The Pfizer Media ‘Roundtable’ For Chantix
44 CommentsBy Ed Silverman // June 5th, 2008 // 5:50 pm
Earlier today we ventured to Pfizer’s 42nd Street headquarters in New York because the drugmaker was holding a briefing on Chantix, to address the controversy over its smoking-cessation drug. In last year’s fourth quarter, the pill was linked to nearly 1,000 serious adverse events, such as potentially lethal cardiac rhythm disturbances, severe skin reactions, acute myocardial infarction, seizures, diabetes, psychosis and aggression. This was on top of national headlines about suicidal behavior.
The meeting, which lasted about 90 minutes, was largely uneventful, in so far as three Pfizer execs sat at a table in front of approximately 30 journalists and analysts, and reviewed details about the drug, the supporting clinical trials, interactions with the FDA, plans to further examine the risks and an upcoming ad campaign (TV ads that discuss the virtues of quitting smoking are already airing).
Having given themselves a platform, Gretchen Dieck, who heads Pfizer’s safety and risk management, insisted current labeling is adequate and downplayed the Institute for Safe Medication Practices report on side effects by saying the study wasn’t peer-reviewed or published in a peer-reviewed journal. And she noted the adverse event reports spiked with media attention, particularly last fall and winter after a Texas musician on Chantix made headlines by menacing a homeowner who shot and killed him.
“This may be indicative that there was some reporting of neuropsychiatric events,” she said. “I’m not saying it is or is not related to Chantix. I’m just saying it’s another factor.” However, she also qualified the barrage of adverse events by suggesting that the numbers may not clearly represent a real safety signal.
Meanwhile, Joe Feczko, Pfizer’s chief medical officer, maintained that more than 90 percent of the reported adverse events that were cited in the recent ISMP report was nothing new and that Pfizer had already shared the data with the FDA. Asked what he thought about Chantix as a second-line drug, Feczko, of course, disagreed with the prospect. “I see it as part of the armormentarium.”
Also on hand was David Gonzales, co-director of Oregon Health & Science University’s Smoking Cessation Center, who led some key Chantix studies. He addressed a particular area of controversy - the trials didn’t include smokers with psychiatric illnesses, which means, as he put it, “the patients in the trials are not terribly reflective of the population of smokers.”
But he explained that such people were excluded from placebo-controlled trials over concerns that their conditions may be worsened. Moreover, “we’re trying to be able to tell what the signal was in the drug, and not the history of the patient.”
In a separate interview with the Associated Press, Martina Flammer, Pfizer’s senior medical director, says people with mental illness should be able to take Chantix. “There is no indication that there is any reason why Chantix should not be taken in this population,” she said.
Insider
Blowin’ smoke!
The FDA video notes:
neuro psych symptoms even BEFORE the patients stopped smoking
patients with psych symptoms excluded from trials (hmmm, why, one wonders)
pg
“In a separate interview with the Associated Press, Martina Flammer, Pfizer’s senior medical director, says people with mental illness should be able to take Chantix. “There is no indication that there is any reason why Chantix should not be taken in this population,” she said.”
If Pfizer’s own Senior Medical Director can’t see why not, then there’s quite clearly not much hope for safer more beneficial drugs from Pfizer in the near future - a sure signal to the fall of an empire (Pfizer’s in this case).
HorusCat
Ed,
From what I can tell, the adverse events report was derived from the FDA website. These events are not all serious (three “arthropod stings”? blisters?); in fact, the seriousness of most of them cannot be determined from the FDA information. To say that almost 1,000 serious AEs have been reported in one quarter is not true and is inflammatory.
It would also be helpful if you would note that the FDA lists AEs without any determination of causality. Thus, there is no implication that Chantix caused an MI or any other serious event (one of those patients was apparently over 400 lbs–is an MI in such a patient surprising?).
Your description of the events makes it sound like the majority were events such as MI, arrhythmia, psychosis, when the VAST majority were of the mundane variety: GI, GI, GI and yet more GI. Oh, and lots of abnormal dreams. Even a descriptor such as “aggression” has no definition–it could mean an incident of road rage, yelling at the kids or slugging the boss.
Nor is it unreasonable to note that many of the emotional side effects reported also occur with attempts to quit smoking: anxiety, irritability, depression.
I find your take on this to be tilting to the anti-pharma side of things–when you have an opportunity to educate some on this site about how exactly an FDA AE report should and should not be read–and where the accusers get their information.
pg
How could Pfizer’s SENIOR MEDICAL DIRECTOR not see “any reasons”
http://www.huliq.com/60043/antismoking-chantinx-lights-strong-safety-signals
“…In the 4th quarter of 2007 varenicline accounted for 988 serious injuries in the U.S. reported to the FDA, more than any other individual drug in this time period. By comparison the FDA received a median of 5 reports of serious injury for 769 different drugs in the 4th quarter. Only 35 drugs accounted for 100 or more reports. This large volume of reports prompted us to conduct an analysis of all adverse events for varenicline since marketing approval in 2006
The FDA has recently issued a Public Health Advisory about one of the most marked adverse effects of varenicline, psychiatric symptoms that included “changes in behavior, agitation, suicidal ideation, attempted and completed suicide.” 2 However, the FDA alert provided no information about the numbers of reported neuropsychiatric events among treated smokers.
