Drug Injury Watch

FDA's 2007 Report On Outstanding Post-approval Studies: No Progress Made By Big Pharma

After Their Medications Get Approved By FDA, Many Drug Companies Have Not Yet Started The Studies Which They Promised To Do

(Posted by Tom Lamb at DrugInjuryWatch.com)

Each year the FDA issues what could be called a "report card" on how the pharmaceutical companies are doing as regards post-approval studies for their products that have been approved for sale in the U.S.  As was the case the year before, in 2007 these companies are doing poorly in getting done what they said they would do.

In an April 23, 2008 Bloomberg article, "Drugmakers Didn't Begin 1,044 Promised U.S. Studies", reporter Justin Blum presents the facts and gets some relevant reactions.

Let's start with the continuing dismal performance by Big Pharma:

The Food and Drug Administration determined that 1,044, or 62 percent, of incomplete studies for conventional drugs and biotechnology medications had yet to be started as of Sept. 30. At the same time in 2006, 1,026, or 63 percent, of the unfinished studies hadn't begun, according to the FDA.

As background, the drug companies often agree to perform additional clinical trials evaluating the efficacy and safety of their medications in order to get the FDA's approval  -- but, seemingly, their agreement is more of a promise than it is an actual commitment.

This apparent failure to get these studies done in a timely manner can be viewed in various ways, according to who you talk to about this situation.  Quoting from the April 23 Bloomberg article, we consider these three "perspectives":

• Peter Lurie, deputy director of the Health Research Group at Washington-based Public Citizen, an advocacy organization: "'Drugs often come on the market with an expectation that studies will be conducted.  In fact, many of these studies begin late or do not begin at all.'"
• Alan Goldhammer, deputy vice president for regulatory affairs at the Pharmaceutical Research and Manufacturers of America, an industry group:  "Studies can take a long time to begin because of discussions with the FDA over how they should be conducted and difficulties enrolling patients."
• Susan Cruzan, a spokesperson for the FDA: "The FDA is considering how to 'integrate' its new power to require studies with commitments that have been made by drugmakers.  The FDA will work to ensure that studies previously promised 'are completed in a timely manner.'"

Unfortunately, like earlier versions, this 2007 FDA report does not specify the number of drugs covered by the various outstanding studies -- Mr. Blum points out in his article that "[d]rugmakers sometimes agree to complete multiple studies for a single product" -- nor does the annual report identify the specific companies involved with the many outstanding post-approval studies.

Maybe next year we will be able to tell you that the "class" has done better on this report card about their post-approval studies.

Ortho Evra, Preemption, And The New York Times: Another Drug Company Response Letter

And, We Learn About More Of Merck's Vioxx Shenanigans -- Another Benefit Of Pharmaceutical Product Liability Litigation

(Posted by Tom Lamb at DrugInjuryWatch.com)

For the second time in as many weeks, it was the Johnson & Johnson (J&J) company blog that tipped us off that Ortho-McNeil is responding to an item from The New York Times by posting a letter on the Ortho Evra web site.

To start, on April 14, 2008 the Times ran an editorial, "The Dangers in Pre-emption", which begins:

The pharmaceutical industry and its good friends in the Bush administration are working hard to prevent consumers from filing damage suits for injuries caused by federally approved drug products. They may soon get a helping hand from the Supreme Court, which has already barred many suits over faulty medical devices....

Next, here's the same-day post on the J&J blog, titled "ORTHO EVRA and Preemption — Revisited":

Today, The New York Times editorial page commented on the concept of preemption, basing much of their position on an April 6 New York Times article on the same subject and once again featuring ORTHO EVRA®, the birth control patch marketed in the U.S. by our Ortho-McNeil unit. Today, Ortho-McNeil published a letter from David Norton, the Company Group Chairman, Worldwide Commercial and Operations, who is responsible for the Ortho-McNeil business that provides more context from our perspective for those who are interested.

If you prefer, go directly to this "April 13, 2008 Employee Follow-up Communication", written by Ortho-McNeil's David Y. Norton.

Meanwhile, in a convenient coincidence, in the past couple of days there has been a tremendous amount of media coverage given to the discovery that Merck used "ghostwriters" for Vioxx articles and failed to disclose to the FDA an internal analysis which found Alzheimer's patients who were taking Vioxx in a clinical study sponsored by Merck had a three times greater risk of death than patients taking a placebo.

