Mass Tort Litigation Blog

Pfizer Settlements for Bextra and Celebrex

Article in the Wall Street Journal -- Pfizer Settles Lawsuits Over Two Painkillers, by Nathan Koppel and Heather Won Tesoriero.  What's interesting is Pfizer's approach to settlement: negotiating settlements with plaintiff's firms that have a large inventory of plaintiffs, rather than attempting (like Merck in Vioxx) to offer a massive settlement to all plaintiffs nationwide.  Here's an excerpt:

Pfizer Inc. has struck tentative settlements with groups of plaintiffs who allege that the painkillers Celebrex and Bextra caused heart attacks and strokes, according to lawyers at three firms involved in the litigation.

These firms represent more than 200 out of the thousands of people who sued Pfizer over the two medications. The drug maker may have struck additional deals and remains in discussions with other plaintiffs' law firms, according to lawyers involved in the talks.

Unlike Merck & Co.'s recent global settlement of litigation involving the painkiller Vioxx, Pfizer is attempting to resolve its liability on a firm-by-firm basis, lawyers say. The Bextra and Celebrex cases didn't present nearly the same threat to Pfizer that Vioxx did to its maker, though.

BGS

Accutane Verdict of $10.6 Million

A New Jersey jury hit Roche with a $10.6 million verdict in favor of a Utah woman who claimed that the acne medication Accutane caused her inflammatory bowel disease.  The jury, finding that Roche provided inadequate labeling, awarded plaintiff Kamie Kendall $78,500 for past medical expenses plus $10.5 million in unspecified compensation.  Here's a brief story in the Star-Ledger.  Pharmalot notes that this verdict is Roche's third Accutane trial loss (another in New Jersey last June, and one in Florida last fall), and that the company faces about 400 Accutane suits.

HME

Drug Companies Push for Easier Off-Label Rules

This morning's Wall Street Journal reports that several major drug companies are pushing the FDA to relax its requirements for off-label drug use.  Here's an excerpt:

Ten major drug companies, including Pfizer Inc.; Bayer Corp., the U.S. unit of Bayer AG; AstraZeneca PLC; and Johnson & Johnson have formed a coalition to push for looser restrictions on off-label marketing. They will submit their arguments Friday to the Food and Drug Administration, which has been soliciting comments on its proposed off-label promotion guidelines. They are represented by former FDA Chief Counsel Daniel Troy, who is working with public-relations giant APCO Worldwide Inc.

Mr. Troy's group includes patient-advocacy organizations the National Alliance on Mental Illness and the National Organization for Rare Disorders. The group supports the ability of companies to disseminate articles from peer-reviewed medical journals to physicians and hospitals to inform them of new conditions for which drugs already on the market could be used but which the FDA hasn't formally approved.

The FDA said it isn't loosening the rules for industry, but clarifying them. Randall Lutter, the agency's deputy commissioner for policy, said the guidelines mandate full disclosure of any conflict of interest by journal authors in articles used in off-label promotion.

The push for off-label changes came just as the Journal of the American Medical Association suggested in two reports that Merck & Co. played down the potential risk to Alzheimer's patients of heart attack from its now-withdrawn painkiller Vioxx, and said the company had ghostwritten many academic articles favorable to that drug.

Drug-industry worries about new rules and a chilly climate in Washington were reflected at a conference here Thursday. More than 60% of participants polled during the annual conference sponsored by drug-marketing magazine DTC Perspectives said they think Congress may move to place limits on television advertising by pharmaceutical companies. Drug makers spend about $5.4 billion annually on TV ads, according to Nielsen Monitor-Plus.

ECB

Vioxx and Medical Ghostwriters

The New York Times today reported on a JAMA article about medical ghostwriting, raising questions about the integrity of pharmaceutical research studies published in medical journals.  Here's how the Times account begins:

The drug maker Merck drafted dozens of research studies for a best-selling drug, then lined up prestigious doctors to put their names on the reports before publication, according to an article to be published Wednesday in a leading medical journal.

The article, based on documents unearthed in lawsuits over the pain drug Vioxx, provides a rare, detailed look in the industry practice of ghostwriting medical research studies that are then published in academic journals.

The article cited one draft of a Vioxx research study that was still in want of a big-name researcher, identifying the lead writer only as “External author?”

Here's a link to the New York Times article, "Ghostwriters Used in Vioxx Studies, Article Says," as well as one to the NYT link to the JAMA article itself.

HME

Regulating the Global Economy: Foreign Pharmaceuticals

An article by Walt Bogdanich in the New York Times on March 30 describes the difficulties of regulating the content of drug imports, with special reference to the heparin scandal.  The article can be found here.  The article explains: "Anti-counterfeiting experts say that the longer the chain, the greater the opportunity for counterfeiters to adulterate the product. In fact, F.D.A. investigators have yet to figure out where in the multistage manufacturing process the chemical that mimics heparin was added."

ADL

Cardiologists Question Continued Use of Vytorin and Zetia

This morning’s Wall Street Journal reports that a panel at the American College of Cardiology Study questioned heavy use of Vytorin and Zetia in fighting cardiovascular disease. Merck and Schering-Plough countered by saying "they believe Vytorin failed to show a benefit likely because most of the study patients had previously been treated with statins, and their arteries were healthier than expected." Here’s an excerpt of the article:

The panel's opinion, which came at the annual meeting of the American College of Cardiology Sunday, could prompt many physicians to switch heart patients away from significant use of the drugs, known as Vytorin and Zetia, and frustrate efforts of the drug companies to shore up sales of the medicines. Together, the perspective and the study results themselves appeared to strengthen the view that adoption of the medicines has far outpaced any evidence supporting their benefits.

