In a response to Growacet and a response to Kelsee, Sarah from IR stated, according to Growacet and Kelsee, that 1) there is a chance that an SSRA won't be done; and 2) it is the Clinical Steering Committee that does the SSRA. Both of these statements are surprising to me and raise even more questions rather than provide "clarification".

In response, Fouremm wrote: "Now I’m a little confused. I was under the same impression as BDAZ that the CSC was blinded but according to Sarah’s reply to Kelsee the CSC does the SSRA so they would have to be unblinded for that."

I'm glad I'm not alone here on the confusion surrounding the CSC/DSMB/SSRA. The Clinical Steering Committee is blinded, as stated in the first, second, third, fourth, fifth and sixth DSMB data reviews, and is not the same as the unblinded DSMB committee. "Resverlogix, the clinical steering committee, and all investigators remain blinded to the actual safety and efficacy results."

Did Sarah mean to write DSMB instead of CSC? Did Sarah misunderstand the question or make a mistake in her replies to Growacet and Kelsee? Did the CSC become unblinded since the February 26, 2018 DSMB report that reiterated that the CSC was blinded? If so, what are the implications of having an unblinded CSC in an ongoing cardiovascular outcomes trial (this would be very abnormal)? Alternatively, if the CSC is still blinded does this info mean that a blinded SSRA and not an unblinded SSRA will be done? Has the decision to not do an SSRA already been made? If so, have 188 events already been surpassed? If so, could BETonMACE hit 250 events any day now? 

Instead of "clarification" we have confusion. Kind of like one step forward, two steps back. In my opinion, it would be abnormal/unexpected/surprising for an interim analysis like the SSRA to be skipped, when the entire purpose of the SSRA is to validate previous trial assumptions/unknown and allow informed adaptations to be made, if necessary, to the trial design. If indeed the CSC is the group performing the SSRA, then I would assume it must be a blinded SSRA, which will not take into account the treatment effect.

"Blinded Sample Size Re-estimation (SSR): Blinded SSR (bSSR) is a type of SSR that uses accumulating, aggregate data in the mid-course of the trial to re-estimate nuisance parameters that have an impact on the power calculation of the trial. Some examples of nuisance parameters are the variance of a continuous variable, the control group event rate, or subject discontinuation rate. When the sample size is adjusted using bSSR, the treatment effect in the ongoing study is not estimated and used in the algorithm of SSR."

Those initial answers from IR to my earlier questions helped us understand: 1) Resverlogix is still blinded in BETonMACE; 2) the results of the SSRA, if and when it occurs, will be press released; and 3) patients are continuing on treatment until end of trial instead of the previously stated 104 week limit. 

But now we have more questions that need answers. If the next quarterly financials/MD&A come out soon, we'll have to pay close attention to the part that previously indicated that the SSRA would happen at 75% of events (188 events). To be continued.......

In other news Resverlogix is attending and presenting at a couple of high profile science conferences over the next few days. Gordon Research Conference in New Hampshire on "Lipoprotein Metabolism in the Brain and Circulation and Its Role in Disease" and International Symposium on Atherosclerosis in Toronto.

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