Ann: DSMB Recommends Continuation of Phase 3 COVID-19 Trial, page-251

From my analysis of likely key dates for the Covid ARDS trial (updated for latest announcement and shared below for those of you inclined to look at the detail), I have concluded that at the next two DSMB interim analyses (if the trial progresses beyond the second) the number of patients that will be already dosed will be around 200 and 250 respectively. Both possibilities still leave MSB with very useful numbers for statistical purposes (compared to if the trial had stopped on 3 September). My personal preference is for the trial to stop only after the third interim analysis on 180 patients or the full 300, as this will lead to more robust data for approvals purposes (not just in the USA). If the trial ends earlier or later than my estimate of 20th November, then all other predicted dates below will be earlier or later in proportion.

I believe that the 30 day period after dosing the 135th patient will be around 21st September, with the next DSMB interim analysis released on about 1st October. If the trial again continues, then I expect the last DSMB interim analysis to be released on about 28th October.

We don't have long to wait, and in the meantime we have likely approval for pediatric aGVHD (I put this at around 99% probability due to safety, efficacy and most importantly the huge unmet need for these steroid refractory children most of whom would otherwise die). I know some others think 95%, which would be reasonable if it were not for these children in dire need.

I must also say that I am quite surprised that the recruitment rate appears to be between 1 and 2 patients per day, a lot slower than the initial expectations.

Patient Group Total	Date Last Patient Dosed	End of 30 Day Period	DSMB Analysis on ASX	End of 60 Day Period	No of Days to Dose	Patients Dosed Per Day
90	25-Jul-20	24-Aug-20	3-Sep-20	23-Sep-20	81	1.11
135	22-Aug-20	21-Sep-20	1-Oct-20	21-Oct-20	29	1.56
180	18-Sep-20	18-Oct-20	28-Oct-20	17-Nov-20	26	1.71
300	20-Nov-20	20-Dec-20	30-Dec-20	19-Jan-21	64	1.88
Facts from MSB Announcements			Announcement Date
First patients dosed			5-May-20
DSMB sets early Sep for first interim analysis			29-Jul-20
DSMB recommends continuation of trial			3-Sep-20
Trial expected to complete recruitment during Q4			3-Sep-20
Assumptions
Last of 300 patients dosed in late November (just past middle of current MSB completion guidance)
Patient group 91-135 has 40% higher recruitment rate (higher infection rates, more hospitals, more familiar process)
Last two patient groups will have 10% higher recruitment rates than previous patient groups (more familiar process)
90th patient was dosed 4 days before the 29 July 2020 announcement on DSMB first interim analysis date
Methodology
90th patient dosed was likely done shortly before MSB announced DSMB first interim analysis date
This determines the "Patients Dosed per Day" for the first group
Set reasonable acceleration rates for enrolling patients in subsequent groups to achieve late November finish
All else just falls into place
Key Conclusions
No of patients dosed if DSMB stops trial at second interim analysis				203
No of patients dosed if DSMB stops trial at third interim analysis				255
Second DSMB interim recommendation date				1-Oct-20
Third DSMB interim recommendation date				28-Oct-20