From May 2006 through December 2007, the FDA had received 227 domestic reports of suicidal acts, thoughts or behaviors, 397 cases of possible psychosis and 525 reports of hostility or aggression. These totals included 28 cases of suicide and 41 mentions of homicidal ideation, 60 cases of paranoia and 55 cases of hallucination. The categories were not mutually exclusive.
However, the adverse drug event reports for varenicline describe other kinds of serious harm for which no warnings now exist, either from the FDA or from the manufacturer, Pfizer Inc. The cases (including those with psychiatric effects) were classified using standardized medical queries developed by the pharmaceutical industry to identify potential adverse events in clinical studies and postmarket surveillance. Adverse event reports in themselves do not establish a causal link to the drug, only that an observer suspected a relationship. Depending on the features of the specific event, it could be counted in multiple categories, and classifications are not definitive. Among the most prominent were:
· Accidents and injuries. A total of 173 serious events described accidental injury, including 28 road traffic accidents and 77 falls, some leading to fractures of rib, facial bones, hand, ankle, spine, and lower limbs. In these cases a variety of potential causes were identified, including loss of consciousness, mental confusion, dizziness and muscle spasms.
· Vision disturbance. At least 148 reports contained medical terms indicating vision disturbances, including 68 cases described as blurred vision and 26 terms indicating transient or other forms of blindness. This reported effect could also describe a mechanism that could or did contribute to accidents and injuries.
· Heart rhythm disturbances. The FDA received 224 domestic reports classified as potential cardiac rhythm disturbances. This category, however, was dominated by reports of sudden loss of consciousness, an event that could also have non-cardiac causes. However, this category also included smaller numbers of cardiac arrests and identifiable abnormal cardiac rhythms
· Seizures and abnormal muscle spasms or movements. Serious reported events included 86 cases of convulsions (seizures), 372 reports of a wide variety of movement disorders, including tremors, muscle spasms, twitching, tics, drooling, and motor hyperactivity. The extent to which these problems resolved with a reduced dose or by halting treatment could not be determined from these data.
· Moderate and severe skin reactions. Reported serious events included 338 cases of hives or swelling of the tongue, face, eyes, lips or other areas. In addition, 65 cases were classified as severe and included blisters, exfoliation of the skin and lips, and Stevens-Johnson Syndrome.
· Diabetes. The FDA has received 544 reports suggesting varenicline may be related to a loss of glycemic control. This category included many cases of weight loss or gain that could have alternative causes, but also identified numerous cases of symptoms and laboratory tests consistent with new onset diabetes.
Recommendations
We have immediate safety concerns about the use of varenicline among persons operating aircraft, trains, buses and other vehicles, or in other settings where a lapse in alertness or motor control could lead to massive, serious injury. Other examples include persons operating nuclear power reactors, high-rise construction cranes or life-sustaining medical devices. Based on reports of sudden loss of consciousness, seizures, muscle spasms, vision disturbances, hallucinations, paranoia and psychosis, we believe varenicline may not be safe to use in these settings. The extent to which varenicline has already contributed to accidental death and injury has not yet been investigated because these adverse effects had not been previously reported. The Federal Aviation Administration approved varenicline for use by airline pilots3 before most of these reports were available.
In addition, we recommend that patients and doctors exercise caution in the use of varenicline and consider the use of alternative approaches to smoking cessation.
Finally, we urge the FDA and the manufacturer to provide warnings to doctors and patients for those adverse effects that can be adequately documented through existing data, and to undertake on a priority basis epidemiological studies or other research to assess other potential risks. We promptly notified the FDA of our findings.
This report was written by:
Thomas J. Moore, Senior Scientist, Drug Safety and Policy, ISMP
Michael R. Cohen RPh, MS, ScD, President, ISMP
Curt D. Furberg, MD, PhD, Professor of Public Health Sciences, Wake Forest University School of Medicine.
Institute for Safe Medication Practices
200 Lakeside Drive, Suite 200
Horsham, PA 19044
215-947-7797
http://www.ismp.org
Corresponding Author
Thomas J. Moore
tmoore@ismp.org“
Ed Silverman
Hi HC,
I used the word ’serious,’ as I have done previously when describing this report, because it comes from the ISMP report…
http://www.ismp.org/docs/vareniclineStudy.asp
I must say that the use of the word ’serious’ shouldn’t make me viewed as biased. I was reporting how it was characterized by the authors of the report. I didn’t pull the description out of thin air to suit my own views.
