Noticed recevied @ 1.15pm., page-56

I’m not sure how far logic gets you with these sorts of things GC. Isn’t it more a blend of experience and cognitive style. Its hard to know what these sorts of announcements mean so we log into HC to see what everybody else thinks.

And so someone with a little bit of a contrarian streak will naturally be quite out of synch with the majority. My thoughts processes for example around the information in the announcement were 180 degrees to what your logic suggests.

And went something like this:

The results didn’t just fall out of sky. Most likely they flowed from an planned unblinded interim analysis conducted by the DSMB. Which tripped the further funding from US Defence. No large differences were observed between the two groups with respect to safety. But safety in terms of a reduction in adverse events is the primary outcome for this study. The reason for this is a lower risk profile than originally assumed and this is reflected in the lower mortality rate. Treatment benefit was also assumed to be a most evident for the most severe.

In theory a lower mortality rate increases power on the secondary outcomes because there are more patients to evaluate. In addition the absence of large differences between group mortality it also has the benifit of reducng the confounding which occurs where patients who would have otherwise died in the treatment arm go on to show poor cognitive or functional improvement.

But the company now posits that showing clinical improvement is challenging because of heterogeneity. In other words the efficacy signal is too noisy. This noise was not (or could not be) accounted for in the design (for example by stratification) so it now intends post hoc to control for it in subsequent analyses using biomarkers.

Remembering that the DSMB couldn’t care less if the trial continues as long as it is safe. Efficacy now both in terms of less adverse events and cognitive / functional improvement are going to be a long shot. But valuable data in terms of better predicting outcomes from biomarkers is hoped for and this now becomes the key purpose of the study and the reason for further recruitment.

In short the company is reorientating the market to the idea that the trial is more about proof of concept (P2a) than efficacy (P2b). The trouble is ... as is evident here ... on HC the opposite reaction occurs. This happens because the key paragraph with the results update is carefully crafted and needs to be read as a whole to decipher its meaning or what the company is actually trying to tell you.

And even then requires a bit of dot joining because other critical information is not provided. So the discussion becomes one of simply whether you are a glass half full or half empty kind of guy. Companies with very good interim data are always happy to elaborate on this at length in great detail and unambiguously. With the converse being true ... sadly from experience.