At the invitation of the George Mason University’s Law & Economics Center, I recently went to Washington D.C. to debate Ana Reyes of Williams & Connolly on the subject of preemption in drug injury lawsuits. The video is available here.

I stated many facts during the discussion, and below are my sources for them.
Continue Reading “Pharmaceuticals: FDA Approved Warning Labels and Pre-emption”

Update: It’s worth pointing out that, a year and a half after Dr. Anick Bérard’s testimony was precluded as “unreliable,” she published in the Journal of the American Medical Association, using many of the same methods the court deemed unacceptable.

Back in 2012, I wrote: “Scientific evidence is one of those rare areas of law upon which every lawyer agrees: we are all certain that everyone else is wrong.”

There have been some missteps in the law’s use of scientific proof as evidence in civil litigation — like when the Supreme Court affirmed a trial court holding in Kumho Tire Co. v. Carmichael, 526 U.S. 137 (1999), that an engineer with a Masters in Mechanical Engineering who had worked in tire design and failure testing at Michelin was nonetheless incompetent to testify about tire failures — but, by and large the standard articulated in Daubert v. Merrell Dow Pharmaceuticals, 509 U.S. 579 (1993) makes sense. Courts review an expert’s methods, rather than their conclusions, to ensure that the expert’s testimony has an appropriate scientific basis.

To go with the baseball metaphors so often (and wrongly) used in the law, when it comes to Daubert, the judge isn’t an umpire calling balls and strikes, they’re more like a league official checking to make sure the players are using regulation equipment. Mere disagreements about the science itself, and about the expert’s conclusions, are to be made by the jury in the courtroom.

In practice, though, the Daubert standard runs into problems when courts erroneously decide factual disputes about methodology and conclusions, issues which are better left to cross examination of the experts at trial. Consider the June 27, 2014 opinion in the Zoloft birth defects multidistrict litigation, which struck the testimony of plaintiffs’ “perinatal pharmacoepidemiologist,” Dr. Anick Bérard. Dr. Bérard holds a Ph.D. in Epidemiology and Biostatistics from McGill University, teaches at the Université de Montréal, and has conducted research on the effects of antidepressants on human fetal development. The expert was going to opine that “Zoloft, when used at therapeutic dose levels during human pregnancy, is capable of causing a range of birth defects (i.e., is a teratogen),” an opinion based upon her review of a variety of studies showing a correlation between SSRI use and birth defects. The court had multiple grounds for striking the opinion, but a key issue relating to statistics jumped out at me.
Continue Reading Daubert Doesn’t Ask Judges To Become Experts On Statistics

[Update, June 24, 2013. The Supreme Court ruled against Karen, holding, in essence, that generic drug companies have no responsibilities whatsoever to patients.]

I’ve written before about the United Supreme Court’s dismal PLIVA v. Mensing opinion. Although Justice Scalia recently co-wrote a book on legal interpretation that admitted that a basic principle of federalism is that “a federal statute is presumed to supplement rather than displace state law,” he had no trouble joining Justice Thomas’ opinion finding “implied” pre-emption of all state tort lawsuits that alleged  generic drug manufacturers failed to adequately warn about their product’s risks.

Nevermind that Congress had never passed any statute restricting state torts against generic drug manufacturers; the FDA itself had no problem with the state tort lawsuits, and indeed filed a brief in favor of the injured plaintiff; that the American Medical Association and 42 States supported the plaintiff. The case was, to put it mildly, “result-driven.”

That’s old news (Professor Bernabe’s Torts Blog has been following the fallout), but PLIVA v. Mensing is back in the spotlight: the Supreme Court has granted certiorari in Bartlett v. Mutual Pharm. Co., Inc., a First Circuit Court of Appeals opinion in a generic drug case from earlier this year that was one of the very few bright spots in the darkness created by PLIVA v. Mensing. Pharmaceutical defense lawyers have written endlessly in the abstract about Bartlett (like here and here and here), claiming that it conflicts with PLIVA and that the Supreme Court would reverse. I, of course, don’t agree with PLIVA and so, of course, don’t think Bartlett’s claim should be pre-empted; whether the Court in Bartlett mis-applied PLIVA is another matter.

But before we get there, I frankly think that no discussion of the case is complete without talking about the extraordinary facts of the case. Cases aren’t just names on a page, they’re real people, often with real injuries. 
Continue Reading Will The Supreme Court Cheat The Woman Living In “Hell On Earth”?

Last week, our firm blog posted a short note about how Actos patients with bladder cancer in Kentucky, Louisiana, and Tennessee should move quickly to file because those states have a one-year statute of limitations for personal injury actions. We (and a whole bunch of other lawyers) assume that Takeda Pharmaceuticals will argue that the statute of limitations began to run on June 15, 2011, when the FDA issued an updated warning that one year of Actos use increases the risk of bladder cancer by more than 40%.