"You've just seen a negative trial that should change practice, especially the way we in this country have prescribed" the drugs, Yale University cardiologist Harlan Krumholz told thousands of cardiologists. He urged doctors to go "back to statins," the class of cholesterol-lowering drugs that includes Lipitor and Zocor. Major studies have demonstrated their ability to save lives and prevent heart attacks.

If the advice is followed by cardiologists and primary care physicians, it would almost certainly spur a significant drop in sales of the drugs. The companies have been trying to revive or hold the line on already slumping sales of the pills, which climbed to a combined $5.1 billion last year.

Officials with both Merck and Schering-Plough took issue with calls to curtail their use. Enrico Veltri, a group vice president for clinical research at Schering-Plough, said Zetia and Vytorin remain an important "practical option" for helping patients to reduce LDL cholesterol, the type associated with cardiac issues.

ECB

FDA Drug Approval Near Deadline Linked to Safety Problems

Article in the Wall Street Journal -- Late Drug Approval Linked To Safety Issues, by Keith J. Winstein.  Here's an excerpt:

Although every unsafe drug is different, most of them have something in common: last-minute approvals by the Food and Drug Administration, according to a new study.

Liver problems led Pfizer Inc. to withdraw its diabetes drug Rezulin from the U.S. market in 2000. Bayer AG pulled cholesterol-lowering Baycol in 2001 because it caused muscle damage in some patients. Vioxx, Merck & Co.'s controversial painkiller, was withdrawn in 2004 because it sometimes caused heart attacks and strokes.

These and other unsafe drugs all received approval shortly before the FDA deadline for deciding on new-drug applications.

Since 1993, the 97 drugs approved near the FDA's deadline had a 14% rate of severe safety problems down the road, compared with 3% for 216 other drugs. That's according to an analysis in Thursday's issue of the New England Journal of Medicine by Daniel Carpenter, a professor of government at Harvard University. The FDA says some of Dr. Carpenter's data are inaccurate, and disputed his conclusions.

BGS

Pfizer Denied Discovery of JAMA Confidential Peer-Reviewer Comments in Celebrex and Bextra Litigation

As the Wall Street Journal reports -- see Pfizer Is Denied Access to JAMA Files, by Thomas M. Burton -- a magistrate judge in federal district court in Chicago has denied Pfizer's request to obtain confidential JAMA peer-reviewer comments in connection with the litigation involving Bextra and Celebrex.  Such peer-reviewer comments on a study can generally be valuable to defendants questioning a scientific study in connection with a scientific evidence challenge under Daubert, as well as for criticisms at trial if the Daubert evidentiary challenge fails.  Indeed, understanding peer-reviewer misgivings may be essential to placing in proper perspective the publication of a study in a prestigious scientific journal.  On the other hand, scientific journals may assert an interest in developing scientific publications without the specter of litigation-driven discovery at every turn.  Given the tremendous implications of the science underlying a mass tort for plaintiffs and defendants, I would be inclined to tread a middle ground -- allow limited discovery that vindicates the law's need for reliable scientific evidence, but does not unduly burden the medical journals in their important work.      

In an editorial in JAMA -- Preserving Confidentiality in the Peer Review Process -- Dr. DeAngelis and JAMA's counsel, Joseph Thornton, provide more details on the dispute and decision.  In addition, here's a related post on the dispute from Pharmalot, and another post from TortsProf Blog.  For more depth, take a look at the following article by Professor Bill Childs (Western New England): The Overlapping Magisteria of Law and Science: When Litigation and Science Collide, Nebraska L. Rev. (2007).

BGS

Spiriva Respiratory Drug May Have Stroke Risk

Article from the March 18 Wall Street Journal  -- Boehringer Inhaler Might Pose Higher Stroke Risk, FDA Says, by Jennifer Corbett Dooren.  Here's an excerpt:

The Food and Drug Administration said Tuesday it is opening a safety review of Boehringer Ingelheim GMBH's respiratory drug Spiriva after the company reported a possible higher risk of stroke to the agency.

In an "early communication" posted on the FDA's Web site, the agency said Boehringer Ingelheim submitted the results of 29 studies involving Spiriva, an inhaler that treats patients with chronic obstructive pulmonary disease, which showed a slightly higher rate of stroke among patients treated with Spiriva compared to those not receiving the drug. Most of the studies looked at Spiriva's HandiHaler, which is co-marketed with Pfizer Inc.

"Additional information is needed to further evaluate this preliminary information about stroke in patients who take Spiriva HandiHaler," the FDA said. The agency said it has requested additional information from the company and is reviewing post-marketing adverse events reported to FDA involving Spiriva.

BGS

Heparin Recall Because of Potentially Dangerous Contaminant

Article in the Wall Street Journal -- Another Company Recalls Blood Thinner Heparin, by the Associated Press.  Here's an excerpt:

A manufacturer of the blood thinner heparin initiated a nationwide recall Friday because some products may contain a potentially dangerous contaminant. Contaminated heparin from a different manufacturer has been associated with 19 deaths and hundreds of allergic reactions.

In the recall announced Friday, B. Braun Medical Inc. said it was recalling 23 lots of heparin as a precautionary measure. No adverse events have been reported in connection with their product, company officials said in a press release.

The company issued the recall after one of its suppliers, Wisconsin-based Scientific Protein Laboratories, disclosed that an ingredient it provided contained oversulfated chondroitin sulfate, a chemical that does not occur naturally. Federal officials are investigating how the contaminant got into the drug.