And yes, the Pfizer argument is that its hard to know whether an AE report is due to the drug, symptoms of nicotine withdrawal, some other health issue or another drug that may have been taken.
This is what Dieck was referring to when I wrote she “qualified the barrage of adverse events by suggesting that the numbers may not clearly represent a real safety signal.” Perhaps it wasn’t clear, but I was reporting what a Pfizer exec was trying to say about the AE reports.
Finally, there seems to be a little game a few folks like to play on this site lately - I don’t have a name for it, but the instructions seem to read something like this: ‘let’s see if we can catch Ed in a turn of phrase that proves he’s anti-pharma, be it a sin of omission or commission.’
As I’ve indicated before, I make mistakes and have lapses in judgement like anyone else. But I try to acknowledge and correct them. I see my mission, however, as presenting info in a way that is useful to learning and discussion. If I want to voice my opinion, one way or the other, I do so and try to be clear about it.
This gotcha game, however, goes nowhere. If I get something wrong, let me know. Of course, anyone is free to question my motives as much they like, but it solves nothing. If I want to be unabashedly pro and anti something, I’ll be upfront about it. But reading tea leaves is just that - speculation.
My only agenda is to make the site interesting and useful to as wide an audience as possible. To indifferently alienate some people - any group of people - as I go about airing my own views and satisfying myself would serve no purpose. So let’s try to stick the issues at hand.
Regards
ed
John Q
I am unsure how Pfizer is unable to see why the Institute for Safe Medication Practices did not give a fair assessment of Chantix when clearly parts of the goverment thought the ISMP study worthy of the drug being banned!
http://freerepublic.com/focus/f-news/2020863/posts
HorusCat
Ed,
I appreciate your argument. But in the first paragraph, you bluntly state that Chantix was linked to almost 1,000 serious adverse events. You don’t mention the Safe Medicine folks until several paragraphs later, and then you don’t directly attribute the “report” to that group. In not explaining the Safe Medicine modus operandi (that is, take the FDA reports, qualify all of them as serious and then imply causality), you leave the reader believing that Pfizer is deliberately obscuring the facts. By using the term “linked” you imply causality where none has yet been found.
Perhaps a primer on what information can be found on the FDA AERS and what can be inferred from this information would be informative to your average reader–who will, I believe, read your post as an indictment of Pfizer rather than a bare reporting of what happened.
I thought Nathan got a little out of hand with his assertions about your bias, and I certainly am not trying to play games with you. I do think that you are somewhat like the fish swimming through the ocean who has no concept of what being “wet” means. The language you employ and the way you present your facts and observations leans toward skepticism about industry and perhaps fails to adequately point out the weaknesses/biases in the industry’s opponents. The reader will clearly understand Pfizer’s stake in the argument and take what they say with a grain of salt. But you don’t expose the “institute” as also having a stake in the interpretation of the data and their name suggests an objectivity and scientific authority they don’t necessarily deserve.
It’s only important to me how you present your information in so far as the reader “in the middle” (i.e., not me, not Lisa Van S, not pg) won’t know what industry insiders know about AE reporting, the FDA process, statistical significance, etc.
pg
ROTFL.
Whoops, sorry.
pg
Readers in the middle?
You Horus are a pharma rep.
I’m not, NOR am I anti pharma.I’m for GOOD pharma practices and against BAD pharma practices.
Ed is quite clearly in the middle.
You want it all YOUR way, ie, the PHARMA way, including letting pharma BAD practices by without any mention.
LOL
John Q
HorusCat, apparently after the study performed by the great “folks” at the ISMP, parts of the goverment thought that it was very “serious”. So much so that they then banned the rx to pilots, truck drivers, ect.
What part did Pfizer not understand? Pretty “serious” when the goverment will not let their employee(s) work while using this product.
http://freerepublic.com/focus/f-news/2020863/posts
pg
Horus, I’m not sure why you give a vague indication you don’t agree with Nathan as you both behave in the same way.
As far as I can see so far, Ed posts things at times that ‘anti-pharma’ wouldn’t like, and at other times that ‘pro-pharma’ wouldn’t like either.
When anyone, whether its ‘anti’ pharma, or ‘pro pharma’ spend time trying to discredit Ed then it shows a tendency to intolerance and bias on the part of the person attacking Ed.
He does a good job at trying to be balanced and it doesn’t do anyone - at either end of the spectrum - any favours to be seen to try to discredit that balanced view.
That, Horus, includes YOU and includes anyone ANTI Pharma behaving like you.
Laurie
And sadly that “game” only discredits the poster, NOT the reporter. They may be surprised to find that those who comment here actually have a brain and can decipher information and come to conclusions without the help of anyone else.
pg
Very true Laurie - and often it seems that anyone playing that ‘game’ suffers from a delusion that they’re the only one that has a brain. And I do mean and include anyone from either end of the spectrum, anti or pro pharma, who chooses to behave that way.
I totally agree Laurie, it is sad.
