Dewey, Chetham, and Howe at it again

[RACastanet]

You don't want regressive taxes on cigarettes

Actually, I do not mind them a bit. That is a sin tax I approve of as it will not affect me except in a positive way. As for Philip Morris, no matter what the sin taxes are, they remain extremely profitable.

Rich

[RACastanet]

Bill: This is really creepy. Linda and I rented Dirty Harry today and just watched it.

So...



Go ahead, make my day!


Rich

[Bill Glasheen]

800 recalled/withdrawn drugs seems high to me - and I work in the industry.

The source was Your Total Health (27Aug2005) and the number was in the hundreds (plural). I may have the exact number of hundreds wrong. But these were drugs approved and removed in less than a year, Gene. The program was trying to make a point.

That number (in the hundreds) is remarkable considering that five drugs were removed from the market between September 1997 and September 1998. (Nurseweek.com)

- Bill

[Gene DeMambro]

Bill

Bring them on

[Gene DeMambro]

The program was trying to make a point.

If the point was that the FDA is approving drugs too quickly, with only short term usage data available, I agree. But it was the drug companies themselves, way back when, who kept complaining that the drug approval process took too long. So the FDA, under law from Congress, took steps to shorten the approval process. So now we have chemcials on the market that haven't been tested like they should, leading to an increased number of recalls/withdrawals when new dangers are discovered. This creates a terrible burden on industry. And I oppose suing the manufacturer under this scenario. It's just too unfair.

And then we have priority approvals, like with AIDS drugs. But I am aware of no lawsuit involveing the safety of these items.

However, where do we put withdrawals that occur because doctors weren't doing the monitoring they were supposed to, or were using drugs in patients that were not proper candidates? Certainly we can't blame the FDA process for that, if the dangers were known when the drug was approved. And I'm not quite sure placing all the blame on the inapproprate prescribers is the proper way either. But, yes, I do see blame here.

And now we come to the Vioxx case, where the dangers were known to the drug company - well before marketing - who had ample opportunity to study the danger closer, or at the very least disclose it. They willingly did nothing to minimize the danger, or at least inform prescribers.

And then we have recalls due to manufacturing issues, or problems with the drug formulations themselves (like subpotent lots or mislabeled bottles). Federal Marshalls raided a Glaxo plant in Tennesee and impounded all lots of Avandamet and Paxil CR because the plant was in violation of manufacturing regulations. Multiple lots of drugs have been removed from market because of this, but other were unaffected. One drug company, Able Labs, was shut down for good - Not because their products had unacceptable side effects, or the company hid adverse reactions, but because the company was not following manufacturing regulations and the FDA pulled the plug.

But these were drugs approved and removed in less than a year, Gene.

No way that numbers in the hundreds.

From 1997 to the present, the number of post-approval recalls has been placed at slightly more than 5% (per Dr. Lester Crawford, the Commisioner of the FDA). If "Your Total Health" is to be believed that there have been hundred of post-approval recalls due to unacceptable side efetcs, then the FDA must approve thousands of new drugs every year. They approve about 50 to 60 a year. The numbers don't add up, in my mind. "Your Total Health" must be using ALL drug recalls, - even those that have nothing to do with adverse effect/side effect issues.

Gene

[Gene DeMambro]

Vioxx was voluntarily withdrawn. FDA ordered Bextra removed from the market. Celebrex has never been removed from the US market, even for a short time, and warnings have ben strengthened regarding its use.

Gene

[Bill Glasheen]

The "hundreds" was over a several year period - since the streamlined FDA process.

If the point was that the FDA is approving drugs too quickly, with only short term usage data available, I agree.

The issue was the average person working with their physician, and I agree with what the program was trying to convey. My wife is reluctant to prescribe new drugs until they've been on the market for a while, and it appears her caution is warranted. The physician interviewed on the program made the point that very few patients need the "new" drugs unless this is a case of a brand new treatment otherwise unavailable in the past.

