Biotech Values

[iwfal]

XOMA - further thoughts on potential confounding from site physicians not ramping down corticosteroids as per plan.

The biggest risk to XOMA that I can think of is that most of the benefit to Gev is during that down ramp in steroids and the physicians are, understandably, trigger happy I that period. So the placebo exacerbations get censored - leaving the easy to treat patients in the placebo arm and the tough to treat patients in the Gev arm. With the result of a not very nice apparent Gev benefit in those remaining patients.

Were I XOMA I'd go back to the FDA before unblinding and point out that their endpoint is clearly not Standard of Care and they should consider a change in the endpoint to something more closely approximating SOC. The FDA *might* be receptive for several reasons:

1) the FDA generally likes to have the placebo arm get SOC for a variety of reasons.

2) the FDA might be more lenient than typical because it is an ultra orphan.

And even if the FDA doesn't allow it, they will undoubtedly be more lenient in the post hoc if the post hoc is precisely what you suggested as the change in SAP.

BTW - ill state again this is a very newbie mistake. My guess is a large fraction of the people on this board would not make this mistake (the benefits of watching 100s of trials). And >>100 other companies before them have learned that to run a good trial you need to take away a lot of site MD discretion. Central adjudication. Air tight protocol. Explain personally to MDs the consequences to the patient population if there are violations that tank the trial.

BTW2 - the scenario I gave above would be easily detected by looking at the ratio of (censored uveitis exacerbation)/(censored uveitis exacerbation+protocol uveitis exacerbation) over time. If it gets substantially lower over time there is a moderately large risk of the above IMO.