Go Ed Go! You’re doing a great job :)
Henry
The following is from the FDA’s Website:
What Is A Serious Adverse Event?
An adverse event is any undesirable experience associated with the use of a medical product in a patient. The event is serious and should be reported when the patient outcome is:
Death
Report if the patient’s death is suspected as being a direct outcome of the adverse event.
Life-Threatening
Report if the patient was at substantial risk of dying at the time of the adverse event or it is suspected that the use or continued use of the product would result in the patient’s death.
Hospitalization (initial or prolonged)
Report if admission to the hospital or prolongation of a hospital stay results because of the adverse event.
Disability
Report if the adverse event resulted in a significant, persistent, or permanent change, impairment, damage or disruption in the patient’s body function/structure, physical activities or quality of life.
Congenital Anomaly
Report if there are suspicions that exposure to a medical product prior to conception or during pregnancy resulted in an adverse outcome in the child.
Requires Intervention to Prevent Permanent Impairment or Damage
Report if you suspect that the use of a medical product may result in a condition which required medical or surgical intervention to preclude permanent impairment or damage to a patient.
Looks to me like a lot of these AEs fit the FD&CA’s definition of serious AE. Plus for the ones that don’t they might fit the FDA’s category of a signal for a serious AE.
Plus we’re seeing the same constellation of AEs over and over again with different drugs. Seems like there may be a single underlying mechanism that relates all these drug classes.
Where there’s smoke there’s fire.
If it looks like a duck, walks like a duck, and quacks like a duck…
Nathan
Since my name came up in this thread, I’ll post my 2-cents worth:
We’ve read repeatedly on this website about the poor reputation of the pharma industry. This is surely somewhat self-inflicted due to the debacles we repeatedly read about. However, much of our poor reputation (I believe) has to do with “outsiders” (like most people on this site) having a poor understanding of the process of drug-development. Drug development involves hundreds of Ph.D. scientists ranging from epidemiologists to chemists to molecular biologists. It’s very difficult EVEN FOR THOSE IN THE INDUSTRY to get their minds wrapped around the complexities involved in testing new drugs.
That brings me back to this website. Ed does a pretty good job of presenting news relevant to the pharma industry. However, those outside the industry seem to take what Ed says as gospel truth. It isn’t always. We all use words to convey meaning. Ed isn’t perfect in the way he words things. Unintentionally, he sometimes conveys things with his words that just aren’t true. Why do I care? BECAUSE I CARE ABOUT THE REPUTATION AND FUTURE OF THE INDUSTRY I WORK IN! I realize we are overzealous sometimes, but I hope that postings by HC, myself, and others in the industry convey to people that measuring drug safety and efficacy is not a trivial matter. You can’t pay a summer intern to count the number of AEs and determine whether a drug is safe or not. It takes epidemiologists, statisticians, and MDs to make those kind of determinations. Ed’s statement “the pill was linked to nearly 1,000 serious adverse events, such as potentially lethal cardiac rhythm disturbances, severe skin reactions, acute myocardial infarction, seizures, diabetes, psychosis and aggression” is technically true. It sure is a nice soundbite. But reread HCs comment above and follow up to see if she is correct. Soundbites are nice — but they are not truth. If it were as simple as this statement sounds, Chantix would already be off the market.
Ed Silverman
Hi HC and Nathan,
If you look at the first graph, you’ll see I included a link where the words ’serious adverse events’ are underscored, and that takes you to my first post about the ISMP report, where there is then a link to the ISMP site and its report. I often use links to take people back to posts - or directly to web sites and documents - so they can read the back story. I’ve been doing that for 18 months. It’s nothing new. The links are a quick way of providing background.
As to the use of the term ‘linked,’ I understand that implies causality to some people, but there’s no easy way to phrase this. Do we write ‘associated with’ or ‘may have caused’ instead? I didn’t write that the drug did cause those side effects, which certainly would be definitive. This is an imperfect siuation not of my making because of the parsing and sparring that occurs among regulators, scientists and marketers when FDA and pharma debate such things.
As for skepticism, I’m a journalist, not a cheerleader. Questions have been raised by others about the drug. Does that make ISMP automatically correct? No, but the door is now open. I stopped to look at what’s inside. I’ve been through the primer before about why I do what I do and I know you’ve read those comments. So….
In this post, I presented the ISMP report as ISMP characterized it and I presented Pfizer’s view of the situation as Pfizer sees it. Someone who is truly anti-pharma might decide I wasn’t skeptical enough simply because I reported what Pfizer said yesterday and didn’t try to tear apart the explanations. (Believe it or not, I’ve been regularly chastised for being pro-pharma by others since running this site.)
