4 ms·

Same comment I posted on the other thread relevant here: Very promising early results. The caveats for non scientists to be aware of is that these are not rand

Same comment I posted on the other thread relevant here: Very promising early results. The caveats for non scientists to be aware of is that these are not randomized trials with a placebo and all - this is just through a mechanism called "compassionate use" that allows Gilead to give people the drug. Also, 68% of patients improved, the title implies that patients say a 68% improvement in their symptoms which is not the case, the 68% is the number of patients improved divided by total number of patients. To get a good picture of how much the drug improves outcomes compared to not having the drug administered, we need large placebo controlled randomized trials so we can get the statistical signal to see if it works and how well it works. As the paper states, those trials are underway.

hilbertseries 7y ago
> More than half of patients on mechanical ventilation were extubated (57 percent, n=17/30) and nearly half of all patients (47 percent, n=25/53) were discharged from the hospital following treatment with remdesivir. Death rate for patients on ventilators has been something like 80 percent.
- numbsafari 7y ago
  But, given that this was not a randomized trial, and was given on a compassionate use basis, we don't know whether... A) This is better than expected because doctors and families only elected to use this for patients who were otherwise MORE likely to die. B) This is worse than expected because doctors and families only elected to use this for patients who more likely than not to survive. C) This result is meaningless because there's too much noise in who was given the drug and who was not.
  - vikramkr 7y ago
    It's a nice signal, but yeah, theres a reason they're running a large randomized controlled trial right now for FDA approval - they arent likely to get approval just based on this.
- mcguire 7y ago
  For reference... https://jamanetwork.com/journals/jama/fullarticle/194560 https://jamanetwork.com/journals/jama/fullarticle/194560 "Results Of the 15 757 patients admitted, a total of 5183 (33%) received mechanical ventilation for a mean (SD) duration of 5.9 (7.2) days. The mean (SD) length of stay in the intensive care unit was 11.2 (13.7) days. Overall mortality rate in the intensive care unit was 30.7% (1590 patients) for the entire population, 52% (120) in patients who received ventilation because of acute respiratory distress syndrome, and 22% (115) in patients who received ventilation for an exacerbation of chronic obstructive pulmonary disease. Survival of unselected patients receiving mechanical ventilation for more than 12 hours was 69%. The main conditions independently associated with increased mortality were (1) factors present at the start of mechanical ventilation (odds ratio [OR], 2.98; 95% confidence interval [CI], 2.44-3.63; P<.001 for coma), (2) factors related to patient management (OR, 3.67; 95% CI, 2.02-6.66; P<.001 for plateau airway pressure >35 cm H2O), and (3) developments occurring over the course of mechanical ventilation (OR, 8.71; 95% CI, 5.44-13.94; P<.001 for ratio of PaO2 to fraction of inspired oxygen <100). "Conclusion Survival among mechanically ventilated patients depends not only on the factors present at the start of mechanical ventilation, but also on the development of complications and patient management in the intensive care unit."
- jennyyang 7y ago
  Yes, I think both NYC and Louisiana were seeing death rates above 80% for intubated patients, which is why they are starting to think they need to change the protocol. In the remdesivir study, death rates on invasive ventilator patients was 13% which is much lower than expected at this point.
- vikramkr 7y ago
  They could have selected withing ventilated patients for patients more likely to survive if they thought compassionate use might be most effective in patients that have a shot. They're running a large controlled trial so we should know more soon enough
londons_explore 7y ago
It should be illegal to run a trial without a control group... For all we know, this trial was run in a good hospital and this drug actually hindered recovery rates. We just don't know. You're literally throwing away human lives without learning anything that can be used to help other humans.
- vikramkr 7y ago
  There are a lot of times that it isn't feasible, and they are running a large trial with a control group right now. The drug has a reasonable chance of working so people requested compassionate use, so the company figured they might as well track the compassionate use patients to get some data out of them. It's not like they're using this as a basis for getting FDA approval.
sdabdoub 7y ago
Unfortunately it also appears to be extremely difficult to make[1] which may limit its usefulness. [1] https://www.acsh.org/news/2020/03/26/problem-remdesivir-making-it-14665 https://www.acsh.org/news/2020/03/26/problem-remdesivir-maki...
- benmaraschino 7y ago
  It’s nowhere near as difficult to make as the article may imply, though. Yes, that first-generation route is quite a doozy, involving some harsh conditions (multiple steps at -78° C, which is actually not as difficult to carry out at the bench as it sounds) and nasty reagents, especially n-BuLi, which explodes into flames upon exposure to air. But it’s fairly easy to carry out on a small scale in a typical med chem lab. If you’re a medicinal chemist and need to make limited amounts, say, maybe in the hundreds of milligrams—which would probably be far more than enough to do preclinical studies—then that route will do. But it definitely can’t be scaled up easily to multi-thousand gallon chemical reactors, although like the article says, that’s where the process chemists come in. The second-generation route looks much better, and I’m sure it’s already being optimized even further.

