Pfizer Plans Chantix Ad Blitz To Counter Scrutiny
99 CommentsBy Ed Silverman // May 29th, 2008 // 7:06 am
The drugmaker is trying to salvage what was supposed to have been a blockbuster drug but is, instead, quickly becoming an albatross, especially after a report last week showing the anti-smoking med was linked to 988 serious injuries in last year’s fourth quarter and a host of side effects, including heart irregularities, seizures and acute myocardial infarcation.
In the wake of the safety questions, the stunned drugmaker today will run ads in five major newspapers in which its medical director explains risk-benefit balance, according to The Wall Street Journal. Next week, the drugmaker will start hosting roundtable discussions for the media and letters will be sent to 300,000 healthcare professionals.
The PR and ad campaign come as fresh questions are raised about whether Chantix is effective at dosage levels that are safe, the paper writes, adding this was a concern for FDA researchers prior to the drug’s approval, according to agency records.
The FDA’s own review prior to its approval of Chantix in 2006 suggested that higher dosages of Chantix appeared more effective in helping users to stop smoking, but also showed a greater incidence of potentially harmful side effects, the Journal writes.
Pfizer’s researchers say the FDA raised concerns about the dosage size as part of the normal approval process, but noted the FDA ultimately approved the drug for the dose recommended in trials that showed Chantix better at stopping smoking than its competitor drug or a placebo.
The campaign comes Chuck Grassley, the Iowa Republican on the Senate Finance Committee, wrote the FDA about the May 22 study by the Institute for Safe Medication Practices because “the report states that the FDA never warned consumers about other kinds of serious harm caused by Chantix,” according to the Journal. A June 3 meeting between FDA and Grassley is planned.
Pfizer says most, if not all, of the newly reported side effects are in the drug’s existing product label, and feels that label accurately reflects the drug’s risk-benefit balance and includes information about adjusting the dose.
The FDA upgraded the warnings on Chantix this year to include neuropsychiatric issues including depression and suicidal thinking. But the ISMP study raised alarms about many non-neuropsychiatric side effects previously reported to the FDA that the agency didn’t flag in warnings to consumers, the Journal notes.
The ISMP study, which prompted the Federal Avaiation Administration and Federal Motor Carrier Safety Administration to ban Chantix from being used by pilots, air controllers and truckers, analyzed the FDA’s own publicly available adverse-events data collected since the drug came to market.
Chantix was given priority review status because of the many deaths linked to smoking, the Journal notes, but wasn’t put before an FDA advisory committee for a public debate and vote before it was approved for market. In May 2006, an FDA reviewer noted “tolerability issues” at the dose of 1 milligram twice a day; problems included nausea, attention disruption, chest pain, drowsiness, depression and abnormal dreams, the Journal writes today.
The FDA reviewer wrote that Pfizer’s final report revealed “many drug-related adverse events showing a dose-dependency” and suggested patients had fewer side effects and stayed on the drug longer when they were allowed to lower the dosage to half the recommended dose, according to the Journal.
Oracle
Chantix (varenicline) Safety
Wednesday, May 28, 2008
Jonathan Foulds, MA, MAppSci, PhD
Problems with the ISMP report and its conclusions
There are a number of fundamental problems with the quality of the data, analysis and interpretation in the ISMP report. Before discussing some of these, it is worth discussing the way that reports of serious adverse events are delivered to the FDA. There are 4 main sources of reports.
1. Members of the public can send reports directly to FDA, either by mail or via an on-line reporting system (and I have provided the link on previous posts on this blog about Chantix to ensure that reports reach FDA).
2. Health professionals can report adverse events to FDA.
3. Lawyers sometimes report adverse events to FDA.
4. The manufacturer is required to report to FDA any reports that are brought to its attention directly. Those adverse events that are already mentioned on the product labeling are reported on a quarterly basis, and novel symptoms must be reported within 15 days (expedited).
Reports from the first 3 of these sources are entirely voluntary and are made in a rather haphazard way. The ISMP report estimated that typically between 1 and 10% of serious adverse events are actually reported to FDA. It is commonly found that AE reports peak around two years after the launch of a drug, even if the drug becomes used more often thereafter. The purpose of the FDA’s reporting and monitoring system is to facilitate post-marketing surveillance and enable detection of patterns of adverse events that could potentially be caused by a medicine but were not detected in the initial placebo-controlled trials leading to drug approval. The main point here is that these reports are not made in a systematic way, and the frequency of reports can be influenced by factors such as (a) the frequency of use of the drug (b) the novelty of the drug (c) media coverage of the drug and (d) efforts by the company to interact with users in a manner that will lead to them hearing of and therefore being required to report on AEs.
With these factors in mind, here are some of the problems with the ISMP report:
1. The report fails to consider the frequency of the use of the drug when considering the number of adverse events being reported. Since its launch in August 2006 (i.e. less than 2 years), Chantix has been used by an estimated 5.5 million smokers in the United States. In 2007 alone it was used by 3.8 million new patients in the U.S. (6.2 million prescriptions). This is many times more than the other drugs listed in the ISMP report. For example, Etanercept (Enbrel, the drug with the 3rd largest number of adverse event reports to FDA) was launched in 1998, and has been used by a total of 450,000 patients WORLDWIDE in those 10 years. Comparing frequency of adverse events without adjusting for the frequency of drug use is so obviously inappropriate as to cast doubt on the reliability of the report as a whole.
As mentioned briefly in the ISMP report, many factors can affect the frequency of reporting of adverse events to FDA. In the case of Chantix, the widely publicized death of a rock musician (who was tragically shot by a neighbor in Texas) which his partner felt could have been related to Chantix, sparked off widespread media speculation about potential side effects. The manufacturer also offers a number of direct to consumer quit smoking services, including a free telephone hotline called “Get Quit”. Because this hotline is run by the manufacturer, whenever a caller mentions a symptom, they are immediately transferred to the medical department, the details are noted and the information reported to FDA. These events and procedures can have a large effect of increasing the number of serious adverse events reported and this was not adequately considered in the ISMP report. It is noteworthy that 92% of the events analyzed in the ISMP report came via the manufacturer.
2. The report fails to adequately consider the possibility that some of the reported adverse events may have been caused by nicotine withdrawal. The vast majority of those using Chantix were attempting to quit smoking, which itself is known to cause a range of nicotine withdrawal symptoms, including many of the symptoms most commonly reported to FDA and mentioned in the ISMP report (depression, insomnia, anxiety, weight increase). It is entirely plausible that many of these reported symptoms were caused by nicotine withdrawal rather than Chantix. In fact in the placebo-controlled trials of Chantix, withdrawal symptoms were REDUCED in those using Chantix.
3. The report doesn’t adequately consider the serious health effects of tobacco dependence. The ISMP report characterizes the other comparison drugs as being “intended for serious illness in patients and have benefits that are accompanied by substantial risks. In comparison, varenicline is intended for use in healthy people to help stop smoking.” Unfortunately this statement indicates a misunderstanding of the nature of tobacco dependence as a serious illness causing the premature death of 50% of continuing smokers, and of the fact that a high proportion of patients using smoking cessation medications are already suffering from or at very high risk for smoking-caused illnesses, including some mentioned as adverse events in the report (e.g. cardiac arrhythmias).
4. The report inaccuratley characterizes the relative efficacy of varenicline versus other treatments. The ISMP report states that Chantix has similar long term quit rates to nicotine gum. This statement contradicts the findings of the new US Public Health Service Clinical Practice Guideline on Treating Tobacco Use and Dependence, which found a mean quit rate of 13.8% with placebo, 19% with nicotine gum and 33.2% with varenicline (p109) and that quit rates with varenicline are significantly greater than with the nicotine patch (p121). This Guideline, written after the recent labeling changes for varenicline, concluded that, “Varenicline is an effective smoking cessation treatment that patients should be encouraged to use.” (p113).
Probably the most basic problem with the ISMP report is its failure to consider the frequency of use of the medicines as a factor influencing the interpretation of the frequency of adverse events reported. It therefore remains unclear whether any of these serious adverse events were caused by varenicline. When added to the other problems of interpretation mentioned above, I prefer to rely on the recommendation of the US Clinical Practice Guideline, which resulted from a very thorough review of the available scientific evidence.
So what does this mean for patients considering quitting smoking? As always, rely on the advice of your own doctor rather than on reports in the media or the internet (including this one!).