As summarized by Peggy Peck for MedPage Today in an April 15, 2008 online article, "Rofecoxib (Vioxx) Studies on Mortality Were Controlled by Drug Company":

Ongoing litigation about rofecoxib (Vioxx) has provided confirmation that Merck employees or hired ghostwriters were the true authors of manuscripts about the drug published as the work of academic researchers.

That finding was published in the April 16 issue of the Journal of the American Medical Association along with a second study -- also mined from a paper flood uncovered by lawyers -- that suggests Merck manipulated data to hide an increased mortality risk with rofecoxib.

Bruce M. Psaty, M.D., Ph.D., and Richard A. Kronmal, Ph.D., of the University of Washington in Seattle, said Merck told the FDA that an intention-to-treat analysis of data from three trials designed to assess the effects of rofecoxib on the occurrence or progression of Alzheimer's disease revealed an increased mortality risk with the drug....

The underlying study is "Reporting Mortality Findings in Trials of Rofecoxib for Alzheimer Disease or Cognitive Impairment: A Case Study Based on Documents From Rofecoxib Litigation (JAMA. 2008;299(15):1813-1817).

For additional detail, we turn to "Merck May Have Misrepresented Vioxx Risks", by Anna Sophia McKenney, and posted April 16, 2008 at Medical News Today: 

The risk-benefit profile of rofecoxib (marketed under the names Vioxx, Ceoxx and Ceeoxx) may be have been misrepresented by the study sponsor, Merck, in clinical trials with patients with cognitive impairment. This was the result of a comparison of internal company documents, data submitted by the company to the Food and Drug Administration (FDA,) and published clinical trial results, according to an article in the April 16 issues of JAMA....

... These documents were made available during litigation related to rofecoxib and Merck, including internal company analyses and information provided by the sponsor to the Food and Drug Administration....

It seems to me that this conduct by Ortho-McNeil and Merck demonstrates that federal preemption is a concept which does not fit the reality of how drug companies "interact" with FDA officials as regards the safety of their products.  Likewise, what we have learned about Ortho Evra and Vioxx as the result of pharmceutical product liability litigation shows why preemption is a bad idea.

Ortho-McNeil's Response To April 2008 NYT Article About Ortho Evra And FDA / Federal Preemption

New York Times Reporters Gardiner Harris and Alex Berenson Bring Attention To How This Emerging Legal Issue Would Affect Drug Injury Cases

(Posted by Tom Lamb at DrugInjuryWatch.com)

To our pleasant surprise, we saw lots of notice and reaction being given to the April 6, 2008 New York Times (NYT) article, "Drug Makers Near Old Goal: A Legal Shield", wherein Times reporters Gardiner Harris and Alex Berenson explore the concept of "federal preemption" as regards some pending Ortho Evra lawsuits. 

The Harris - Berenson NYT "Ortho Evra" article is worth a read, especially if you have an interest in either the preemption issue or this particular drug injury litigation:

For years, Johnson & Johnson obscured evidence that its popular Ortho Evra birth control patch delivered much more estrogen than standard birth control pills, potentially increasing the risk of blood clots and strokes, according to internal company documents.

But because the Food and Drug Administration approved the patch, the company is arguing in court that it cannot be sued by women who claim that they were injured by the product — even though its old label inaccurately described the amount of estrogen it released.

This legal argument is called pre-emption. After decades of being dismissed by courts, the tactic now appears to be on the verge of success, lawyers for plaintiffs and drug companies say.

The Bush administration has argued strongly in favor of the doctrine, which holds that the F.D.A. is the only agency with enough expertise to regulate drug makers and that its decisions should not be second-guessed by courts. The Supreme Court is to rule on a case next term that could make pre-emption a legal standard for drug cases. The court already ruled in February that many suits against the makers of medical devices like pacemakers are pre-empted....

What had not gotten as much attention was Ortho-McNeil's written response to this April 6 NYT article that the drug company published on their website.  One reason for the lower profile might be that the company-statement item is a bit difficult to find: It goes by the obscure title of "April 2008 Employee Communication", and the link is found on what appears to be a new, specially created web page, i.e., it had no page title nor was it listed on the Sitemap when accessed at 4:20 p.m. on April 7, 2008.

Perhaps wanting to make sure that the word got out, however, the Ortho McNeil "retort" was the subject of an April 7 post, "The New York Times, Pre-Emption and ORTHO EVRA", found over at "About JNJ BTW" -- the in-house blog for Johnson & Johnson (Editor: Marc Monseau).