The drug companies will send young beefcake and cheesecake in the physician offices with free samples of the new drugs to dispense to patients, along with some freebie luches while they educate the provider staff on their use, indications, and contraindications. It's something that has caused no end of annoyance to the insurance industry which knows that the standard drug (say a beta blocker for hypertension) works pretty damn well in most cases for several orders of magnitude less cost (once the free sample runs out). But that's marketing. I'm not a fan of marketing, but it is what it is. Some physicians are more ethical and patient-centered than others in dealing with all this. I tell my wife that she can accept the freebies if she wants, but I will not partake. I've missed out on games to local sporting events, movie tickets, meals at restaurants for talks by academic experts, etc. I considered it a conflict of interest long before the companies I worked for mandated it as such.

These days, that has been curtailed a lot. The drug companies do well enough with the direct-to-consumer advertising. The program attempted to convey that they don't necessarily need what the ads say they gotta have.

It's like getting the first year model of a new vehicle. Buyer beware. It takes time to iron out all the bugs, and identify all the ideosynchracies. With so many drugs on the market today, Rx to Rx interactions has got to be the major concern. And the number of such possible interactions goes up exponentially with the number of available drugs increasing.

It is what it is.

- Bill

[Bill Glasheen]

Bring them on

What may at first appear to be a tempting, delicious target...



...may end up being more than you bargained for.



Beware the corporate 800-pound gorilla. They walk softly but carry a big political stick. Anything that survives the modern global economy does not take an inappropriate threat lightly.

- Bill

P.S. And should we really ban crack after all??

[Panther]

Ian, it's as if you didn't read my post. I do not ask for lenghty discussions on risks and benefits for each of the many necessary steps we take every time we see someone who's actually sick. I require patients be given information enough - no less - to make informed choices regarding THEIR health care decisions and treatments. And so does the courts. And so does modern society. And I bet so does your hospital. I know mine does. I can provide medical ethicists recommendations (see article from the Globe I linked), legal opinions and regulatory requirements to back me up.

I do not wish to mistakenly quote or infer an opinion that you may or may not have, Ian. But I get the feeling that you do not agree with informed consent, and you do not agree that physicians have a responsibility to tell patients of the benefits and risks of the treatment you recommend. I get the feeling that you think what the doctor says goes and patients are not part of the decision making at all. Again, I don't mean to infer the wrong conclusion, but I don't see it any other way.

STOP!

After your first paragraph espousing what "society believes", what "courts require", what the "hospitals" have for rules, and what "ethical" and "regulatory" requirements are, you proceed to the second paragraph where you state your "feeling" that Ian's positions are contrary to those "requirements", "ethics", "regulations", and "rules".

That has gone WAY too far!

I read Ian's posts (and the rest of this thread) and your "feeling" on what he meant, says, or does is NOT correct. You've basically accused a respected Doctor (and member of this forum) of actions or beliefs that go against the very code of conduct that he's sworn to uphold!

Understand this: That is uncalled for. I strongly suggest you decide to "see it another way".

And don't even try to claim that it was just "debating". If that's the way you want to "debate" go somewhere else, because, at the very least, that was a VERY low blow.

[Gene DeMambro]

Panther,

Your point is well taken and it will not happen again.

Gene

[Gene DeMambro]

From time to time, I go to conventions and expos. I come home with all kinds of freebies. Most of it giveaways. My nephews like trinkets and my older brother likes drug company pens. And, yes, I do go to the free dinners when mood permits. But I engage the sales reps whenever possible, asking for more clarification on the negatives of their drugs. Sometimes, a company or a drug has so broken the WSJ rule, that I don't even bother. Biogen Idec is a good example. I don't even bother since Tysabri was yanked. At least with the Merck reps I can focus on other stuff to keep them happy.

