmaceutical products fell short of meeting FDA requirements.

During this interactive DIA workshop, “Prescription Drug Marketing Regulatory Primer,” held June 27 in Philadelphia, Sauers provided some basic tenets of prescription drug promotion regulation and then led the audience through a sampling of promotional pieces that the agency found to have violated the regulations.

For example, in describing omission of risk information – a violation commonly cited in OPDP Warning Letters and Untitled Letters – Sauers showed DIA session attendees a promotional flyer for ISTA Pharmaceuticals’ BROMDAY, which was cited in a July 13, 2011, Warning Letter. Although the flyer making claims regarding the use of Bromday in cataract surgery discloses the most common adverse reactions associated with that use, it does not reveal any of the warnings and precautions for the drug.

Promotional materials that make product claims must also provide risk information, according to Sauers, who noted that this risk information should include contraindications, warnings, precautions and pertinent adverse events. Further,

even though the Bromday flyer included the statement, “Please see full prescribing information on reverse,” that reference does not fulfill regulatory requirements, Sauers explained.

In discussing problems with the presentation of risk information, he presented a stall cling for GELNIQUE – cited in a Nov. 30, 2010, Untitled Letter to Watson Pharmaceuticals Inc. – to demonstrate that formatting factors, including the shape, size and general layout of presentations in a piece, are important in achieving adequate risk presentation. The Untitled Letter cited the company for relegating the risk information “to the bottom of the piece and written in white text on a purple background in an extremely small font size and in single-spaced paragraph format, making this information very difficult to read.” In describing how risk information should be adequately conveyed, Sauers also indicated that framing and sequence are important.

Sauers made it clear in his presentation that oral statements not made in response to a request for such information from a physician can be problematic if they discuss unapproved uses. For example, he cited oral statements made by a physician on behalf of Merck & Co. Inc. regarding the company’s SAPHRIS at a lunch presentation. Saphris is approved for schizophrenia and bipolar disorder, but the speaker stated that he prescribes the drug as an adjunctive treatment for major depressive disorder (MDD) and that it works just as well.

Promotional materials should not suggest that a drug is safe and effective for conditions or patient populations that it is not approved to treat, according to Sauers, nor should they suggest that a drug treats outcomes or consequences of a disease if the drug has not demonstrated such an effect on those outcomes or consequences. He added that claims of superiority generally must be supported by adequate and well-controlled head-to-head comparative studies.

Further, claims about efficacy and safety in promotional materials must be consistent with the PI and be supported by substantial evidence derived from adequate and well-controlled studies, Sauers asserted. To illustrate the substantial evidence requirement, Sauers showed attendees a Noven Pharmaceuticals Inc. flash card for PEXEVA.

This marketing piece, cited in a May 24, 2011, Untitled Letter, misleadingly implies that Pexeva is effective in treating patients with co-morbid MDD and generalized anxiety disorder (GAD), when this has not been demonstrated by substantial evidence or substantial clinical experience, the Untitled Letter states: “While Pexeva is indicated to treat MDD and GAD individually, no clinical studies demonstrated efficacy

of Pexeva in treating patients experiencing these two conditions concurrently.”  

Overstatement of efficacy – often conveyed through testimonials or imagery – also is a violation that is commonly cited by OPDP. Sauers’ presentation made it clear that patient testimonials and individual case studies may be an accurate reflection of one patient’s experience, but that alone does not constitute substantial evidence.