As for the text of Ortho McNeil's retort to this Ortho Evra - federal preemption story, here's the gist:

While the [April 6 NYT] article deals predominantly with the issue of pre-emption, it also questions our commitment to patient safety and scientific integrity. And in so doing, it inaccurately depicts our actions leading up to approval of the patch by the U.S. Food and Drug Administration (FDA) in 2001, and the data reporting procedures we have followed since. I want to make sure you have our point of view, in part because some of the characterizations in the article, including references to internal company documents, are taken clearly out of context.

This April 2008 NYT report demonstrates how important it is to learn more about this issue of federal preemption.  As I wrote recently on this site, in this post, "Issue: Should We Be Prohibited From Filing Product Liability Lawsuits Against Medical Device Manufacturers And Pharmaceutical Companies?":

According to some critics, the prohibition of drug injury lawsuits by operation of the federal preemption doctrine may have some merit in an ideal world where the FDA was performing its drug-safety regulatory functions at 100%.  But that has not been the situation in the past, nor is it the case today.

Our thanks to two of the leading Pharma reporters, Gardiner Harris and Alex Berenson, for shining a light on this critical legal issue of preemption in the context of drug injury claims.

March 2008: Higher Doses Of Celebrex Are Associated With Heart Attack And Stroke Risks

Lower, More Popular Dose Presumed To Be Safe, But Definitive Study Results Will Not Be Available For Few More Years

(Posted by Tom Lamb at DrugInjuryWatch.com)

On March 31, 2008, at the American College of Cardiology's annual meeting, a recent analysis of several studies involving Pfizer Inc.'s arthritis drug Celebrex was presented.  In short, it showed that only higher doses of Celebrex are associated with an increased risk of heart attacks and strokes.

That same day the medical journal Circulation published (online before print) an article by Scott D. Solomon, director of noninvasive cardiology at Brigham and Women's Hospital in Boston, and colleagues about this latest data analysis concerning the safety of Celebrex, "Cardiovascular Risk of Celecoxib in 6 Randomized Placebo-Controlled Trials. The Cross Trial Safety Analysis".

From the abstract for this medical journal article about the side effects associated with high dose Celebrex (celecoxib):

Conclusions—We observed evidence of differential cardiovascular risk as a function of celecoxib dose regimen and baseline cardiovascular risk. By further clarifying the extent of celecoxib-related cardiovascular risk, these findings may help guide treatment decisions for patients who derive clinical benefit from selective cyclooxygenase-2 inhibition.

The significance of this Circulation article as well as the American College of Cardiology (ACC) presentation in Chicago is explained by Wall Street Journal reporter Jennifer Corbett Dooren in her March 31, 2008 article, "Higher Doses of Pfizer's Celebrex Are Linked to Heart, Stroke Risks":

The analysis, supported by the National Cancer Institute, broadly shows patients receiving the highest dose of Celebrex of 400 milligrams twice daily had a nearly three times higher risk of heart attacks and strokes than patients not taking the drug. Patients taking a lower dose of Celebrex, 400 milligrams once daily, had a 10% higher risk of a cardiovascular event....

[This is] an analysis of six studies that lasted for at least three years comparing patients taking Celebrex to those taking placebo. The combined analysis involved 7,950 patients.

The analysis showed Celebrex was associated with an increased risk for a combined study endpoint of cardiovascular death, myocardial infarction (heart attack), stroke, heart failure or thromboembolic event, or events related to blood clots, compared to patients not taking the drug. The risk was not affected by aspirin use.

For some contextual information we turn to a Bloomberg article, "Pfizer's Celebrex at High Doses May Raise Heart Attack Risk", by Shannon Pettypiece:

Most arthritis patients take a total of 200 milligrams or less of Celebrex a day. The study didn't examine risk for those lower doses, Solomon said.

Celebrex belongs to a category of drugs called Cox-2 inhibitors, which includes Merck's Vioxx and Pfizer's Bextra. Merck withdrew Vioxx in September 2004 after a company-sponsored study found the rate of heart attacks and strokes among people who took Vioxx for at least 18 months was 15 per 1,000 patients, about double the rate for those given a placebo.

Pfizer later removed Bextra and said Celebrex should remain on the market because there was no data showing a risk at the most commonly prescribed doses.