Ed Silverman
Hi Oracle,
Thanks for the note. This comes off a bit like Pfizer’s charm offensive in so far as that Foulds is a Pfizer consultant and member of Pfizer’s speakers bureau, as well as an expert witness against tobacco companies. Does that make him wrong? Not necessarily, but since you took the trouble to post this much, the added info may provide some context in which to understand what informs his views.
This is Foulds…
http://sph.umdnj.edu/staff/staffDetail.cfm?tblPers_ID_pk=6
And this offers a little more…
http://www.annals.org/cgi/content/abstract/148/7/554?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=The+case+for+treating+tobacco+dependence+as+a+chronic+disease&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT
If Chantix helps some people, without causing an adverse event, that’s a good thing. By the same token, if serious adverse events are being reported - however imperfect the reporting system - they should be taken seriously and examined. Seems only right.
Pfizer, meanwhile, hasn’t been terribly forthcoming about the number of adverse events. If the numbers aren’t so big - in the scheme of things, as Fould suggests - perhaps more candor would have been helpful all these weeks.
Cheers
ed
Insider
Attention Ladies and Gentlemen, this is your Captain speaking:
http://pharmagossip.blogspot.com/2008/05/chantix-found-in-ad-agencys-wastebasket.html
PR - bring it on!
Oracle
Thanks Ed
It’s always tough to hear both sides as it diminishes the sensational impact but I like to see all the qualifications up front rather than have them buried or omitted in the original story..
You should also realize that you come off as fairly biased against anything or anybody from pharma.
Where’s the middle ground??? I believe it’s in the details
Insider
Hey Oracle,
Leave Ed alone. He is fair and balanced.
I claim the anti-pharma ground. And, as an insider, I should know!
Cheers
Jack
Ed Silverman
Hi Oracle,
Let’s see, where to start. Well, if Pfizer wants its story told, they can do a PR and ad campaign, which reaches however many people. If Pfizer wants to provide me directly with more info, there are plenty staffers who can spend quality time with me, as they do with the WSJ. They’re even free to submit an op-ed, a few of which I’ve run recently. Questions are answered on the phone or e-mail, but no one from Pfizer has approached me at all, except to invite me to a blogger dinner next month, but that was in the cards before the ISMP report. They may have a new chief of communications, but they’re still behind the curve on this issue.
Which brings me to your second point - the accusation of bias. I believe we’ve had this conversation before. As to Chantix, I’ve run posts working off the news, whether it was from the FDA or Pfizer or somewhere else. You can do a search. There are safety questions about the drug and that’s news. So that’s what gets posted.
As to your accusation, I am not biased. And I will repeat myself for your benefit - I am a journalist and I follow the tension. And this is an industry saddled with tension due to challenge and change. There are a great many ways in which the tension plays out - through stories about patents, pricing, safety, legislation, promotion, to name a few - and that’s why you see what you see on this site. It’s not my job to be a cheerleader or critic - for that, you have PR departments and agencies, trade groups, consumer groups, congressional investigators and on and on. I try to post - for digestion and discussion - pertinent issues and what, if anything, those various folks are doing about those issues.
On a personal level, I take meds, as do my family members, for any number of reasons, some of which require regular prescriptions. And I bask in the economic warmth provided to my region thanks to the many drugmakers located nearby and the companies and individuals that feed off them. If they go away, my area suffers. Anti-pharm? I don’t think so.
I don’t mind the attacks, but I don’t believe I’m the issue. In any event, thanks for writing in.
Cheers again,
ed
Nathan
Ed,
Here’s a quote from your above statement:
“If Chantix helps some people, without causing an adverse event, that’s a good thing.”
You can’t even commit to saying “Chantix helps some people without causing adverse events.” Instead, you qualified the statement with an “if”. The FDA has approved Chantix. It *is* safe and effective in the opinion of experts. You don’t have to qualify your statement with an “if” thereby giving the impression that Chantix (in your opinion) may not help people without causing adverse events. No one here is argueing about the effectiveness of Chantix. We are arguing about the relative risk profile. Foulds makes some very good points that should have been addressed in your article.
I agree partially with Insider — you do try very hard to be unbiased. But this article (and your subsequent comments) prove that you aren’t always successful. We’re all human — we all have our biases. I don’t count that against you. But don’t pretend that you don’t have biases — you do. You can try to cover them up — but at some level we all are stuck with our biases. Even journalists.
Justice in Michigan
I don’t want to get into the bias issue - which I agree we all have - but I think there is a real semantic difference between saying a product _is_ “safe and effective” and FDA’s approval of it. Approval means that, based on NDA materials, it is “safe and effective” _enough_ to be initially marketed. Whether, in fact, it _is_ those things will depend on post-marketing experience, whether as analyzed by the FDA or anyone else.
In other words, “safe and effective” are inevitably relative terms, depending on who is doing the evaluating an the criteria employed. The terms are meaningful only within that context. So, again, an FDA-approved product - at the time of approval - is safe and effective _enough_, by FDA criteria, to go forward. (And knowing that there may have been considerable disagreement within FDA about that decision).
If post-marketing experience shows that those who opposed approval were - in retrospect - correct enough for eventual withdrawal; does that mean it was _not_ “safe and effective” at the outset? Not really. Only that the criteria changed in light of new info and analysis, which is always extremely complex (e.g., depending on other tx options, seriousness of condition, etc. etc.).
Ed Silverman
Hi Nathan,
Suddenly, I’m the issue. So here’s my answer: I qualified my statement for a very simple reason - I believe in safe and effective meds and, if possible, without a harmful adverse event.
I know adverse events occur. I understand there are risks - never said otherwise. I’m also under the impression that people would simply prefer not to experience one; at least, that’s how I feel. And so I refer to the hope that a med would do the job without harm. I don’t see that as a bias. Sorry that you do, but I think you’re looking for something that isn’t there.
In general, I do my best to avoid bias. And when I have an opinion, I’ve shared it. There were posts on this site where I have raised questions or made statements indicating my opinions or thoughts. I wrote what I did because I had a particular view. Otherwise, though, I do my best to keep my views to myself.
Now, back to work,
ed
Nathan
Ed says:
“And so I refer to the hope that a med would do the job without harm. I don’t see that as a bias. Sorry that you do, but I think you’re looking for something that isn’t there.”
You could be right. But re-read your statement: “If Chantix helps some people, without causing an adverse event, that’s a good thing.”
I just don’t understand why you qualify that statement with an “if”. Chantix clearly DOES help some people without causing adverse events. That is very, very clear. There is no “if”. The only thing in question is how much risk is involved.
Based on your sentence, it sounds as if you are questioning whether Chantix is helpful to ANYONE. I don’t think that’s what you mean, but it is what you said.
Oracle
Safe and effective can mean statistically safe and effective or safe and effective for every single person on the face of the earth and then there’s the unborn…
What would you do if the latter?..shut down the entire industry
Cars are not totally safe or effective
I don’t think radicals are going to be invited to the table you want to sit at..The conflict can be solved with a war or by negotiations. I take the Obama approach
Nathan
Getting back to the real topic, for those of you who didn’t take the time to read Oracle’s lengthy post, I want to summarize the key points. It’s very important and pertinent to this issue.
1) Chantix has been used by more than 10x the number of people in any other drug in the ISMP report. Therefore the raw numbers are meaningless. It’s the FREQUENCY (events per dose) that is important — not the sheer number of events.
2) The report fails to adequately consider the possibility that some of the reported adverse events may have been caused by nicotine withdrawal. Withdrawal symptoms include many of the symptoms most commonly reported to FDA for Chantix.
3) The ISMP report states that Chantix has similar long term quit rates to nicotine gum. This statement contradicts the findings of the new US Public Health Service Clinical Practice Guideline on Treating Tobacco Use and Dependence, which found a mean quit rate of 13.8% with placebo, 19% with nicotine gum and 33.2% with varenicline (p109) and that quit rates with varenicline are significantly greater than with the nicotine patch (p121).
These are very important points. I don’t care if these points came from the CEO of Pfizer or from Lisa Van S. They make sense and should be a part of any discussion of the side effects of Chantix.
Pharma Giles
Ed:
You are just SO biased! Anyone who on reports on things such as FDA concerns or product side-effects must automatically be “anti-pharma”, QED.
I’m not surprised the Drug Wonks boys are spamming you again…
Ed Silverman
Hi folks,
I’ve already explained this - please go back and read my comments above. I suggested the preference for using a med without an adverse event, which isn’t the same thing as saying a med shouldn’t be taken if an adverse event may occur, which we all know is hard to predict and impractical.