Previously, on March 20, the Wall Street Journal published FDA Identifies Contaminant in Heparin Batches, by Anna Wilde Mathews and Thomas M. Burton.  Here's an excerpt:

A contaminant found in recalled batches of the blood-thinner heparin was deliberately altered in a way that mimicked the real drug, the Food and Drug Administration said, a finding that will add to pressure on U.S. regulators and pharmaceutical companies to step up oversight of burgeoning Chinese drug production.

Yesterday, the FDA said the contaminant, which has surfaced in batches of heparin made from active ingredient sourced in China, appears to be a chemically altered material derived from a cheap and widely available substance found in animals, particularly in cartilage.

The agency said it isn't clear if the contaminant, called over-sulfated chondroitin sulfate, is the cause of allergic reactions, some fatal, that occurred in people who took heparin supplied by Baxter International Inc., which has recalled the drug batches linked to the problem. The contaminant has been found in heparin taken by people who had reactions.

BGS

Drug Import Safety and the FDA

A New York Times Article by Gardiner Harris published today highlights the problems in FDA monitoring of imported drugs due largely to lack of funding.  The article is available here.   The bottom line is this:

The Institute of Medicine, the Government Accountability Office and the F.D.A.’s own Science Board have all issued reports saying poor management and scientific inadequacies make the agency incapable of protecting the country against unsafe drugs, medical devices and food.

Indeed, in the years since the last China drug scandal, the share of drugs coming from that country has soared while the F.D.A.’s inspections of overseas drug plants have dropped. There are 566 plants in China that export drugs to the United States, but the agency inspected just 13 of them last year.

According to the article, 80% of "of the active pharmaceutical ingredients of drugs consumed in the United States are manufactured abroad." 

Congress is apparently considering proposals for fee-based funding of inspections of foreign plants.  Consumer groups oppose it because it creates a potential conflict of interest for the FDA.  The article quotes the CEO of a European pharmaceutical manufacturer supporting user fees.

ADL

FDA Adds Additional Black-Box Warnings to Anemia Drugs

Article in the Wall Street Journal -- FDA Adds More Black-Box Warnings To Anemia Drugs From Amgen, J&J, by the Associated Press.  Here's an excerpt:

Drug maker Amgen Inc. says regulators have added new warnings about risks of death and tumor growth to its blockbuster anemia drugs.

The new warnings approved Friday by the Food and Drug Administration warn that the company's drugs increased death and accelerated tumor growth in patients with several types of cancer, including breast and cervical. Prior labeling added to the drugs in November warned of similar risks in other types of cancers.

The warnings apply to Thousand Oaks, Calif.-based Amgen's Aranesp and Epogen, as well as Procit, sold by New Brunswick, N.J-based Johnson & Johnson. The drugs treat the blood-disorder anemia in patients with kidney failure or who are undergoing chemotherapy.

Labeling approved by FDA said risks occurred when doctors treated patients with elevated levels of the drugs, which stimulate red blood cell levels.

BGS

The Law of Unintended Concequences: Warner Lambert v. Kent

The folks over at Drug and Device Law Blog make an excellent observation about the 4-4 decision in Warner-Lambert v. Kent.  Here's the idea:

Pharmaceutical litigation often results in masses of cases being filed.  When there are many cases that all raise common issues of fact or law, it may be duplicative for every federal court where such cases are filed to go through the discovery process or motions.  For example, should the CEO be deposed in litigation, thousands of times?  This would be onerous and wasteful.  Therefore there is a special panel of judges (the Multi-District Litigation Panel) which is statutorily empowered to collect all these cases and transfer them to a single court.  This panel is created pursuant to 28 US 1407 which states:

When civil actions involving one or more common questions of fact are pending in different districts, such actions may be transferred to any district for coordinated or consolidated pretrial proceedings. Such transfers shall be made by the judicial panel on multidistrict litigation authorized by this section upon its determination that transfers for such proceedings will be for the convenience of parties and witnesses and will promote the just and efficient conduct of such actions.

Beck/Hermann point out that since there is a Circuit split on the issue of whether fraud on the FDA claims can go forward, and since many pharmaceutical tort cases are consolidated under the auspices of the Multi District Litigation Panel, the MDL Panel's choice of transferee court will determine the substantive law applicable.  Here is quote from their post:

The court that receives those cases -- the "transferee" court -- will apply local federal circuit precedent to all pretrial rulings.  See In re Korean Air Lines Disaster, 829 F.2d 1171 (D.C. Cir. 1987), and its progeny. Thus, if the MDL Panel chooses to centralize the cases in Cleveland, all Michigan plaintiffs automatically lose under controlling circuit law. But if the MDL Panel chooses to centralize those same cases in New York, Michigan plaintiffs do not automatically lose.

When the DC Circuit affirmed the In re Korean Air Lines Disaster ruling, then Judge Ruth Bader Ginsburg gave three reasons for allowing the transferee court's law to apply: (1) "[a]pplying divergent interpretations of the governing federal law to plaintiffs, depending solely upon where they initially filed suit, would surely reduce the efficiencies achievable through consolidated preparatory proceedings"; (2) "because there is ultimately a single proper interpretation of federal law, the attempt to ascertain and apply diverse circuit interpretations simultaneously is inherently self-contradictory"; and (3) the parties could always seek review by the Supreme Court for an authoritative and final interpretation.  See 829 F.2d 1171, 1176 (D.C. Cir. 1987).  That last condition, of course, is not met because the Supreme Court had the opportunity to decide and gave us a 4-4 non-decision.

But this case is not the last word, nor will it be.  Last year around this time, a court held that the law of the transferor court (that is, the court where the case came from) was binding with respect to the question of class certification because class certification is "not merely a pretrial issue" but instead is "inherently enmeshed with considerations of the trial."  "Neither party should be prejudiced in preparing for trial because the case was removed and transferred to another district in a different circuit." In re Methyl Tertiary Butyl Ether (MTBE) Products Liability Litigation, 241 F.R.D. 185  (S.D.N.Y. Feb 20, 2007).  That court then applied the transferor court's interpretation of the class action rule and certified the class.    