As if on cue, the next day Pfizer moved for summary judgment on a whole swatch of consolidated Chantix neuropsychiatric lawsuits (not to be confused with the SSRI birth defect lawsuits), arguing that the statute of limitations for those claims began to run on July 1, 2009, when the FDA mandated the box for the medication warn that the medicine was associated with “serious neuropsychiatric events, including, but not limited to depression, suicidal ideation, suicide attempt and completed suicide …”  On that day, Pfizer also sent out a “Dear Healthcare Provider Letter” notifying prescribing physicians about the change, and there was also some media coverage. 
Continue Reading When Should The Statute Of Limitations Run For Medication Lawsuits?

As I’ve written before, anti-consumer legislators and judges have so thoroughly eviscerated claims against pharmaceutical companies that in most states there’s only a single claim left: the claim that brand-name drug manufacturers failed to warn about the risks of the drug. For example, the IUD Mirena causes pseudotumor cerebri, but the label says nothing about that.

As long as the company warned about the risks of the drugs, they’re essentially immune from liability, even if the drugs weren’t properly tested, even if they were deceptively marketed, and even if the drug didn’t perform as promised. (Sometimes state and federal attorneys general can sue over drugs that were falsely marketed, like how Johnson & Johnson was just walloped for $1.2 billion in Arkansas for improper marketing of Risperdal, but consumers can’t, because those same legislators and judges have delivered mortal wounds to most consumer class actions.)

A slim 5-4 majority of the Supreme Court disappointingly killed the vast majority of generic drug liability last year with PLIVA, Inc. v. Mensing (#1 on my list of most unfair drug and medical device court opinions). Manufacturers of the brand-name drugs that are still under their patents could kill almost all of the rest the litigation if they just bothered to warn consumers about the real side effects of their drugs. But they won’t. As I wrote in November about Propecia, the pharmaceutical industry is simply too dependent on blockbusters and marketing, and so try to squeeze every penny out of each drug, patient safety and lawsuits be damned.

That is, of course, until the FDA awakens from its slumber every now and then and makes the companies fix their labels. Just last week, the FDA released two prescription drug label changes, one for Propecia, another for Beyaz, Safyral, Yasmin and Yaz.

Propecia (new label here, FDA release here) will warn about “libido disorders, ejaculation disorders, and orgasm disorders that continued after discontinuation of the drug” with the patient insert noting “reports” of “difficulty in achieving an erection that continued after stopping the medication,” the same sexual side effects in the consolidated lawsuits in New Jersey.

Yasmin / Yaz (new label here, FDA release here) will warn about blood clots or, in the uniquely hand-wringing way drug labels describe deadly risks, it will warn that:

[S]ome epidemiologic studies reported as high as a three-fold increase in the risk of blood clots for drospirenone-containing products when compared to products containing levonorgestrel or some other progestins, whereas other epidemiological studies found no additional risk of blood clots with drospirenone-containing products.

Yasmin’s patient insert is more informative than the warning label itself, noting, “Like pregnancy, birth control pills increase the risk of serious blood clots … Women who use birth control pills with drospirenone (like Yasmin) may have a higher risk of getting a blood clot.”

What Bayer, Merck, and the FDA expect consumers to do with that sort of equivocation is anybody’s guess. (At least it’s better than NuvaRing, which has those same blood clotting risks only they’re twice as likely, not that the prescribing information mentions that.) Given the financial incentive drug companies have to conceal risks, and how slow the wheels turn at the FDA’s bureaucracy, it usually takes a long time for labels to be updated to show their true risks. Hundreds of Actos lawsuits have been filed, but the Actos warning label still only admits “There may be an increased chance of having bladder cancer when you take Actos,” and hundreds of Pradaxa deaths have been reported, but the Pradaxa patient medication guide says only “Pradaxa can cause bleeding which can be serious, and sometimes lead to death,” without a word discussing the lack of a reversal agent or the comparative risk to warfarin.

I raise the actual text of the labels not to address their adequacy per se, but to address another issue near and dear to my heart as a plaintiff’s lawyer: whether or not a FDA labeling change is a “subsequent remedial measure.”


Continue Reading Yaz and Propecia Labels Updated; Are They Subsequent Remedial Measures?

The big shift in thinking about antidepressant use in pregnancy began in late 2005, when the FDA warned that Paxil “increases the risk for birth defects, particularly heart defects, when women take it during the first three months of pregnancy,” and demanded  GlaxoSmithKline to change Paxil from a “Category C” drug to a “Category D” drug, i.e. a drug known to produce birth defects or injure fetuses.

In February 2006, the landmark “Selective Serotonin-Reuptake Inhibitors and Risk of Persistent Pulmonary Hypertension of the Newborn (PPHN)” study was published in the New England Journal of Medicine, showing that Prozac use in the third trimester of pregnancy increased the risk of PPHN. That study prompted the first formal SSRI FDA warning in July 2006 across the board for Celexa, Lexapro, Paxil, Prozac and Zoloft. In 2009, the British Medical Journal showed Prozac, Celexa, Paxil and Zoloft were all associated with an increased risk of congenital heart defects, particularly if a pregnant woman used more than one. In January 2012, the British Medical Journal reviewed over 30,000 pregnancies involving SSRI use and found the risk of PPHN was doubled when the baby’s mother used an SSRI. Just a week ago, the Archives of General Psychiatry published a study concluding that pregnant mothers treated with SSRIs had higher rates of premature birth and delayed infant head growth.

