Guidant is off-course

J & J, Take Me Away!

Guidant has been maufacturing cardiac resynchronization therapy (CRT) units, that stimulate different parts of the heart independently. Recently, they have recalled tens of thousands of units due to short-circuiting problems. See this article for some background. Of course, Guidant isn't new to safety fraud...

Seeding trials?

I don't know much about clinical trials for devices, and how much they differ from drug trials, but in one respect, there seems to be a striking similarity. This New York Times article describes a that Guidant allegedly practiced, using an "evaluation" trial as a method to spur sales. This is right out of the pharmaceutical playbook of old. The company paid physicians to fill out a survey about the devices, $1000 for five forms. Chump change for Guidant, it turns out, since the survey resulted in

"...>$2 million in new sales with physicians who are not necessarily Guidant
friendly. We paid each physician who completed all five surveys $1,000 so
our
total cost was $80,000."

This is what used to be called a seeding trial - using a scientific pretext to generate sales, market share, buzz, or whatever.

Several documents were sent to the Times by someone professing to be an employee of Guidant, but there is no mention of whether there was a protocol for this "evaluation" or whether there was any consultation with IRBs or ethics boards where the participating physicians practiced.

Kick back and read on....

But you can't pay physicians to use your product - that's plainly illegal. So these evaluations have to be considered research to avoid the federal anti-kickback laws. To avoid violating the law, the research purpose for which you pay the physician has to be legitimate. See this presentation to get a better idea of the requirements. To quote:

"Clinical trials or other research with little scientific value implicate the
federal Anti-kickback Statute and IRS requirements. In addition, clinical
trial proposals that offer inducements to physicians to participate implicate
the federal Anti-kickback Statute."

The document then references the AMA definition of "Genuine Research Purpose" which you can find here.

"How can a physician tell whether there is a "genuine research purpose?"
A number of factors can be considered. Signs that a genuine research purpose
exists include the facts that there are (1) a valid study protocol, (2)
recruitment of physicians with appropriate qualifications or expertise, and (3)
recruitment of an appropriate number of physicians in light of the number of
study participants needed for statistical evaluation."

The drug industry has developed, through their trade group PHRMA, a Code for Interactions with Healthcare Professionals. More recently, we have promulgated new standards for clinical trial conduct and communicating their results. The first document was a voluntary code for industry, but has now been incorporated into law, in the sense that the most recent federal regulations on anti-kickback for the drug industry specifically cites the Code for Interactions, considering them to be a minimum standard. We may see similar treatment for the clinical trial standards.

At first blush, this may seem offensive. Since the industry wrote The Code, it sounds like the industry is therefore determining the law of the land for regulating themselves. I mean, who is supposed to write the laws? Should we have all industries write their own "Codes" and simply have the regulators defer to them?

However, we are persuaded that the PHRMA Code is actually not a bad starting point. In fact, we even heard Jim Sheehan, Associate US Attorney for the Eastern District of PA (Philadelphia) and frequent industry foe, refer to The Code as a good start, that fails only in that it does not address certain areas of conduct. In addition, by having The Code cited in the Federal Register, it makes adoption of this voluntary conduct a necessity to industry. No decent compliance or legal department would allow their sales folks to ignore it.

The Ectasy of Device Manufacturers

After a few more Guidant episodes, perhaps we'll see some similar reactions from the Medical Device Manufacturers Association (MDMA). A comparison between their website and PHRMA's website is instructive. PHRMA practices defensive medicine, knowing that it's an industry under siege. There are all kinds of articles and links to items showing how responsible and honorable they think they are. If we keep the pressure on, perhaps someday they'll live up to their own rhetoric.

Getting the Label

How depressing.....
is this?. I might just have to take some Prozac.

Getting the Label

OK, let's talk a little about Vioxx. This is a pharmaceutical legal blog, and Vioxx is the big drug litigation story, so you'd think I'd spend more time on this.

Today, there's a telling AP story about Merck officials "getting the label" they wanted for Vioxx. The "label" is the package insert, which contains all the warnings and side effects about a drug, in addition to indications, pharmakinetics, chemistry information, etc. Getting the label you want for a drug is what clinical trials is all about - negotiating with the FDA, based on whatever trial data you have, to avoid warnings and precaution statements as much as possible. Negotiations sounds like a strange word in this setting, but it's what really happens. The drug company argues that there are too many confounding factors that prevent any assignment of causality. For a drug that is generally taken by sick people, this is an easier process for the company, since there is probably a substantial background rate of all kinds of ailments. For a pain drug, you have to consider the patient population who took the drug during the trials. Did they take it for arthritis pain, and are thus probably elderly? They probably take all kinds of other drugs then, with a whole bunch of side effects of their own. The VIGOR study was for rheumatoid arthritis, and if the patients were anything like my mom, they take a pharmacy every day.

In the big continuum that is drug development, before you even have a compound, you have a Target Profile. The profile tells you that you want a drug that does X, does not have side effect Y or Z (that the existing drugs in the therapeutic area have) and has a sales potential of $$$. Thus, you already have the beginnings of the label you want before you even have a compound.

I heard a lecture once from a drug safety physician in my company concerning a particular psychotropic medicine that had a warning about cataracts on the label, based only on animal studies. He had been told that getting rid of that warning was a high priority for drug safety, since it was responsible alone for losing hundreds of millions in sales annually. This was the first time that I heard a dollar figure attached to a safety issue, and it was clear that our marketing folks wanted us to go to the FDA with every argument possible to get rid of that warning.

