Lots of colleagues & friends remain sore after the #FauciLeak on the interim #ACTT trial analysis that compared #remdesivir to placebo in patients hospitalized with severe #COVID19 2 days ago.
My thoughts on the events as a #clinicaltrials and #DSMB doctor—thread 1/10
My thoughts on the events as a #clinicaltrials and #DSMB doctor—thread 1/10
Data Safety Monitoring Boards (#DSMB) are independent groups of doctors & statisticians that analyze unblinded data in clinical trials, key to assure safety of patients enrolled, think about it as a safety satellite or control tower for the blinded investigators & patients.
Although unblinded, data is not real time. Investigators & teams need to enter the data, the data is vetted and proofread, then you want to have enough patients and data to analyze, you want patients to have gone through the trial (14 days for primary endpoint in #ACTT)
There are data cutoffs, then the data is tabulated, analyzed sent to the #DSMB members at least a 2-3 days before a pre-scheduled meeting to be digested by the members, then the data is presented to the members again, usually online these days (even in the pre-Zoom era).
The #DSMB members opine, the statistician provides strength of evidence for harm, benefit or futility, the DSMB chair needs to make a determination. The discussions are not open to anyone outside of the DSMB members. Then the decision is given: continue, stop, or modify the trial
Back to the #Remdesivir #ACTT trial. If the DSMB had a meeting on April 27, data cutoff for the meeting likely occurred at least 1 week prior in #pandemic times, included data on patients who had completed 14 days of treatment, this puts you back to patients enrolled by April 4.
As enrollment accelerated with the #SARS-CoV2 pandemic wave, the trial completed enrollment right before the DSMB meeting.
So one could argue why meet if the trial is done? There is nothing practical to decide as recruitment is completed! Let the full trial run its course!
So one could argue why meet if the trial is done? There is nothing practical to decide as recruitment is completed! Let the full trial run its course!
That was my #clinicaltrials purist reaction. Then I put myself in the DSMB members and chair shoes.
They had seen the interim analysis unblinded data with a strong benefit (p<0.001) on the primary endpoint, days to recovery.
They could not #unsee the data.
They had seen the interim analysis unblinded data with a strong benefit (p<0.001) on the primary endpoint, days to recovery.
They could not #unsee the data.
The DSMB could not stop a trial that had already completed enrollment, but they could recommend the patients’ treatment assignment of those recently enrolled be unblinded, and those who could still be benefit from #remdesivir be offered treatment, what #Fauci alluded to.
As a clinical trial led by a US public agency and with drug provided by a for-profit sponsor, they both had obligations to disclose the decision and the disclosed #DSMB decision within 48h of becoming aware of them, no different that in non-pandemic times. #Remdesivir was working
So blame (or thank) the #DSMB for being a #clinicaltrials Wild West party-pooper.
We thank them for their thankless job, for making the right call, for looking out for our patients.
This is just clinical #science with the emotions of pandemic times.
Time to regroup and think.
We thank them for their thankless job, for making the right call, for looking out for our patients.
This is just clinical #science with the emotions of pandemic times.
Time to regroup and think.
