Friday, December 31, 2004

Re-importation - time to take sides?

Not so much on the drug safety issue recently in the press. Instead, we have found several pieces relating to re-importation from Canada.

The Washington Post has an article by financial writer Steven Pearlstein that blasts the recent Bush Administration report on drug prices. Among other things, it asks the simple question, if you defend our prices on the idea that they help subsidize R&D for the world, then should why should there be any policy to help lower drug prices?

Rhode Island became the latest state to approve re-importation of drugs from Canada. The testimony for the state Health Department included a reference to the USA Today article that described greater reluctance on the part of Canadians, including Health Minister Ujjal Dosanjh, to subsidize our drug bill. Apparently, when drug re-importation becomes a matter of state policy rather than an individual act, there is puch-back from the suppliers.

We have actually been eagerly awaiting this development, since push-back from Canada will force lawmakers to stop trying to placate the few loudest grey-haired types, and find a way to give us all real relief from this industry boot on our throats.

Anybody notice that the $35 million aid package announced by Colin Powell is $5 million less than the Republicans are planning to spend on inaugeral festivities?

Please take a moment to lend a hand to those who are suffering from the tsunami. We think that the extent of this tragedy may not be known for quite some time, and the death tolls updated daily on the news are gross under-representations. You can donate here or here.

We hope your new year is healthy, and may you have unlimited access to your pain control of choice. We will be spending the evening with friends in an orgy of fondue and fellowship. May your evening be safe and enjoyable.

Monday, December 27, 2004

Pfizer exec tells all! and Fraud on the FDA?

Today we found a remarkable story in Sunday's Los Angeles Times (link may require free registration), written by Peter Rost, VP of marketing at Pfizer. We urge you to read the entire piece, but we'd like to point out a few items that caught our eye. For instance:

"A 2001 study by the consumer advocacy group Public Citizen found that drug companies' favorite customers paid just a little over half the retail price. This leaves the 67 million Americans without insurance to pay cash, with no rebates, at double the prices paid by the most-favored customer"

Most drug company execs would piss on any report created by Public Citizen, like this one that discusses the real cost of drug development. We find Public Citizen's quest to have every objectionable drug banned to be irritating, because they refuse to acknowledge the real-world benefits that some patients have with newer drugs like Celebrex, after the patient has failed older therapies that Public Citizen approves of. While aggregate efficacy is compelling, and older therapies should always be tried first, there are always outliers that have fantastic responses to new therapies, and their health should be considered, too.

But we digress. To find a Pfizer exec quoting Public Citizen is remarkable. To read him also dissing Pharma indigent programs, like he does two paragraphs later, is stunning: "If they really worked, the Kaiser Family Foundation wouldn't have reported that 15% of uninsured children and 28% of uninsured adults had gone without prescription medication in 2000 because of cost, and 87% of uninsured individuals with serious health problems reported trouble obtaining medication." Wow.

So, how far off the reservation is Mr. Rost? At Pharmablogger, we have no clue. We assume that marketing execs (we don't know any personally) come from the ranks of sales reps, and they generally have drowned in the Pharma Kool-Aid. Yet, we know several high-ranking drug development types who believe that dramatically lower prices will bring about much greater utilization, since there are so many under-medicated patients out there. Hard to believe, since Grandma seems to be popping her pills all day? It's true, though. So many people with untreated hypertension and hyperlipidemia, for example. That's why firms continue to get into these markets with me-too drugs - their advertising is designed not only to take away market share from competitors, but to get more people to have themselves examined for these conditions, and expand the market for everyone.

We would like to examine the issue of Fraud on the FDA in this space today, since we were prompted by an article on tort reform in the Philadelphia Inquirer. The article details the attempt to create tort immunity for Pharma firms whose drugs have passed FDA approval, and have met other "FDA standards." A Merck spokesman states that they support the proposal.

"Proponents of the bill and the pharmaceutical industry have contended that manufacturers should not have to pay punitive damages for an FDA-approved product unless it can be shown that they misled the agency or failed to follow FDA strictures."