So, the Merck folks came to the same conclusion about their drug, but they were more successful in their negotiations. They managed to convince the FDA to keep the heart attack information from VIGOR in the "Precautions" section of the label, instead of the "Warnings." This is significant not because the prescribers would notice the warning by themselves (they wouldn't), but rather the helpful competition would be sure to point it out to them, and feature it prominently in their sales materials. Imagine the script for a Pfizer rep - "Celebrex: the ONLY Cox-2 inhibitor without a heart attack warning."

The damning part of all of this is the attitude of the Merck players, as well as their stupid use of email. EMAILS LIVE FOREVER. Write them like they do. And remember - Merck was the most respected drug company in the country. If you asked a focus group about Merck two years ago, you'd get reactions like science, integrity, and so on. The evidence introduced in these trials should forever pierce that veil. How much of Scolnick's emails about VIGOR and the FDA had anything to do with patient well-being, do you suppose?

Tomorrow - Guidant was off-course!

See what happens while I'm away??

Obnoxious...must stop...need guidance
Alright, fellow bloggers, how do I get this to stop? I posted about five minutes ago, and my inbox is getting filled with anonymous, clearly automated messages that read something like this:

Nice blog. Keep it up. I found this directory on How to drink and stay safe driving . I think it is a good thing that someone is educating us all on How to drink and stay safe driving. Simply PRICELESS!Imagine giving someone you love the opportunity to LIVE by giving them the proper stuff on How to drink and stay safe driving TODAY.

This is new since August - how can I make it stop?

Catching up with the news

Much has happened since my last post. Headlines include the Vioxx verdict, medical device fraud with Guidant, many interesting articles about pricing lawsuits.

But I wanted to focus this evening on issues that are away from the news. One has to do with my criticisms of Medicare Part D and pricing.

A reader criticized my writing about government drug pricing (even accusing me of being a lawyer - what a cheap shot!). He referred me to a book on economics, and briefly explained how government interference in pricing distorts markets.

He was completely correct about the interference of government, but was too limited in his critique of government as a purchasing agent. He reminded me (and I can't believe that I haven't already mentioned this to you) that the Feds require that pharmas sell to them at their lowest price. This is true, and does indeed distort markets. I remember when my company was concerned about their Indigent Patient Program - if we gave away drugs for a few bucks in co-pay to the poor, would that constitute a price? And the TogetherRX program required a waiver from the pricing policy as well, according to my reader.

I am for market pricing - I haven't complained to anyone about the recent gas prices, for example, and found merit in the Wall Street Journal article "In praise of price gouging" or whatever is was called. But there is much more distorting the price of pharmaceuticals than the VA supply schedule. The three largest contributors to price distortion are the patent system for drugs, the regulatory burden of pharmas, and the enormous scientific subsidies they receive.

I'm not going to argue for the abolition of patents or regulations. Hello 1902. No, instead I want to give some perspective to help explain why exempting Medicare Part D from any pricing regulations rubs me the wrong way. The factors that drive up pharma pricing are almost overwhelming, and call for a restraining hand. For example, there is no such thing as a start-up garage-based drug company. Pharma CEOs do not look over their shoulders at lean and hungry start-ups the way Bill Gates has to. Also, you can't look at a drug patent, figure out a quick way to come up with an approved product, and have it on the market in weeks or months. Finally, there are huge gaps between the consumer, the learned intermediary (the doctor) and whoever is paying for the drugs. For most consumer transactions, these three elements are the same.

Think about the impact these elements have on pricing. And think what a small counterweight it is to have regulated pricing for programs paid for with tax dollars.

I've Done This Before...
but I can't help myself. There was a large ad for this item in the coupon section of my Sunday paper a couple of weeks ago, and I almost snarfed my cornflakes. I think I've mentioned before that I know many people who work for McNeil Consumer Products, and it's fun to call them and tease about this. Five years ago, this would never have happened, or so my friends like to believe. Get a real drug company, guys.

Switcheroooooo
You had to know I would mention this item, about the atypical anti-psychotics versus perphenazine. It's important to keep in mind that the headline writers are missing a big point revealed by the studies. While perphenazine performed well, it had a large number of patients who had to discontinue, like the rest of the drugs. So a large armamentarium for anti-psychotics is more important than, say, adding another statin or non-sedating anti-histamine to the market.

By the way, I wouldn't lose too much sleep (har har!) if I worked at AstraZeneca, makers of the maligned Seroquel (maligned in this article, at least). The drug is the market leader in prescriptions, but not sales. Why? Because most of the use is for sedation ("Sleepoquel") at sub-therapeutic doses. Let's just hope they aren't promoting it that way. T'would be bad.

Gardening away
Yep, the movie was awesome. I also watched City of God recently, by the same director, and found it somewhat over-rated. But watch this space in December for shameless promotion of "The Constant Gardner" for Oscar consideration. I cried like three times.

Interesting note - check out this post on essentialdrugs.org, concerning the movie poster. Kind of bizarre. I was struck by the fact that Ralph Fiennes appears with an outstretched arm holding a gun on the movie poster, which never occurs in the film. Also, in the movie's trailer, there's clearly a scene that was set in a snowy area, presumably in Western Canada, where part of the book is set. This is also not in the film.