I think you probably covered them and perhaps open it up to others, maybe. But I'm glad just coming that the issue of futility, I mean, maybe we've addressed that now, you said you didn't enter it for your other charters. And I think something I've realized in experience of trials is that it is important what you write in the charter. And so in my trials of 400, 500 patients, we don't have futility. So we only stop for safety, I think, in a small trial is my

personal view and address that going forward. You don't want to regret what you put in the protocol. If I could just a moment to address one other thing that I did catch, the comment about induction agent I think is important. And that may be another opportunity in addition to the one you mentioned, which I think is also important, prophylactic vasopressor use. But the choice and dose of sedative induction agents in another understudied area, it's not entirely unstudied, of course. But we recently had, speaking of propofol and accommodate, the secondary analysis of the intubestudy come out in Blue Journal just recently suggesting that there may be an independent association between cardiovascular collapse and choice of propofol as an induction agent. And of course the rate of cardiovascular collapse that they observed in the intubestudy was pretty high and perhaps driven in part by that factor, which is evidently more common in the centers that we're in intubed than in our trial centers. So I think you raised a lot of really wonderful points. Most of them were questions we are also asking ourselves and appreciate your

insight. Thanks, sir. Okay, so time for the panel. But first, let me reintroduce many of these folks that we met earlier. So on the far left is Professor Liz Wilcox from the University of Toronto. Welcome. Next is Professor Lenny Dareday. She's also involved in remap caps. That UMC in the Netherlands. Tony, you've met Lars Anderson yesterday. He is at say this, our house university. Yeah, pretty good. Thank you Lars. And Andrew All House who lives on the road from meet in University of Pittsburgh has joined us from a statistical perspective. So I have a question to go to Andrew first. But even before that, since most of the audience probably has an opportunity to read the manuscript or the detail, I was wondering if we could just comment on the regulatory approach for the trial and how sort of was consent involved and how that worked.

Yeah, it's a great question, Chris, and one that I think is important in this space. So what we're talking about now is a condition of emergency treatment motivation for which patients are usually unconscious or in distress, surrogates are frequently unavailable. So it's clearly a case like cardiac arrest where prospective informed consent is not feasible. And I'll highlight that this is the seventh trial we've talked about in the critical care space in the last two days. And I don't know if anyone else has noted, but six out of the seven have not obtained prospective informed consent and have had to deal with the same issue of how you respect patient autonomy in emergency conditions where you have to intervene before you're able to have informed consent conversation. I think there are real challenges to that. So consent on the back end is different than consent on the front end. And I think you see that in the consort diagrams of these trials. So informed consent prior to a trial, there are 30, 40% opout rates. What we see in the trials in the last few days is that one or two people withdraw consent. I think whether you notify patients after the trial is over or get consent on the back end is an open area of debate and much of this work. But I think from a larger perspective, I think what we're talking about is these are interventions that patients are being exposed to every day. So every day across the country, half of patients are getting this intervention and there are guidelines that are recommending it. And I think that that kind of clinician variability, patients are already being exposed to that, but we're not learning anything from it. So the criteria in the US for when consent is impractical, there are only two options. There's a waiver of consent and a process called exception from informed consent or EPIC, the criteria for waiver are two basic criteria, so you have to demonstrate that consent is infeasible, that's clearly the case for cardiac arrest and emergency treatment and debation.