Just to add to the good answers from sic4me.From the annual...

Just to add to the good answers from sic4me.

From the annual report 2012:

Reach2HD – HD - phase2a – primarily about safety and dosing and less about efficacy.

Imagine – AD - phase2b – primarily about mechanism of action to support efficacy claims.

Phase2b trials are often an intermediate step prior to moving to a Phase3 trials. Typically done by small companies to attract funding from big players. The big player wants more certainty around any positive results about efficacy than are typically produced from a Phase2a study before committing the big dollars involved in a Phase 3 study.

I don’t think anything is being let out of the bag by the comment that the favourable results from the earlier AD studies give grounds for encouragement about the results from the HD study. This has been the theory all along – and in fact that paragraph word for word was used in Jan 2012 when the IND application was approved. Sorry.

Increasing the N is an interesting one. An attrition rate would have been assumed in the sample size calculation. In reality it might have been higher – hence recruit more so effective sample size remains consistent with the design.

Or alternatively some of the distributional assumptions around outcome measures might not have been accurate – and so less power. You’d need to see the detailed study design (which you and I can’t) to get a better handle on what’s going on. It is unusual in the sense most trials run over budget and time for subjects – and so don’t have this option.

I tend to use recruitment success or lack of it as a proxy for how good the team is. When recruitment goes well it suggests the team knows what they are doing – and have got clinicians on the ground on side and keen. In this case being a phase 2a study increasing the N is no big drama because it is less about efficacy. In a Phase 2b increasing the N is more problematic – and raises the issue of whether it was done blinded or unblinded. So in summary being in the position to increase the N in a Phase2a study within timelines and budget is a very good thing imo.