So please stop trying to parse my words to try to prove bias simply because I didn’t post the Foulds memo. And by the way, I wasn’t aware of the Foulds memo until ‘Oracle’ posted it, but somehow I’m accused of bias because I didn’t refer to it in my post about the pr and ad campaign, and the dosage issue.
As I also indicated above, if Pfizer wants to address the whole matter point by point, they can contact me anytime they want. Or they can leave it to anonymous commenters to issue stealth attacks, I suppose.
Regards
ed
Just A Thought
Are school bus drivers banned from using this drug as well?
Pharma Expert
Ed,
Love this tread, more fun than I’ve had reading about pharma in quite a while!
And, you’re not biased. But Big Pharma seems to start taking Pharmalot seriously.
Jaynesday
So here are the numbers for the adverse events.
988 serious events.
Worst case only 1% of the actual total.
Actual total serious adverse events could = 98,800 IN THREE MONTHS.
I don’t care how may million people have taken the drug, if you feel OK with this many people experiencing adverse events and don’t care to look in to the situation, you’ve put your finger on why so may people are anti-pharma and why we’ve seen too many disaster drugs lately.
As far as the other *possible* reasons this many seriously harmed people (adverse events) are out there, well don’t you think we should find out rather than speculate?
Concerning the parallel to driving a car, I can tell you that when a car manufacturer finds out that it has a quality issue with their product they are all over it. The greatest fear is that you will loose one customer that will tell someone else and the snow ball is rolling. Those customers will never come back. When the day comes that pharma quality issues reach the ears of the customer in the same vain, they will rue the day that they comforted themselves with statistics and did nothing about the problem. I don’t think that day is far off.
Jaynesday
Here’s what I would like to see.
A rating system, by manufacturer and product, that exposed:
- the raw number of harmed customers (adverse events)by manufacturer
- the raw number of harmed customers per product
- the percentage of harmed customers by manufacturer /total sales count
- the percentage of harmed customers by product taken / total sales count
By doing this I feel that the best manufacturers will come to the top. The best drugs will be developed both in terms of helpfulness and safety.
Rather than give me a statistical analysis of the chances that I will be harmed or killed by a drug, I would like to see these numbers. Let me decide if I am willing to pay for a drug (or device) that has kill 500 people and harmed another 5000. Regardless of what it will do for me. Let me know that a particular manufacturer is more or less known for producing products that are dangerous or not dangerous.
We do the same thing in other industries. Many people only buy products that the Consumer Reports recommends or that various safety and quality organizations recommend after testing and inspection. Companies under these constraints are scrambling to get to the top of the list. Who benefits? Both the company and the customer.
We’ve talked about pharma being an open book. We’ve seen how the FDA has failed to be our safeguard. We trusted that they were looking out for our best interests and found out that they had other interests in mind. The true regulator is the market place. Make these things known and we won’t need the FDA. The drug companies themselves will make sure they have quality products by satisfying the free market force and that’s the way is should be and must be.
Oracle
Jaynesday
First of all, many claims of harm are self reports that can’t be verified except by your lawyer. i.e. a drunk musician goes crazy and blames only one of the substances he abuses. This won’t hold any water with any IQ above 90. How do you propose to know ahead of time whether a drug will harm 500 people after it has passed all the animal models / tox studies etc that can be thought of. No one is trying to harm anyone and the drugs work for the vast vast population targeted. Sorry to disappoint. Will you volunteer in the next clinical trial or will you leave that to others so you can be fully informed? You sound like a conservative. Will you help pay for broader clinical trials that involve more patients? That’s the only way to achieve safer medication. Or do you just want to keep complaining that cars and drugs should be as safe as airplanes. I’m sorry this topic is above your current understanding..
Jaynesday
Oracle,
You have hit on the key to this solution.
The first thing that would be needed would be an upgrade to the reporting system. True reports would be carefully kept. If needed some means to verify reports would be required. Lets get rid of excuses such as - A few of the reports are fraudulent so lets dump the whole lot of them and go on our merry way. Either have reliable reports or don’t waste time reporting, sorting and not acting on any of them.
How easy it is trust your own statistics on a relatively few trial patients and throw out post market reactions because you don’t like the results.
With reference to the 500 reactions - I’m talking about an ongoing users tally, grading if you will, that informs patients that there are problems with the use of the drug/device. This would be actual results from the product on the market, not statistical probabilities that you will or won’t be harmed. Although that’s where we have to start. Also grading the manufacturer as a whole. Hold the manufacturer accountable. Simple as that. If I went to the hospital and the doctor prescribed a drug I would love to know on a scale of 1-5 how the manufacturer’s products as a whole have performed and how this particular drug performs. If I saw a (1) (poor), I would take a pass (and here’s the clincher) even if I had to pay more for a different drug. ie. the reward for quality. Obviously we would have to hold our insurance companies accountable in this case also. They would not be allowed to support poorly performing company’s or drugs.
So concerning volunteering for the next clinical trial - don’t we all do that when we take a drug? If we have a reaction it should be taken seriously, not swept under the rug as an adoration or fraudulent occurrence.
You say that no one is trying to harm anyone and I agree for the most part. Its just that too many people *are* being harmed and we need to make a better effort of doing something about it.
I’ll be the first to admit I don’t have the insider’s picture about pharma. I do know that something is wrong and I do have a bit of experience in manufacturing related to quality, customer satisfaction and designing a better product.
I’ll leave you with a couple of questions since you apparently have a better answer. (I hope)
1. Is pharma, FDA, etc perfectly fine as it is? In other words, there’s no problem here.
2. If the answer was no - what would you propose we do to improve?
Jaynesday
Oracle.
In case you answered yes (there’s no problem here!) to question 1) above, please read the attached report
–
Adverse Events Study titled - Serious Adverse Drug Events Reported to the Food and Drug Administration 1989-2005 –
Authors - Thomas J. Moore, AB; Michael R. Cohen, RPh, MS, ScD; Curt D. Furgerg, MD, PhD
http://www.ismp.org/pressroom/PR20070910_1.pdf
Not sure if this has been posted prior but…
Some highlights -
* From 1998 through 2005, reported serious adverse drug events increased 2.6-fold from 34,966 to 89,842, and fatal adverse drug events increased 2.7 fold from 5519 to 15,107. Reported serious events increased 4 times faster than the total number of outpatient prescriptions during the period.
* Conclusions: These data show a marked increase in reported deaths and serious injuries associated with drug therapy over the study period. The results highlight the importance of this public health problem and illustrate the need for improved systems to manage the risks of prescription drugs.
* Implications: This study shows that substantially growing numbers of patients are experiencing serious injuries from drug therapy, although the exact magnitude of the population increase cannot be estimated from these data. Future initiatives to improve drug safety require more accurate and capable systems to monitor post marketing ADEs. This growing toll of serious injury shows that the existing system is not adequately protecting patients and underscores the importance of recent reports urging far-reaching legislative, policy and institutional changes.
I would add - let the truth be told and let the customer decide who will survive.
HorusCat
Jaynesday,
Extrapolating to almost 1 million AEs from the possibility of only 1% being reported is disingenuous. Especially considering the points Oracle made that the GET QUIT call line means that every time a caller MENTIONS an AE, it gets reported. This means that if he says, “I took Chantix and got a bladder infection,” it gets reported as an AE. Thus, the percentage of AEs reported with Chantix reliably can be assumed to be far above the 1% number, thus reinforcing Oracle’s point that on a “per use” basis, Chantix’s AEs aren’t as mind-boggling as the “Safe Medicine” guys want us to thing.
Jaynesday
HorusCat,
That would be 98,800 not 1 million. I agree it isn’t good to do too much extrapolation. But (forgive me if I’m wrong about this) isn’t that what all pre market trials do? But anyway, what I think we all can agree on is that we need to firm up the reliability of AE reports. It’s the first step, the basis of what anything else (whatever it might be) is built on. We live and die by statistics, if they’re bogus what a waste of time and money to collect them and how misleading to act upon them.
The study that I posted makes mention of the issue of erronious AE’s and they tried to adjust for such in some portions of the study. So the authors admitted the problem but even still came to the conclusion that the problem is big enough to recommend we make drastic changes to the system.
Back to Chantix though, even if the percentage of reported AEs is closer to the actual number, 980 serious AEs in a *3 month* period in my mind is a problem that needs a solution.
We can also agree that there are more than 980 actual AEs. What that number is, is up for debate I suppose.
HorusCat
Jaynesday,
Sorry about the ten-fold increase in your math!
