The investigational anticoagulant drug asundexian held great promise as a safer anticoagulant. Its early failure in a Phase 3 trial teaches many lessons
I wonder if it’s an indication that the system, one where people can sue big corporations for killing and injuring people with unsafe products, might actually work. I was curious which drug company was conducting legit honest clinical trials and was a little surprised to see it’s Bayer. The HighWire recently did a segment on the company’s near implosion due to their cover up of Round Up/glyphosates. Serious ouchy:
I wonder if there is something else going on here. I can hardly recall any drug trials that were prematurely terminated due to lack of efficacy. Usually it is due to other problems such as excessive side effects or excessive mortality. There are probably thousands of trials where the desired effect of the investigational drug showed only marginal effectiveness and often that was after several years of trial. It is especially peculiar here where the major side effect of concern---bleeding--was somewhat less than the control drug. Usually this sort of difference is touted by the manufacturer as sufficient reason to prescribe their drug rather than the ones used for comparison. It would also be interesting to include a placebo control group in the trial. But this is seen much less often these days. Rather they test against an existing drug with efficacy already "proven" even though that may be quite marginal.
Great read and summary! If physiology were truly king (biologic plausibility), we’d still be using Swan Ganz catheters on the regular. Trials show respect for what we do not know yet. While sad to see an innovative approach fail, a good reminder of the intellectual humility required to practice medicine.
I am so old that we had MIs and everyone got a SG to get a PCW of 17 with fluids and or lasix. So many hours in the CCU -the patients and I would have been equally served by me spending the time becoming fluent in Spanish (was in San Antonio!)
I think I remember the Swan-Ganz catheters coming into general use during my Cardiology fellowship in the mid-1970s. Before that we used clinical signs and symptoms along with CXRs and the occasional CVP line. I can't recall that the S-G catheter ever changed what was required for optimal treatment other than what we derived from the earlier clinical and x-ray information.
Yeah, I remember floating a few Swans in the early 2000s in med school and residency. When I asked my attending how it helps, he said, "Ultimately? It doesn't. But the procedure is cool as hell." I think upon those days with great fondness as well as shock. We were still doing them knowing full well they didn't improve outcomes.
Excellent illustration of "an inconvenient truth" that is always potentially in the shadows when it comes to evaluating ANY therapeutic or prophylactic poultice, powder, pill, ointment, or operation.
Reading this, I could hear ESPN's Chris Berman's voice in my head in his drawn out rendition of his catchphrase, "That's WHY they PLAY the game!" But substituted for "play the game" was "do the RCT!" Winners and losers do not always comply with the experts' prognostications!
I wonder if it’s an indication that the system, one where people can sue big corporations for killing and injuring people with unsafe products, might actually work. I was curious which drug company was conducting legit honest clinical trials and was a little surprised to see it’s Bayer. The HighWire recently did a segment on the company’s near implosion due to their cover up of Round Up/glyphosates. Serious ouchy:
https://thehighwire.com/ark-videos/bayers-legal-free-fall/
Perhaps their legal woes have finally convinced them to make good on their responsibility to create safe products?
Lends credence to the idea that reversing the 1986 Vaccine Act may actually solve the major problems with the vaccine program.
A consumer can dream.
We often see the literature that succeeds, rarely the literature that does not. Good on them; we will learn more as a result of this.
I wonder if there is something else going on here. I can hardly recall any drug trials that were prematurely terminated due to lack of efficacy. Usually it is due to other problems such as excessive side effects or excessive mortality. There are probably thousands of trials where the desired effect of the investigational drug showed only marginal effectiveness and often that was after several years of trial. It is especially peculiar here where the major side effect of concern---bleeding--was somewhat less than the control drug. Usually this sort of difference is touted by the manufacturer as sufficient reason to prescribe their drug rather than the ones used for comparison. It would also be interesting to include a placebo control group in the trial. But this is seen much less often these days. Rather they test against an existing drug with efficacy already "proven" even though that may be quite marginal.
Great read and summary! If physiology were truly king (biologic plausibility), we’d still be using Swan Ganz catheters on the regular. Trials show respect for what we do not know yet. While sad to see an innovative approach fail, a good reminder of the intellectual humility required to practice medicine.
I am so old that we had MIs and everyone got a SG to get a PCW of 17 with fluids and or lasix. So many hours in the CCU -the patients and I would have been equally served by me spending the time becoming fluent in Spanish (was in San Antonio!)
I think I remember the Swan-Ganz catheters coming into general use during my Cardiology fellowship in the mid-1970s. Before that we used clinical signs and symptoms along with CXRs and the occasional CVP line. I can't recall that the S-G catheter ever changed what was required for optimal treatment other than what we derived from the earlier clinical and x-ray information.
Yeah, I remember floating a few Swans in the early 2000s in med school and residency. When I asked my attending how it helps, he said, "Ultimately? It doesn't. But the procedure is cool as hell." I think upon those days with great fondness as well as shock. We were still doing them knowing full well they didn't improve outcomes.
It was Swan ; fluids and Lasix
Excellent illustration of "an inconvenient truth" that is always potentially in the shadows when it comes to evaluating ANY therapeutic or prophylactic poultice, powder, pill, ointment, or operation.
Reading this, I could hear ESPN's Chris Berman's voice in my head in his drawn out rendition of his catchphrase, "That's WHY they PLAY the game!" But substituted for "play the game" was "do the RCT!" Winners and losers do not always comply with the experts' prognostications!