The risk is there, and the body of scientific research is growing, but many patients still don’t know the risks of using SSRIs in pregnancy, and today more than 5% of pregnant women take antidepressants. Other than changing the birth defect risk category of Paxil, though, the FDA hasn’t done anything to fix the situation. In December 2011 the FDA issued a drug safety communication that frustratingly said “it is premature to reach any conclusion about a possible link between SSRI use in pregnancy and PPHN.” Zoloft, Lexapro, Celexa, and Prozac are still listed as a Category C drugs, and none of them warn patients or doctors about the risk. Buried in the fine print of Prozac’s warning label there’s a reference to PPHN and congenital heart defects, but then the risk is dismissed: “There are no adequate and well-controlled clinical studies on the use of fluoxetine in pregnant women.” Zoloft’s warning label doesn’t even mention the possibility of birth defects except through a vague reference to studies of pregnant rats.

All told,  birth defect lawyers have probably done more to educate the public about the dangers of SSRI use in pregnancy by way of television ads than the FDA has. Which brings me to the core of this post: the increasing role of the First Amendment in drug liability lawsuits.


Continue Reading Antidepressant Birth Defects and The First Amendment

This post was written for my legal blog — patients injured by Pradaxa should read my Pradaxa bleeding problems  page.

In our medical malpractice and nursing home abuse work, we see one case with disturbing frequency: warfarin overdoses. A recent CDC study confirmed that warfarin, anti-platelet medications, and diabetes control medications together accounted for a whopping two-thirds of all drug-related emergency hospitalizations of senior citizens. Errors in dosing and monitoring warfarin by health care professionals, too, account for a significant (over 1%) of medical malpractice claims. It’s a great drug, but a dangerous one.

Warfarin has a fascinating history. In nature, the molecule on which warfarin is based is produced when the plant compound coumarin — which produces the sweet smell of freshly cut grass or hay — is metabolized by fungi and then reacts with formaldehyde. (The name “warfarin” is a combination of “Wisconsin Alumni Research Foundation” and coumarin.) The chemical was first discovered by veterinarians trying to figure out what killed their cattle (they were eating spoiled sweet grass), and warfarin was literally used as a rat poison before it was used in humans.

Warfarin works in treating or preventing the deadly conditions venous thrombosis, blood clots, and pulmonary embolism by almost creating a different deadly condition: excessive bleeding. It doesn’t take much to push a patient into dangerously high prothrombin ratio (INR) levels, and so healthy patients need to have blood tests weekly or at least monthly, and hospitalized patients need to be monitored every few hours. Warfarin is thus both a wonder drug — which has saved the lives of my own family members diagnosed with pulmonary embolism — and a double-edged sword, because it causes major bleeding episodes in 3-5% of people taking it. Scientists have been trying to find safer replacements for the whole fifty years that it’s been used.

Pradaxa (dabigatran etexilate), manufactured by Boehringer Ingelheim Pharmaceuticals, was supposed to be one of those replacements. In September 2009, the initial results of the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) study sponsored by the company were released, with the study’s authors — the bulk of whom reporting in the study “receiving consulting fees, lecture fees, and grant support from Boehringer Ingelheim” — concluding:

In conclusion, we compared two doses of dabigatran with warfarin in patients who had atrial fibrillation and who were at risk for stroke. As compared with warfarin, the 110-mg dose of dabigatran was associated withsimilar rates of stroke and systemic embolism and lower rates of major hemorrhage; the 150-mg dose of dabigatran was associated with lower rates of stroke and systemic embolism but with a similar rate of major hemorrhage.

Note the use of the word “similar” in the study’s conclusion. It’s not a scientific term, it’s a term of art. In fact, when the RE-LY study came out, there was already concern among the FDA advisory panel members that the drug didn’t really offer an improvement over warfarin in preventing stroke in patients with atrial fibrillation, but rather offered just a different balance of the risk of bleeding versus the risk of stroke:

“The 110-mg dose, while associated with reduced bleeding, had a 12% higher incidence of ischemic stroke,” said [advisory panel member Dr. Sanjay] Kaul. “In my opinion, it would not offer much of an advantage over warfarin and would likely be an ineffective alternative.”

Asked about the approved doses, FDA spokesperson Sandy Walsh said that FDA reviewers felt the data strongly support the 150-mg dose, noting that it was superior to warfarin on the primary end point and similar in terms of bleeding rates. In reviewing the data, FDA officials noted, like Kaul, there were numerically more ischemic strokes in the dabigatran 110-mg arm when compared with warfarin, and this dose was only statistically noninferior to warfarin in terms of efficacy.

In other words, a 110-mg dose was substantially less effective than warfarin in reducing strokes, while the 150-mg reduced strokes but had the same bleeding rates as warfarin.

On the surface, that makes it sound like Pradaxa is an improvement over warfarin, but it’s not the whole story. 
Continue Reading Pradaxa Bleeding Lawsuits Begin; Still No Reversal Agent Available