I agree with you that AE reporting is not useful as it stands. The company is required to report all AEs (as a rep I call Med Affairs with AEs or submit them via computer). Physicians are supposed to do so, but most don’t. With patients of course it is voluntary, which is as it should be. There may not be a better system which honors individual liberty; I would not advocate enforced reporting on the part of consumers or physicians.
One of the problems with “links” to AEs is that such verbiage may suggest a causal relationship that doesn’t exist. Closer perusal of these reports by anyone other than the FDA is precluded by HIPAA, and probably even the FDA can’t access possibly relevant details in the patient’s medical records. A report of a serious event may be made, but unless the patient is currently or has very recently taken medication which indicates he has an on-going medical concern, the FDA may not know of complicating factors. I don’t know, for example, whether the FDA would know if a person with a diagnosed but untreated arrhythmia had such a problem when cardiac arrhythmia is “linked” to Chantix. I suspect not, and I wouldn’t rely on claims by the patient or the patient’s family that they were in “perfect health” prior to taking the med.
Jaynesday
What about requiring the treating physician to report and/or requiring all self reports to be funneled through an independent evaluator of some kind?
HorusCat
Jaynesday,
I am almost never in favor of our government requiring us to do anything. Government coercion always has a chilling effect on personal liberty and should be avoided at all costs.
I just went to an epilepsy conference where data from pregnancy registries was presented. The presenter highlighted the trouble with reporting here in the US–because of HIPAA, the ability of a third party to report is limited. (In the example of a pregnancy registry, the physician simply can’t do it.) Thus, almost all truly useful information here in the States must come from self-reporting. Patients often don’t want to take the time, even for a few 15 minute phone calls with a pregnancy registry. Then there is the issue of the variables that must be taken into account–maternal age, folic acid intake, other medications, background rate of defects, genetic predisposition. It was much more complicated than I had envisioned to assign causative effect.
In the case of adverse events, again, similarly I suspect that physician reporting is limited by HIPAA. They can give the nature of the AE, but cannot provide any details that would allow patient identification. Thus, really digging down into a cause and effect relationship with serious AEs is almost impossible until it gets to a lawsuit, where discovery preempts HIPAA. At that point, you have a jury trying to understand a multivariate relationship, an emotionally charged atmosphere, biases for and against pharma and doctors…not a scenario to discover “truth” no matter what Justice says.
The complex relationships of AEs, medications and multiple complicating factors (such as genetics, medical history, other meds, etc., etc) make determination of cause and effect difficult. When the dust has settled, it is easy to cast stones and say a company committed “fraud” or was “covering up” or “spinning” when what they may have been trying to do is untangle all the complicating issues before they trash their billion-dollar investment.
The press takes all that complicated mess and boils it down to a headline: Drug X causes THIS BAD THING. And the public buys it. It does no one a service.
pg
Favorite bits of this thread. Firstly because of the content of the link, particularly the “claim” that Pfizer will probably never be able to make regarding Chantix:
“Insider
Attention Ladies and Gentlemen, this is your Captain speaking:
http://pharmagossip.blogspot.com/2008/05/chantix-found-in-ad-agencys-wastebasket.html
PR - bring it on!”
Secondly:
“Pharma Giles
Ed:
You are just SO biased! Anyone who on reports on things such as FDA concerns or product side-effects must automatically be “anti-pharma”, QED.
I’m not surprised the Drug Wonks boys are spamming you again…”
(LOL)
and last, but not least, one line from Oracle:
“How do you propose to know ahead of time whether a drug will harm 500 people after it has passed all the animal models / tox studies etc that can be thought of.”
A difficult one. Animals in drug tests don’t get issued with guns or ropes. Even if they were, they wouldn’t know how to use them when they felt murderous or suicidal.
truthman30
As usual the PRO-Pharma damage limitation brigade completely misses the point..
Let’s not get bogged down in Semantics here..
Whatever way you want to gloss it up ..
The issuse is, this drug looks extremely dodgy…
If people want to quit smoking they can do it with “willpower” ..
But you can’t patent that can you?
This drug is a total con job..
It is opportunistic and expolitative to target smokers who are desperate to quit smoking with a drug which is quite obviously dangerous and has dubious efficacy…
The side effects are obviously very serious and the “risk-benefit” ratio is scandalously bad…
It reminds me of Paxil..
Jim
I have read some of the postings listed above and on a previous site at this location. One of the questions raised was is Chantix a safer alternative then smoking.
That seems like it should be a rhetorical question, but in my case it is not. I smoked for 40 years and as yet have not suffered any consequences through my use of tobacco; I took Chantix for 4 weeks and approximately one year later I have not fully recovered from the adverse reactions that I attribute to my use of Chantix. You do the math, 4 weeks versus 40 years. Also though Quarter 3 of 2007, the FDA received at least 8 reports of Mutiple Sclerosis, in which either a physician or another health care provide alledged that the probable cause was Chantix.
In the studies published fully 28% of the individuals participating in the Chantix studies dropped out because of adverse reactions.
As far as the 33% claim by the US Health Department, Pfizer’s own studies place this number closer to 23%, a 6% improvement over Zyban and I am talking about Long Term Quit Rate, that is for a period of at least 52 weeks. The numbers cited for the 33% do not state the period reviewed and have as much staistical relevance as the 44%, 12 week quit rate posted in the original Pfizer ads without an indication as to period of time in question.
As to the studies, is a 6% increase over Zyban a significant increase, I would guess that most people would agree that it is, however when you look at the side effects for Zyban as opposed to those listed for Chantix, I believe the FDA did not exercise prudent judgement in approving this drug. It is also interesting to note that in their original studies Pfizer deliberately attempted to skew the results of their product against Zyban.
In addition, Chantix is a derivative of the drug cytisine, a drug already tested and disapproved by the FDA because of potential damage to the Central Nervous System.
As far the number of prescriptions written, I keep reading conflicting accounts on this number. It appears that Pfizer is attempting to manipulate the numbers to downplay the number of adverse events reported.
The original patient information copy I received was a joke, it listed 5 or 6 realtively benign side effects and that was it. Had I been more adequately informed about the potential side effects I would have never taken this drug.
The thing that makes this more galling is the FDA is exercising extremely prudent care in their recommendation for a anti-schizophrenia drug applied for by Lilly. Final approval is not expected for at least another 3 years. The FDA’s major concern is the that anti-schizophrenia drug easily passes the blood/brain barrier and there is potential for permanent brain damage. Well Chantix also easily crosses the blood/brain barrier and these same concerns were never addressed.
One final note, I am tired of the tired it’s the nicotine withdrawal that is causing the majority of the problems. I quit on three separate occasions and my major withdrawal symptoms were fatigue and weight gain, and the fatigue usually subsided after one month.
However, I know the Volstead mentality surrounding smoking today will prevail and Pfizer will be allowed to keep their watered down patient information labelling and there will be a continued push to keep this drug on the market and to promote its use. Everytime I see a “MyTime to Quit” advertisment I want to put a chair through my television.
S. Perry
Jim,
I’m sorry that Chantix didn’t work for you, and I certainly hope it didn’t negatively affect you to that degree, and I’m not outright denying that it did. However, I cannot find any data to support your claim of “at least 8″ reports of people being diagnosed with MS, with the “probable cause” being Chantix. If that data is true, it would be extremely difficult to establish a link between MS and Chantix. MS affects about 100 in 100,000 people in the general population. Going by those numbers, I’d expect MORE than 8 people to be diagnosed with MS while on Chantix, simply because of how many people have been prescribed it.
I cannot find any data to support your claim of “28% of the individuals participating in the Chantix studies” dropping out. I’ve heard reports that people were turned away in trials because they already had psychiatric conditions, which may be what you’re thinking. If that seems odd to you, I can understand that. However, that’s the way drugs that aren’t geared toward people with psychiatric illnesses are tested, and that’s the way they’ve been tested for a long time. Also, please try to check your numbers before you use them—especially if you don’t provide any sources for your claims.
Please provide all of us with any sort of evidence supporting your claim that Pfizer “deliberately attempted to skew the results of their product against Zyban.” Are the results of the 52-week follow-up your evidence? If anything, those results support Pfizer and Chantix.
I’m quite sure you are incorrect in saying that the FDA “disapproved” cytisine. I’m assuming you mean that it was “rejected” by the FDA and not “disapproved” by the FDA. But I’ve found no data, from the FDA or elsewhere, to support this claim.