What's the problem here? Several. This bill assumes a competent FDA, for example. We generally approve of the job the FDA does, but it is incredibly understaffed, particularly in the post-marketing surveillance area. So if the FDA fails to act on a drug that has several safety "signals" - warning signs, why should the manufacturer get a free pass for this? There isn't any comparable protection in other industries, as far as we can tell. The Consumer Product Safety Commission issues a number of recalls every year, for example. So any product that is not recalled should be held unaccountable for design flaws? Nonsense.

This also assumes that the Pharmas are fully diligent in reporting to the FDA all safety signals that it finds. Assuming that they're looking. In fact, this bill would encourage them to not look for safety problems in their data.

That leads us to Fraud on the FDA. This is a claim that was asserted in a seminal medical device case called Buckman Co. v. Plaintiffs' Legal Committee, 121 S.Ct. 1012, 148 L.Ed.2d 854, (U.S. 2001). The Supreme Court rejected the idea that there is a private action possible against companies regulated by the FDA (including device firms) for state-law fraud on the FDA cases.

"The conflict here stems from the fact that the federal statutory scheme amply empowers the FDA to punish and deter fraud against the Agency, and the Agency uses this authority to achieve a delicate balance of statutory objectives that can be skewed by allowing state-law fraud-on-the-FDA claims. "

So, you can't sue Merck on a claim that states that they defrauded the FDA by failing to provide timely safety data for Vioxx, for example. Perhaps Merck isn't the best example. How about the makers of Phen-fen, who actually stuffed safety reports in desk drawers concerning lung and heart problems? If the FDA fails to act against the manufacturers, and then this "tort reform" is passed, what kind of claim is left for those who have been harmed? Remember, the FDA has a "delicate balance of statutory objectives," only one of which is patient safety. The others are more like industry promotion. These can and do conflict, which was at the heart of David Graham's testimony.

There is an attempt to get around the Buckman ruling, by stating that a drug is not really approved if there was fraud in the approval process, thereby abrogating the FDA's right to punish fraud, since a drug or device should never have been approved to begin with. This is the Gilligan case in the Sixth District, but we are not optimistic. The same rationale in Buckman could be used here as well to shoot down this theory.

Lastly, we have a stark reminder of what we posted in the inaugural edition of Pharmablogger - that Pharma is first and foremost a business, with a fiduciary responsibility to maximize return to investors. Tom McKillop of AstraZeneca is learning that right now.

Thursday, December 23, 2004

Michael Moore attacks; and first Archive Holiday Assignment!

Rotton Tomato news has a story about Michael Moore's forthcoming film "Sicko" which will be about American Health Care, possibly focusing specifically on our wonderful industry. The story notes that some companies sent out a warning to employees concerning the film, and to watch out for Michael Moore ambushes at the gates. We can attest that this is true - our company made such a warning earlier this Fall. My opinion about Michael Moore's films can be found in the comments beneath the article, and I won't repeat them here. Look for the Pharmablogger comment.

Little other news today, except for the bitch-slapping warning letter to AstraZeneca concerning their face-saving adverts for Crestor that appeared shortly after David Graham fingered the drug as one of five potential Vioxx cases. Here's the New York Times take on the letter, where they pull no punches in listing other AstraZeneca woes of the recent past.

We are not sure how often we will post in the coming few days, due to Christmas. For your holiday reading pleasure, I am assigning an article that appeared in the Times in March, 2001. The article is about the development of Claritin by Schering Plough, and their attempt to prolong the brand patent. Normally, the Times charges for access to articles over 7 days old. But for special features like this or Magazine articles, free access appears to be indefinite. The crux of the article is that so much money has been spent, and so much litigation has taken place over a drug that barely beat placebos in the efficacy trials. We just take a little piece of a Benadryl when we need something for our Spring allergies. Remember - there's no such thing as a non-sedating anti-histamine. By definition, any drugs that block histamine receptors (including many neuroleptics) cause drowsiness. Claritin, Allegra et al are simple weak anti-histamines. And our allergies laugh at them.