But I never let it effect my professionalism. I use evidence-based decison making and sometimes that pisses them off, especially young beefcake and cheesecake. And when our clinical director (with two Doctoral degrees) gets a hold of them and blasts right through their polished sales pitch, they wonder aloud why they never went into something easier, like nuclear physics.

I would ban DTC drug advertising altogether, and let the primary literature control. But that's me.

Build a better mousetrap.....

[Panther]

Gene,

Thank you.

However, Ian is the one that deserves an apology.

Take care all...

[IJ]

Appreciate the support, Panther. Thanks.

Gene, I go farther most in discussions with patients. I give them more information than the doctors from which I learned and that is customary in a variety of hospitals, including several VA's, several of "Americas Top 100 Hospitals," teaching institutions, and so on. I describe the caveats that come with diagnoses and the risks of treatment, and document them, far better than most. And I know if *I* were a patient what I would want and that would include detailed information and the right to choose plus i would closely scrutinize my caregivers, for everything from conflicts of interest to hand washing.

MY POINT, again, is two fold and straightforward:

What you're advocating requires an indepth discussion. To CHOOSE you must have comparative knowledge on several options. A doctor cannot CHOOSE medicines unsupervised until she or he has done college and 4 years of medicine THEN 3 of residency PLUS fellowships ranging 1-5 years. Only an overview can be given to patients. This is more to make them understand the process of our recommendations than it is for them to choose independently. In areas where there is serious dispute, say, a PSA, then they basically have to choose based on gut feeling, and a biased presentation, because as I'vce said before, MDs are still arguing about the PSA, the literature is compliex, and national experts disagree.

Patients who are well off, well connected, and sometimes TOO empowered often get themselves into trouble revising their care. For example, one CEO who brushed aside my information on drug side effects and the microbiology of recurrent cellulitis after saphenous vein harvesting for bypass surgery and could have gotten nafcillin (penicillin friend), demanded piperacillin-tazobactam-vancomycin because he knew these were "strong." He was over treated, risked superinfections and resistant bacteria and wasted hundreds of your healthcare dollars. One small example.

Here's mine from today: new service, 15 patients, all new to me, receiving between 4 and 23 medications, with some 2-16 conditions under treatment, some fatal, some minor. To discuss every detail of care with them and then let them choose would be like strapping a novice into the space shuttle befor reentry, then discussing which switches to switch on the way down in detail and letting the book reviewer make informed decisions about what to operate.

I am not telling you that I do not want 100% perfection for my patients, I am telling you that it is not possible, that we are doing the best we can, that we are constantly working to improve, and that getting painted as bad guys WHILE our private time decreases, job freedom is curtailed, and paperwork and threats of litigation increase, is not going to help. If one has x hours and y dollars to make things better, a lawyer will not be involved with the most effective intervention, period. Why can't you conceive that the 11 hours I worked today with a five minute lunch and a two minute pee break was spent as best I could for those 15 people? What did you want me to do, discuss things instead of... examining them? listen to their stories? talk to relatives? What was I supposed to cut out? Or, would you like me to add 6 more hours, work 17 hours a day for 2 weeks, and then sit thru a lecture on tired physicians making mistakes? Walk a mile in my shoes and you'll see that the 4 physicians, 2 students, the pharm student, case manager and all the nurses and pharmacists and others who worked today are GOOD but FLAWED humans doing their best...

But Bill..... the FDA's rulings on VIoxx and other drugs are irrelevant. Merck is a respectable company. But they misbehaved and concealed data that harmed patients, for money. Why are you astonished they landed in trouble? Their behavior--muzzle the drug reps on key information, fight the earliest release of heart concerns--would have left them blushing if a patient confronted them. And that's all there is to it.