Regarding your claim that Pfizer is “attempting to manipulate the numbers to downplay the number of adverse events reported,” if you are reading different numbers, it’s because the professionals who are writing the numbers are referring to different points in time in the last two years. Last year, there were 4 million prescriptions or so. This year so far, there have been two million more, so a total of six million, approximately. The exact numbers are difficult for a layperson like myself to find, but to automatically say that Pfizer is manipulating any numbers, with absolutely no evidence to support that is extremely dishonest and has no place in any argument.
Regarding your statement that, had you known about the side effects (which aren’t necessarily from Chantix) you have now, you wouldn’t have taken it: Every drug has bad “potential” side effects. The issue here is exactly how high of a potential there is, based on what the trials suggested. Since the years of trials of varenicline suggested that the potential for serious side effects was incredibly low, if not non-existent, there is no reason to put them on the label. Do you see “death” as a side effect to aspirin? No. You see warnings not to use it with some other drugs, not to use it for more than several consecutive days, and not to use it too much. It also explains that you should tell your doctor if any serious side effects occur. It’s common knowledge that most drugs, OTC and prescription, have potentially fatal consequences when not used properly or without giving enough information about yourself to your doctor.
Regarding Chantix passing the blood-brain barrier: Many drugs pass the blood-brain barrier, including most antidepressants, alcohol, caffeine, and wouldn’t you know it, nicotine. It is the chemical make-up of the drug that is important, and how it will react—to put it in very simple terms—with the really important stuff in the brain. The years of trials of Chantix showed no brain damage, or anything close to brain damage.
You say you’re tired of people’s claims that the serious adverse effects linked to Chantix are actually due to nicotine withdrawal, and you use your own experiences with quitting before as evidence. Please note that Chantix is a partial agonist and partially activates nicotinic acetylcholine receptors, something that quitting cold turkey or using nicotine replacement therapy doesn’t do. The nervous system is affected differently and different reactions to the changes are exhibited. The other times you quit, for how long did you quit?
Is Chantix a safer alternative to smoking? The risk of serious adverse effects caused by Chantix is very, very, very, very low, if it truly exists, but Chantix should really still be a last resort. People who experience adverse effects cannot truly show that Chantix, and not nicotine withdrawal, is causing those effects. People with psychiatric illnesses should not take Chantix unless it is absolutely necessary.
That being said, I’ve seen friends and family members become victims of cigarettes. I’ve seen people very close to me with emphysema and lung cancer caused by those cigarettes, and I’ve seen them suffer. Meanwhile, at least tens of thousands of people—other people’s friends and family members—have quit smoking around the world because of Chantix, and at least tens of thousands of people will now have healthier, longer, more enjoyable lives because of it.
That sounds like a good alternative to me.
pg
http://www.fda.gov/cder/foi/label/2006/021928lbl.pdf
Following is a list of treatment-emergent adverse events reported by patients treated with CHANTIX during all clinical trials.
The listing does not include those events…for which a drug cause was remote…and those events reported only once…”
“…NERVOUS SYSTEM DISORDERS. Frequent: Disturbance in attention, Dizziness, Sensory
disturbance. Infrequent: Amnesia, Migraine, Parosmia, Psychomotor hyperactivity, Restless legs
syndrome, Syncope, Tremor. Rare: Balance disorder, Cerebrovascular accident, Convulsion,
Dysarthria, Facial palsy, Mental impairment, Multiple sclerosis, Nystagmus, Psychomotor skills
impaired, Transient ischemic attack, Visual field defect…”
pg
http://www.regencerx.com/docs/physicianRx/chantix1206.pdf
“…Evidence
- All of the clinical trials evaluating varenicline (Chantix) for smoking prevention were fatally flawed.
- Drop-out rates ranged from 24% to 37%. These high rates erode randomization and confound the results…”
pg
“…Conclusion
• Varenicline (Chantix) is non-preferred/non-formulary because there is:
- No useful evidence for improved efficacy over existing formulary agents.
- No useful evidence for improved safety over existing formulary agents.
- Higher cost relative to other formulary agents…”
(Same link)
pg
Drop out rates:
http://www.fiercepharma.com/story/fda-chantix-may-pose-psych-risks/2008-02-04
“…patients with a history of psychiatric illness were excluded from Chantix trials…”
S. Perry
Pg,
In response to the FDA’s listing of MS as a “rare” adverse effect (note the term “rare”), I reiterate the fact that there was no way for their studies to show any link between Chantix and MS. The few occurrences of MS in their studies may have been natural and may have had nothing to do with the drug. Thank you for the link though.
As for the link which “concluded” that “All of the clinical trials evaluating varenicline (Chantix) for smoking prevention were fatally flawed,” it is clearly not reading into the clinical trials, all of which say something to the degree of what this one (http://www.clinicalstudyresults.org/documents/company-study_2606_0.pdf) says: “Eighteen subjects experienced events that met the predefined criteria for a serious adverse event (SAE) during the trial: 15 subjects in the varenicline group and 3 subjects in the placebo group. Many of the SAEs were cardiovascular conditions known to be co-morbid with cigarette smoking. In addition, the medical histories of many of these subjects documented conditions that may have contributed to the events.”
In response to quoting “patients with a history of psychiatric illness were excluded from Chantix trials,” I noted this in my post. Patients with a history of psychiatric illness are almost always excluded from all trials that aren’t for drugs for patients with psychiatric illnesses. Most people do not have psychiatric illnesses. Chantix is targeted toward the general population of smokers, not people with psychiatric illnesses. The prescription of it to people with psychiatric illnesses is a decision a doctor makes.
John Q
S. Perry, give it a rest dude! The drug is the first ever to be pulled by the FAA and the Department of Transportation without even giving the NIDA test.
Why?
Jane
SPerry,
According to the pro-pharma crowd nearly all smokers have a psychiartic illness. If this is in fact true, pharma new they would be servicing patients with psych illness, thus should not have excluded them from their trial. Could it be possible they were excluded so the maker of Chantix could claim people who experienced and adverse event had a latent psych illness?
pg
Hi S Perry - I was aware (going backward up your comment) that you noted ‘psych illness was excluded’ in your post, perhaps I should have been clearer. I placed it there solely to ensure nobody was under the misunderstanding that psychiatric disorders were the cause of dropping out. As you’ll know, the article itself wasn’t focussed around “drop out rates”.
I think we probably disagree with each others’ comments on ‘fatally flawed’ (thank you for the link you left) partially, on my part, because Pfizer may not be the most reliable source of analysing the results of their own trials for a drug they want widely on the market, they have manipulated and hidden negative data on drugs before, and after all, even they use the term “conditions that MAY have contributed to the events.”
Their use of “may” loses a little more of its weight when you consider that those with any history of depression, panic disorder, heart disease, alcohol or drug abuse, diabetes, or people with kidney or liver issues were apparently excluded from the trials.
Re the MS link (now up at the top of your comment) and the theory that MS may have had nothing to do with it, that is one view but, as quoted above from the FDA publication:
“The listing of adverse events does NOT include those events…for which a drug cause was REMOTE…” and it also does class them as “Treatment Emergent Adverse Events”.
Yes by the way, I was clearly aware that it stated “rare” and think the frequent, infrequent and rare in drug ADRs are
Frequent is at least 1 in 100 patients - presumably theoretically any number between 1 and 100 - in a 100 patients? Infrequent are those occurring in 1/100 to 1/1000 patients - presumably any number between 101 and 1000 in every 1000? Rare adverse events are those occurring in fewer than 1/1000 patients.
Or something like that.
With regard to the link on the rate of dropouts of these trial participants (who it seems had been cleared of a number of health issues before being accepted) I posted the drop out rate link to help out as apparently you were unable to find any data backing Jim’s claim up.
Hopefully, if Jim returns he will provide what you ask and support his claim that Pfizer “deliberately attempted to skew the results of their product against Zyban”, although if he doesn’t, maybe I’ll look into it a bit further and if he’s right perhaps I’ll have a go at attempting to show the evidence here myself :)
pg
Correction:
Re the MS link (now up at the top of your comment) and the theory that MS may have had nothing to do with it, that is one view but, as quoted above from the FDA publication
Obvious this should have been
…and the theory that Chantix had nothing to do with it…
DOH and sorry :)
atlex
John Q, you are completely incorrect regarding the FAA. There is a long list of drugs banned by the FDA including all antidepressants, antipsychotics, traditional antihistamines (Benadryl, eg). NIDA has to do primarily with banned substances that are the subject of drug testing and mostly involve illicit drugs. The action by the FAA is appropriate given the Chantix labeling that cautions against among other things driving or operating heavy machinery, as well as reports of neuropsychiatric issues.
