Overtreated

If I haven't linked to this author, I should have. Shannon Brownlee wrote a good book, and she reiterates some of her arguments in this Washington Post article.

She gets a lot of milage from debunking osteopenia in this article, but as I read her criticism, something struck me as being inconsistant. True, most women with osteopenia will not break a hip, and true, most people with actinic keratoses will not have skin cancer. But my perspective has always been from the side effect world. The statistics that we use to determine a "signal" is similar to the statistics used to predict whether someone will come down with a serious ailment if they have a "pre-disease." So why is one predictive model more valid than another? Well, if you're taking a medication, there's an assumption that its actually doing something positive for you, to make the benefit/risk ration worthwhile. She's right about one thing - there is definitely a growing movement to treat conditions before they even are manifest by using surrogate markers such as low cholesterol or bone density. But don't throw out that surrogate marker philosophy completely. Isn't blood pressure a surrogate marker? Does anybody feel bad just because they have it, or don't they have to wait for the kidney damage first?

From NPR's "Talk of the Nation" - Saline issues?

Wax on, wax off

OK, if Peter Rost can devote unseemly amounts of column inches to Elliot Spitzer, than I'm going to feel free to wax poetical on the heels of our current financial crisis. The following is an excerpt from a poem I wrote a long time ago, called Who Wants to Play? from the perspective of an investment banker:

Our wages come not from the things we create,
but the miniscule squeezings of this or that rate.
I'll earn more than my father by producing much less.
He worked as a craftsman; I'll learn about stress.

The Fed is our lackey; it works toward our ends.
The families we shred, we demand that they mend.
You won't see it coming, then you'll blame the wrong fools.
You can't change a thing when you play by our rules.
We'll crush you beneath our invisible hand
'Cause you cannot resist what you don't understand.

Cheerful, huh? I was in an uncharitable mood at the time. Unlike today! I also wrote an Ode to the Federal Reserve back then. No, really. If you say pretty please, I may even publish it here.

Compare & Contrast

I've been doing some fascinating reading about the admissability of adverse event data in a pharmaceutical product liability case. "Post-sale" duty to warn concerns the marketing experience, and the related spontaneous adverse event reports, and accumulation and analysis of data.

The Third Restatement of Torts specifically addresses post-sale failure to warn duty, and states that the duty arises "when new information is brought to the attention of the seller." There's no affirmative duty to continue to test (forgetting for the moment any Phase IV commitments) but the manufacturer is supposed to keep abreast of scientific literature and related developments.

Now, the Federal Register specifically states that ADRs are not conclusive of causality (21 CFR 314.80(a)). In fact, a company "need not admit, and may deny" causality of an individual report (21 CFR 314.80(k)). The FDA has also stated that “[a]ccumulated [AE] cases may not be used to calculate incidences or estimates of drug risk" in a 1996 report. These tidbits have been used by defendants to exclude expert testimony on the incidence of ADRs, and actual ADR reports themselves, which is a shame for the plaintiffs, because they make such fun reading for a jury. There are exceptions, particularly in a Bendectin case which allowed expert testimony in 1985. ADR reports can be used to prove notice, however. A plaintiff could argue that the mere existence of reports indicates that a company had notice of possible issues, and a clever lawyer would refer to a large volume of reports, hoping a jury would assume that a big stack of 3500A reports meant that the drug had problems, even if they don't get to hear about the content.

Anyway, this is all leading to the Baycol litigation, where the defense for Bayer had evidence about "AER data" excluded from consideration. The decision cited the Federal Register, and those FDA reports warning against using ADR data inappropriately. A quote from an affidavit from Dr Janet Arrowsmith-Lowe, formerly with the FDA and CDC: "It is a well accepted pharmaco-epidemiologic principle that the biases affecting AERs preclude their use in calculating rates of events or in comparing rates of adverse events among pharmaceutical products." The court cited her affidavit several times, and accepted her arguments.

But what if a company chooses to use that type of data in their own defense (click link for "Spontaneous Adverse Event Reporting Information...)? If they make the case that post-marketing reports demonstrate the relative safety of their drug, will they later be able to make the claim to exclude such data in litigation?

Back to the Eighties weekend....

So, have you seen the advertisements for Yaz, the pill that also has indications for PMDD and acne?

If Yaz fails, and the woman gets pregnant, do they sell a morning-after pill called Erasure?

(Hat tip George H.)

The latest screed
New York Times book review of Melody Petersen's "Our Daily Meds."

Day One

at the Health Law Institute was OK. Tomorrow looks more promising.

I had lunch with a woman working for a law firm which has some Big Pharma clients. She posed an interesting question to me, and I responded in kind.

Her client was asking about employees who have licenses as practitioners, who need to log some clinical time to keep their licenses. Some of these nurse practitioners are also sales reps, whose pay is structured on how practitioners in their geographic areas prescribe. What should be done about these nurse practitioners, whose prescriptions could theoretically affect their pay? Would this arrangement violate some kind of anti-kickback statute?

Well, Stark is not a consideration, since they are not physicians. But there may be state regs that mimic Stark, but apply to a wider array of prescribers. An obvious recommendation to the client would be to restructure their pay for the period when they are in the clinic. Fascinating question though. I'd love to know what they eventually do.

I posed a question back to my lunch friend. If a clinical nurse educator is hired to address an interest group like an Alzheimers association, and they are required to discuss only the disease state and not their employer's medication, how might they still violate the Pharma code by inappropriate promotion? Well, the answer may lie in the clinical development strategy the company pursues, through line extensions and sNDA applications.

Did you ever compare labels and indications between two or more drugs in the same therapeutic family, which are fundamentally identical in mode of action. Go ahead - look it up with the statins, for example. PB will wait.

OK, you back? The clinical strategy for these compounds has been geared toward creating something unique in their indications that the other compounds haven't got. So, when nurse educator Betty speaks to a bunch of cardiologists about lipid-lowering strategies, and discusses the need for the patient to reach certain benchmarks in their therapy, wouldn't it be convenient if her company's compound happens to be the only one indicated to reach those benchmarks? She never needs to mention the drug name, as long as she pounds the message about the therapeutic end-points repeatedly. Then the sales reps for the attending docs can follow-up with a visit sometime later.

Free pharmaceuticals for everyone!

Industry executives have banded together to announce a program to distribute health-affirming pharmaceuticals for free for every American. According to a press release from the world's most profitable industry, the program is already in place, and Americans have been benefitting by ingesting drugs that will help to lower their blood pressure and cholesterol, relieve pain, and encourage bodily growth(s). The program is being touted for its low price and convenience. The industry is rolling out the program with no charge to patients, and distributing the medications conveniently through drinking water. "We may consider a way to try to charge patients for this largesse in the future," stated one industry insider, who wished to remain anonymous. "It's outrageous that patients can derive a pharmaceutical benefit like this without any remuneration whatsoever. This makes the Canadian problem seem trivial in comparison."