AIDS drugs were mentioned and Gene said he knew of no lawsuits regarding them. Here's something to note... those drugs routinely cause... anemia, pancreatitis, kidney stones, dangerous abnormal lipids, diabetes, nerve damage, rashes, potentially fatal metabolic disturbances, and so on. There is a good example, abacavir, among them. There is an unpredictable allergic reaction with flu like symptoms, fever and rash. If the drug is continued, it can be fatal. If the drug is restarted, it can kill. How do we know this? By KILLING patients by mistake. Learn from that mistake. Why no lawsuit? Because these drugs were desperately wanted and needed from people who saw every last one of their friends dying from AIDS and were willing to take risks.

When Sally from the burbs sees her healthy husband die possibly from a drug for arthritis, that rare reaction seems preposterously too high a price to pay, outrage results, and people must pay. Merck's ethical error was a blank check at that point.

What I'm saying is, Gene, if you want to hurt patients, hurt drug companies, terrorize doctors, and go to bed rich, find the survivors of one of those early AIDS patients who died while we were learning how to use abacavir, get it off the market so we can't use it for the needy anymore, and win one for the "little guy." That is.... if the lawyer is little.

[Bill Glasheen]

But Bill..... the FDA's rulings on VIoxx and other drugs are irrelevant. Merck is a respectable company. But they misbehaved and concealed data that harmed patients, for money. Why are you astonished they landed in trouble? Their behavior--muzzle the drug reps on key information, fight the earliest release of heart concerns--would have left them blushing if a patient confronted them. And that's all there is to it.

First, I enjoyed the eloquent discussion of what you have to go through.

Now... Walk a mile in my shoes. You're a smart guy Ian (big understatement) so I think I can convey this to you.

I wanted to tell you what I am doing at work this week to tweak a product we sell. Then I realized that the folks may get mad if I spill the recipe for the secret sauce. Damn... It was a great example.

The whole issue of cardiac events and analgesics is a big problem. If you have a population taking a brand new analgesic and you note that they have a higher-than-normal incidence of a cardiac event, what does that tell you? Well, it could be any of the following:

* The new drug is causing cardiac events

* Those who are at high risk for a number of different clinical conditions such as stomach bleeding are being steered away from the traditional analgesics (name your NSAID) and towards this COX II inhibitor.

Think of the kind of patient who should be taking a COX II instead of ibuprofen. That person probably has a chronic issue such as osteoarthritis. We know that long-term use of NSAIDs can cause gastric bleeding, and that's not a good thing.

Now, split out the folks who need long-term analgesics and/or anti-inflammatories from those who just need a few rounds of aspirin or ibuprofen. Are they identical cohorts? Of course not. I would bet you a dinner at the finest restaurant that those people who protocol would dictate should be getting a COX II (before anyone knew of the cardiac risk) are at higher risk of a cardiac event. You have a natural selection bias towards those who are sicker and will be having their "final event" sooner than later. (Sooner or later, one out of three of us is going to bite the bullet in this fashion. Medicine just delays the inevitable.)

Today I'm having to come in and do a multivariate analysis where someone who didn't know any better did a simple comparison of two cohorts where there was a selection bias. They drew inappropriate conclusions, and wanted to screw up a perfectly good predictive model. If you do epidemiologic studies, this is the way you have to do it. You have to account for everything going on that contributes to overall variability, and remove these extraneous sources so you can separate out the effect you want to measure.

Or...

You can run a very expensive but important randomized, double-blinded, controlled trial. And it must be large enough, run well enough, and survive the peer-review process.

I am telling people not to draw inappropriate conclusions today so someone won't screw up our product because they don't understand some basic principles of causality and experimental design. This is no different from folks at Merck telling people not to draw inappropriate conclusions from epidemiologic data, or RTC trials too small to show statistically significant odds ratios. I completely understand where the folks from Merck were coming from, and I would be one of those folks telling people to wait until the data appropriately tell us God's truth.

Yes, you can look at raw data and get a hunch. I do this all the time. I suspect these "hunches" were what drove people to do the published study that caused Merck to pull their product from the market.

That's the way the system works today. If you want it to work better, maybe you slow the approval process down, and demand that bigger (and MUCH more expensive) clinical trials be done first. But that's not what the system asks for today. The FDA approved the drug by today's approval standards. Merck met that standard.