And to Nathan, you write that ‘unintentionally,’ I sometimes convey things that ‘just aren’t true.’ Again, if I make a mistake, I’ll correct it. An inaccurate fact is an inaccurate fact and I don’t want to perpetuate such a thing because the posts are archived and circulate on the Internet and, therefore, live forever. But mostly, you argue with me about your belief in my views, and not particular facts that you believe I’ve stated incorrectly. Tthe gotcha game in which someone tries to tease out hints of bias in turns of phrase is something else.
So I’m done with this now, folks. I understand there will always be people who question a journalist’s motives. That’s fine. I’m not perfect. But I’ve spent a great deal of time over the past week responding to this issue and my time is at a premium. If I get something wrong, let me know. I’m interested in improving my work so that the site is useful. But if you want to read something into a mistake or a description with which you disagree, well, that’s your right. And you can continue to discuss that as much as you like right here. But I need to move on.
Cheers
ed
HorusCat
Ed,
No worries. I understand. I obviously value what you do, because I keep coming back! In fact, the link to the Novartis FTY720 for MS was extremely helpful to me. And the whole business of AEs led me to report one that one of my kids had with an asthma med–which I never would have done otherwise, despite being a drug rep and knowing about the process!
Have a great weekend!
HC
Nathan
Ed, one (lighthearted) comment for you:
You and I seem to have the same problem: We just can’t seem to ignore the critics. I just can’t seem to help myself from responding to pg and Truthman’s ignorant criticism of the industry I work so hard for. You, also, seem to be unable to ignore the ignorant criticism from myself and HC about the industry that you work so hard for!
It’s hard not to feel passionate about defending what you do for a living — whether it’s journalism or pharmaceutical research!
HorusCat
Hey Nathan!
I have developed an immunity to pg. CSF immunoassay would show high titers of IgPG. At least you and I have some insight into ourselves and our biases, unlike many others on this site.
It is always interesting to go back out into the real world and deal with physicians and patients who find our products useful and at times, life-saving. Every time I am around my mother and she is no longer smoking, I think about her risk of stroke already being cut in half (both of her parents died of CVA), and I thank God for Chantix. Perhaps my kids will have her around to enjoy for another decade.
Henry:
Despite your reproduction of the FDA’s definition of “serious,” please note that the FDA does not monitor its AERS and weed out reports based on whether they fit that definition or not. Anyone can make a report of just about anything, and it gets recorded. If I am in the field and hear a report that one of my drug caused a side efrfect OF ANY KIND, I enter it into my computer and it gets reported to the FDA and entered into the AERS.
One of my meds causes sleepiness. I suspect if I look its AEs up on the FDA website, I am going to see many, many reports of sleepiness. Hardly a surprise, and probably not “serious” as you define it above.
Ed Silverman
Hi Nathan,
Your criticism isn’t ignorant, nor are the others cited, in my view. You all bring interesting opinions and experiences to the discussions, even if some may be expressed rather sharply at times. But I, for one, have learned from all of you, and that’s a good thing, for me anyway.
And I responded because, as the guy who is responsible for the content on this site, I have an obligation to clarify, as best I can, accusations or questions about motive. Of course, I also feel I should reply when addressed directly because that’s just courteous. I am the host, after all.
And thanks for your note, HC. Have a nice weekend yourself.
See you later,
ed
S. Perry
Since no one else will address John Q’s two similar comments–both trying to say that, since parts of the government banned Chantix (in one way or another), that must mean it’s bad–I will.
The FAA and the FMCSA do not fully comprehend the report. They see the high numbers of Chantix AE reports and understandably jump to a conclusion. Unfortunately, as it has been discussed on here before, the high numbers of reports for Chantix do not reflect the actual number of problems with Chantix. The numbers are disproportionately high because of the way that the numbers are reported in the first place.
Although he has some connections to Pfizer, Dr. Jonathan Foulds explains the problem very well here: http://www.healthline.com/blogs/smoking_cessation/2008/05/chantix-varenicline-safety.html
As I’m sure you know, Big Pharma is not exactly loved around the world, especially in some parts of the media, and when something like this report comes out–a non-academic, non-peer-reviewed report, not a study or anything legitimate, just a poor analysis of raw numbers that makes Chantix and Pfizer look bad–people will jump on it, wanting what’s best for others. Unfortunately, this report has too many problems to be taken seriously.
I hope that helps.
Atlex
S. Perry,
I agree that John Q has no clue as to what he is talking about. I don’t think that he realizes how long the list of drugs is that is banned by the FAA. It includes most antihistamines (eg, Benadryl and other OTC products), antidepressants, antopsychotics, and many, many other drugs. I do disagree with you regarding Chantix. I think they are justified in adding it to the banned list for now. The product’s label clearly indicates certain affects that cannot be ignored. That being said, it doesn’t mean that the products risk to benefit ratio is very acceptable for the vast majority of smokers.
harpy
I, for one, think you do a great job Ed. I read many blogs on the industry and yours is definitely in the top three most balanced. In fact, I think your balance is what leads to the endless nitpicking of your beliefs because there is no obvious bias in your reporting. One has only to consider Jack Friday, Peter Rost or DrugWonks - they never have to put up with questions about their bias - it’s self-evident. As annoying and tedious as it gets to have to constantly defend yourself from whiny attacks about how you present stories (yes, they’re whiny - deal with it) perhaps it would help to see them a something of a backhanded compliment. You inspire this scrutiny because you are not easily pigeonholed as being one or the other. Keep up the good work!
