Very important story by Steve Usdin in this week's edition of BioCentury.
The first paragraph sets the stage:
"FDA's rejection of Replidyne Inc.'s farapenem medoxomil has removed nearly all doubt the agency has resolved a long-running internal debate over the acceptability of non-inferiority studies to support efficacy in most community-acquired bacterial infections. But the absence of agency guidance forces developers to guess what protocols might work, a burden industry may not choose to take on despite the fact that the U.S. spends $8.5 billion on oral antibiotics in the U.S. annually."
And further ...
"The agency's action reflects arguments that the effectiveness of comparator antibiotics has not been established against placebo, making a non-inferiority result of doubtful value. And with the exception of CAP (community-acquired pneumonia), where the role an antibiotics isn't questioned and where FDA will still accept non-inferiority studies, the other indications are self-limiting, and thus the urgency to treat is said to be lower."
Many issues here, not the least of which are the ethical implications. As Usdin points out, "By requiring superiority trials in ABS (acute bacterial sinusitis) and AECB (acute exacerbation of chronic bronchitis), FDA has taken sides in a debate among clinicians, academic researchers, politicians and industry over whether it is necessary, ethical, or possible to conduct such trials."
On one side is Donald Poretz, Georgetown School of Medicine and a member of the FDA's Anti-Infective Drugs adcomm, "For years we thought is was unethical to do placebo-controlled trials in sinusitis, bronchitis, and otitis media, but now it seems it is ethical" ... because it isn't clear that antibiotics are helpful.
On the other side, James Hadley, University of Rochester Medical Center and past president of the American Academy of Otolaryngology, "It is very difficult in the U.S. under current law and regulations, and with IRBs that regulate clinical trials to offer a placebo to patients in view of an active disease process."
Show me the guidance!
The first paragraph sets the stage:
"FDA's rejection of Replidyne Inc.'s farapenem medoxomil has removed nearly all doubt the agency has resolved a long-running internal debate over the acceptability of non-inferiority studies to support efficacy in most community-acquired bacterial infections. But the absence of agency guidance forces developers to guess what protocols might work, a burden industry may not choose to take on despite the fact that the U.S. spends $8.5 billion on oral antibiotics in the U.S. annually."
And further ...
"The agency's action reflects arguments that the effectiveness of comparator antibiotics has not been established against placebo, making a non-inferiority result of doubtful value. And with the exception of CAP (community-acquired pneumonia), where the role an antibiotics isn't questioned and where FDA will still accept non-inferiority studies, the other indications are self-limiting, and thus the urgency to treat is said to be lower."
Many issues here, not the least of which are the ethical implications. As Usdin points out, "By requiring superiority trials in ABS (acute bacterial sinusitis) and AECB (acute exacerbation of chronic bronchitis), FDA has taken sides in a debate among clinicians, academic researchers, politicians and industry over whether it is necessary, ethical, or possible to conduct such trials."
On one side is Donald Poretz, Georgetown School of Medicine and a member of the FDA's Anti-Infective Drugs adcomm, "For years we thought is was unethical to do placebo-controlled trials in sinusitis, bronchitis, and otitis media, but now it seems it is ethical" ... because it isn't clear that antibiotics are helpful.
On the other side, James Hadley, University of Rochester Medical Center and past president of the American Academy of Otolaryngology, "It is very difficult in the U.S. under current law and regulations, and with IRBs that regulate clinical trials to offer a placebo to patients in view of an active disease process."
Show me the guidance!
