Commentary Explores FDA Reboot: What Brought it on, What’s Being Done


CONTACT: Jim Sliwa


WASHINGTON, DC – August 29, 2013 -- The increasing public health threat posed by continuing rise of antibiotic resistance combined with inadequate development of new antibiotics is largely the fault of the U.S. Food and Drug Administration (FDA) according to a commentary published ahead of print in the journal Antimicrobial Agents and Chemotherapy. But fortunately, write the authors, the agency now understands the problem and is working to address it.


The commentary, written by a group of prominent microbiologists including lead author David Shlaes of Anti-Infectives Consulting in Stonington, CT, and author of the book Antibiotics: The Perfect Storm, examines the FDA’s May 2012 announcement that the agency would reboot their entire approach to antibiotics, analyzing how they got to that point and what they have done since.


The problem began with a rethinking of clinical trials, catalyzed by a group of “radical skeptic statisticians who doubted whether antibiotics were actually effective for bacterial infections,” despite the fact that absent resistance, antibiotics are among the most effective medications, says coauthor Brad Spellberg, of Harbor-UCLA Medical School, Los Angeles. The situation was aggravated in 2006, when a recently approved drug, telithromycin, was found to cause a very rare but life-threatening liver toxicity, leading FDA to further tighten its regulations for clinical trials of antibiotics.


The new rules and regulations rendered clinical trials for antibiotics virtually impossible to conduct, and prohibitively expensive, according to the commentary authors. For example, regulations barred patients from taking part in clinical trials if they had taken antibiotics prior to enrollment. It would be dangerous and unethical to leave desperately sick patients waiting six hours—the average time it takes to enroll a patient into a clinical trial—to begin treatment, according to Spellberg.


Other regulations, having to do with a mandate to use statistical methodology that was based on a 1937 study, boosted costs by doubling the number of patients needed to satisfy the statistical exigencies, says Shlaes. That problem was worse than it might have been for other drug classes, because the return on investment for antibiotics is already the lowest in the world of drugs, due partly to their success. Unlike drugs for blood pressure, cardiovascular disease, diabetes, arthritis and so many other maladies, which must be taken for years, if not for life, antibiotics generally cure the patient within a few weeks, says Spellberg. Plus, they are priced lower than other classes of drugs.


When the FDA the announcement in May 2012 the agency acknowledged that its own changes in clinical trials design had contributed to the crisis and going forward emphasized the need for a new pathway for development focusing on patients with unmet medical needs—that is, those with infections due to pathogens that are pan-drug resistant or that are extremely drug resistant.


Nonetheless, the FDA has yet to provide much in the way of specifics on changes in regulations for drug development, say the authors, although just two days after they submitted their commentary the FDA released a guidance document on antibacterial therapies for patients with unmet medical needs.


“They are trying to turn themselves around,” says Shlaes. “But we want them to do that quickly. We need to make sure companies can get a good return on investment.” The current crisis “is not just a regulatory problem.”


“We hope that value-based pricing and a rebooted FDA process will both come to pass,” the authors conclude in the commentary. “The alternative is too terrible to contemplate.”


The commentary represents the opinions of the authors and does not necessarily reflect the views of the journal or the American Society for Microbiology.


 A copy of the manuscript can be found online at  Formal publication is scheduled for the October 2013 issue of Antimicrobial Agents and Chemotherapy. 


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Antimicrobial Agents and Chemotherapy is a publication of the American Society for Microbiology (ASM).  The ASM is the largest single life science society, composed of over 39,000 scientists and health professionals. Its mission is to advance the microbiological sciences as a vehicle for understanding life processes and to apply and communicate this knowledge for the improvement of health and environmental and economic well-being worldwide.