Friday, September 3, 2010


Watershed or Waterloo

In a previous blog, Watershed or Waterloo, I discussed the upcoming September 7 FDA Anti-infectives Advisory Committee (AIDAC) meeting on Forest/Cerexa’s antibiotic, ceftaroline.  I noted that the data presented by the company either in abstract or in publication form was impressive and robust. Well, the briefing materials for the meeting have just been released to the public by the FDA (FDA briefing document ceftaroline) and they indicate that the FDA agrees with me and with Forest/Cerexa that the data are, in fact robust, no matter which way you analyze them. It looks like the FDA will agree that their endpoints correlate well enough with the new early endpoints proposed for pneumonia and skin infections that they will be satisfied with these data. So, I think it is likely to be watershed rather than Waterloo, but I’ll be watching on September 7.


The infectious diseases society has recently sent a letter to Janet Woodcock of the FDA regarding the development of new antibiotics for resistant bacterial infections. In their letter, they correctly note that current clinical trials guidance fails to meet the needs for new antibiotics active against our most difficult resistant pathogens.  They urge the FDA to focus on this problem.  They further suggest that one approach might be to establish a consortium of centers, perhaps through the NIH, where there are higher populations of patients infected with such pathogens such that clinical trials can be practically executed.  My own view is that this will require that the FDA go back to Mark Goldberger’s suggestion from 2002 – use a low quantity of high quality patients.  If the FDA would be willing to allow salvage studies of small numbers of patients where the studies would not really be statistically powered, and then add other supporting data such as in vitro data and non-clinical and clinical PK/PD studies, we might be able to get somewhere.  This was the essence of Mark’s suggestion (which got nowhere). While I think the IDSA is once again to be commended for their efforts, it will be important to keep the discussion sharply focused on feasibility.

Government and Roadblocks

While catching up on journals over the past month, I ran across a wonderful Perspective from the New England Journal on government roadblocks to comparative effectiveness research.  Having worked for the VA for many years, the article immediately caught my eye. The authors, Martin et. al., discussed the example of trials of Avastatin compated to  ranibizumab in the treatment of “wet” age-related macular degeneration (AMD).  These trials became necessary because ranibizumab had an extremely high cost whereas Avastatin, which had a similar mechanism of action, was much less costly. The National Eye Institute jumped into the void and approved monies for such a trial. The cost to Medicare for ranibizumab alone for the trial would have been on the order of$25 million. Medicare initially refused to cover this cost. Medicare also would not pay the copay (20%) that would be required for trial participants who did not have supplemental insurance and who received ranibizumab. The grant did not cover this cost. Finally, the National Eye Institute was able to identify a mechanism to provide funds for these costs – but the trial was delayed for over a year. Then the investigators ran into the problem of masking drugs (for a blinded trial) so that neither patients nor physicians would know who was getting what.  But with billing systems, this became impossible. The trial finally got underway but enrollment was slowed by the cobbled together payment and blinding systems. None of this gives one confidence that antibiotics trials run by the NIH where elderly patients will be treated with approved drugs will do any better.

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