Update 2 hours later: Check out this article in Editor & Publisher about the Michael Moore film. Hidden cameras in doctor's offices? This could get ugly. We once had a discussion about doctors with a sales rep, who insisted that "establishing a relationship" with a doctor by providing dinner and other goodies was good for everyone, including patients. These Kool-Aid drinkers cannot ever see their role as corrupters of good medical practice. When our wife (first-person plural gets difficult sometimes) was diagnosed with post-partum hypertension, and the doctor's first choice for a prescription was a Calcium Channel Blocker, we "fired" that doctor immediately. Sometimes, it's hard to tell who is worse - the doctor whore, or the sales rep pimp.

Merry Christmas and good health to all!

Wednesday, December 22, 2004

A correction; and healthy skepticism at last!

Yesterday we posited the idea that there was a media script for the "confused consumer" who did not know how to handle the news about Vioxx, Celebrex, Naproxen, etc. We are happy to say that we are wrong about this, as the script has been revised along lines we approve, namely the pissed off consumer.

We saw in yesterday's Wall Street Journal an article (free to subscribers only) about people with pain who were not happy about having the option to weigh risks versus benefits taken out of their hands. Similarly, while listening to NPR's Talk of the Nation, we heard John Klippel (heading of "Treating Pain"), president and CEO of the Arthritis Foundation, make the same case. OK, the Arthritis Foundation Supporters Page clearly shows that it's in Pharmas pocket. Still, a broken clock is right twice daily (cliche watch).

An article in today's New York Times shows us some healthy skepticism from members of Congress, particularly Republican, concerning the results of the Bush Administration's study on the safety of drug re-importation. Really, where do people think those Canadian drugs come from, anyway? And what would they find if they performed the same kind of study on drugs processed through the world's largest "repackaging" facility in Bentonville Arkansas (guess for whom?). If they don't take the Administration seriously on this, why did they swallow the $400 million pricetag for the Medicare Modernization Act (drug bill)?

On the subject of drug safety and the FDA's role in policing, I want to recommend Philip Hilts' history, Protecting America's Health. As I state in my Amazon reading list, while reading about the patent medicine era, consider how many conservatives/libertarians want us to return to those days, having the marketplace weed out the bad actors and products, after we can no longer ignore the bodies piling up on the streets.

Shop happy. I hate slamming into annoyed people in the mall.

Tuesday, December 21, 2004

Oh the PAIN! Celebrex, Naproxen, Accupuncture?

Naproxen is next on the block, with evidence that it may also contribute to cardiovascular problems. The consumer reaction that we hear from the media does not juve with our personal experience, however. That's because there's a media script here, and they only feature people who fit the part - the Confused Pain-Sufferer!

Bollocks, to use a great British term. Don't you think the average consumer can understand the difference between a 1 in 1000 chance of having a heart attack or stroke versus a 2.5 in 1000 chance? That's the difference between Vioxx users and non-users. Now, we know that in the aggregate data, there is no efficacy difference between COX-2s and NSAIDS. But this is the type of medicine that has unpredictable outcomes for individual patients. I'd like Syney Wolfe to go to our mother's house, and tell her that she doesn't really need her Vioxx for her crippling rheumatoid arthritis, despite the fact that NSAIDS clearly did nothing for her after many years of use. How do you explain someone taking their first few doses of Vioxx, and shortly thereafter feeling a freedom of movement that they haven't had in years? Placebo effect? Bollocks again!

We're picturing a new drug ring in this country, a gang of little old stooped-over ladies (shades of Monty Python here) who traffic in COX-2s, and get pissed off whenever a consumer activitist tries to tell them what's best for them. Wolfie's gonna be found face down in a pool of Ensure someday, knitting needles protruding ominously from his back with a clear message from Grandma - don't mess with my meds!

Seriously though, it is definitely a headache to restrict usage of a drug once it's on the market, despite its potential dangers, unless you want a patient registry like thalidomide has. The genie wants out of that bottle. So could we trust Merck and Pfizer to carefully restrict the sales of these drugs, to only be prescribed to those who have failed other older therapies, have no additional risk of CV illness, and have a miserable QOL (Quality of Life) without COX-2s? The overutilization is a joint effort between the Pharmas and physicians, who can't be bothered to do any drug research beyond what the reps give them, and who also probably didn't have pharmacology in med school. Still, we believe these drugs should have some place in the armamentarium.

