Over at Drug and Device Law, Jim Beck highlights a new law review article, “Researchers’ Privilege: Full Disclosure,” published by Dr. Frank Woodside, described by the article as “of counsel to the law firm of Dinsmore & Shohl and [ ] a nationally known trial lawyer representing manufacturers of pharmaceutical and medical devices, chemicals, and flavorings, as well as producers of consumer products.”

 

Woodside argues:

 

Sometimes the authors of published studies or counsel relying on these researchers’ work have attempted to place barriers in the way of academicians or counsel who wish to challenge the validity of the published studies and their underlying data. These barriers originate from a misunderstanding, or misuse, of the concept of academic freedom—a litigation strategy that asserts the existence of the so-called “researchers’ privilege,” also known as “academic privilege,” “academic freedom privilege,” or “the research scholar’s privilege”—as well as the improper application of the Freedom of Information Act (“FOIA”). These challenges create a legal environment where opinions based on the published results of flawed research are admitted into evidence without providing opposing parties the opportunity to develop the facts necessary to assess the opinion’s validity. This admission of uninvestigated evidence creates the potential for unjust results.

 

Although published literature plays a big role in large-scale litigation these days, subpoenas against third-party researchers have generally fared poorly in the courts. One of the few successful examples I know of involves the Prempro products liability litigation, where Wyeth was able to compel the Women’s Health Initiative to turn over hormone treatment assignments and trial data collected. (In case anyone is wondering how that issue turned out, although Wyeth continues to fight these cases in the courts, there is a scientific consensus that hormone therapy increases the risk of breast cancer.) Continue Reading Should There Be A Researchers’ Privilege For Junk Science?

August was a rough month for the Food and Drug Administration. On August 7, a federal judge in New York entered a preliminary injunction in Amarin Pharma, Inc.’s lawsuit against the FDA, holding that the FDA could not prevent a drug manufacturer from marketing its drug for uses that haven’t been approved by the FDA, so long as the marketing was “truthful,” a loaded word we’ll get to in a moment. Then, on August 20, Forbes published an analysis that concluded the FDA approves 96% of new drugs or; in essence, “the FDA is basically approving everything.”

 

Let’s start first with the Amarin lawsuit. The primary weapon in the FDA’s legal arsenal is the “misbranding” statute, which allows the FDA to prosecute anyone who markets a drug or medical device “if its labeling is false or misleading in any particular.” For decades, the FDA has attempted to keep pharmaceutical companies in line by telling them that, if they market a drug for uses that were not approved by the FDA, so-called “off-label marketing,” the FDA will prosecute them. However, the pharmaceutical industry, emboldened by Citizens United, has tried to make this into a free speech issue in recent years.

 

On the one hand, the pharmaceutical companies have a point: why shouldn’t drug companies be allowed to “truthfully” market their drugs?

 

On the other hand, this argument about the “truth” falls apart when we consider the complexity of drug efficacy and safety, and when we recognize the billions of dollars that drug companies will use to push their “truth” on unwitting doctors and patients.

 

Amarin makes a prescription drug called “Vascepa,” which is essentially an expensive version of fish oil. The FDA approved Vascepa for use in patients with severe hypertriglyceridemia based on the results of a single clinical trial. The FDA did not, however, approve Vascepa’s use in patients with very high triglycerides for the rather straight-forward reason that it doesn’t work. Read for yourself the FDA’s 94-page Advisory Committee Brief. Vascepa lowers triglyceride levels, but it hasn’t been shown to actually reduce the risk of cardiovascular disease. This isn’t some sort of attack on Amarin or Vascepa particularly; medical science as a whole has come to realize that, apart from severe hypertriglyceridemia, omega-3 supplementation doesn’t do anything to reduce patients’ risk of “all-cause mortality, cardiac death, sudden death, myocardial infarction, or stroke.” As a matter of medicine, unless a person has truly severe hypertriglyceridemia, omega-3 supplementation isn’t going to make much of a difference.

 

From the FDA’s standpoint, this was a no-brainer: Amarin failed to show that Vascepa was effective. I doubt anyone at the FDA figured they would lose in court over this one. Continue Reading Amarin v FDA: Are Judges Really Equipped To Resolve Scientific Disputes?

