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.
Bottom line, none of us will know the true success or failure of any of the new anticoagulants for several more years. Give it a rest already.
Sorry can't 'give it a rest' because the 'positive' reviews are more PR slanted/biased? (I'm not talking about a personal 'take' or experience/testimonial from a patient who is actually taking the medication. Those are valid, even though anecdotal.)
Perhaps you haven't read that 'reassuring' article by Sue Hughes (and the complete opposite a month later) that I posted, can't remember where, just today?
And I would think that a very respected physician/researcher's thoughts like Dr. S. Nissen"s would carry more weight and garner something more that a knee jerk 'give it a rest' comment. Do you not think so?
I'm sorry I've gotten on you and your cohorts nerves (again). DS is here for support and if only 'positive' thoughts are allowed then the other part of their mission (be helpful) isn't going to happen.
"This is a support group for Pulmonary Embolism. We trust you will do your best to remain positive and helpful."
How that word 'positive' is used does not mean ONLY handing out platitudes and reassurances---- it also means 'constructive'. Dr. S. Nissen's article was constructive, I believe.
Sorry, but as you said yourself try to stay positive and helpful. As far as I can see, all you have been doing has been digging and twisting just one side of these drug research studies.
What do I mean by twisting reality?
You have slightly altered the order that these two articles by Sue Hughes have been published on The Heart. If you would had read and followed the development of Pradax since the begining, you, might, understand why she did this.
As a user of Pradax (for the last two years) I think that I can be a candidate to actually talk about this drug that you have only showed the negative side.
I can't use warfarin, because of the side effects that AFFECT ME, I can't get behind the wheel of a car, no driving, no work, no work no $.
I did my own studies about Pradax, as oppose to listen to somebody that is ONLY digging the dirt.
I'm under the age of 75 and I have no liver problems(those are the only two issues that the medical association has with Pradax, yes they should make the 110mg available to the elderlies)
But for now, I have no issues with the drug.
I don't have to go to the clinic and have an INR done on me or purchase an self testing monitor.
I don't have to worry about any food that I eat and I do mean any food.
Vitamin K, never heard of it...
So yes your song is in fact getting tiresome, please give it a break. Let people do their own research the proper way, we don't need another witch hunt...
'xcuse my french.
For a while now, I've thought, man why does Cave hate the new meds so much. I'm being serious. Maybe you're unaware of how pessimistic and sort of disparaging you come across anytime anyone mentions they're considering going on one of the new meds or says they are on the new meds or who shares something about the new meds.
It's feels like you have some kind of personal agenda to just shoot it all down for some reason. Maybe that's not intended but that's how it translates. Also, when your mission is to relentlessly cut and paste any negative thing you can find, it smacks more of of fear mongering and conspiracy than of being supportive .
None of the meds we take are perfect and for crying out loud, we have to start somewhere. As a anticoagulant lifer, I'm glad to see all the new developments and approvals, and that we don't have to stay in 1954 forever. Poodle skirts were never my thing.
Just a tidbit FWIW----Even though the trial that Dr. Nissen was talking about, it's well known that trials have to have a 'focus'---- the designers have to 'name' something that is narrow enough to qualify for that trial.
So ACS data will eventually spill into VTE. The trial can't be named The No-Name Trial for Pulmonary, DVT, and All Other Conditions That Might Benefit Later. Wouldn't fly.
And to pick more nits (grin) this thread isn't the first, nor will it be the last, that segues has the whiff of off-topic.
I would like total transparency available for the average person like myself so they can make up their own minds knowing all the facts.
That's not going to happen, I understand.
I can't imagine that the presentation of 'all that stuff' derived from what are considered valid sources can be considered negative; they're just another side to the coin. Sometimes right, sometimes wrong perhaps but certainly ripe for debate. I believe that civilized debate is the only way for me and others to learn.
Transparency. That's all.
Reply #6 - 12/29/12 7:42pm
*witch hunt
'xcuse my french.
I'm sorry, I don't really know what you mean by that. But it does sound like it needs a 'tsk tsk' as an answer. And it does sound a bit childish.
BTW---- your comment in another thread:
""Lately, all the negative literature about Pradax, has been based on patients that are over 75y.o. or have issues with renal functions and believe me, I have been following closely"
I have to respectively disagree with the word 'all'. Yes, some are. But not nearly 'all'.
Go to http://clinicaltrial.gov/ and read all the trials about Pradaxa.
"But why so snarky when a new drug gets approved?"
I'm sorry you perceive some of my posts as 'snarky'. Eye of the beholder? I don't know. Not many other people call my posts snarky and some even PM me with their appreciation for the research I present.
But I might ask of you and all the others who are highly incensed by my copy/paste abilities and my other posts:
"But why so be so upset at what I'm posting? I haven't been mean or nasty to anyone here. I've even endured, in the past, some pretty crazy and foul mouthed taunting, which I ignored.
Ad hominem attacks are discouraged here at DS, BTW.
I would ask anyone who thinks my posts are snarky or 'negative' or 'pessimistic' to simply put me on your 'ignore' list. That won't hurt my feelings at all.
Just the subject alone is a little snarky in tone, no?
No one in this recent discussion has attacked you. Tom asked you to give it a rest. That's not an attack. Come on. You can certainly tell him no and do what you want. And I didn't attack you. I made an observation which I didn't think was rude. Where did I hit below the belt? I don't think it's an unfair question to ask you why you seem like such a hater of the new meds. You really do come across that way to me.
Also, I'm not highly incensed. That's a ridiculously disproportionate word for what we're talking about here. Not even close. There is nothing you can say that would be of such importance that it would warrant me getting incensed, trust me. What irritates me at times is this assault of articles in what seems to be an attempt to fulfill some kind of personal agenda. None of it feels like you're just trying to be supportive, but rather, trying to derail some people's choices here. And maybe that's in the eye of the beholder, as well, but it sure comes across that way to me.. Still you can post what you want. And I'll question what I want.
No I'm sorry, I will not put you on ignore. I don't use that feature for anyone. I actually decide when I want to ignore a discussion. I've done it without the use of a button countless times for an array of discussions, some of them yours and some not, when whatever is being said is just something that is either of no interest to me or is just kind of inane. But I'll comment on any discussion thread I like.
Post whatever you want. I'll do the same.
I can't imagine that what I might say that could possibly 'derail' other people's choices. Maybe reading some of the articles might. That's their decision.
When you asked "what would you like to see happen with new drug development?" I thought that was a very astute question and I spent some time seriously thinking of what to answer, feeling it was an important point.
Then to see that my answer was more or less ignored when the only response from you was---- 'why so snarky?' as if that was foremost in your mind --- not what I thought.