This issue really makes one appreciate the incredible importance of pre-trial proceedings and reminds us again of the trickiness of the substance/procedure distinction.  (This is why we Civil Procedure professors love to teach Erie).  MDL transfer is intended merely to make processing of cases easier, but it does also affect the merits.

What's to be done?  Beck/Hermann urge that the MDL Panel "be beyond reproach" and that the Supreme Court decide the issue for good.  I don't disagree with their suggestion, but I think the MDL Panel is placed in a terrible situation when the outcome of the case is based on transfer and is already known in advance of the transfer.  This leaves them in a position to decide the merits, really, and I don't think that is what the statute creating the MDL intended. 

I have another suggestion.  When faced with such a scenario, the MDL panel might consider transferring and centralizing the cases to several regional forums.  I suggest two forums.  Plaintiffs who filed within the regions covered by the preemption precedent would be consolidated in one court, plaintiffs who filed in the regions covered by the non-preemption precedent would be consolidated in another court.  This would not lead to duplicative discovery because all the cases in region 1 would be dismissed, and all the cases in region 2 would proceed.  This idea violates the principles behind (1) and (2) of then-Judge Ruth Bader  Ginsburg's  rationale, and raises an important question about the tension between the just and efficient conduct of actions in the federal courts.  Centralization is efficient, but is it just to allow the MDL Panel to choose which law applies through their transfer decision, which has to include other factors such as judicial experience, caseload, the spread of cases over the entire system, convenience of the parties in terms of the conduct of discovery and cost of litigation, etc.?     If the Supreme Court doesn't like this outcome, as Beck/Hermann point out, they can decide the issue once and for all.  But for the moment, it seems to me perhaps we can proceed with multiple centralized forums, rather than just one, and solve the problem without driving Article III judges crazy.

The reality is that region 1 cases (those that will be dismissed) will not be brought because the law is clear.   Beck/Hermann are concerned that the plaintiffs will forum shop and all the new cases will now be region 2 cases.  Point taken.  I think the idea that the MDL Panel's decision should reflect the disagreement, rather than effect it, is still right.

I have an article coming out in Tulane Law Review making such a proposal, which should be posted on SSRN soon, and would be interested in learning the thoughts of others about it.

  
ADL

Heparin Recalled

Baxter International, the manufacturer of heparin, issued an urgent nationwide voluntary recall of its blood-thinner, Heparin. According to the New York Times, there were problems with a Chinese plant that supplied an active ingredient. Here’s a link to the FDA’s recall and an excerpt from the New York Times article:

The Food and Drug Administration said the number of deaths possibly associated with the drug, made from pig intestines, had risen to 21 from 4. But it cautioned that many of those patients were already seriously ill and that the drug might not have caused their deaths.

The F.D.A. emphasized that it had yet to identify the root cause of the problem, and that it had not concluded that the Chinese plant was responsible. The agency also said it was investigating two Chinese wholesalers — also called consolidators — that supplied crude heparin to the Chinese plant, Changzhou SPL, as well as those that sold raw ingredients to the consolidators.

The New York Times reported Thursday that at least one of the consolidators received supplies from small, unregulated family workshops that scraped mucous membrane from pig intestines and cooked it, eventually producing a dry substance known as crude heparin.

The F.D.A. admitted this month that it had violated its own policy by failing to inspect SPL, located west of Shanghai, before the factory began shipping the heparin ingredient to Baxter in 2004. China’s drug agency also did not inspect the plant.

The FDA’s failure is troubling, particularly in light of the Supreme Court’s recent preemption leanings.

ECB

AEI Panel on Federal Preemption and the Supreme Court

The American Enterprise Institute has posted the audio and video for its panel presentation on February 21 on Federal Preemption and the Supreme Court.  AEI's Ted Frank moderated the panel, which included Michael Greve (AEI), Catherine Sharkey (NYU), Daniel Troy (Sidley Austin), and Brian Wolfman (Public Citizen).

BGS

Botox Mass Tort?

Very interesting article on cnn.com --  FDA warns of Botox side effects, deaths.  The FDA currently says it's only probing a "relative handful" of reports, but the widespread usage of Botox certainly raises the possibility of a mass tort.  Here's an excerpt:

The popular anti-wrinkle drug Botox and a competitor have been linked to dangerous botulism symptoms in some users, cases so bad that a few children given the drugs for muscle spasms have died, the government warned Friday.

The Food and Drug Administration's warning includes both Botox, a wrinkle-specific version called Botox Cosmetic, and its competitor, Myobloc, drugs that all use botulinum toxin to block nerve impulses, causing them to relax.

In rare cases, the toxin can spread beyond the injection site to other parts of the body, paralyzing or weakening the muscles used for breathing and swallowing, a potentially fatal side effect, the FDA said.

Botox is best known for minimizing wrinkles by paralyzing facial muscles -- but botulinum toxin also is widely used for a variety of muscle-spasm conditions, such as cervical dystonia or severe neck spasms.

BGS

What's Left of Merck?