[Update, March 2013: I originally wrote this post in December 2012. Three months later, the FDA announced it “is evaluating unpublished new findings by a group of academic researchers that suggest an increased risk of pancreatitis, or inflammation of the pancreas, and pre-cancerous cellular changes called pancreatic duct metaplasia in patients with type 2 diabetes treated with a class of drugs called incretin mimetics.” Several news agencies ran with the news, including AP and Bloomberg, as did some pharma industry bloggers. The JAMA Internal Medicine medical journal ran a column urging more research into the link between the drugs and pancreatic cancer, an article with a concerning, but perhaps harmless, revision after it was published. We think the latest attention and research makes the case against these drugs even stronger, and we’re moving forward in our own litigation.]

 

Diabetes is a global epidemic, affecting over 25 million Americans and ten times that worldwide. That also makes it an economic opportunity: the diabetes control medication market is worth more than $40 billion in the United States alone. There are thirteen types of approved Type 2 Diabetes medications on the market today (comprising over two dozens drugs), with another seven therapies in various stages of research and development. There’s big money to be made, if you’re a pharmaceutical company — hence the recent advertising push for Januvia, Byetta, and Victoza (the one Paula Deen endorses), relatively new entries to the overcrowded diabetes control market.

 

I’ve discussed before on this blog how one of the biggest public health problems in America is the pharmaceutical industry’s reliance on the “blockbuster” drugs that exceed $1 billion in annual sales. The whole industry, from research, to clinical trials, to physician education, is oriented around creating and promoting drugs that will become household names — to the exclusion of other useful medicines and to the detriment of patient safety. A year ago, I wrote about why Merck still didn’t admit Propecia caused persistent erectile dysfunction more than eight years after competent research showed the problem. The reason is quite simple: Propecia / Proscar was routinely bringing in more than half a billion dollars a year for Merck, and they wanted to keep it going for as long as possible.

 

Which brings us to Januvia, a drug that stock market analysts call a “real success story” for Merck. The Type 2 Diabetes market is huge, and Januvia (marketed as “Janumet” when mixed with metformin) has captured 75% of the dipeptidyl peptidase 4 (DPP-4) inhibitor market — for $4.6 billion in revenue in 2011 and likely topping $5 billion this year. It’s not hard to see why Januvia and other DPP-4 drugs have been successful and their sales are growing. They’re a one-a-day pill, not a shot, they haven’t been shown to cause weight gain, and they have a lower incidence of the nausea, abdominal pain, and digestive problems that characterize most diabetes treatments.

 

But there’s a big problem brewing. Continue Reading Do The Drugs Januvia, Byetta and Victoza Cause Pancreatic Cancer?

It’s déjà vu all over again. Remember how, three years ago, Pfizer paid $2.3 billion to the Department of Justice to settle off-label claims relating to Bextra and other drugs, and Eli Lilly paid $1.4 billion for Zyprexa marketing?

If so, then last week was no surprise: GlaxoSmithKline agreed to pay a whopping $3 billion to settle criminal and civil charges brought against it by the Department of Justice. Quoting from the DOJ press release, GlaxoSmithKline was accused of:

  • distributing a misleading medical journal article that misreported that a clinical trial of Paxil demonstrated efficacy in the treatment of depression in patients under age 18,
  • GSK did not make available data from two other studies in which Paxil also failed to demonstrate efficacy in treating depression in patients under 18.
  • GSK sponsored dinner programs, lunch programs, spa programs and similar activities to promote the use of Paxil in children and adolescents.
  • GSK paid millions of dollars to doctors to speak at and attend meetings, sometimes at lavish resorts, at which the off-label uses of Wellbutrin were routinely promoted and also used sales representatives, sham advisory boards, and supposedly independent Continuing Medical Education (CME) programs to promote Wellbutrin for these unapproved uses.
  • GSK failed to include certain safety data about Avandia, a diabetes drug, in reports to the FDA that are meant to allow the FDA to determine if a drug continues to be safe for its approved indications and to spot drug safety trends.   The missing information included data regarding certain post-marketing studies, as well as data regarding two studies undertaken in response to European regulators’ concerns about the cardiovascular safety of Avandia.
  • GSK promoted Avandia to physicians and other health care providers with false and misleading representations about Avandia’s safety profile … GSK stated that Avandia had a positive cholesterol profile despite having no well-controlled studies to support that message. The United States also alleges that the company sponsored programs suggesting cardiovascular benefits from Avandia therapy despite warnings on the FDA-approved label regarding cardiovascular risks.
  • GSK paid kickbacks to health care professionals to induce them to promote and prescribe these drugs [Paxil, Wellbutrin, Avandia, Advair, Lamictal, and Zofran] as well as the drugs Imitrex, Lotronex, Flovent and Valtrex.