Jim
The statistics I provided above came mostly from the FDA’s website:
http://www.fda.gov/cder/foi/nda/2006/021928_s000_ChantixTOC.htm
Good Luck wading through it.
The information on cytisine came from Wikipedia and though this is not what would be considered a primary source Pfizer acknowledges that Chantix is a cytisine derivative
http://pubs.acs.org/cen/news/83/i23/8323antismoking.html
http://en.wikipedia.org/wiki/Cytisine
As far as Pfizer attempting to skew the results, this also comes from the FDA website and is found under documents and correspondence. The specific document begins with the hand written notation 1-27-03; this document is the minutes of a meeting held between Government and Pfizer officials. Pfizer proposed a test study which did not conform to the Zyban labelling instructions. The FDA rejected the proposed study. The test number is 1028.
While this may simply have been an oversight on the part of Pfizer, I am not inclined to take that generous a view.
Finally, as to the M/S statistics, these again come from the FDA and can be found at the following website:
http://adverse-drug-reaction.net/
S.Perry
Try comforting these people with the statistics you cite about M/S. In addition while 5 out of 8 do not have the individuals age, 2 of the 8 were over 50. Since you are aware of the M/S statistics you must also be aware that most cases of M/S are diagnosed at a much earlier age. Individuals diagnosed in their 50’s are uncommon and when diagnosed they ususally suffer from the worst form of M/S which is primary progressive M/S. There is currently no treatment for this condition.
John Q
Atley, I am absolutely correct!
With Chantix, the FDA has not issued a ban.
You have missed my point. I agree that it is a dopamine transmitting drug thus being banned by the FAA and failing drivers of DOT before giver the chance of taken a NIDA test.
As I stated, never in histoy has this happened, even before the pilot, driver, ect has had the chance to take a NIDA screen. (as in lose their jobs because of this drug!)
Jim
S.Perry
“The years of trials of Chantix showed no brain damage, or anything close to brain damage.”
You cited the above remark can you please provide the source of your information other then your own opinion.
HorusCat
MS has its roots in childhood and genetic predisposition, not in brief adult exposure to a medication. Geez, people, you are starting to sound stupid.
HorusCat
Jim,
MS in people over 50 is rare, but not unheard of. And it is not always PPMS.
Laurie
“MS has its roots in childhood and genetic predisposition, not in brief adult exposure to a medication. Geez, people, you are starting to sound stupid.”
Interesting…since even the MS Society writes that the cause of MS is still unknown, and there appears to be a number of factors involved, autoimmune, environmental, genetics. You should really check your facts before you call people names.
HorusCat
Laurie,
I know my facts. MS is believed to occur in people with a genetic predisposition who are exposed to something environmental–perhaps a virus–in childhood that ultimately leads to development of the disease. The environmental factor is borne out by the fact that MS occurs much more frequently in those who lived in temperate climes during their childhood. Genetically, it is more likely to hit woman than men. NO ONE would say that MS is caused by an acute injury to the CNS such as a 2-month exposure to a medication. Statistical anomalies occur all the time. It doesn’t prove cause and effect.
Interestingly, from what I found on the FDA website, the reports of AEs are from the 3rd quarter of last year. They are not classified as “severe” or “serious.” They include multiple reports of blisters, several insect bites, and a lot, lot, lot of GI distress. I think one needs to take inflammatory reports of “severe” AEs “caused” by a drug with more than a grain of salt. Nor does the FDA infer causation from the report–it simply notes whether the drug is a primary suspect. That does not imply causation.
Jim
To Laurie
Thanks
Jim
To Laurie
I submitted before I finished, but thank you for your response on my behalf.
Jim
pg
http://208.101.7.228/boards/showthread.php?t=264688
HorusCat
Jim wrote
“The thing that makes this more galling is the FDA is exercising extremely prudent care in their recommendation for a anti-schizophrenia drug applied for by Lilly. Final approval is not expected for at least another 3 years. The FDA’s major concern is the that anti-schizophrenia drug easily passes the blood/brain barrier and there is potential for permanent brain damage. Well Chantix also easily crosses the blood/brain barrier and these same concerns were never addressed.”
Jim, you are not understanding the FDA concerns correctly. ALL psych drugs pass the blood-brain barrier–that’s how they work. If the FDA is holding up Lilly’s atypical, it isn’t because they are afraid of “brain damage.” It could be metabolic issues, movement disorders, weight gain, cardiac issues, drug interactions, or simply lack of efficacy.
The reports of MS do not imply that the physician thinks Chantix caused the MS, just as the reports of “sting by arthropod” do not imply that Chantix makes one prone to getting stung by an ant. The report simply tells us that a patient taking Chantix developed MS. Patients who develop MS take all sorts of drugs. Your assertion is patently false.
pg
In ‘treatment emergent adverse events’ MS could indeed be due to exposure to something environmental - like chemicals, made by the drug industry.
HorusCat
pg stands for “pharmalot god”–i.e., one who believes she is the arbiter of who may or may not post on this site. As usual, she can’t respond to my facts, so she tries to discredit me by pointing out that I am, indeed, a drug rep. But, obviously, a drug rep who knows how to read and understand adverse events reports, unlike most on this site.
pg
http://www.themcfox.com/multiple-sclerosis/cause-of-multiple-sclerosis/cause-of-multiple-sclerosis.htm
“Cause of Multiple Sclerosis
What Causes Multiple Sclerosis?
The cause of multiple sclerosis remains a mystery…”
Except to HorusCat - the genius.
pg
“…Many different causes have been proposed and investigated but as yet the cause of multiple sclerosis remains elusive.
There are however, some leading contenders by way of theories although none can fully explain how multiple sclerosis develops and some theories actually seem to fly in the face of others!…”
HorusCat
pg,
Stick to your artwork. Your medical knowledge is less than limited. I suspect that virtually every current MS patient in this country has taken a drug of some kind in their lifetime. Are you going to blame every drug for causing MS? Oops! That does complicate things, doesn’t it. Maybe you should blame the antipsychotics or Zoloft.
pg
“Jim
The statistics I provided above came mostly from the FDA’s website:
http://www.fda.gov/cder/foi/nda/2006/021928_s000_ChantixTOC.htm
Good Luck wading through it.
The information on cytisine came from Wikipedia and though this is not what would be considered a primary source Pfizer acknowledges that Chantix is a cytisine derivative
http://pubs.acs.org/cen/news/83/i23/8323antismoking.html
http://en.wikipedia.org/wiki/Cytisine
As far as Pfizer attempting to skew the results, this also comes from the FDA website and is found under documents and correspondence. The specific document begins with the hand written notation 1-27-03; this document is the minutes of a meeting held between Government and Pfizer officials. Pfizer proposed a test study which did not conform to the Zyban labelling instructions. The FDA rejected the proposed study. The test number is 1028.
While this may simply have been an oversight on the part of Pfizer, I am not inclined to take that generous a view.
Finally, as to the M/S statistics, these again come from the FDA and can be found at the following website:
http://adverse-drug-reaction.net/
S.Perry
Try comforting these people with the statistics you cite about M/S. In addition while 5 out of 8 do not have the individuals age, 2 of the 8 were over 50. Since you are aware of the M/S statistics you must also be aware that most cases of M/S are diagnosed at a much earlier age. Individuals diagnosed in their 50’s are uncommon and when diagnosed they ususally suffer from the worst form of M/S which is primary progressive M/S. There is currently no treatment for this condition.”
Thanks for providing all that information Jim :)
pg
Horus, please try to stop calling people stupid, it isn’t “nice”. Jim had a bad reaction to a drug and while you may want to “slap” people who, as you see it, engage in “woe-is-me pharma bashing”, they have a right to research up on drugs and when during that reasearch they discover various facts - in this case on Pfizer, they also have a right to some respect for doing that.
By the way, perhaps you could try to think a little harder before you accuse people, it wasn’t me that commented how perhaps you shouldn’t be posting on here and should be back on the Pfizer board of cafe pharma - it was someone else. I have no objection to you posting whatsoever. I don’t run the site. But I won’t be responding to you anymore.
Ed Silverman
Hi Folks,
Just a gentle reminder to ask that everyone try to keep cool at our little lawn party. I know some discussions can get frustrating. I felt it myself this past week when chatting with others here about disclosures and conflicts of interest. The written word sometimes lacks inflection and is easily misconstrued. So try to take the proverbial deep breath for a moment. I hope everyone takes this in the spirit in which its written.