The Washington Post gives us lots of pain today, as they have articles on the Naproxen findings, as well as using accupuncture for arthritis, and physicians getting upset at the DEA for giving them chills. While we certainly want physicians to more aggressively treat pain, with opioids if necessary, we still can't help but laugh at this passage:

"[T]he government can open investigations on the suspicion that a doctor is diverting controlled drugs or to make sure there is no improper activity. In reply, the three pain groups wrote: 'Reading that the government can investigate merely on suspicion that the law is being violated will send chills down the spine of practitioners who are treating patients with [narcotic painkillers] ....'"

"Merely on suspicion"? We don't watch much crime TV, but isn't suspician usually what causes investigations? Investigation does not equal indictment. Does the fact that an investigation may be underway cause problems for a practitioner who is not violating the law? What level of evidence should the DEA require for starting investigations...Rush Limbaugh parking in front of the doctor's house?

Friday, December 17, 2004

Is Celebrex Going Down? and Tauzin Chutzpah!

It seems that maybe all COX-2 inhibitors may be the same indeed. Pfizer announced that a trial similar to Merck's for preventing adenomas revealed a 2.5 greater chance of having a major fatal or non-fatal cardiovascular event than those on placebo. Pfizer's release is here, and the AP coverage is here. Note that the dosage used is at the higher end of what is prescribed for arthritic pain, so maybe Pfizer can hope this is a dose-dependant effect, and salvage some sales of Celebrex, which are about 6% of Pfizer sales.

Billy Tauzin has scored a major pay increase, by accepting a position as the head of PhRMA (no relation). There are of course the usual disclaimers that this is not a reward for his authorship of the Medicare Drug Bill. My favorite part of this article is the quote from Tauzin - "This industry understands that it's got a problem...It has to earn the trust and confidence of consumers again." Ironically, surveys have suggested that the more a senior citizen is aware of the parameters of the Medicare drug bill, the more likely they are to oppose it. So, Mr Tauzin, why do you imagine the industry has lost the trust and confidence of consumers?

Another dumb person story hot on the heels of yesterday's woman in the Post who isn't happy enough with her daughters: a survey showing that smokers are ignorant about health issues of smoking. The only unfortunate thing is that these folks will generally live long enough to pass on their stupid genes to the next generation. Well, at least they won't be sucking benefits out of Social Security for too long into retirement, since AstraZeneca's Iressa doesn't seem to improve survival over placebo.

Thursday, December 16, 2004

A few new links for today....

Today we're keeping it simple, providing some links to interesting reading. With apologies to James Taranto and the Daily Howler, we are also adopting the first person plural.

First up, we have the NIH admitting to flubbing safety standards in African trials for nevirapine, trying to reduce mother-baby transmission. What is disturbing here from our perspective is that the NIH performs so much of the basic science that brings us new medications - we would hate to see Congressional rats drag this organization over the coals, the way they tried to dismantle the FDA after the Republican takeover. The NIH contribution to drug development is not as well known as it should be, but some recent books are trying.

Next up, an article in the Washington Post (we like to link to them, because they don't yank access to articles after seven days, like SOME publications we could name) about choosing the sex of your baby by genetically examining the embryos before implantation. Nothing about drugs here - we were just appalled at the bitch mom who states "My husband is a 'Junior' and has a family business that he wants to continue in the family name...I'm excited, [w]e always wanted a boy" with the picture showing her surrounded by her three unworthy daughters. This reminded us of articles that appeared a few months ago in various places about "missing" tens of millions of girls in China and India. Unfortunately, they aren't missing because of genetic testing - they are aborted more frequently now due to increased access to ultrasound machines in rural areas. Since the fetus has to be far along to see the sex on ultrasound, we're talking about a LOT of second term or later abortions. It's all about devaluing girls.

Lastly, we cannot resist the urge to make crash-test dummy jokes about the Consumer Union's new website comparing drugs in the same therapeutic class, like NSAIDs and PPIs. Seriously though, this sort of information is invaluable, until non-placebo controlled trials are mandated, as they should be.

We would also like to note that to gin up some publicity, we have posted a couple of book reviews on Amazon, hoping to lure a few innocent pairs of eyeballs to this blog, as well as a "Listmania" list. Let me know if it works.

