Saturday, November 20, 2010
The Infectious Diseases Society Sounds Off on the FDA and Skin Infections
Well, boys and girls, it looks like at long last, the Infectious Diseases Society of America (IDSA) has taken off the gloves. I guess they are now as frustrated as the rest of us with the FDA’s inability to provide a clear and feasible path forward for antibiotic development. Their frustration takes the form of comments (you have to scroll down to the IDSA Comments section in this link) to the FDA’s latest guidance on clinical trial design for studies of acute bacterial infections of the skin and skin structures. This is ironic, because I was just relieved that we finally had guidance that proposed, at least, a feasible design. But the IDSA has a number of critical comments.
First, they note that in their view, “ There is no doubt that the lack of clear and feasible FDA guidances has contributed in a significant way to the growing crisis (of our poor antibiotic pipeline in the face of growing resistance).” Their first specific criticism is of the crazy estimate of the treatment effect (M1) of antibiotics for skin infections of 12%. As I explained in a previous blog, they use excessively conservative estimates and pseudoscientific discounting to arrive at this preposterous figure. Luckily, in discussions with sponsors, they have been ignoring their own calculations, probably because trials based on the assumption of a 12% treatment effect would still be infeasible.
The IDSA then takes aim at the proposed endpoint of cessation of spread of the lesion at 72 hours arguing that since even the sulfonamides worked 99% of the time, such an endpoint would not discriminate among different therapies. They also note that for the practicing physician, this is a completely irrelevant endpoint. The IDSA proposes a much more rational endpoint of clinical cure encompassing mortality at 28 days.
They also take issue with the lesion size requirement (>75 cm2) since that has never been validated anywhere. The IDSA takes the FDA to task in a number of other specific areas of the guidance as well. They take aim at the use of the Snodgrass trial comparing sulfonamides to UV light from the 1930s as the modern totem to which all trials must compare.
As I noted, this is the most aggressive stance I have seen by the IDSA vis a vis the FDA. I guess that I have become so numb over the years that I was just grateful to have a trial that I thought industry could actually accomplish. But the IDSA wants more. They want the FDA to withdraw from the guidance their crazy stance on margins even though the FDA accepts margins larger than what they propose. I suspect that the FDA’s proposal was more for political consumption than for sponsors. See my blog on Markey and Grassley.
IDSA – Kudos! And welcome to my world of fantasyland where science and the rational approach to solving problems disappears in the face of politics and pseudoscience. I only ask that as you and the FDA continue to work on issues of guidance for the study of antibiotics, you keep one concept in mind above all – feasibility.
FDA – these are the US physician experts in infectious diseases laying down the gauntlet. They are telling you that your approach to regulation of antibiotics has been misguided and inappropriate. What are you going to do about it?
Next on this blog – Otitis and Antibiotics – Round 2.