Lisa Van S
Hey HC,
Thought you stated in an earlier post that your Mother died in child birth?.. Just a bid of advice, be careful what you ask for!
As far as this warning is concerned,..its always better to be safe, than sorry.
John Q
S.Perry, Atlex, It does appear that you “guys” do not understand the position of NIDA. NIDA has worked with pharma from the beginning to keep their meds on the market AND to keep employees working. Never in history has the FAA or DOT banned their employees from a certain drug without a NIDA screen(drug screen) As in not let the employee work.
S.Perry, you are absolutely wrong about the the FAA ban on antihistamines. Please site your sources.
The FAA and the FMCSA do not care what a few bloggers think. They have the safety of the world in their hands.
For more on NIDA and prescriptions.
http://www.washington-aviation.org/drugalcoholpost.pdf
http://www.nida.nih.gov/about/organization/DPMCDA/programs.html
Jack2
Important limitations of adverse events/reactions reported postapproval:
1. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency.
2. Events can be temporally related to drug, but are not necessarily causally related.
3. For a variety of reasons, HCPs *generally* more diligently report advere reactions for newer drugs compared to older drugs.
Insider
Time (and the FDA) will tell about Chantix.
Ed, you are a gem. Keep on truckin’
To anyone who hates PharmaGossip - you know what to do and where to go!
Have a great weekend y’awl. ;-)
Atlex
Ed,
As a participant in the pharma industry (me not you), I am curious as to your personal view of this event. Was it a company-generated attempted at obfuscating the data or was it a medically-driven attempt to offer Pfizer’s view of the situation (or something else entirely)? Is this approach something that should be done more often or is it a waste of time? Did it provide worthwhile insight into the working of a company and its activities?
I’m curious as to your takeaway from this.
Atlex
Jaynesday
To All,
It’s obvious that there are good points on both sides of the AE issue. Are they valid, are they biased, are they effective in checking the safety of a drug or device?
Rather than argue and accuse endlessly (unless you like to) wouldn’t it serve a better purpose to determine how we might improve the system? (I think the FDA is looking at this if I’m not mistaken) Because either way, you have to agree that this kind of information (AEs) are vital to the drug companies, the FDA, and the consumer. If they are worthless why spend the time and money supporting the system? Just given the energy we have used to argue for or against AE validity, think of the waste that is spent on collection, analysis and review of AEs if in fact they have no validity. Or if they are valid make darn sure everyone agrees that they are so something can get done.
Any ideas?
Jack2
It would be nice if the AEs were collected more systematically. Right now, since they are not, it’s more like a whole laundry list of things you might, maybe, could possibly see when someone takes the drug. In my experience, docs just ignore the list because it’s overwhelming, filled with a lot of things not necessarily attibutable to the drug, or things so rare that the doc doesn’t really need to know.
I won’t say it’s useless, just limited. Some events may be rare, but so serious (eg suicide), that we should at least monitor it.
Would the increased cost of a more systematic AE monitoring for approved drugs improve safety? I think so, although it will always be limited by the lack of placebo control. Would it be cost-effective? I’m sure I don’t know.
Laurie
Jack&Jayne, I think you hit it on the head. We can argue about AE reporting forever. Bottom line is the reporting system is flawed and ultimately ends up doing nothing for the consumer. Signals discovered are ignored as “anecdotal” and reactions that are obviously from another causes are diluting the importance of the true reactions.Without a clear cut reporting system documenting causality is impossible.
Jaynesday
Generally speaking, a flawed data system is even worse than no system at all. A flawed system causes misdirection, or can be used as a tool *to* misdirect or deflect. Usually it is ignored altogether which is unfortunate because I personally feel (and I’ve read my fair share MAUDE AEs) that there is invaluable information in the AE system.
User reports have to be valid, understood and acted on.
Jaynesday
Laurie, Jack, too bad, seems the collective intelligence of this group (which *is* impressive)is more interested in accusing and disproving than creative discussion. Have you noticed the silence in our corner of the lawn party?
I wonder what the collective intelligence of this group *could* accomplish if it were directed in a positive and unified manner? I’m sure it would be a wonderful thing to see.
Laurie
LOL! I guess it’s easier for some to see the whole story.
“User reports have to be valid, understood and acted on.”
That is the key right there. I attended an FDA hearing on this subject, and they are well aware how inadequate the system is….still haven’t seen any information on possible changes.
Dr. Sal Giorgianni
Dr. Deick is a scientist of unimpeachable integrity and a globally recognized expert in post-marketing surveillance. Regardless of who may sign her pay check I would take her analysis and perspectives very seriously and authoritatively.