The study presented today examined the highest doses. The study that supported the removal of Vioxx looked at the most commonly prescribed dose, Solomon said. There is no data available showing whether Celebrex carries a heart risk at the lower doses....

A more definitive assessment on the risks of Celebrex won't come until 2010 or 2011, when a $100 million study of 20,000 patients comparing Celebrex with the pain pills ibuprofen and naproxen is expected to be completed.

In light of what we heard reported at the March 2008 ACC meeting in Chicago about how some negative study results about Vytorin and Zetia were seemingly delayed, or withheld, by Merck and Schering-Plough, it makes me a bit uneasy that we must wait for several more years before learning whether or not the lower, more popular dose of Celebrex is safe for use.

New Article With 25 Big Pharma Facts, And Free Online Tool To Search MedWatch Report Data

A Couple Of Recent Offerings From Our Readers, For Your Consideration

(Posted by Tom Lamb at DrugInjuryWatch.com)

As you will see, we have two readers who emailed me recently to thank for today's post.

First, Sally Thompson sent an email to let me know that "25 Shocking Facts About the Pharmaceutical Industry" had been published on the Nursing Online Education Database web site.  This interesting article by Laura Milligan starts out as follows:

Researching and snagging an adequate, wallet-friendly health care plan is tough these days, despite its high-profile presence in political debates. A large part of the controversy over expensive health costs stems from criticism of high-priced medications marketed by powerful pharmaceutical companies. From Medicare fraud to CEOs worth billions of dollars, big drug companies are accused of putting profits above patients, spinning false PR campaigns and more. We've uncovered 25 of the most shocking facts about the pharmaceutical industry in this list.

The 25 facts presented are wide-ranging and even-balanced; here's the last one, for example:

Pharmaceutical Companies donated millions to Hurricane Katrina relief programs:  Americans are used to bashing pharmaceutical companies, just as they criticize health insurance companies, rising gas prices and monopolies. It may come as a shock, then, to discover the philanthropic efforts undertaken by big drug companies. Medical News Today writes that companies like Abbott, Eli Lilly, Merck, Pfizer and others have donated millions of dollars in cash and supplies to the Hurricane Katrina relief efforts.

Each of the 25 facts is linked to the source material used by the author so if you want to learn more about any of the items all you need to do is click-thru for more information.

This article by Laura Milligan on the Nursing Online Education Database site is worth a read by people interested in the doings -- good, bad, and ugly -- of Big Pharma.

Moving back in time, last week Paul N. Danese, Ph.D., the co-founder of FDAble LLC, contacted me after seeing a comment I had left on another site  regarding Consumer Union's proposal for a consumer-based adverse-events reporting system.

Dr. Danese wanted to bring to my attention his company's adverse drug events search engine at FDAble.com, which allows one to access and search the vast compilation of data which the FDA obtains from MedWatch reports that the agency receives. 

Here's how Dr. Danese described this search tool to me:

FDAble allows users to search all modern U.S. FDA-related adverse events (Q4 1997 to Q3 2007).

Users may search for adverse-events by drug name, outcome, patient age, weight and other metrics.

All searches are free.  We also offer a yearly subscription service, which allows users to generate an unlimited number of custom adverse event reports.

The FDAble.com search page interface is clean and conspicuously shows this disclaimer:

FDAble is not associated with the Food and Drug Administration.

The search results from the FDA adverse drug events database are, due to their nature, probably of more use to researchers than consumers and patients. 

What is remarkable, based on my experience doing drug injury litigation over the years, is that this information is now so readily available.  It use to be the case that one had to submit a Freedom of Information Act (FOIA) request to the FDA for this type of data -- and, believe me, that was a very, very slow process.

Anyone with a need to review the FDA's MedWatch database for reports of side effects concerning a particular prescription drug will greatly appreciate this new search tool at FDAble.com.  We thank Dr. Danese and his company for their efforts in getting this much needed service online and, moreover, letting us use it for free.

If you have any information or news relevant to the topics covered here on Drug Injury Watch, please feel free to contact me using the link in the sidebar.

Zyprexa And Diabetes: Is This A Tale Of Company Greed Coupled With FDA Failure?

Alaska v. Eli Lilly Trial: Focus Is On What Was Known About This Alleged Side Effect, And When They Knew It

(Posted by Tom Lamb at DrugInjuryWatch.com)

News reports about the case Alaska v. Eli Lilly & Co., 3AN-06-05630 CI, Alaska Superior Court (Anchorage), have been limited but interesting thus far.

