In response to the article by Stephen J. Playe, MD, entitled “Money Lies and the Dwindling Antibiotic Pipeline” in the July issue (2007;29:9) and having looked at the backdrop of evidence regarding Ketek, which he laudably cited from the April 19, 2007, issue of the New England Journal of Medicine, I am perplexed by what must be seen as an apologia on behalf of the manufacturer of this probably ill-advised drug.
Readers can, and I strongly advise them to, review the commentary by David Ross, a member of the FDA review committee in charge of the Sanofi-Aventis application for approval of telithromycin at the time it was considered, the downloadable interview with Dr. Ross, and the FDA defense statement published in the same issue. On the basis of this, I am confident that EMN readers will be able to judge for themselves whether this drug ever should have been approved for any indication.
I saw a patient in my ED a couple of years ago who was having non-life-threatening side effects to Ketek, which had been prescribed by an otolaryngologist for sinusitis. After reviewing the PDR insert on the drug, as posted on Micromedex at that time, I concluded that this drug should never be prescribed for anything but a life-threatening indication. At that time, no scandal regarding this drug was close to emerging into the public or peer-reviewed domain.
Dr. Playe suggested that the crackdown on Ketek potentially reflects unfair discrimination by the FDA against needed new antibiotics in the age of resistance in favor of high-priced, long-term therapeutics such as Lipitor. He perhaps ignored the fact that the need for new antibiotics has been generated largely by overmarketing by manufacturers to gullible practitioners of broad-spectrum agents for marginally important clinical indications, such as sinusitis, bronchitis, otitis, and sore throat.
Dr. Playe made note of one major fraud conviction connected to the data included in the pivotal study that led to the FDA approval of Ketek for a broad range of indications, including those currently targeted by national and international guidelines for curtailment of antibiotic use. He ignored the facts made clear by the New England Journal of Medicine articles and interview that he cites; namely, that this overtly fraudulent data, together with other data almost as certainly fraudulent, constituted a major portion of the study submitted by the manufacturer to the FDA to support approval of telithromycin.
He also ignored the fact, also documented in the cited sources, that the manufacturer was fully aware of the facts of this fraud, but admittedly elected to withhold its awareness from the FDA committee until called to account during the review process. Inadequate FDA funding (an escape hatch excuse apparently offered to the FDA by Dr. Playe) had nothing whatsoever to do with the breakdown in question, to the extent that it occurred. Contamination of data on this level is incompatible with a responsible approach to development and marketing of health care interventions affecting the lives and welfare of the public.
In the U.S., we seem to currently enjoy making examples of people and of companies by awarding hundreds of millions of dollars in settlements to victims whose financial burdens amount to fractions of those awards. Perhaps it is time that such examples be made of pharmaceutical manufacturers involved in fraudulent applications by just saying no to their products at the point of approval. Such penalties and examples might ultimately count for much more. Doubtless, Sanofi-Aventis has already recouped most or all of their potential losses on Ketek by their overmarketing of the drug during the years following its questionable approval. Suits from patients will be covered by insurance companies.
The issue of non-inferiority criteria as the basis of new antibiotic approval, made much of by the FDA and by Dr. Playe, has nothing to do with the issue posed by the Ketek debacle. The issue here was one of obvious and apparent research fraud. Fraud must be called fraud, and treated as such when it comes to health care.
Finally, and perhaps saliently, the patient that Dr. Playe describes as appropriate for Ketek, the one with the moderate but multidrug resistant pneumonia intolerant of beta lactam and quinolone antibiotic therapy, does not exist. Such a patient could not possibly be prospectively identified in the emergency department at presentation. I work in a tertiary referral center with an active and subspecialized pulmonary and infectious disease service. I treat patients with severe forms of pulmonary disease, complicated by infection that I have never heard of. It has yet to occur in my practice, even within this kind of sub-subspecialized practice setting, even in a patient with a severe lower respiratory tract infection for whom the relevant consultants recommended telithromycin. Maybe that's just me.
Taking Dr. Playe's commentary at face value, however, I strongly advise, regardless of the evidence of the Ketek debacle (as I view it), we, as a first-line interface between the public and the health care industry in this country, need to be very concentrated on our patients' actual immediate needs and be very careful about going out of our way to defend interests that may be completely orthogonal to theirs and therefore to ours. We better make very sure that it is, indeed, us that our patients can trust!
Peter Wyer MD
New York, NY
The authors are the principal investigators in the Olive View-UCLA Department of Emergency Medicine/Division of Infectious Diseases, and have been awarded a five-year, $9 million grant from the National Institutes of Health to study the use of off-patent antibiotics for treating uncomplicated skin and soft tissue infections. The study will be conducted at Olive View-UCLA, Johns Hopkins University, Maricopa Medical Center in Phoenix, Truman Medical Center and the University of Missouri in Kansas City, and Temple University Medical Center in Philadelphia.