The Legal Intelligencer reports that Merck agreed to pay more than $671 million to settle whistleblower claims arising out of marketing tactics to encourage doctors to write more prescriptions for drugs like Vioxx and Zocor. I read an article that came out in Hastings Law Review last May, Informed Consent: Requiring Doctors to Disclose Off-Label Prescriptions and Conflicts of Interest (58 Hastings L. Rev. 967), by Margaret Johns (UC Davis) suggesting that patients should give informed consent before a doctor prescribes off-label prescription drugs. The informed consent would, in a nutshell, include not only information that the drug is being used "off-label" but any "perks" that the doctors received for prescribing the drug. From the Legal Intelligencer’s article this morning, it sounds like doctors should disclose their perks before prescribing drugs, period. Here’s an excerpt:

A settlement of almost $400 million in the Philadelphia case stems from a seven-year investigation that began when H. Dean Steinke, a former Merck district sales manager, blew the whistle by filing claims under the False Claims Act that alleged Merck was using several illegal marketing practices. Steinke -- who was represented by attorneys Steven H. Cohen of Chicago, BethAnne Yeager of Madison, Wis., and Mark Kleiman of Santa Monica, Calif. -- will be paid a reward of nearly $44.7 million, prosecutors said.

The $250 million settlement of the Louisiana case stemmed from a whistleblower suit brought by William St. John Lacorte, a physician who alleged that Merck gave steep discounts for Pepcid to hospitals that agreed to primarily use Pepcid instead of competitor drugs.

Prosecutors said both settlements include interest that will boost Merck's total payout to $671 million.

Under the terms of the Philadelphia settlement, federal agencies will receive $218 million and the 49 states with Medicaid programs and the District of Columbia will share $181 million.

The Louisiana settlement is similarly divided, with $137.5 million for the federal government and $112.5 million for the states. LaCorte's reward from the Louisiana settlement has not yet been decided, prosecutors said.

...

Steinke's suit also accused Merck of paying kickbacks to doctors under the guise of marketing training programs such as "preceptorships," in which physicians were paid to allow a Merck sales rep to "shadow" them for half a day, and "tutorials," in which doctors were paid to listen to a Merck employee's presentation and then evaluate it. The suit said one physician was paid 22 times by Merck, at $250 a session, and seven times at $300 a session, for preceptorships.

Steinke's suit also alleged that Merck treated high-prescribing physicians to lavish vacations that the company termed "consultant meetings." One such consultant meeting was held in September 1998 at the luxurious Crystal Mountain Resort in Thompsonville, Mich., the suit said. During the event, the suit said, doctors were asked to serve as a Merck representative training consultant and to evaluate the sales message of Merck sales reps. In return, Merck paid each physician a $500 honorarium for the training and consultative services, Friday and Saturday nights' lodging expenses and an additional $100 for incidental expenses.

ECB

Plavix Cessation Linked to Heart Attacks and Death

This morning's Wall Street Journal reports on a recently released JAMA study that found that patients halting their Plavix use had an increased chance of heart attacks or death within 90 days after they stopped taking the drug.   Here's an excerpt:

The study, published in this week's Journal of the American Medical Association, focused on 3,137 patients discharged from 127 Veterans Affairs hospitals from 2003 to 2005. Plavix is generically known as clopidogrel.

The doctors found the increased rate of adverse events both in patients who initially received only medical treatment and in those treated with angioplasty and stents.

"We observed a clustering of adverse events in the initial 90 days after stopping clopidogrel," the researchers wrote, "supporting the possibility of a clopidogrel-rebound effect."

The doctors found that the rate of heart attack and death during the 90 days following cessation of Plavix therapy nearly doubled.

ECB

Vladeck on Direct-to-Consumer Drug Advertising

Professor David Vladeck (Georgetown) has posted his article, The Difficult Case of Direct-to-Consumer Drug Advertising, Loyola L.A. L. Rev. (forthcoming 2008).  Here's the abstract:

This article will appear in a symposium to pay tribute to Professor Steven H. Shiffrin, one of the leading First Amendment theorists of our time. The author was asked to focus on Professor Shiffrin’s contribution to the development of the commercial speech doctrine. To reflect on the wisdom of Professor Shiffrin’s refusal to rely on general First Amendment theories, the article focuses on the difficult First Amendment problem of regulating direct-to-consumer (DTC) advertising of prescription drugs. In his famous dissent in Virginia Pharmacy Board, then-Justice Rehnquist forecast that, as a consequence of the Court’s ruling, drug companies would soon advertise directly to consumers on television and other media. Justice Rehnquist argued that “there are sufficient dangers attending” the use of drugs “that they simply may not be promoted in the same manner as hair creams, deodorants, and toothpaste.”

Today drugs are promoted in much the same way as other products. Drug companies devote forty percent of their advertising expenditures — over $4 billion per year — to DTC ads. The average American views as many as 16 hours of prescription drug ads per year, far exceeding the average time spent with a primary care physician. The question is whether proposals before Congress to limit or ban DTC advertising would pass constitutional muster. The article canvasses the arguments in some detail and concludes that legislation restricting DTC advertising to enable the FDA to assess the risks of a drug might withstand constitutional attack, but that an all-out ban on DTC advertising would not likely be sustained. The point of this discussion is to illustrate the complexity of commercial speech questions and to demonstrate that Professor Shiffrin was correct when he observed that “the commercial speech problem is in fact many problems,” and that “the small questions [it poses] will not go away.”

BGS

Supreme Court Grants Cert in Two Preemption Cases

The Supreme Court today granted cert in two preemption cases that will have significance for mass tort litigation.  In Wyeth v. Levine, No. 06-1249, the Court will decide whether the FDA's prescription drug labeling judgments preempt state law liability claims for failure to warn.  In a case involving Wyeth's anti-nausea drug Phenergan, the Vermont Supreme Court ruled that the FDA regs only provide a floor on labeling requirements, so states are free to enforce their own.  In Itria Group v. Good, No. 07-562, the Court is asked to decide whether federal law preempts state-law challenges to FTC-authorized statements in cigarette advertising about "light" or "low tar" cigarettes. 

