Pharmalot: What prompted your organization to look at side effects so closely? Cohen: We've collected medication error reports for many years, actually, starting in the 1970s. If you went to our website, you'd see a lit of what we call high alert drugs, where outcomes are generally more serious. We've done surveys and some research and maintain a list of drugs most likely to injure patients. We've been an organization that collects med errors from practitioners who want to tell us their stories. So we collect anedoctal reports and we publish them along with prevention strategies that are peer-reviewed, and we have a newsletter that goes to every hospital every two weeks, another that goes to nurses every month and one for consumers. We've been doing this for years, and it's had an impact...Sometimes, these are product related - a device with some flaw. Some errors are due to names that sound or look alike, and were later changed. Some are practice-related - a doctor's handwriting or a nurse checking an arm band...But it's always anecdotal reports that prove things are happening and you don't want to see them repeated. So you publish and hope they don't keep happening.
But we aren't an organization that collects thousands and thousands of reports and runs large databases. We've always been a practitioner reporting program. But the FDA's database has many more reports than we would ever hope to attract, and we thought we should look to see what's there. So we made software modifications to extract some info and see what's getting reported most frequently - which drugs and categories asociated most with patient harm. And what we've done is not necessarily an accurate count of something happening out there and we've included those caveats in our articles. Anyway, we started that last year.
Pharmalot: Why the focus on Chantix? Cohen: That is the one we saw most frequently causing harm. That's just what showed up. As we tried to include in the (most recent) report, there are many factors out there that include events with Chantix. Fentanyl was second most frequently noted drug. But the reaction went beyond what we expected. We attempted to make contact with Pfizer and let the FDA know and had drug safety exprets look at it before it was published. We didn't hear back from Pfizer. But there's been no argument as far as the count (of adverse events).
I certainly understand why Pfizer would be concerned that we may have stoked some reports from our first report earlier, but I don't think enough attention was paid to accident and sudden loss of consciousness as we did. The Federal Aviation Administration brought a lot of attntion to this, and since then, addtionol actions by the Department of Defense - for people handle missile launching devices - and the Department of Transportation with drivers. I think that was a good move. For people who control a vehicle, you want to know if these occur and are reported. And this hasn't been denied. The FDA confirmed accidents in the database and are looking into it now. It wasn't clearly delineated in product labeling, although it did say use caution when driving. But we had a hard time finding the driving language...
But we're not just going to focus on Chantix in every report. We're looking to see what kind of problems are reported to the FDA Medwatch database. If we see other drugs, we might focus attention there.. We're a little concerned with the number of reports with Fentanyl, which is being abused and leading to adverse events that are leading to overdosing. We don't know if we'll look into that for sure.
Pharmalot: If you use the FDA database, why is ISMP is the first to release this kind of data? Cohen: I guess were the only ones who have done this so far. I don't know why the FDA hasn't done this on a regular basis. Maybe they have good reasons. They did release a quarterly report that listed 20 drugs that they are paying special attention to, but it didn't have any quantitative data. I don't know what kind of software they have that allows them to look at the Adverse Event reporting system. In any event, I think it's good to have an outside organization doing this.
Pharmalot: Has the problem of side effects gotten bigger because more people are taking more meds, or is it that you found a new way to pay attention? Cohen: I think some reports come from doctors and some from patients... We always have concerns that side-effect reports are increased by different factors, including publicity given the news media, but we have no way to control that... We have a lot of drugs and categories that weren't even available several years ago. Now, a lot of good has come from that, but at the same time, there are more adverse effects. We're not saying drug therapy is bad, but when we recognize there are serious problems, it's important to follow up... We hope people understand this. We're trying to provide a public service.
With Chantix, there's a balance. It's important to get it in the labeling and make people aware of the side effects, like driving or operating machinery while you're taking the drug may not be a good idea. By the same token, it is a drug that can help a certain number of patients stop smoking...I think people just weren't aware of the downside, and with almost every medication, there's an up side and a down side. And that's what we're seeing here.
9 Comments
It appears that ISMP has analyzed data from the Adverse Events Reporting System (AERS) to draw attention to Chantix. Although Mr. Cohen states that their reports recognize the limitations of the FDA data, he does not recognize in this interview that they preclude using the data as mentioned.