hilbertseries 7y ago

> More than half of patients on mechanical ventilation were extubated (57 percent, n=17/30) and nearly half of all patients (47 percent, n=25/53) were discharged from the hospital following treatment with remdesivir. Death rate for patients on ventilators has been something like 80 percent.

numbsafari 7y ago
But, given that this was not a randomized trial, and was given on a compassionate use basis, we don't know whether... A) This is better than expected because doctors and families only elected to use this for patients who were otherwise MORE likely to die. B) This is worse than expected because doctors and families only elected to use this for patients who more likely than not to survive. C) This result is meaningless because there's too much noise in who was given the drug and who was not.
- vikramkr 7y ago
  It's a nice signal, but yeah, theres a reason they're running a large randomized controlled trial right now for FDA approval - they arent likely to get approval just based on this.
mcguire 7y ago
For reference... https://jamanetwork.com/journals/jama/fullarticle/194560 https://jamanetwork.com/journals/jama/fullarticle/194560 "Results Of the 15 757 patients admitted, a total of 5183 (33%) received mechanical ventilation for a mean (SD) duration of 5.9 (7.2) days. The mean (SD) length of stay in the intensive care unit was 11.2 (13.7) days. Overall mortality rate in the intensive care unit was 30.7% (1590 patients) for the entire population, 52% (120) in patients who received ventilation because of acute respiratory distress syndrome, and 22% (115) in patients who received ventilation for an exacerbation of chronic obstructive pulmonary disease. Survival of unselected patients receiving mechanical ventilation for more than 12 hours was 69%. The main conditions independently associated with increased mortality were (1) factors present at the start of mechanical ventilation (odds ratio [OR], 2.98; 95% confidence interval [CI], 2.44-3.63; P<.001 for coma), (2) factors related to patient management (OR, 3.67; 95% CI, 2.02-6.66; P<.001 for plateau airway pressure >35 cm H2O), and (3) developments occurring over the course of mechanical ventilation (OR, 8.71; 95% CI, 5.44-13.94; P<.001 for ratio of PaO2 to fraction of inspired oxygen <100). "Conclusion Survival among mechanically ventilated patients depends not only on the factors present at the start of mechanical ventilation, but also on the development of complications and patient management in the intensive care unit."
jennyyang 7y ago
Yes, I think both NYC and Louisiana were seeing death rates above 80% for intubated patients, which is why they are starting to think they need to change the protocol. In the remdesivir study, death rates on invasive ventilator patients was 13% which is much lower than expected at this point.
vikramkr 7y ago
They could have selected withing ventilated patients for patients more likely to survive if they thought compassionate use might be most effective in patients that have a shot. They're running a large controlled trial so we should know more soon enough

londons_explore 7y ago

It should be illegal to run a trial without a control group... For all we know, this trial was run in a good hospital and this drug actually hindered recovery rates. We just don't know. You're literally throwing away human lives without learning anything that can be used to help other humans.

vikramkr 7y ago
There are a lot of times that it isn't feasible, and they are running a large trial with a control group right now. The drug has a reasonable chance of working so people requested compassionate use, so the company figured they might as well track the compassionate use patients to get some data out of them. It's not like they're using this as a basis for getting FDA approval.

sdabdoub 7y ago

Unfortunately it also appears to be extremely difficult to make[1] which may limit its usefulness. [1] https://www.acsh.org/news/2020/03/26/problem-remdesivir-making-it-14665 https://www.acsh.org/news/2020/03/26/problem-remdesivir-maki...

benmaraschino 7y ago
It’s nowhere near as difficult to make as the article may imply, though. Yes, that first-generation route is quite a doozy, involving some harsh conditions (multiple steps at -78° C, which is actually not as difficult to carry out at the bench as it sounds) and nasty reagents, especially n-BuLi, which explodes into flames upon exposure to air. But it’s fairly easy to carry out on a small scale in a typical med chem lab. If you’re a medicinal chemist and need to make limited amounts, say, maybe in the hundreds of milligrams—which would probably be far more than enough to do preclinical studies—then that route will do. But it definitely can’t be scaled up easily to multi-thousand gallon chemical reactors, although like the article says, that’s where the process chemists come in. The second-generation route looks much better, and I’m sure it’s already being optimized even further.