You can see brief descriptions of these cases on ScotusBlog.  I'm sure more will follow from the defense perspective on the Drug and Device Law blog.  Public Citizen is a good resource for the consumer's perspective on this issue.

ADL

Merck Recalls Child Vaccine

An article on cnn.com -- Merck recalls kids' vaccine -- discusses Merck's recall of 1.2 million doses of child Hib vaccine, because of contamination risks and possibility of infection.  The article also summarizes Merck's status in light of the proposed Vioxx settlement:

While the company took a black eye with its September 2004 withdrawal of the painkiller Vioxx due to increased risk of heart attacks and strokes, Merck has been performing well recently. On Tuesday, it gave an upbeat assessment in its annual briefing for analysts.

Five weeks ago, Merck reached a deal to settle up to 50,000 Vioxx lawsuits for $4.85 billion, an amount expected to save the company millions in trial costs.

Its stock price has more than recovered from its post-Vioxx slump, a two-year-old restructuring plan is going well and profits are up. For example, Merck posted a 62 percent increase in its third-quarter profit as revenues jumped by double digits

BGS

USA-China Product Safety Pact

Article in the Wall Street Journal -- Product-Safety Pacts Put Greater Burden on Beijing, by Jason Leow and Jane Zhang.  Here's an excerpt:

The Bush administration signed product-safety agreements with China that place a greater burden on Beijing to regulate exports of food, animal feed, drugs and medical devices.

The agreements require exporters of those products to register with the Chinese government, which will issue certificates stating they meet U.S. Food and Drug Administration standards. The agreements are aimed at closing some loopholes that let Chinese companies export unsafe food, drugs and other products.

Mike Leavitt, secretary of health and human services, signed the two agreements yesterday with Chinese officials in Beijing as part of three days of trade talks with China. "The agreements satisfy our firm principle that any country that desires to produce goods for American consumers must do so in accordance with American standards of quality and safety," he said in a statement.

The agreements cover such products as olives and canned mushrooms, pet food, raw materials for processed foods, farm-raised fish, drugs and medical devices. Drugs covered include: human-growth hormone; oseltamivir, an antiviral drug; and gentamicin sulfate, an antibiotic. The limited list of covered products is an initial step, U.S. officials said, suggesting Washington wants to gain confidence in the Chinese system before expanding the program.

BGS

FDA Questions Child Safety of Glaxo Asthma Drugs Serevent and Advair

Article in the Wall Street Journal -- Questions the Safety Of Asthma Drugs for Kids, by Jenifer Corbett Dooren and Anna Wilde Mathews.  Here's an excerpt:

Food and Drug Administration drug-safety reviewers questioned whether the GlaxoSmithKline PLC asthma drugs Serevent and Advair are appropriate for use in pediatric patients, and said the issue needs further review.

The asthma-drug findings came in documents posted Friday in advance of a meeting of the FDA's pediatric advisory committee. The session, which starts Tuesday, is expected to focus on the safety of a number of drugs, including the influenza medications Tamiflu, from Roche Holding AG, and Relenza, made by Glaxo.

Serevent and Advair, which both contain the active ingredient salmeterol, already carry a strong "black box" label warning about a risk of asthma-related death. The agency's reviewers said they hadn't identified side effects unique to children.

BGS

FDA Recommends Child Neurological Warnings for Flu Drugs Tamiflu and Relenza

Article on cnn.com -- FDA wants behavior warning on flu drugs.  Here's an excerpt:

Government health regulators recommended adding label precautions about neurological problems seen in children who have taken flu drugs made by Roche and GlaxoSmithKline.

The Food and Drug Administration on Friday released its safety review of Roche's Tamiflu and Glaxo's (Charts) Relenza. Next week, an outside group of pediatric experts is scheduled to review the safety of several such drugs when used in children.

BGS

Pfizer Wins Daubert Motion in Celebrex Litigation

Pfizer has won a Daubert motion in the Celebrex litigation that may significantly reduce the size of the litigation.  Here's an excerpt from the Wall Street Journal article, Pfizer Legal Win Might Block Some Lawsuits Over Celebrex, by Nathan Koppel and Heather Won Tesoriero:

Pfizer Inc. scored a victory yesterday through a federal ruling that might wipe out some lawsuits alleging that the drug maker's painkiller Celebrex caused heart attacks and strokes.

U.S. District Judge Charles R. Breyer of San Francisco ruled that plaintiffs in the litigation haven't presented scientifically reliable evidence that Celebrex caused heart attacks or strokes when taken at a daily dosage of 200 milligrams. That is the most common dosage, according to Pfizer.

Celebrex is the last drug in the COX-2 inhibitor class that is sold in the U.S. Merck & Co.'s Vioxx and Pfizer's other COX-2 painkiller, Bextra, were withdrawn from the market amid safety concerns.

There are more than 3,000 Celebrex plaintiffs, according to the ruling, but it isn't clear how many the ruling will affect. Paul Sizemore, a plaintiffs' attorney with Girardi & Keese in Los Angeles, estimates that about 900 Celebrex cases involve plaintiffs who were prescribed the 200-milligram dose. However, he says, many of the plaintiffs took the drug twice a day.

BGS

Bayer Suspends Anti-Bleeding Drug Trasylol Amid Evidence of Higher Risk of Death

Article in the Wall Street Journal -- Bayer Suspends Sales of Trasylol, by Anna Wilde Mathews.  Here's an excerpt:

Bayer AG said it was suspending sales of its antibleeding drug Trasylol world-wide after requests from regulators, amid growing evidence that the drug may be linked to a higher risk of death than that of competing drugs.