The Read Me file that comes with the AERS data specifically state: "Accumulated reports cannot be used to calculate incidence (occurrence rates) or to estimate drug risk", all of which is implied by Mr. Cohen. Secondly, it states that, "Comparisons between drugs cannot be made from these data." Clearly variability in drug risks are being insinuated by these reports. I urge you to investigate these points at http://www.fda.gov/cder/aers/default.htm, and conduct a second interview with Mr. Cohen.
I would just like to thank Mr. Cohen and his colleagues at ISMP for the work that they do, it was the side effects from Chantix that originally led me to this site.
Hi Tom,
Thanks for the note and I've written Cohen to ask him to reply. Hopefully, something will come back.
Regards ed
Hi Ed,
Thanks for following up on my suggestion. Any response?
Best, Tom
Hi Tom,
I've reached out twice and await a reply, either directly or, perhaps, on the site itself. So....
Regards ed
I am project director for Quarter Watch report and am pleased to respond to Tom's question.
When our monitoring program detected a large number of reports for Chantix, it was important to define "large number" meant. So we provided several comparisons to help regulators, doctors and patients understand the magnitude of what we were seeing. We reported:
1. More reported serious or fatal adverse events for Chantix than for any other prescription drug for two calendar quarters.
2. More reported serious or fatal adverse events for Chantix than for the 10 most frequently prescribed brand name drugs combined in 2008 Q1.
3. More reported serious or fatal adverse events than for alternative treatments for smoking cessation.
4. The typical (or median) number of reports of serious injury or death for a monitored prescription drug was 6 reports a quarter. In 2008 Q1 Chantix accounted for 1001 reported cases the United States.
This is a strong signal of a potential safety problem any way you look at the data. This does not tell us how "frequently" injury is occurring in the patient population. But people would say that the principal tool for post market surveillance of approved drugs has detected a safety problem worth priority attention.
For our frank and detailed discussion of the strengths and weaknesses of adverse event data please see the full text of our two reports:
http://www.ismp.org/docs/vareniclineStudy.asp http://www.ismp.org/QuarterWatch/2008Q1.pdf
Thomas,
Thank you for your insightful responses, and sharing links to your publications. I reviewed them and appreciate the discussion of the data limitations. And let me state that I agree that these data suggest further safety studies are warranted.
With that being said, I continue to find the use of these data (which I will infer are the AERS data since that question was not directly answered) for anything other than rationale for further study troubling. The severe limitations of these data, including no means for establishing causality, should preclude any scientist from drawing conclusions or making public health recommendations.
Lastly, all of your points (1-4) are in direct conflict with the caveats published by the FDA that I quoted in my original post: "Comparisons between drugs cannot be made from these data." All of your points are comparative and should not be made.
Ed, thank you for facilitating this candid exchange. I would suggest exploring the impact that quasi-scientific publications such as those discussed here have had on public policy decisions. It appears to be an excellent example of "flawed data in, spurious conclusions out". I'm sure the public would be interested.
Thank you again.
Best Regards, Tom
I would like to know how much money has been paid to key opinion leaders and Pfizer's experts to boost Chantix for approval and safety data. Interesting also to universities and smokimg cessation centers paid by Pfizer for Chantix studies where clearly universities and these clinics stand to profit from the best data reported. I think that is where a lot of the questions can be answered.
It is clearly a slap in the face to all the patients and their families to have Pfizer uniformly denying the many problems with this new "novel drug". It is conclusive that this is a first of its kind medication, so naturally problems could arise. What is deplorable is how Pfizer somehow makes it seem as if the patient is the one with the problems, not the drug.
That is a commonplace defense when a drug goes wrong, but in the case of Chantix a better defense can not be found by Pfizer.
As Chantix will one day have to stand alone, I hope that some of the back-pedaling and name calling stops by Pfizer as they begin to work with others to help find a solution to this medication nightmare. Too many lives are at risk to have a company be so underhanded and flippant about the most reported AEs to the FDA. Pfizer was aware of the alarming rise in number of AEs being reported to the FDA, but chose in Pfizer fashion to point fingers and make accusations when the truth was told by others.
The defense for Pfizer is no longer plausibly to even the die hard-pharma drs. I think this wretched defense of blaming the patients is reserved for the criminal. It is past time for action.
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