The most prolific news coverage to date has come from Lisa Demer, reporting for the Anchorage Daily News.  Her March 22, 2008 article, "Defense opens in Zyprexa trial", informed us about some interesting comments made by the trial judge during a court session that involved only the lawyers for the parties -- such that jurors did not get this earful:

Without lawsuits like the one the State of Alaska brought against Lilly, claims that drugs cause health problems "might well go unaddressed," Anchorage Superior Court Judge Mark Rindner said from the bench this week....

Rindner was reacting to an assertion by Lilly lawyer George Lehner that drug regulation is a matter for the federal Food and Drug Administration, not any state. Alaska's Unfair Trade Practices and Consumer Protection Act shouldn't apply to drugs, Lehner told the judge.

Rindner disagreed. Evidence presented by the state over the past two weeks established that the FDA "isn't capable of policing this matter," he said.

As background, Zyprexa is Lilly’s top-selling prescription drug, with worldwide sales of $4.8 billion in 2007.  Zyprexa was approved in September 1996 for the treatment of schizophrenia. Starting soon thereafter, doctors began to report to the FDA and to Lilly that some patients using Zyprexa seemed to experience severe weight gain and high blood sugar which seemed to lead to diabetes in some instances.

The State of Alaska has sued Lilly to recover medical costs paid by the State when treating Medicaid patients who have developed diabetes after taking Zyprexa. The jury trial of that lawsuit, which started earlier this month, is being heard in an Alaska state court located in Anchorage.

A March 8 article, "Lilly Waited Too Long to Warn About Schizophrenia Drug, Doctor Testifies", by Alex Berenson, of The New York Times, provided this account of some early expert testimony in support the state's contention that this Lilly downplayed the serious side effect risks associated with Zyprexa in order to make more money:

Eli Lilly, the drug maker, could and should have warned physicians as early as 1998 about the link between Zyprexa, its best-selling schizophrenia medicine, and diabetes, an expert witness told jurors Friday in a lawsuit that claims that Zyprexa has caused many mentally ill people to develop diabetes.

Instead, Lilly hid Zyprexa’s risks from doctors to protect the drug’s sales, according to the witness, Dr. John Gueriguian. Lilly waited until 2007 to add strong warnings to Zyprexa’s label to reflect the drug’s tendency to cause severe weight gain and blood sugar changes.

Lilly put “profit over concern of the consumer,” Dr. Gueriguian said Friday near the end of four hours of testimony....

By the fall of 1998, the combination of adverse-event reports, clinical trial data that showed hyperglycemia and weight gain, and problems in animal studies should have been enough for Lilly to warn doctors about Zyprexa’s links to diabetes, Dr. Gueriguian said. Instead, the company did nothing.

Documents from 1999 and 2000 also showed that Lilly was accumulating evidence of Zyprexa’s risks but not sharing it with doctors, he testified.

With this and other similar testimony being heard by Judge Rindner, it is understandable why he is doubtful about the proposition that the FDA is on-the-job and, therefore, federal preemption is warranted.

In closing, if you are interested in learning more about this Alaska v. Eli Lilly trial, you need to visit the Anchorage Daily News online pages with Zyprexa articles by Lisa Demer, such as her March 14, 2008 report, "Japan made Zyprexa labels reflect risk to diabetics".  On these pages there are links to resources that will give you insight to past and present developments, both, that are significant to this ongoing Zyprexa trial in Alaska.

Issue: Should We Be Prohibited From Filing Product Liability Lawsuits Against Medical Device Manufacturers And Pharmaceutical Companies?

Opinion: Patient Lawsuits Are A Significant Incentive For These Manufacturers And Companies To Ensure That Their Products Are Safe For Use By American Patients

(Posted by Tom Lamb at DrugInjuryWatch.com)

First of all, I presume most of you believe – because as Americans we have always looked to our court system to vindicate our rights – that we are allowed to file these lawsuits today. 

With regard to most cases against medical device companies, however, as of February 2008 you are wrong; and, soon, injured patients may not be allowed to get any legal compensation from a pharmaceutical company for serious side effects caused by their prescription drug.

On February 20, in the Riegel v. Medtronic case, the U.S. Supreme Court granted legal immunity to manufacturers of medical devices which had been approved by the FDA.  This  means that in the future, for most instances, the medical device manufacturers will have no financial accountability for their mistakes if and when their products harm a patient. 

