RE: Clinical Trial19 Apr 2018 11:07
@4jams
Here is a response from pharmagilles.....
I posted the below on the iii BB on the 9th of Feb 2018 (and still on there). I�m reposting now just to say that if someone working in the industry, who rarely posts, is trying to give warning signals it�s probably worth considering as a red flag. I recall this was reposted by someone on this site and called �fake news�? A little strange as all was factually correct.. All is dependent now on whether the trial is successful. As this is a Phase III study, success means reaching statistical significance (p value <0.05) on the primary endpoint (at week 52). Although the FDA may look at the secondary�s, unless the trial hits on the primary, the secondary�s will really only be of academic interest (and another study will almost certainly be required). So the key question is what�s the probability of the study hitting its primary? To evaluate this if we first look at the likely placebo response rate. (Note: this isn�t a true placebo group as it�s an �add-on� to standard of care, thus increases the placebo groups response rate). If we look at the Benlysta study with a similar primary endpoint, study design, at the same primary time-point, we saw placebo rates of around 48% (as per GSK website). If we look the Lupuzor phase II we saw at week 24 the placebo rates were 53% (placebo patients off treatment). This gives a starting point for assumed placebo rates at the longer term (primary) time-point of week 52. It�s harder to gauge the likely Lupuzor response rates at week 52 as I could only find one other trial at the longer term time-point (Study C33457/2047), which failed to demonstrate a difference between placebo and active. So working backwards, if we assume a best case scenario of 40% placebo response rate and we have 200 patients in the trial, we would need a >60% response rate in the Lupuzor group to achieve statistical significance (based on an 80% power). Power determines the ability to detect a treatment difference when one exists. Phase IIIs are often powered to 90%, but you would need at least 258 patients to achieve a 90% power, based on a 20% difference in treatment arms (hence the Benlysta Phase III studies recruited over 800 patients to each study, and achieved statistical significance with a smaller difference). Now, we have to consider �drop-outsR21;. In a trial of this nature the normal drop-out rate, over 1 year, would be around 20% (and this appears to be the case with other SLE trials). The trail will most likely consider drop outs (missing data) as non-responders (i.e. assuming no LOCF will be used). What this means is although 100 patients will start on Lupuzor, around 80 will complete to week 52. The denominator however will be based on the starting number of 100 (ITT population � those who received at least one dose of study drug ). This means to get a >60% response rate
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