Don't like it? Change the process!! And don't complain when it takes longer to get a drug or product to market, and lives are lost waiting for life-saving treatments. And those drugs, treatments, and medical devices that do make it are going to be more expensive. Ultimately I suspect this may happen, and that's not an altogether bad thing. Either that, or some people are going to need to understand the higher risks involved in getting the latest and greatest. Fortunately some healthcare providers I know preach this to their patients.

Believe me, if the insurance industry knew the risks associated with COX II inhibitors they would have been screaming from the top of the mountain. Go to your average insurance plan and pick out the top ten drugs by dollar volume. I bet you that the Average Joe on the street would recognize the name of 8 out of the 10. They are the newest, and most heavily advertised.

But no... Insurance companies took a BIG beating saying "No" to their patients who wanted Vioxx, Celebrex, or Bextra, or from making them pay 3rd tier copays that heavily discouraged the use.

IF they only knew, they would have saved beaucoup bucks. But they didn't. And collectively they had more (and better) data than the drug companies.

And that, BTW, is one reason the company I work for started a special relationship with the government to troll data for such issues. It's about time!

- Bill

[chewy]

chewy

I disagree with your blanket assessment. You can no more say that Merck and other companies ONLY do things for money than I can say all lawyers are evil (however tempting it can be from the actions of a few).

I've worked for several very large (Fortune 500) companies now. If I was only in it for the money, I would have stopped my education at the bachelors or masters degree level. It takes too long to get a Ph.D. to make that path the most profitable one. My undergraduate engineering degree and the time value of money would have allowed me to retire a very rich man by now. I pursued a Ph.D. because in my working years I discovered I had a talent for research and I hated production work. In other words, MY WORK was my most important reward in the long run.
- Bill

Bill,

I've also worked for several of the 500 companies, but I think you are confusing the ethics of individual employees with those of the "corporate entity". I also have high standards for my work (electrical engineer). I've never had to design a medical device or other life-saving product, but I still make great effort to prevent "known bugs" from entering the field on my watch. I also know several engineers that work at companies that DO design medical equipment and they all work to the same standard. Not just because lives depend upon it, but because, like you and I, they feel a job well done is its own reward.

I also have little doubt that many corporate executives try to behave ethically and take pride in their work. What I'm getting at is that all these "feel good intentions" get brushed aside by the corporate entity itself. We often speak of a "mob mentality" at soccer matches and during race riots. Even good people start doing bad things in these situations "because everyone else is doing it." The same thing happends at the top rungs of a Fortune 500 company.

The executives jobs and incentives depend upon the amount of value-add they can bring to their share holders. We are talking big $$ Bill... more that most people can actually fathom (just try to picture $1B in your head... really... it's tough). So an board of directors "cooks the books" or hides the negatives in their product, not because the people working for the company are all evil, but because it is easy to do when everyone "goes in on it". In the Board Room and all throughout the top of the executive chain ethically improper decisions are approved because the mob mentality says its good for the company and everyone else around me agrees.

It's OK to take pride in your work Bill. I do it all the time, but don't blindly believe everything your company tells you and their reasons for doing it. I've said it before and I'll say it again... $$ is king and whereever you see big $$ there is a level of corruption and ethical impropriaties to go along with it.


cheers,

chewy

PS- An engineering degree guarantees you wealth?!? I'll mention that to some of my unemployed friends next time I see them. It should lift their spirits!

PPS- The return on an investment on a Ph.D. is only as good as the field you are in. A Ph.D. in philosophy or theatre isn't going to fetch a lot of cash. I know many Ph.D engineers, programmers, and medical researchers, however, and, assuming one can hold your job for 8 years, they've break even. Anything beyond that pays great dividends. BS and MS degrees are also well rewarded in these cutting edge fields assuming you can keep your job long enough to break even. Risk/Reward.