Let’s call GlaxoSmithKline what it is: a criminal enterprise. GSK didn’t miss the finer points of a couple red-tape regulations: the DOJ alleged they tampered with scientific studies, concealed safety data, then lied to doctors and patients and, if that didn’t work, outright bribed the doctors. Why? Continue Reading The Big Pharma Business Model: Deception And Bribery

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?

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

Some of the largest drug companies in the United States are based in, of have their U.S. headquarters in, New Jersey — e.g., Johnson & Johnson is in New Brunswick, Merck is in Whitehouse Station, Roche is in Nutley, Barr (now owned by Teva) is in Montvale, Sanofi is in Bridgewater — and so New Jersey state courts are home to a huge volume of pharmaceutical injury litigation.

There’s so many Accutane (Roche) and Fosamax (Merck) cases they’re deemed a mass tort, and there’s a good chance that Propecia (Merck) might end up as one, too. Same goes with a large number of the vaginal mesh erosion cases, because Ethicon / Gynecare are made by Johnson & Johnson, and C.R. Bard is in Murray Hill. (But not the two new huge drug cases: Boehringer Ingelheim, maker of Pradaxa, is in Connecticut, while Takeda, maker of Actos, is in Illinois.)

All of which to say is: when the New Jersey Supreme Court releases a new drug or medical device opinion, it’s a big deal. A thousands-of-cases big deal.

There’s thus been a lot of anticipation surrounding the Court’s opinion in Kamie S. Kendall v. Hoffman-LaRoche, Inc., et al., which was decided Monday. The opinion is here. Some reporting has already come out at Pharmalot, and there’s commentary from the mass torts defense firms Ballard Spahr and Dechert (I’ll get that in a moment).

Kendall is an Accutane case, in which the plaintiff developed inflammatory bowel disease (apparently both ulcerative colitis and Crohn’s Disease; her symptoms were so severe she had her colon removed) as the result of Accutane. A jury awarded her $10.5 million back in 2008, then the case then went into a complicated appellate posture. Roche argued (1) that the case should have been barred by the statute of limitations and (2) that its defense was unfairly prejudiced by the trial court’s restriction on the way the parties could present the number of adverse case reports as evidence that Roche acted too slowly in responding to reports that Accutane caused IBD. The New Jersey Appellate Division held the case was filed within the statute of limitations, but nonetheless ordered a new trial on the adverse case reports issue.

The New Jersey Supreme Court then granted an appeal on only the statute of limitations issue. It was a bit of a “head’s you lose, tails I win” situation for the plaintiffs: if they lost in front of the New Jersey Supreme Court, they lost for good, whereas if they won they still had to go through a retrial to fix the adverse events issue. I don’t fault the New Jersey Supreme Court for that — it’s appropriate for Supreme Courts to cherry-pick issues from cases — but I mention it to further dispel tort reform myths that these types of cases are easy money for injured patients and trial lawyers. Kendall’s lawsuit was filed in December 2005, and now, seven years later, neither she nor her lawyers have been paid a dime, and they still have to go through another trial where they could lose.

So let’s move to the big issue in the Kendall case. New Jersey, like every state, has a statute of limitations for negligence and product liability lawsuits, and also has an exception called the “discovery rule” for cases where the plaintiff didn’t learn until later that their injury could have been the result of negligence. The rule is:

Those considerations [of fairness] comprise the so-called “discovery rule,” the goal of which is to avoid [the] harsh results that otherwise would flow from mechanical application of a statute of limitations. Accordingly, the doctrine postpones the accrual of a cause of action so long as a party reasonably is unaware either that he has been injured, or that the injury is due to the fault or neglect of an identifiable individual or entity. Once a person knows or has reason to know of this information, his or her claim has accrued since, at that point, he or she is actually or constructively aware of that state of facts which may equate in law with a cause of action.

