As background, I highly recommend viewing the video of the presentation by Ellenberg presented at an NIH conference on trial designs for emerging infectious diseases. It is very informative. The statistical problems for such trials are numerous but hinge on the following assumption that we must try and meet/validate – that the distribution of patients with good vs. poor prognoses are the same in the experimental and control groups. This is a key basis for preferring a randomized trial. In designing trials to address rare infections, rare pathogens, and pathogen-specific indications, the patient numbers may not be able to support a randomized design. We might not even be able to achieve statistical inference with an externally controlled design – but, in my view, this is where we will have to go. According to the paper by Byar (requires subscription) and later Elllenberg, an externally controlled trial design can be justified if the following conditions can be met . .
- ·Get your PK/PD house in order. If you buy the UDR vs. XDR argument from the previous blog, then we can use PK/PD to show that pathogens resistant to comparator agents will be effectively treated by our experimental drug. .
- o Have clearly and adequately designed PK/PD targets.