Pulmonary Embolism Support Group
By far the most common form of pulmonary embolism is a thromboembolism, which occurs when a blood clot, generally a venous thrombus, becomes dislodged from its site of formation and embolizes to the arterial blood supply of one of the lungs. Symptoms may include difficulty breathing, pain during breathing, and more rarely circulatory instability and death.
Data issues that plagued Xarelto a much wider problem, Nissen says
May 25, 2012
BayerJohnson & Johnson
Much discussion during Wednesday's advisory panel meeting on whether to approve Bayer/J&J anticoagulant Xarelto (rivaroxaban) for a new use centered around a pivotal trial called ATLAS. Advisors complained of missing data and inconsistent record keeping (click here for a recap). A final decision is expected in late June.
In this Q&A, Dr. Steven Nissen, a panel member and chairman of the department of cardiovascular medicine at the Cleveland Clinic Foundation, explains why he voted against approving Xarelto for use in acute coronary syndrome (ACS) patients already taking dual antiplatelet therapy, and how the problems plaguing ATLAS are disturbingly common.
Q. MM&M: What was it about the benefit-risk profile that swayed you to vote that way?
A. Dr. Steven Nissen: Marginal statistical evidence of benefit; a p' value of 0.039 for benefit at the target dose of 2.5mg b.i.d.; increased risk of intracranial hemorrhage and life-threatening bleeding; and a study that had issues with respect to the quality of study conduct, particularly the high rate of withdrawal of consent that undermined the ability to interpret the results of the study.
Q. The sponsor has vowed to supply the FDA with the data that the panelists said was missing. What will the companies have to show for you to be convinced?
A. Another trial, which is what I said.
Q.The panelists seemed taken aback by Bayer/Janssen's data omission. What was it about the companies' preparation for the meeting that inspired such passion among the panel members?
A. Look, this is not personal. So I wouldn't make those sorts of comments. I would just simply say that we were not convinced that the benefits exceeded the risks. And we wanted more information. And I will leave it at that.
Q. Much discussion was focused around, as you said earlier, issues that related to data collection, maybe some would say poor data collection. The rejection of the drug, albeit a narrow one, was almost a condemnation of that practice. Do you agree or not?
A. Well, the problem of patients withdrawing consent or incomplete ascertainment of outcomes is a problem that extends across the entire clinical trial enterprise. And certainly the committee was making a generalized statement that we are worried about it, and that we think it needs to be addressed in this application, and in future applications for drugs.
Q. And another data question: Three study sites were eliminated due to misconduct, with the company claiming it couldn't find the subjects because privacy laws barred them from doing things like checking death notices or contacting them. The FDA person said that if the local laws are getting in the way of clarity, don't have trials there. Increased use of international locations is a growing trend. Can the FDA really bar their use and kind of impose safeguards, or will it need to just fall in line with the data it's given?
A. I think that that is the choice of the sponsor. The FDAthe companies are taking their own risks if they go to places that they are not confident of the quality of the data. It is their risk to take. It is not the FDA's job to tell them not to take the risk. But companies need to know that if they don't supply data that the FDA or its advisers believe is reliable, then it may impact approvability.
Q. And one final question: Do you think that drug will eventually reach the market for the indication in ACS?
A. I have no way to know. I think they need another trial and if it's successful then it will convince many of us. If it's unsuccessful, it won't make it. It's just speculation entirely.
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I've been following Dr. Steve Nissen for a while. One thing that impressed me is this:
"As a physician/scientist, Dr. Nissen consults for many pharmaceutical companies on the development of new therapies for cardiovascular disease, but maintains his longstanding personal policy of requiring companies to donate all related honoraria directly to charity."
WOW. I wonder how many others do that?
May 25, 2012
BayerJohnson & Johnson
Much discussion during Wednesday's advisory panel meeting on whether to approve Bayer/J&J anticoagulant Xarelto (rivaroxaban) for a new use centered around a pivotal trial called ATLAS. Advisors complained of missing data and inconsistent record keeping (click here for a recap). A final decision is expected in late June.
In this Q&A, Dr. Steven Nissen, a panel member and chairman of the department of cardiovascular medicine at the Cleveland Clinic Foundation, explains why he voted against approving Xarelto for use in acute coronary syndrome (ACS) patients already taking dual antiplatelet therapy, and how the problems plaguing ATLAS are disturbingly common.