Caravaggio v. D’Agostini, 166 N.J. 237, 245 (2001).  Continue Reading New Jersey Supreme Court Re-affirms Discovery Rule For Statute of Limitations in Pharmaceutical Negligence Lawsuits

As I’ve written before, as a legal matter, drug companies have it easy. Consider what drug company lawyers called their ten “best” court opinions of the past year, many of which involved courts re-writing laws to dismiss lawsuits brought by injured patients. In the notorious PLIVA v. Mensing case, a 5-4 Supreme Court tried its hardest to wash away any claims injured consumers could have against generic drug manufacturers by ruling that, as a matter of law, any lawsuit would conflict with the FDA’s regulations — even though the Supreme Court couldn’t point to any actual conflicting regulations, and even though the FDA itself said there wasn’t a problem. That’s a big reason why commercials for Actos lawsuits and Pradaxa claims are so big now: they’re still patented, brand-name drugs.

Any hopes that consumers of generic drugs would be protected by the FDA’s own oversight of generic drug manufacturing came to a crashing halt earlier this week when the Department of Justice and the Food and Drug Administration jointly announced their Consent Decree with Ranbaxy Laboratories:

Through investigation by the department and the FDA, the government uncovered numerous problems with Ranbaxy’s drug manufacturing and testing in India and at facilities owned by its U.S. subsidiary, Ranbaxy Inc. These problems include failure to keep written records showing that drugs had been manufactured properly; failure to investigate evidence indicating that drugs did not meet their specifications; failure to adequately separate the manufacture of penicillin drugs from non-penicillin drugs in order to prevent cross-contamination; failure to have adequate procedures to prevent contamination of sterile drugs; and inadequate testing of drugs to ensure that they kept their strength and effectiveness until their expiration date.

The government also determined that Ranbaxy submitted false data in drug applications to the FDA, including the backdating of tests and the submitting of test data for which no test samples existed. All of these actions constituted violations of the federal Food, Drug and Cosmetic Act, making many of Ranbaxy’s drugs adulterated, potentially unsafe and illegal to sell in the United States.

As one member of the DOJ’s civil division said in the press release, “Submitting false data to the FDA in drug applications will not be tolerated.” These weren’t minor mistakes. It was a gross disregard for public safety covered up by deliberate falsifications to authorities.

And then we find out the penalty: Continue Reading “No Tolerance” for Drug Manufacturers Fabricating FDA Data Doesn’t Mean Much

A few days ago I reviewed the list of “worst” pharmaceutical and medical device liability court opinions of the last year as chosen by the defense lawyers at Drug & Device Law, so I feel obligated to follow-up on their post on the “best” prescription drug and medical device decisions.

The short version is quite simple: drug and device companies really like activist judges legislating from the bench or overruling juries’ factual findings. How else to explain the love for PLIVA, Inc. v. Mensing, in which the United States Supreme Court couldn’t find a federal statute or regulation in support of granting generic drug manufacturers legal immunity and so contrived an argument the Court admitted “makes little sense,” or Garza v. Merck & Co., in which the Texas Supreme Court held that it was unreasonable for a jury to agree with two cardiologists that Vioxx caused a heart attack?

As with their “worst” list, the “best” list is most interesting for what it reveals about the current state of drug and medical device company liability: heads defendant wins, tails plaintiff loses. In Mensing (#1), a plaintiff’s claim was dismissed because the Court didn’t want to speculate about what the FDA would do if a drug company proposed strengthening a warning label, while in Dobbs (#8) a plaintiff’s claim was dismissed because the Court speculated that the FDA wouldn’t accept a drug company’s proposal for a strengthened warning label. In Williams (#4), a plaintiff’s claim was dismissed because her doctors disposed of the pieces of the device in question, while in Wolicki-Gables (#6), a plaintiff’s claim was dismissed because, even though the plaintiff asked in writing for her doctors to preserve the device, a representative of the device manufacturer slipped into the surgery without the patient’s consent, took the device, lied to the patient about testing it and destroyed it, leaving the plaintiff nothing to examine or to test.

Let’s roll the tape. Continue Reading The Most Unfair Prescription Drug And Medical Device Opinions Of 2011