The issue of signal generation is very complex. It is one important tool to be used in monitoring drug use in the real world. But it is not clean data as many on this site have noted. It must be taken in context of many other variables, few of which are definitive.
Some asked why were patients with psychiatric conditions excluded from the early studies? Valid point, but working with as few variables as possible in an approval study is one of the weak points of the FDA requirements. This is not the place to regenerate a debate on this long standing approach to drug approvals. For Chantex it now may make good sense, from a scientific standpoint, to go in and do a safety-efficacy study in smokers with psychiatric disorders but from an ethical and litigation perspective I don’t know if it would pass an IRB.
In the mean time, folks, what should we do?
Over caution or even put a black-box on yet another very useful product to help curtail utilization of a medication to curtail one of the top killers of people? With today’s litigious society this is a real concern. If you think I am over dramatizing this risk take a relook at the story on that old-as-dirt drug, phenergan.
There is ALWAYS going to be a risk with prescription drugs. There will NEVER be a completely safe product with ALL aspects known. That is why, folks, they are and must be prescribed by a leaned-intermediary. As a society we could take the view of zero-tolerance for side effects (as some at ISMP may advocate for) but this would simply not be realistic and most everything, including aspirin, would be considered dangerous. Or we as a society could insist that learned-intermediaries pay closer attention to how to properly use medications. The formal training in pharmacology and therapeutics is woefully under whelmed in most medical, dental, nursing and PA schools and training programs. Yet, these folks prescribe. (I know that I will be heavily criticized for this view – but I believe it to be true). Ironically, the professional group who receives the most formal training in this area, pharmacists, can only prescribe in limited circumstances.
Laurie
Dr. Sal..some good points. I work with ALOT of residents and the education in pharmaceuticals is woefully lacking. It ends up being treatment with a drug because “another doc told me to use this drug”, not because they did any research into that drug. We always know when a new drug is in the hospital formulary because that becomes the drug of choice amongst doctors, regardless of cost and comparison to older drugs. We say this with Natrecor. Although it was supposed to be limited to use with those who didn’t respond to “traditional” therapy..all of a sudden we were giving it to every patient with CHF..until the update that it wasn’t as good as it was marketed, and then we gave it to no one!
Pharmaceutical education needs to be elevated to core studies…and not left for the 30 minutes inservice.
Jaynesday
Dr Giorgianni,
Thanks for your valuable perspective.
You note that the data is not “clean” and also that (if I understand)at some point the data leads us to the decision to start followup studies. Also that the FDA requires/requests that the initial studies have as few variables as possible.
Given all of these points could we not say that
1. The cleaner the data the quicker we might be led to make a decision to start followup studies and thereby avoid more harm.
2. Because the initial study variables are purposefully limited, the post market “signal generation” is doubly important.
(I hope these points agree with your statement above if not please correct)
My point being - Adverse Event Reporting is vital. The system is less reliable than it should/could be.
In other words the current system might over indicate that black box warnings be used or it might underindicate that there is a real problem with a drug or device.
What can be done to establish a system that we can rely on to properly direct us on a path that is effective for both pharmaceutical companies and public safety?
John Q
I think the point of the article is one of being as simply as asking why would a company with the credentials like Pfizer’s have to come out at this time and give a briefing on Chantix? If the product can stand up against the AEs,(as in from the trials)why all the new warnings from the FDA, and ultimately its demise from the FAA and the FMCSA?
I don’t think anyone would argue that without the development, research, and deliverance of of wonderful drugs that many lives would be saved. That is not the topic.
I think if one is a rep they can not get past someone seemingly dishing on pharma.
HorusCat
Hi Jaynesday,
I wasn’t ignoring you, just busy with the kids. Went to see Kung Fu Panda–highly recommend it. Just the right blend of funny and profound moments. And really good, hot popcorn!
You are right about the AE reporting system–but I think I’ve pointed out before that HIPAA makes it difficult to have good reporting. The docs can’t provide patient identifiers. And as a closet libertarian, I don’t think the government should force us to do much of anything.
Lisa,
I never said my mother died in childbirth. I have noted before that she is alive and well, taking Zoloft, for which I was roundly criticized. If that was your attempt to be funny, I fail to see the humor in it.
Ed! I was astonished to see the “new look!” Think I like it, although I don’t have time right now to navigate around it and check it all out. Going to see yet another movie–Adam Sandler this time.
Jaynesday
Hello HorusCat,
Love good popcorn. Thanks for getting back.
Question - Is it necessary to provide patient identifiers to get good data? The AEs I’ve read still provide what seems to me to be valuable data without indicating names. Can’t some number index be used that will provide a link for follow-up but keep identity confidential? Could some official group be sworn in as a keeper of the records? Could all the data be codified for compiling?