Q. MM&M: What was it about the benefit-risk profile that swayed you to vote that way?
A. Dr. Steven Nissen: Marginal statistical evidence of benefit; a p' value of 0.039 for benefit at the target dose of 2.5mg b.i.d.; increased risk of intracranial hemorrhage and life-threatening bleeding; and a study that had issues with respect to the quality of study conduct, particularly the high rate of withdrawal of consent that undermined the ability to interpret the results of the study.
Q. The sponsor has vowed to supply the FDA with the data that the panelists said was missing. What will the companies have to show for you to be convinced?
A. Another trial, which is what I said.
Q.The panelists seemed taken aback by Bayer/Janssen's data omission. What was it about the companies' preparation for the meeting that inspired such passion among the panel members?
A. Look, this is not personal. So I wouldn't make those sorts of comments. I would just simply say that we were not convinced that the benefits exceeded the risks. And we wanted more information. And I will leave it at that.
Q. Much discussion was focused around, as you said earlier, issues that related to data collection, maybe some would say poor data collection. The rejection of the drug, albeit a narrow one, was almost a condemnation of that practice. Do you agree or not?
A. Well, the problem of patients withdrawing consent or incomplete ascertainment of outcomes is a problem that extends across the entire clinical trial enterprise. And certainly the committee was making a generalized statement that we are worried about it, and that we think it needs to be addressed in this application, and in future applications for drugs.
Q. And another data question: Three study sites were eliminated due to misconduct, with the company claiming it couldn't find the subjects because privacy laws barred them from doing things like checking death notices or contacting them. The FDA person said that if the local laws are getting in the way of clarity, don't have trials there. Increased use of international locations is a growing trend. Can the FDA really bar their use and kind of impose safeguards, or will it need to just fall in line with the data it's given?
A. I think that that is the choice of the sponsor. The FDAthe companies are taking their own risks if they go to places that they are not confident of the quality of the data. It is their risk to take. It is not the FDA's job to tell them not to take the risk. But companies need to know that if they don't supply data that the FDA or its advisers believe is reliable, then it may impact approvability.
Q. And one final question: Do you think that drug will eventually reach the market for the indication in ACS?
A. I have no way to know. I think they need another trial and if it's successful then it will convince many of us. If it's unsuccessful, it won't make it. It's just speculation entirely.
******************************************
I've been following Dr. Steve Nissen for a while. One thing that impressed me is this:
"As a physician/scientist, Dr. Nissen consults for many pharmaceutical companies on the development of new therapies for cardiovascular disease, but maintains his longstanding personal policy of requiring companies to donate all related honoraria directly to charity."
WOW. I wonder how many others do that?
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Look at what my best friend did with my picture!
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We all have 24 hours in a day. How we spend these hours is important. Watching a little bit of a video about how sitting affects us made me aware of how much sitting and laying down I do. Gonna have to work on that.Your turn. Tell me another truth.
REPEAT: I'm not 'down' on them. It all speaks to lack of transparency and lack of full disclosure ---- when most people only read the bits that are praising them.
I may wind up using one in the future.
I have no problem with anyone else using them.
Perhaps you (and everyone else here) should put http://www.pharmalot.com/ in their Bookmarks and read read read.
Then you might understand what actually goes on. That site isn't just about anticoag drugs-----oh, no! We're not the only group that needs to understand what goes on (or what doesn't) in the back rooms.
Think Vioxx. Think Avandia. A long list of withdrawn drugs at Wiki.
They were all praised to the high heavens when first presented.
Follow the money---- that's where it's all happening.
"actually for the first time, I feel like you were coming through in a real way'
Thanks?? I think??
So,my last reply...
WHATEVER.
Is it Spring YET?
You're post is a superlative example of snark and I bow my head in defeat.
Yes, I know. There are different kinds of 'support'. People here, you included, are given great emotional support of the "I know what you're going through" and "take care" type. That's important, I understand.
Another kind of support is presenting information that some (not ALL) members didn't know. A good example of that is the recent talk about having LFT tests performed regularly. Some members didn't know that. I'm sure you already did, but some didn't.
And yes, I'm also sure that you know how to research, if you say so. But some people barely know how to use Google effectively.
And, finally, you have absolutely no idea what I 'go through' daily.