Bayer said its decision came in the wake of requests or orders from regulators in the U.S., Canada, Germany and other countries. Trasylol, which is supposed to reduce blood loss and allow patients undergoing heart-bypass surgery to avoid transfusions, is the third drug this year whose sale in the U.S. has been halted under scrutiny from the Food and Drug Administration, a signal of how the agency is weighing safety issues heavily in drug decisions.

Still, the history of Trasylol, which was approved in the U.S. in 1993 and has been tied to high-profile safety concerns at least since early 2006, is likely to draw questions from Congress and plaintiff attorneys.

The drug had world-wide sales of £230 million ($338 million) in 2005. Sales dropped by about a third last year.

BGS

Bayer Blood-Clotting Drug Trasylol May Increase Risk of Death

A Canadian study was halted after growing evidence suggested that Bayer's blood-clotting drug, Trasylol, which is used to reduce bleeding during heart-bypass surgery, increases the risk of death compared to other medications.  See the Wall Street Journal article, Bayer Drug May Raise Risk of Death, FDA Says, by the Associated Press.

BGS

Merck's RotaTeq Vaccine Not Associated With Life-Threatening Intestinal Problem

Article in the Wall Street Journal -- Merck Vaccine Seems Unlinked to Infant Malady, by Jennifer Corbett Dooren.  Here's an excerpt:

A Merck & Co. vaccine designed to protect infants against rotavirus doesn't appear to be associated with an increased risk of a potentially life-threatening intestinal problem known as intussusception, according to information compiled by federal health officials.

The Food and Drug Administration and the Centers for Disease Control and Prevention have been tracking the vaccine, sold under the brand name RotaTeq, to look for any links to intussusception because a rotavirus vaccine made by Wyeth was pulled from the market in 1999. The Wyeth vaccine was linked to an increased rate of intussusception, which is a twisting or obstruction of the intestine.

The FDA issued a public-health notice earlier this year saying it had received 28 reports of intussusception in vaccinated infants, and it asked health-care providers to be certain to report any suspected cases of the problem. At the time, the FDA said the intussusception rate wasn't higher than the rate that would be expected among nonvaccinated infants.

BGS

FDA Says Aventis Ignored Reports of Problems in Ketek Safety Study

Article in the Wall Street Journal -- FDA Says Aventis Failed To Act on Ketek Drug Fears, by Anna Wilde Matthews.  Here's an excerpt:

The Food and Drug Administration said drug maker Aventis failed to act on reports of serious problems with a safety study on its antibiotic Ketek and didn't properly oversee the trial's conduct.

The FDA detailed its concerns in a letter posted yesterday on its Web site and sent to Sanofi-Aventis SA, the successor company after a merger. Ketek, which has been linked to a risk of liver damage, was approved by the FDA in 2004, though the agency has said it didn't rely on the questionable safety study in approving the drug.

The doctor who ran the site that enrolled the most patients in the study ultimately pleaded guilty to fraud. The study was supposed to answer questions about whether the drug was tied to side effects including liver damage.

BGS

Amgen Earnings Drop Following Safety Problems of Anemia Drugs Aranesp and Epogen

Amgen's earnings slumped following its safety problems with its anemia drugs Aranesp and Epogen.  Here's an excerpt from the Wall Street Journal's article, Amgen Earnings Slump, by Andrew Edwards:

Amgen Inc.'s third-quarter net income tumbled as the biotechnology company posted restructuring charges, and Aranesp sales continued to decline.

The results include a $590 million write-off on in-process research and development related to the acquisitions of Alantos and Ilypsa, $293 million in restructuring charges, and a $90 million write-off of inventory because of changed regulations and reimbursements in the quarter, the Thousand Oaks, Calif., company said. International sales rose 12%, while U.S. sales fell 1.9%. Excluding the impact of currency fluctuations, the company said total product sales fell 1%.

....

Sales of anemia drugs Aranesp and Epogen, which account for almost half of Amgen's sales, dropped 23% and 5%, respectively. The two drugs increase red-blood-cell production, reducing the need for blood transfusions for patients on dialysis and chemotherapy. Their sales have hemorrhaged since a Food and Drug Administration warning in March that the drugs, when used in high doses, can increase the risk of blood clots and death in cancer and kidney-disease patients.

The study prompted Medicare to set limits on reimbursements for the drugs, which cost the agency billions of dollars every year.

BGS

Glaxo to Cut Jobs Because of Avandia Problems

Article in the Wall Street Journal -- Glaxo to Cut Jobs As Generics Hit Sales, Profit, by Jeanne Whalen.  Here's an excerpt:

GlaxoSmithKline PLC became the latest drug company to announce layoffs and cost cuts after competition from generic medicines and sharply lower sales of the diabetes drug Avandia hurt third-quarter earnings.

The world's second-largest pharmaceutical company by sales said it would take a £1.5 billion ($3.08 billion) charge as part of cost cuts that it estimates will save the company £700 million a year by 2010. Glaxo Chief Executive Jean-Pierre Garnier said layoffs would be involved, but he declined to say how many.

....

Glaxo, based in Brentford, England, was particularly hard hit by plummeting sales of Avandia, a once-popular diabetes drug now linked by some research to heart-attack risks.

BGS

FDA May Add Black Box Warning of Heart Attack for Glaxo's Diabetes Drug Avandia

Article in the Wall Street Journal -- Tougher Avandia Warning Is Urged: New Label for Drug Would Detail Risk Of Heart Attack, by Anna Wilde Mathews.  Here's an excerpt:

The Food and Drug Administration wants GlaxoSmithKline PLC to add the strongest form of safety warning about heart-attack risk to the label of its diabetes drug Avandia, according to people with knowledge of the matter, a move that would compound the commercial woes of the once-popular medication.