To reach this decision, the Supreme Court used the legal doctrine of  “federal preemption”.  Ironically, this doctrine comes from our Founding Fathers’ Constitution, but in recent years it has been used by the current Bush Administration to abolish a person’s right to sue when injured by a company’s product.

As a start, let us focus on the FDA-approval part of the Supreme Court’s Riegel decision. 

During this past year, the Institute of Medicine, the Government Accountability Office, and the FDA’s own science board have all issued reports that essentially reach the same conclusion: The FDA is largely incapable of protecting the public from unsafe medical devices and drugs.

Moreover, the FDA does not do its own testing; rather, the FDA is almost totally dependent on the companies that it is suppose to oversee to provide the agency with data concerning the safety and effectiveness of new prescription drugs and medical devices. 

Further, the vast majority of FDA approvals occur without there being any representation of patients’ interests; and, safety decisions after the drug or device is approved rarely include input from patient advocacy groups.

Meanwhile, the medical device manufacturers and the pharmaceutical companies clearly have an inherent conflict of interest when addressing safety issues concerning their products, which are intended to make them a profit. 

In addition, these business corporations have stronger legal obligations to their stockholders than they do to the patients who use their products.

Let’s return to the question at hand: Should patients have access to our court systems in oder to file lawsuits for injuries caused by unsafe drugs and medical devices?

In October of this year, 2008, the Supreme Court will hear oral arguments in the Wyeth v. Levine case.  The primary issue in that case is whether people who suffered a drug injury should be able to get any legal compensation from the pharmaceutical company responsible for that drug. 

You will probably be surprised to learn that, at this hearing, the drug company’s lawyers will be assisted by the Bush Administration’s Solicitor General in making their argument that an injured patient should not have any legal right to compensation.

In more detail, the drug company Wyeth and the Bush Administration will be arguing in this Levine case that the Food, Drug and Cosmetic Act of 1938 -- under which the FDA regulates prescription drugs -- has "implied preemption" due to the structure of this statute, i.e., the law's actual text does not include any preemption clause. 

The Levine case involves a Vermont woman who lost a hand and forearm to gangrene after being improperly injected with the drug Phenergan. At the trial of this lawsuit, Wyeth argued that its drug had met FDA’s federal labeling requirements and, therefore, the drug company should not have any legal liability under state law for this patient’s injury. 

The trial court judge disagreed with Wyeth on this issue, and the jury in that case went on to award $6.8 million in legal compensation to Mrs. Levine for her injury. 

The Vermont Supreme Court ultimately upheld the judge’s ruling and the jury verdict; but the U.S. Supreme Court later accepted this case for review – upon the request of the drug company and the Bush Administration.

As stated above, oral arguments regarding the federal preemption issue will be made to the nine Supreme Court Justices in the Levine case later this year, in October 2008. 

Sometime thereafter, and no later than the summer of 2009, our Supreme Court will decide whether the FDA approval of a prescription drug will serve as a prohibition against patients filing their personal injury and wrongful death lawsuits against drug companies.

According to some critics, the prohibition of drug injury lawsuits by operation of the federal preemption doctrine may have some merit in an ideal world where the FDA was performing its drug-safety regulatory functions at 100%.  But that has not been the situation in the past, nor is it the case today.

It is my opinion that the U.S. Congress should move quickly to pass legislation that would correct the Riegel decision by the Supreme Court, and serve to prevent such a ruling against patients’ rights in the Levine case.   

This legislation is needed because, in my experience, the possibility of becoming involved in product liability litigation is a significant incentive for the medical device manufactures and the pharmaceutical companies to ensure that their products are safe for use by American patients.

I would like to hear what you think about this issue as well as my opinion about use of the federal preemption doctrine in this context.  You can do so by submitting a Comment, below. 

Also, I encourage you to share this piece with others by email, bookmarking, etc.  Of course, I understand that not all people will line-up with me on this issue.  I believe, however, that all citizens will agree that this federal preemption issue is too important to remain as low-profile as it has been to this point in time.

(Thanks for reading this issue-and-opinion piece, which is a departure from the usual news and information about prescription drug side effects that is presented here at Drug Injury Watch.)

P.S.  I have posted this issue on the HeyMonkeyBrain! part of Squidoo: 

"What if you were hurt by a drug and couldn't sue?"