Monday, December 13, 2004

Drugs as "Unavoidably Unsafe" products

I have a huge range of topics that I could explore following the previous post, but I decided to first discuss in part the topic of torts, and answer the question posed earlier – why are pharmaceuticals treated differently from all other consumer goods, when it comes to harming user? The phrase to remember is “unavoidably unsafe products.

Pharmaceuticals have a special "carve-out" from product liability laws, because there is no way for them to exist without someone experiencing harm when taking them - side effects or "adverse events." There would be no drug industry if they were evaluated by the courts the same way a toaster manufacturer would. The link above discusses the different ways that a product can be found to be defective. Manufacturing defects are the first that come to mind, but if there is an alternative design for a product that would make it less hazardous, then there can be a Design defect. If the product is sold with inadequate instructions or warnings, it may have a Warning or Labeling defect, even if the product itself can remain on the market. The question for drugs is in the risk/benefit ratio - is the drug a net health benefit for medicine, to justify its risk? That depends on how severe and frequent the side effects are, and what the drug is used for. We accept far more dangerous side effects like leukopenia from chemotherapy medications than we would from an anti-histamine.

These definitions were codified in a document called the Restatement of Torts (Second) and the sequel, the Restatement of Torts (Third) in 1962 and 1997 respectively. The American Law Institute wrote these documents, to try to create a uniform approach to torts that state courts could adopt, but they have all interpreted the Restatements with shades of difference, keeping lawyers (and law professors) at full employment.

This link will take you to a case that had the manufacturer of Accutane as the defendant. Scroll down a bit to the section titled "IV. Analysis" and there's a nice summary of the Restatements, including Section 402A of the Second Restatement which deals with product liability, and Comment k, which deals with unavoidably unsafe products, including drugs.

If you’re a pharmacist, there's and excellent review of pharmacist liability here, at Medscape. You have to register to see the article, but it's free. If you prefer not to, Google has the article cached a huge document available that gives the latest stats on the utilization of drugs in the US. The .pdf is 14.4 MB, but you can look at individual sections, or an executive summary, if that suits you. We're taking more drugs than ever, more people are taking multiple drugs, yadda yadda. Any surprises here? It's good to know the scale of what we are here to discuss, however, so take a look.

Rep. Pete Stark of California, who gave us the Stark Ethics in Patient Referrals Act (Stark I and II), wrote an article last Friday concerning drug re-importation from Canada, reprinted widely. I have nothing more to add to the article at this time, other than to note the absence of dead Canadian bodies piling up outside of Vancouver pharmacies.

Thursday, December 09, 2004

Pharmablogger Welcome

Welcome to the Pharmablogger page. My mission here is to showcase information relating to the negative practices of the pharmaceutical industry, particularly focusing on the legal issues that arise from fraud, defective products and labeling, and so forth. I will also comment and link to any aspects of health care that tickle my fancy. It's my space, after all.

The passage of the Medicare Prescription Drug Improvement and Modernization Act of 2003, and the related lobbying effort that went into the passage of this ridiculous giveaway bill was the catalyst for my immersion into the literature of Pharma fraud. Much of that material I was already familiar with, but recent publications have pulled a lot of material together well, and I will be recommending titles and articles as I go along.

I've also witnessed truly innovative medicines being developed and brought to market, but frankly, that's such a small part of what the Pharmas do that I almost hesitate to mention it. But I've seen the faces of people whose lives had been improved or even saved by medications, and I can't discount that. I'll talk about that in the future as well, and talk about where those innovative meds really come from.

To get started, I would like to direct you to sources of material on the internet, so you can see what lies behind the nice Lance Armstrong ads and The World brought to you by Merck (NPR). Let's start with something provided by the companies themselves (because they have to!)