Agency officials are pushing for a "black box" warning, these people say. The new label is still being discussed with the company and its final form isn't yet clear. In high-profile safety matters, the agency tends to have strong leverage.

The new warning would be a blow to GlaxoSmithKline, which had said there isn't clear evidence Avandia is more dangerous than competitors. Avandia already carries a black-box warning about a different side effect -- heart failure -- but a heart-attack warning would be more serious. Avandia's main rival drug, Takeda Pharmaceutical Co.'s Actos, carries a heart-failure caution, but doesn't have one for heart-attack risk.

BGS

Resolving the Class Action Crisis: Mass Tort Litigation as Network

I finally got around to creating an ssrn author page, and have posted my article, Resolving the Class Action Crisis: Mass Tort Litigation as Network, 2005 Utah L. Rev. 863 (2005).  Here's the abstract:

In the last few decades, mass tort litigation has wrestled with widespread, multijurisdictional problems that have greatly stressed the caseloads of courts. Certifying for trial multiple-incident, product-liability class actions for personal injuries has promised the resolution of expansive problems. But as appellate courts have increasingly held, these actions are not appropriate for class treatment because they involve numerous individualized issues that require unmanageable individualized adjudication. Without a perceived workable alternative, many trial courts have continued to try radical class action trial plans that violate state substantive law and federal constitutional law, but which bring tremendous pressure to settle upon defendants who fear they may not be able to obtain appellate review. Attempting to defuse this crisis, Congress recently passed the Class Action Fairness Act of 2005, greatly expanding federal jurisdiction for class actions. Once class actions are removed to federal court, however, the Act still provides no alternative for federal courts to the Hobson's choice framed by plaintiffs' counsel: certify a class, or be inundated with thousands of unmanageable, wasteful, and repetitive individual cases.

But that is a false dichotomy. This article argues that the alternative to mass tort class actions is not such isolated repetitive litigation, but instead an expansive set of litigation networks of counsel, judges, and clients, using recent advances in information technology, that provide much of the efficiency promised by class actions without violating state substantive or federal constitutional law. As an example, the article discusses the functioning of litigation networks in the ongoing litigation concerning phenylpropanolamine (PPA), an ingredient in cough and cold remedies and appetite suppressants that has been alleged to cause stroke. By sharing information, pooling resources, developing specialized expertise, and coordinating strategy, these networks not only reduce the costs and improve the representation of individual litigation, but also develop accurate claim values for settlement of numerous cases and allow for improved case management over time through pragmatic experimentation. The article concludes that mass tort litigation networks provide a fruitful alternative to impermissible product-liability class actions for personal injuries, and that judges should deny requests to certify such class actions and instead encourage and assist in the creation and functioning of litigation networks.

BGS

FDA Panel Recommends Against Cough and Cold Medicines for Children 6 and Under

Article on cnn.com -- FDA panel: No cold medicines to children under 6.  Here's an excerpt:

Over-the-counter cold and cough medicines don't work for children under age 6 and giving the common medicine to young children cannot be recommended, a Food and Drug Administration advisory committee said Friday.

The panel of health experts looking at how safe and effective antihistamines, decongestants, antitussins and expectorants are in children said it is not appropriate to take data from adults and apply it to children under 12.

After a two-day hearing on the safety of the medicine, the panel called for more studies about how these drugs affect children.

Although the panel's recommendation is nonbinding, it could lead to changes in how cough and cold medicine is used.

The article also notes that since 1969, there have been 54 reported deaths in children from decongestants and 69 deaths in children from antihistamines.  Will the recent publicity and FDA Advisory Panel recommendation result in many lawsuits being filed for child deaths putatively from cough and cold medications?  The Consumer Healthcare Products Association argues that consumer misuse of the cough-and-cold medications may be the cause of deaths, which suggests that any cases filed will turn heavily on individual product use, as well as other individual issues of medical causation.

BGS

Blog Roundup

Drug and Device Law Blog has posts on Tort Reform Works in Texas; Notes from the Scientific Underground; Preemption Scorecards; The Vanishing Trial; and Riegel Survives.

Food Law Prof Blog has posts on Cargill meat recall based on e.coli; Bush signs FDA Amendments Act of 2007; More on the Recall Process; CRS Report on Recall Authority; Roberts on Role of Regulation in Minimizing; Thinking About Recalls; and  Yet another meat recall -- this one enough for one picnic.

Point of Law has posts on Refik Kozic v. Merck; Absurd RI lead abatement plan developed; 
"Defendants See a Case of Diagnosing for Dollars"; and Zyprexa protective order enforcement VI: Egilman settlement.

Torts Prof Blog has posts on Topps Meat Recall: Let the Filing Begin; 9/11 Opt-Outers Settle; Lead Everywhere; Stent Safety and Patents;  USSC Denies Cert In Engle (Tobacco) Case; FDA Warns Against Use of Cold Meds by Toddlers; and Sebok's Part II on NJ Supreme Court's Vioxx Ruling.

BGS

FDA Letter to Eli Lilly to Stop Misleading Cymbalta Promotion

Article on cnnmoney.com -- FDA tells Lilly to halt Cymbalta campaign.  Here's an excerpt:

Eli Lilly has been asked to stop a Cymbalta promotion that makes misleading claims and understates risk, according to a letter sent to the drug maker by the U.S. Food and Drug Administration.

The letter said a mailer for the fast-selling drug overstates effectiveness and "omits some of the most serious and important risk information associated with its use." The letter was posted on the federal regulator's Web site.

It asked Lilly (Charts, Fortune 500) to "immediately cease" disseminating the material.

BGS