The FDA Can Change Its Requirements After Completion of a Trial and then Require New Trials for Approval

Another really interesting development at the FDA is the policy that they can change their minds about previous agreements. In the old days, maybe even up to 7 years ago or so, if you had a discussion with the FDA on your trial design and they agreed with it in writing, they would not reject your data because they had come out with new policy requiring a different design. This is important. A company will pay about 30 million for a single Phase III antibiotic trial. To get approval, you need to...

Pneumonia The New Frontier New Trial Requirements for Pneumonia Will Make Approval Much More Difficult and Costly and

Along the same lines as their inquiry on otitis, sinusitis and bronchitis, the FDA recently examined the role of antibiotics in pneumonia. Those of us in the infectious diseases community held our collective breath waiting to see if the FDA would decide that they did not understand whether antibiotics had an effect on bacterial pneumonia. To us clinicians, that antibiotics have a dramatic beneficial effect in the treatment of pneumonia was obvious and well proven by our own personal experiences...

Mild Infections Require Placebo Controlled Trials Industry Balks

Otitis media or middle ear infection might be the clearest example. These are the typical ear infections occurring mainly in childhood starting at around 6 months of age. Otitis media is painful and for many years clinical practice in the US was to treat them with antibiotics in the belief that killing the bacteria that cause the infection would result in more rapid relief of pain and would prevent potentially serious complications. Many parents in the US have had the experience of taking their...

The Perfect Storm

On the antibiotics front, the weather has occasionally been bad ever since I can remember. But things have never been as bad as they are today. Bacteria are becoming resistant to the point where none of our available antibiotics work for some of the infections that confront patients and physicians in hospitals around the US and the around world. For these patients we are slipping back in time to a pre-antibiotic era where we have little to offer but comfort for diseases which we have been...

Antibiotics Are Not Financially Attractive in the Consolidated Industry

The companies remaining after this massive consolidation were much larger. This means that to drive an increase in their bottom lines from year to year, their revenues had to increase by much larger amounts. For example, lets take the giant that is about to be formed with the purchase of Wyeth by Pfizer. Pfizer had 48.3 billion in revenues in 2008. Wyeth earned 22.8 billion. The combined company will therefore have revenues of something on the order of 60B. These revenues will have to grow for...

Do We Want New Antibiotics for Mild Infections Is Bacterial Bronchitis in the Setting of Chronic Lung Disease a Mild

The FDA and Europe could make an enormous difference immediately. First, for mild, acute infections like otitis, sinusitis and bronchitis, they need to reconsider their entire approach. For example, for otitis, where most authorities agree that expectant therapy is a reasonable approach, placebo-controlled trials remain difficult to accomplish, especially in the US. Guidelines from the American Society of Pediatrics suggest that patients with severe symptoms, those age 2 or less and those where...

Our Communities are Not Spared

We all agree that hospitals are to be avoided if possible. Are we safe from antibiotic resistance in the community Most of the antibiotics that we use every year for human health are used in our communities. The principle of you use it, you lose it therefore would predict that our communities would not be spared either. Let's look at a common cause of urinary tract infection (UTI) in our communities, E. coli. This is a normal inhabitant of our intestinal tract that occasionally gets somewhere...

Biotech Is Still a High Risk Proposition

For every biotech success story like Cubist, there are many less happy stories. Some experts estimate that only 10 of biotech companies will succeed. One example of the other 90 is Replidyne, of Louisville, Colorado. Replidyne started with technologies for finding new antibiotics, but then realized that it too needed a near term product to attract investor capital. They licensed an antibiotic from Glaxo Smith Kline that could only be developed as a topical product. This was not sufficient to...

Antibiotics Form a Cornerstone of the Pharmaceutical Industry

The pharmaceutical industry has its origins in the folk remedies of ancient times. Our first historical records of this activity come from the ancient civilizations of Asia. Apothecaries were established during medieval times especially in Europe. Most of the modern pharmaceutical companies or their precursors were established in the nineteenth century. These small companies and even individual producers commercialized, to various levels of scale, products thought to benefit health in one way...

Industry Takes a Risk Averse Approach to Its Clinical Trials but Deprives Us of the Most Important Information

While I think that the pressure on those companies still committed to antibiotic research is enormous, I feel compelled to pile on The example I am going to use for this critique comes from clinical trials conducted by industry for drugs to treat resistant Gram positive infections like MRSA. As you have read earlier in the book, vancomycin has been a real workhorse antibiotic for the treatment of MRSA infections in our hospitals. At the same time, there have been a number of scientific and...

The FDA Increases Clinical Trial Design Stringency and Costs Companies Abandon Antibiotic Research

In 1999, I was working at Wyeth Pharmaceuticals. Wyeth had discovered a new chemical series of tetracycline derivatives that was active against a variety of resistant bacteria including those resistant to the tetracyclines. We were getting ready to enter the last (and most expensive) stage of clinical trials prior to submitting our request for marketing approval. We followed the FDA guidelines in designing our trials. They allowed us to set the statistical stringency of the study, within...

The Ketek Scandal

As I noted earlier, there are lots of antibiotics, including penicillin, approved for otitis, sinusitis and bronchitis based on the old approach (comparative rather than placebo-controlled trials). Some of these older antibiotics even have some level of toxicity. According to the FDA's own calculus, these products have a risk benefit ratio of zero since their benefit has never been shown using superiority or placebo-controlled trials. Has the FDA moved to remove marketing approval for these...

The Miracle

The history of antibiotics goes back to mercury and bismuth, heavy metals which are toxic to people, but in correct doses, were more toxic to the organism that causes syphilis, Treponema pallidum. Mercury as a therapy for syphilis was first discussed back in the 1400s, but the heavy metals were not widely used until the end of the nineteenth century. Whether they were efficacious or not is not entirely clear since no systematic studies like those we use today were carried out in those times....

In Our Hospitals Things Are Getting Critical

Cdcp Resistant Strains Spread

The chart from the Centers for Disease Control (Fig. 3.2) shows the increase in multiply resistant staph (MRSA), enterococci (VRE) and Pseudomonas aeruginosa (FQRP) over the last 30 years in US hospital intensive care units. The ICU is the last place we want to see very resistant pathogens, and yet this is where they seem to be the most frequent. Table 3.1 below shows the latest data from the Centers for Disease Control on frequency of resistance of these and other pathogens to key antibiotics....

How About a Totally New Approach to Drug Development

A few years ago, I worked with the Manhattan Institute on providing a way for the FDA to deliver on its own critical path initiative where the FDA proposed a new paradigm for drug development. The new paradigm was based on the new genomic science where toxicities and efficacy could potentially be tailored to individual patient-drug combinations if we could know the exact site(s) of action of the drug (which we will probably never really know up front) and the exact genetic nature of the patient...