My favorite part of any Pharma annual report is the Contingency section in the Financials, where you can find information regarding ongoing and potential litigation. Any Pharma company is going to have a significant (and growing every year) section that details suits against them by class action plaintiffs, shareholders, the Department of Justice, various Attorneys General, or in the case of Merck, all of the above! (and more!) You have to look deep for this stuff, though. For Merck, the litigation liabilities is found in Note 9 of the financial section, not widely read. It starts on page 42 -
If you follow that link, you'll see a reference to lots of different kinds of litigation. However, the headlines all come from civil cases involving personal injury. It's important to understand the unique position that drugs have in the realm of product liability. Think for a moment - if you buy just about any kind of consumer product, use it as intended, and you end up in the hospital or a morgue due to an injury that unmistakably results from the use of that product, you've got a case, and that product won't be around for long, thanks to product recalls, voluntary or otherwise. But this happens to hundreds of people everyday who take prescription or OTC (Over The Counter) drugs. These drugs are not removed from the market, yet for the most part, these hundreds of people every day have no compensation for their injuries. Why? Pharmaceuticals have a type of immunity that just about no other product has. I'll provide further information about this concept later. I'll also have a numbers day, to provide the scale of some issues I'm bringing up.

Here's a few more Annual Reports available online:

AstraZeneca - Page 104, inside the section "Assets pledged, commitments and contingent liabilities"...enough to make any casual reader flop unconscious on his/her keyboard. Note the Zoladex Corporate Integrity Agreement at the bottom of page 106, resulting from when they were very bad. This will be a future topic of discussion, concerning fraud against the government.

Pfizer - Page 49, Note 20 of the financial section. Items to note include the patent action "against the manufacturers of competing PDE5 inhibitors for infringement" of their "broad patent...covering the use of orally-effective PDE5 inhibitors for the treatment of male erectile dysfunction." Say what? Pfizer makes Viagra, which is an "orally-effective PDE5 inhibitor." They have a patent on the Viagra molecule, naturally. But in October 2002, they got a patent not just for that molecule, but for the entire method of treatment of impotency. So Cialis and Levitra manufacturers (surely you've seen the ads!) have their own molecule patents, dating prior to October 2002, but are infringing on Pfizer's patent on an entire disease "target." Incredible. Imagine if the first manufacturer of the fork had received a patent not only on the fork itself, but on the method of using an implement to bring food from the plate to your mouth, and got that second patent after the spoon had also been invented by someone else!

Schering-Plough - Starting on page 62. Take a look particularly at the "Investigations" sections starting on page 64. Under the "Pennsylvania Investigation" and "Massachusetts Investigation" heading, there's information regarding attempts to defraud the government by failing to report information that would impact what Medicaid programs would be charged for their drugs. Also note the US Attorneys who are investigating these issues - Eastern District of Pennsylvania, and Massachusetts (Philadelphia and Boston offices). You'll see these folks again and again, as they are the most aggressive (and successful) litigators against Pharma fraud.
Just pick any company that you can think of, put their names in front of www. and put .com at the end, go to the investor relations section of the site, and look for the Annual Reports. I picked the above companies at random, and was not disappointed!

Get an idea of what a huge product liability suit can cost from this Businessweek article on Merck and Vioxx. The two analysts cited disagree on the costs, but the lower figure is $15 billion (ouch!). But with earnings (EBITDA) of $8.76 billion in 2003, don't look for bankruptcy proceedings anytime.

The Washington Post has a review article on those five drugs cited by David Graham of the FDA as being potential Vioxx - type disasters, and discussed alternative to the meds. All of the companies are rigorously defending their franchises, including this rather extraordinary attempt at public disclosure of safety issues regarding the AstraZeneca drug Crestor.

Again regarding AstraZeneca - new trial results showing that their drug Anastrozole (Arimidex) cuts the risk of breast cancer recurrence over the standard therapy of Tamoxifen. This is good news of course - estimates of lives saved by Tamoxifen (despite life-threatening side effects of blood clots and uterine cancer) are enormous when added up over the years, and Anastrozole does not seem to have the negative estrogenic effects that result in the clots and uterine cancer. Curious how the drug name is not mentioned in this article until Paragraph 9, while the Associated Press article, likely to be printed by most newspapers, mentions the name in Paragraph 2. You would think that these results would be bad for the Tamoxifen manufacturers (generics are available) except for the fact that Tamoxifen is also sold by AstraZeneca.

As I've said before, I'll visit all of the liability issues in future posts, as well as post links to the daily news coverage of Pharma issues. The examples above were meant to whet your appetite. Have I succeeded?