Thanks,
ed
pg
Deep breath taken Ed, and for my part, I’m sorry. Do you want me to mow the lawn while we’re here? :)
pg
Interesting pharmagossip page here with the title of “Chantix - the pulled FDA video” and it has the video that was pulled which can be watched, and an explanation of what happened.
http://pharmagossip.blogspot.com/2008/06/chantix-pulled-fda-video.html
pg
I might be wrong, as its late and I’m tired, but I don’t think this bit is mentioned.
Within the list of “treatment-emergent adverse events reported by patients treated with CHANTIX during all clinical trials” and those under “The listing does not include those events…for which a drug cause was remote…and those events reported only once…”
that was mentioned earlier re MS, the FDA link: http://www.fda.gov/cder/foi/label/2006/021928lbl.pdf
it also has other categories alongside Central Nervous System, one of which is
“PSYCHIATRIC DISORDERS. Frequent: Anxiety, Depression, Emotional disorder, Irritability,
Restlessness. Infrequent: Aggression, Agitation, Disorientation, Dissociation, Libido decreased,
Mood swings, Thinking abnormal. Rare: Bradyphrenia, Euphoric mood, Hallucination, Psychotic
disorder, Suicidal ideation. ”
Given any hisory of mental illness was excluded from the trials, it seems strange that in clinical trials suicidality occured and yet in the FDA video it seems to imply that only those with mental illness would be affected by issues like suicidality.
I understand a number of people will assert that was due to giving up smoking, but if it was - then Chantix isn’t very good at doing its job anyway as it supposed to stop the craving for cigarettes, and there are many other categories listed that couldn’t possibly be due to withdrawal from tobacco and therefore have to be an effect of Chantix - why should suicidality be any different? Or MS?
pg
Jane LOL, I’m really sorry but Ed never answered so I mowed it in penitence for reacting to Horus’ use of the word “stupid”.
I hope you weren’t passing by and got spattered by flying matter - I’ve got a cloth and some soapy water if you need it.
pg
Oh dear, the comment I was replying to has gone - so I think this one and the reply to Jane needs removing too ?? :)
pg
Ed, much as I know you’re a nice guy, I’ll stitch all the grass ends back AND the dandelions in the mower if you don’t remove my reply to Jane’s message that disappeared :)
Nathan
pg,
I know I’m guilty of this sometimes too, but can you limit your comments to one or two posts at a time? When you post as many times as you do, it makes the conversation difficult to follow. (you posted 9 out of the last 12 comments on this thread — I have no idea where the conversation started and what the general topic is)
pg
I’m afraid I can’t Nathan and that isn’t being sarcastic. And the last 3 posts Ed will be aware of and knows why they’re posted and why there’s 3 of them… I think.
Just like me, you’ll have to read back (except for the messages re Jane which you may reasonably not understand) and work it out - like I do in my way, or just give up on the thread and as I also do sometimes :)
pg
RE CHAMPIX, here are the recent comments not connected to Horus and not connected to Jane (who’s comments have disappeared) - and, by the way, did you check out the info posted re alzheimers on another page? Never mind:
pg
Interesting pharmagossip page here with the title of “Chantix - the pulled FDA video” and it has the video that was pulled which can be watched, and an explanation of what happened.
http://pharmagossip.blogspot.com/2008/06/chantix-pulled-fda-video.html
June 4th, 2008 at 8:41 pm pg
I might be wrong, as its late and I’m tired, but I don’t think this bit is mentioned.
Within the list of “treatment-emergent adverse events reported by patients treated with CHANTIX during all clinical trials” and those under “The listing does not include those events…for which a drug cause was remote…and those events reported only once…”
that was mentioned earlier re MS, the FDA link: http://www.fda.gov/cder/foi/label/2006/021928lbl.pdf
it also has other categories alongside Central Nervous System, one of which is
“PSYCHIATRIC DISORDERS. Frequent: Anxiety, Depression, Emotional disorder, Irritability,
Restlessness. Infrequent: Aggression, Agitation, Disorientation, Dissociation, Libido decreased,
Mood swings, Thinking abnormal. Rare: Bradyphrenia, Euphoric mood, Hallucination, Psychotic
disorder, Suicidal ideation. ”
Given any hisory of mental illness was excluded from the trials, it seems strange that in clinical trials suicidality occured and yet in the FDA video it seems to imply that only those with mental illness would be affected by issues like suicidality.
I understand a number of people will assert that was due to giving up smoking, but if it was - then Chantix isn’t very good at doing its job anyway as it supposed to stop the craving for cigarettes, and there are many other categories listed that couldn’t possibly be due to withdrawal from tobacco and therefore have to be an effect of Chantix - why should suicidality be any different? Or MS?”
I hope that helps, Nathan.
John Q
Atlex, here is a link to help you better understand the position of the FMCSA regarding Chantix.
Take note of the 3rd paragraph and note that never in history has a drug been pulled in this manner by this agency.
http://www.fmcsa.dot.gov/statement-5-23-08.htm
John Q
Atley, for a statement from administrator John H. Hill with the FMCSA, please follow this link. You can read paragraph 3 for the first time in history reference that I was speaking about on the DOT ban.
http://www.fmcsa.dot.gov/statement-5-23-08.htm
Nathan, as for the phrase of “if Chantix works for some people” is a correct statement. If all meds that are approved by the FDA worked for ALL the conditions ALL the time, well, no new meds in that category would need to be invented! Say for IBS, constipation, hemroids, well you get the picture.
Pfizer’s PR will take them all the way down.
Jim
Hurocat
Get your facts straight, the following quote is from wikipedia:
“Since MS seems to be more common in people who live farther from the equator, another theory proposes that decreased sunlight exposure[42] and possibly decreased vitamin D production may help cause MS. This theory is bolstered by recent research into the biochemistry of vitamin D, which has shown that it is an important immune system regulator. A large, 2006 study by the Harvard School of Public Health, reported evidence of a link between vitamin D deficiency and the onset of multiple sclerosis.[2] Other data comes from a 2007 study which concluded that sun exposure during childhood reduces the risk of suffering MS, while controlling for genetic factors.[43]”
If you are indeed a pharmaceutical representative you should at least know what you are talking about.
As far the anti-schizophrenia drug and brain damage, the drug involved targets the levels of glutamate, a previously untested neurotransmitter for the treatment of schizophrenia. The problem with the drug is administering and controlling the amount of glutamate released. Too much glutamate induces seizures, too little causes brain damage and strokes. Interestingly enough this same article states that very little is known about brain chemistry (NY Times February 24, 2008). This is my point about Chantix.
HorusCat
Jim,
I doubt whether many MS specialists post on Wikipedia. Vitamin D is one theory among many–again tying in with my point that where one lives as a child is a predisposing factor. But certainly, it is arguing against your assertion that Chantix somehow causes MS, since it is childhood exposure or lack thereof that is of interest. Then, further insult must occur in some people, since not all of us who grew up in the cave that is the Midwest and the Northeast develop MS. Genetics are certainly a factor–one study has shown that autistic kids are more likely to have mothers with MS, leading some to speculate an inflammatory/autoimmune feature of autism.
I am sorry I called you stupid; my frustration grew out of the misreading of the AE reports. The AE reports on the FDA site are not monitored by the FDA for linkage–they simply report what they are told. That is why “blisters” and “arthropod stings,” both unlikely to have anything to do with any drug someone is taking, appear on equal footing with nausea, which almost certainly is related to the Chantix. When Lopid first came out two decades ago, two of the trial participants had freak accidents (I think one got hit by a bus). These got reported as AEs–and for awhile, there was speculation that lowering cholesterol might make one prone to accidents. (The small lowering achieved with fibrates compared to statins makes that theory laughable now.) The North American Pregnancy Registry for use of antiepileptics in pregnancy reported a high frequency of cleft deformities in babies of mothers taking lamotrigine–a finding that has not been borne out by any other registry. Before one jumps to the conclusion that lamotrigine causes cleft palate, one must peruse all the numbers and understand the statistics involved.
These statistical anomalies occur all the time–just like clusters of cancer that would seem to point to environmental exposure, but then don’t upon further investigation. Without many more details and many more cases, it is irresponsible to suggest that a medication causes a serious adverse event.
The MS reports could mean many things–a patient was first diagnosed with MS while taking Chantix, but further studies showed the patient had been in the disease process for some time; a patient had an exacerbation while taking Chantix; the weakness/ataxia/fatigue apparently sometimes caused by Chantix was mistaken for an exacerbation; the patient’s primary care doc diagnosed MS and referred the patient on to a specialist; nicotine might have been “medicating” the MS in some way and its loss caused symptoms to appear…the word MS in an AE report don’t tell us enough to draw conclusions.
