David's New Book

Wednesday, September 15, 2010

Bronchitis - a Foot in the Door?

In discussing the FDA Guidance for mild infections with a highly placed FDA official recently, I discovered something new – an appreciation of reality.  The FDA realizes that no one has stepped forward to try and conduct trials in acute bacterial exacerbations of chronic obstructive pulmonary disease (COPD) since the superiority trials required are simply infeasible.  Of course, we do not need (mostly) a new antibiotic for these infections today – but who knows what we will need in 10-15 years.  During our discussion, the FDA official underlined the fact that the current guidance does not apply to severe exacerbation where patients are intubated, since they recognize that antibiotics play a lifesaving role in therapy and that withholding antibiotics from such patients is clearly unethical. But the Cochrane database suggests that even patients with moderate disease exacerbations will benefit from antibiotic therapy (http://www.ncbi.nlm.nih.gov/pubmed/16625602). Furthermore, the treatment effect of antibiotics overall was on the order of 50% for clinical endpoints and 23% for mortality.  A careful analysis of the database and additional attempts at examining antibiotic benefit in patients more moderately as opposed to very severely ill would be very helpful in this regard. 

Based on my discussions, I am looking for a volunteer sponsor.   They would need to do the appropriate literature research, propose an NI margin, provide a protocol synopsis and discuss a clinical trial plan with the FDA. Another option is for the FNIH group to do this work. 

But I believe the door to non-inferiority trials in acute bacterial exacerbations of COPD could be opening just slightly if we can make the right arguments. Are there any volunteers out there?