Aren’t all medical records kept in some kind of database anyway? What about an extension of this system? Could some penalty be imposed for reporting fraudulent medical information? Like insurance fraud.
Could hospitals be charged with followup of any AE, each having charge for a territory in their respective local?
Sorry, just groping in the dark now.
HorusCat
Jaynesday,
Yeah, it was kind of a movie binge–Sex and the City on Friday with my sister (didn’t care for it), then Panda, then Adam Sandler.
I have all the same questions you do. As you know, I sell an epilepsy medication, and pregnancy data are really hard to come by. The problem with registries here is that doctors can’t register the patient; the patient must do so, and many don’t take the time.
I believe the same problems arise with AE reporting. The physician makes the report, but the FDA is limited in its ability to follow up–I THINK, I’m not 100% sure. There is no back and forth between the FDA and the physician to determine causality. They do collect as much data as possible–concommitant meds, patient age, sex, height, weight, but I don’t think they have access to patient records. Thus, they don’t know if a patient who has an MI, for instance, had a history of cardiovascular disease. They only know if he/she is currently taking heart meds–or if the doctor tells them he had a previous event. Then, there is no way to put that information in the AE report, so the public perusing the reports doesn’t have any context.
I would think that somehow a unique patient identifier could be given when a report is made–the problem is that identifier can’t be communicated to all treating officials and the patient. Thus, a PC could make a report and then a specialist could make a report, but the FDA has no way of knowing it is the same patient.
The other issue is that of getting context–like I said, the AE report doesn’t indicate whether the patient has on-going disease, nor does it indicate severity or causality. That is why I was laughing at the “arthropod sting” reports. And all the GI distress and abnormal dreams. When the AE report is 90% noise like that, it is disingenuous to describe it as “1,000 serious events.”
Another issue is one you pinpointed–we don’t have a universal data base. There are several groups working on such a database (Google, for one), but nothing is in place yet. Even then, HIPAA strictly limits access. Without patient permission, one physician treating a patient cannot even request records from another treating physician.
Finally, the level of sophistication with physicians is not always what you would expect. Physicians aren’t always familiar with side effects, nor do they exercise discrimination in attributing SEs to meds. Thus, the assumption that just because a physician made the AE report it must be serious is not a valid one.
As for reporting fraudulent information–I don’t know how many reports are actually fraudulent, although that would be a great way to sabotage a drug (one of those groups could make all sorts of reports), but it is virtually impossible to verify the reports because of HIPAA.
HIPAA bears out my favorite law: the Law of Unintended Consequences.
John R. Polito
Ed, I’m looking for a transcript of Pfizer’s June 5 roundtable, or an audio or video clip. If available or a link exists I’d be much appreciative.
Regards,
John
John R. Polito
john@whyquit.com
Ed Silverman
Hi Atlex,
First, my apologies for a very belated reply. A couple of technological mishaps and the crush of news conspired to prevent me from posting an answer to your question on Friday afternoon. But I confess I also waited initially while mulling over my response.
So, I think the attempt was a genuine effort by Pfizer to explain its side of the story, which included some spin, but that’s human nature and, therefore, not at all surprising. That’s to be expected. To their credit, the Pfizer folks put three people with knowledge and responsibility in front of us to review material and answer questions. And there was enough time for both.
However, one problem, in my view, was that the presentation included slides, but these weren’t made available, during or after the session. So I was at a disadvantage, because I didn’t have the same material to review as the explanations were given. As a result, I felt like I was attending a tutorial and blinded by science just a bit. If one is going to invite people in for a presentation, corresponding materials should be distributed at the outset. This much of the affair was one-sided and, in its way, unhelpful.
Was it a waste of time? No, it’s almost always worthwhile to meet and listen. I’m not sure this held any great revelations, though. And I think Pfizer could and should have done this earlier, because the crisis was clearly brewing months ago. But it was better than nothing.
Finally, I didn’t come away with any great insights into the company. I’ve been doing this a long time and crisis pr is crisis pr. Insights are provided when key decisionmakers are put out there to discuss the normal course of business. In general, though, pharma execs are rarely available or accessible in that way, except to analysts, fund managers and other investors. This was a one-off in response to a crisis, so its not going to offer much more than a glimpse of some worried managers.
Hope this helps,
ed
GSmiley
can Chantix / Champix survive through 2008 - Pfizer needs to wake up to reality - this cow is already dead you’re just milking it until someone (FDA/EMEA) tells you it’s dead.
And did no-one else see the irony between these 2 statements:
Martina Flammer, Pfizer’s senior medical director, says people with mental illness should be able to take Chantix. “There is no indication that there is any reason why Chantix should not be taken in this population,” she said.
David Gonzales, co-director of Oregon Health & Science University’s Smoking Cessation Center, who led some key Chantix studies. He addressed a particular area of controversy - the trials didn’t include smokers with psychiatric illnesses, which means, as he put it, “the patients in the trials are not terribly reflective of the population of smokers.”