MS is not a “point” diagnosis in any except the most egregious cases. It usually takes months to diagnose–at least two exacerbations and an MRI with multiple lesions. High titers of IgG in the CSF are usually found. Several other disease processes can be mistaken for MS at first, including lupus. Nonetheless, as I will be spending all day with several MS specialists, I will ask them about the possible link to Chantix–and get back to you with what they say.
As far as the Lilly drug–your further clarification of its mechanism makes much more sense. Simply to state “brain damage” is not very edifyng. Certainly, glutamate toxicity is a tremendous concern to neurologists–it is involved with multiple injuries to the brain, including ischemic stroke (glutamate INCREASES acutely with ischemia actually), possibly Alzheimer’s in the latter stages, again increasing (hence the use of Namenda, a glutamate antagonist) and a possible role in schizophrenia (at least in some people; glutamate agonists such as Ecstasy, ketamine and PCP cause hallucinations). There are several meds already on the market that attenuate glutamate release in the brain–pregabalin and gabapentin. Brain damage is not a concern with these drugs; neither do they work in schizophrenia, so I suspect the issue with Lilly’s drug is more complex than simply damage caused by lessened glutamate activity.
That is a very specific concern with glutamate–not one that would necessarily extend to Chantix unless it also increases glutamate. Thank you for your clarification of the FDA concerns with the Lilly drug–I am no longer in that arena and don’t know what the newest research is covering, although I do remember now that several companies are working on glutamate antagonists.
As far as Pfizer suggesting a trial that included Zyban but did not follow Zyban’s dosing instructions, that is hardly manipulation of data. And it gives no insight into how they were planning to dose the Zyban–it could have been more or less than the indicated dosing; longer or shorter duration of use; faster or slower titration. It could have followed common usage for dosing, but not the FDA indication–attempting to mimic real life use.
One of the drugs I used to sell was used in a head-to-head trial with a Lilly drug, and they dosed it differently in the trial than it is dosed in real life–but according to the FDA schedule. The results favored the Lilly drug, precisely because our drug is dosed differently in real usage than the FDA approved, but Lilly probably had no choice about the dosing, even though it weakened their trial results. Without more detail about the Zyban head to head with Chantix, we can’t make any assumptions about “manipulation.”
HorusCat
Since I am vitamin D deficient, it is a good thing I ran around outside all summer as a kid and got multiple sunburns as a child–maybe I had high titers of D during childhood!
HorusCat
Another point to consider around all this hoopla with Chantix is this:
I am no expert in nicotinic receptor activity and I have never smoked, but I suspect, since cigarettes seem to help with stress and also provide some sort of reward, the receptors are tied in with the frontal cortex and the limbic system. They probably interact with the dopamine system and the serotonin systems. Thus, cutting off nicotinic activity may have far-reaching consequences–and perhaps more so in some people than others. My mom smoked from the time she was 14 until she was 70. Her brain probably had so many connections cemented in that used the nicotinic receptors that whenever she quit, she became hell on wheels. My dad would beg her to start smoking again. Interestingly, she used Chantix, quit and had no psychiatric sequelae. But perhaps in some people, disrupting that constellation of interconnectedness really, really messes them up. So–it’s not the Chantix PER SE that is causing the psychiatric difficulties–but it is insofar as it disrupts all that neurotransmitter activity. The limbic system is nothing to fool around with.
John Q
HorusCat, you never smoked but was locked in a smoke-filled home? Come on now. You can’t have it both ways. You can only be the spin dr in so many directions.
Funny how I have never once heard of a person who commited suicide because they stopped smoking or had to go to the psychiatric floor because of the lack of niciotine. Well, not while I was working…..
Nathan
John Q writes: “Funny how I have never once heard of a person who commited suicide because they stopped smoking…”
Funny, I’ve never met anyone harmed by an SSRI or by Vioxx.
In all seriousness, however, there are studies that link smoking to suicide. See the following three links:
http://www.webmd.com/smoking-cessation/news/20050307/smokers-may-think-more-about-suicide
http://www.jointogether.org/news/research/summaries/2008/smoking-and-suicide-linked.html
http://www.earthtimes.org/articles/show/182371,suicide-strongly-associated-with-smoking-german-experts-warn.html
John Q
Nathan, you leave links to sites that state there were NO attemp at suicide during these trials. Unlike Chantix.
Thanks for the back-up!
I stand by my first report of never seeing, knowing of, or hearing of any suicides due to smoking cessation.
pg
Participants were excluded from Chantix trials with any history of:
depression & panic disorder
heart disease
alcohol or drug abuse
diabetes
kidney problems
liver problems
Some of the “Treatment Emergent Adverse Events”
during those clinical trials, many of the trials were over 12 weeks:
FREQUENT “Depression”
RARE “Suicidal Ideation”
FREQUENT “Chest Pain”
INFREQUENT “Myocardial infarction” (Heart Attack)
INFREQUENT “Diabetes Mellitus”
INFREQUENT “Nephrolithiasis”
RARE “Renal Failure Acute”
FREQUENT “Liver Function Test Abnormal”
http://www.fda.gov/cder/foi/label/2006/021928lbl.pdf
John Q
Nathan, I need to correct myself. I wrote “NO attempt suicides”. Instead it should read, NO suicides were committed during these trials.
MY bad!
Nathan
John Q, did you both reading any of the links? Here’s some quotes from them. My point is that smoking seems to be related to suicide. Comparing Chantix suicides to the general population is not a fair comparison. One needs to compare Chantix-related suicides to suicides in SMOKERS.
“8% of study participants reported suicidal thoughts or suicide attempts. Among current daily smokers, 16% reported thinking about or attempting suicide.”
“Further, 0.6 percent of nonsmokers actually attempted suicide, compared to 1.6 percent of occasional smokers and 6.4 percent of smokers.”
“The non-smokers had the lowest rate (less than 15 per cent) of what the scientists call “suicide ideation” - that is, having made plans to kill oneself and/or having seriously wanted to die for a period of at least two weeks.
The rate was around 20 per cent among occasional and non-dependent smokers. However, nearly a third or 30 per cent of smoking addicts had experienced suicidal ideation”
Jim
Horuscat
I fully understand adverse events reports do not conclusively prove that a specific product was the direct cause of the adverse event. These are reports only and not studies, they are triggers for studies.
I am also fully aware that M/S is not easily diagnosed; it is usually a diagnosis of exclusion. I don’t believe too many Primary Care Physicians would be foolish enough to make a diagnosis of M/S until the tests you reference had been conducted.
In addition, there were more then 8 reports of M/S to the FDA, I purposely excluded those reports where the consumer made the claim. It is my belief that most physicians are not going to make a cause and effect diagnosis unless they are reasonably sure that there may be a link.
As to who posts on Wikipedia, you are correct, I do not kow that it was an M/S specialist who posted the information, I admitted in a previous post that Wikipedia would not be considered a primary source for information. However it directly contradicted your initial premise. A premise I might add you seemed to state with certainty.
Finally, the theories behind the possible causes of M/S are irrelevant: if Pfizer accepts the fact that Chantix may cause M/S why can’t you? It’s in the physician’s prescribing information.
It is my personal belief that this particular side effect is listed because of the link between Chantix and cytisine, a drug that has a long history and is known to cause damage to the CNS.
John Q
As I stated…There has never been a reported case of suicide from smoking cessation! Period.
Unlike Chantix.
Nathan
pg,
You are looking at these reports out of context. Have a look at the same report for Aleve. (link below)
Here’s some of the side effects listed for this dangerous over-the-counter medication: (page 16)
Seriously EVERY ONE of these (and many more) are listed as a side effect or possible adverse effect of Aleve:
pruritus (itching), skin eruptions, ecchymoses, sweating, purpura, edema, palpitations, heartburn, abdominal pain, nausea, constipation, diarrhea, dyspepsia, stomatitis, flatulence, gross bleeding/perforation, GI
ulcers (gastric/duodenal), vomiting, abnormal renal function, anemia, elevated liver enzymes, increased bleeding
time, rashes, CONGESTIVE HEART FAILURE, vasculitis, hyperglycemia, hypoglycemia, inability to concentrate, DEPRESSION, DREAM ABNORMALITIES, insomnia,
malaise, myalgia, muscle weakness, aseptic MENINGITIS, cognitive dysfunction
http://www.fda.gov/cder/foi/label/2004/17581s99,100,18164s50,51,18965s9,10,20067s4,6lbl.pdf
pg