So my friend, Justin Morgenstern recently put up a post on Idarucizumab, aka Praxbind. He seemed pretty fired up on the issue, so I got him on the line to talk about it. What follows is a conversation on evidence and what to do when there is not a good amount of it.
Schtuff
Justin Wrote an Additional Post after our Discussion
On to the Wee…
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Scott Weingart
An ED Intensivist from NY.
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Fantastic debate, thanks to both of you. Over time I’m continually surprised by how smart people can disagree over the same evidence. This is a good case-in-point. The issue here is one of perspective, with the following two perspectives in play: #1: The policy-maker: If we accept a treatment as standard of care, then research about it will stop. We must be the gate-keepers, guarding against bad science. (This is the perspective of regulatory agencies such as the FDA, and clinical trialists.) #2: The clinical grunt: I need to treat the patient in front of me with the best available evidence (whether its good or crummy). I am a peon: the policy-makers of the world aren’t going to pay attention to me. I just need to do the best I can for my patients. There is some validity to both of these perspectives. Neither is right or wrong. People with different perspectives will disagree, often intractably. Personally, I find the clinical-grunt perspective more appropriate for me. I’m a clinician. I don’t design health policy nor clinical trials. My goal is to be an excellent clinician. That’s bloody hard, without pondering the wider ramifications for science and society. The vast majority… Read more »
I have been struggling with these contrasting perspectives since writing the initial blog post. (You phrase it much better than I do, though). I don’t think there is any doubt that the vast majority of clinicians should be focused on the patient in front of them. If they believe the chances are better than 50% than idarucizumab is going to help their patient, they absolutely should use it. (I still think it is hard to know if that is actually the case, though.) The problem is that if we all take this perspective, we can end up doing a lot of harm in the long run. I think the real question is what perspective blogs and podcasts should take. My initial problem with hearing very definitive statements about idarucizumab on EM:RAP is that EM:RAP has a special place in the emergency medicine community. As a program, it is a thought leader. Whether they like it or not, EM:RAP plays a role in shaping standard care across the entire community. That is a huge responsibility, and in that context I wonder whether the larger social and scientific issues shouldn’t be considered or mentioned. When it comes to my own blog, I… Read more »
Justin, there is a lot of what you said in the podcast that I agree with, and see my post above here for my response to Scott. The one thing I took issue with was you saying “we have to get science out of the hand of Pharma and back into the hands of clinicians”. The one sure-fire way to destroy drug development and decimate the arrival of new medicines is to exclude the people who literally have the most experience in actively developing a drug from start to finish. I can count on one hand the number of non-pharma clinicians I know of who are qualified to run multiple, concurrent, multi-center, global, large, Phase 3 pivotal trials of adequate regulatory conduct. It would also mean doing away with Clinical Research Organizations (CROs), who often run the day to day minutia of the trial, AND maintain the database. Want to ensure that even more (as you pointed out) Phase 3 trials are negative? Then eliminate those who have the most experience at monitoring the blinded database for anomalies and investigators pretty much entering all their data wrong every single day. In your post above you point out a prime opportunity… Read more »
Thanks for your comments Dave, I don’t think there is any doubt that we need to significantly change the way that the FDA does business. Unfortunately, the current political climate seems to be pushing things in the wrong direction, with less regulation and less science being required. I stand firmly behind my comments around getting the money out of science. When patients’ lives are on the line, it is no place for conflict of interest. Allowing companies to test their own products, when they stand to make billions of dollars, is a clear conflict of interest. There is a lot of empirical evidence that demonstrates that pharma sponsored trials are more likely to be positive than trials without pharma money, a clear indications of that conflict of interest. Although you are correct that many of our best researchers are currently working in the pharma system, there is no need for them to be working there. That is solely an artifact of the way research is currently funded. If we removed the conflicts of interest and put research in the hands of independent entities like universities and government, those same excellent researchers could get jobs and perform excellent research free of… Read more »
[…] was invited on EMCrit to discuss my position on idarucizumab and I fear I didn’t do a great job explaining myself. I […]
Scott, I listen to your podcasts all the time, some many times over because they have a ton of great information. However, this time, I think you’ve gone just a bit too far in your open disdain toward pharmaceutical companies, that without the proper context, is misleading and inaccurate. Yes, I totally agree that the open-label single arm design is not the optimal method, nor does it generate the highest level of evidence. However, when you go to the FDA with your Investigational New Drug Application (IND), you are subject to their requirements, their whims, and their final direction for how to proceed. Yes, you as a company can push back in your End of Phase 2, Phase 3, and pre-NDA meetings, BUT if the FDA says you have to compare your drug to a dancing panda bear playing a violin, that’s it. End of story. The FDA will also hold joint meetings with the European Medicines Agency to provide a unified feedback framework for a globally developed drug. Sometimes our agency across the pond will go off the rails and the FDA will say “Yeah ok, do what they said”. You pointed out that in the publication, they specifically… Read more »
[…] Weingart discusses Idarucizumab and its lack of robust evidence to reverse dabigatran. So what should we do? Justin Morgenstern […]
Though there was some robust discussion and language, I still came away from this with a slightly opaque ‘would you give it?’- with a rough ‘well, there might be 60% chance it works etc etc’ and then some non committal chat. Come on, have the kahunas to say, nah, this is bull, not going there as yes IT MIGHT ALSO DO HARM?? I think Scott mentioned the ket word here which is equipoise. If it’s present (re-knowledge), then there should be a study done, unless there is overwhelming experience and knowledge that something just works, such as giving local anaesthetic for pain relief of wound suturing (I’m guessing there isn’t any for this……!).
[…] identical to the approval of idarucizumab, a debacle I have discussed previously. (At that time, I was chastised by Scott Weingart for saying “this is not science”. Because the activity of uncontrolled observation certainly fits into a broader definition of […]
[…] I talked to (debated) Scott Weingart about this post on EMCrit. […]