David's New Book

Friday, July 8, 2011

Current Regulations Distort the Competitive Environment for Clinical Trials


I have recently been thinking about the number of small companies trying to develop antibiotics.  They are all pursuing indications like skin infection, urinary tract infection (UTI) and intraabdominal infection (IAI) since trials in pneumonia are not feasible in the current FDA environment and trials in mild bacterial infections such as otitis media, acute bacterial sinusitis and acute bacterial exacerbations of COPD are not feasible under the aegis of either EMA or FDA.  But this means that in order for companies to just get their product on the US market, they must be approved in skin, UTI or IAI even if their product might be very well suited for use in respiratory tract infections.  It seems to me that the most egregious distortion of the competitive environment for trials will occur for skin infections, but UTI and IAI will not be spared.

What this means is that everyone about to pursue phase III trials in the US will be ignoring respiratory infections and studying their antibiotic in one of these indications. The trial sizes will be large since most of these indications will require non-inferiority trials with a 10% non-inferiority margin leading to trial sizes (for two trials) of 12-1600 patients. I am beginning to question whether there is enough capacity globally to carry out the number of such trials that I see coming forward in the near future – especially for skin infections. I think that the availability of indications like pneumonia and other respiratory infections would take at least some of the pressure off these other indications in terms of patient numbers.  In addition, of course, the area of greatest medical need today is for agents to treat patients with hospital acquired pneumonia, which is the very area where no one will be going at least with the FDA.

This distortion of the antibiotic clinical trial environment will have several consequences.  It may take longer to enroll these large trials since there will be more competition for the same patients.  Companies will be forced to go to countries where there may be less experience in trials simply to compensate for the loss of centers to competition in more experienced countries. Trials may become more expensive since they will have to enlist additional centers to improve enrollment rates.  Some centers may take advantage of the competitive environment to increase their rates further adding to the additional expense.

I think that this is an area of concern that has not received much attention anywhere. But for those considering such phase III trials, especially those smaller companies trying to embark on phase III, I believe that this distortion in the competitive environment for trials will be an important problem in the next several years.