That page can be found here:  http://www.squidoo.com/preemption

Perhaps you can help get this debate started?

Thanks for your effort and time.  (3/20/08)

P.S.  Read an interview with Diane Levine which was done by Ed Silverman and posted on his blog, Pharmalot, earlier this year.  (3/24/08)

Tequin Revisited: Health Canada And The FDA Failed To Take Action, At Our Expense

Bristol-Myers Squibb Was Allowed To Withdraw Their Unsafe Drug For "Economic Reasons", And Only After Selling Off Its Inventory

(Posted by Tom Lamb at DrugInjuryWatch.com)

An article by Joel Lexchin, MSc MD, "Information about a discontinued drug", published in the March 11, 2008 edition of the Canadian Medical Association Journal (CMAJ), reminded me about how Health Canada and the FDA failed to order a recall of Tequin (gatifloxacin) a couple of years back.  Instead, Bristol-Myers Squibb (BMS) was allowed to do a gradual withdrawal of Tequin and, in so doing, the drug company largely succeeded in not drawing any additional attention to Tequin's safety problems.

In the spring of 2006, Bristol-Myer said that a continuing decline in Tequin sales was the reason for deciding to stop selling Tequin.  In fact, however, Tequin was an unsafe drug that had been linked to various blood-sugar disorders -- but the FDA as well as Health Canada let the drug company have it their way.

For the following review of developments and events leading up to how BMS ended its Tequin sales in the U.S. and Canada, I draw from two of my earlier reports about this dangerous antibiotic:   

• Bristol-Myers Squibb To Stop Selling Antibiotic Drug Tequin
• Antibiotic Tequin Should Be Banned By FDA, Says Public Citizen Petition

Mid-February 2006: BMS, the FDA, and Health Canada announced that the Tequin label would be changed to include stronger warnings about the threat of life-threatening events from blood-sugar changes.

March 1, 2006: The New England Journal of Medicine (NEJM) published online an early-release version of a study which found that patients using Tequin had four times the risk of hypoglycemia (low blood sugar) and an astounding 17 times the risk of hyperglycemia (high blood sugar) -- collectively referred to as dysglycemia -- when compared to other antibiotics.

April 27, 2006:  A newspaper article is the first announcement that BMS has decided to stop selling Tequin.  According to this Wall Street Journal article, however, Tequin product shipments would not end in most markets until sometime in May or June 2006.

May 1, 2006: Public Citizen asked the FDA to ban Tequin in order to immediately get this unsafe drug off pharmacy shelves in the U.S.  According to the Public Citizen petition, an analysis of adverse event reports submitted to the FDA reveals that during the period January 1, 2000 through June 30, 2005 there were 388 cases of hypoglycemia and hyperglycemia; 20 on those reports involved patient deaths.

To my knowledge, the FDA never banned Tequin in the U.S. as requested by Public Citizen.

The March 2008 CMAJ article which is mentioned at the outset of this piece confirms that Health Canada did nothing:

Health Canada issued a number of alerts about the potential for this product to interfere with glucose metabolism but never bothered to formally inform either the public or health care professionals that oral and intravenous forms of this drug were withdrawn from sale in Canada. The only place where one can find this information is by searching the discontinued products in Health Canada's Drug Product Database (http://cpe0013211b4c6d-cm0014e88ee7a4.cpe.net.cable.rogers.com/dpdonline/searchRequest.do). This failure to communicate important information about a drug raises serious concerns about Health Canada's ability to keep health care professionals and the public informed about safety issues.

I believe the same thing -- "raises serious concerns" -- can be said about how the FDA let the drug company Bristol-Myers Squibb seemingly sell-off its inventory of Tequin instead of the FDA ordering an immediate recall of Tequin. 

In the end, this history of Tequin appears to be a prime example of putting profits over public safety.

Sprint Fidelis Recall Showed That FDA's Medical Device Safety System Is Flawed

Dr. Hauser: "Just because a device is FDA-approved does not necessarily mean it is safe."

(Posted by Tom Lamb at DrugInjuryWatch.com)

In his March 5, 2008 article -- "Medical device safety in spotlight; M.D. uses Medtronic recall in critique of FDA, manufacturers" -- reporter Christopher Snowbeck explores how the Sprint Fidelis lead wire recall in October 2007 by Medtronic Inc. showed the medical device safety system as it currently operates here in the U.S. is fundamentally flawed.

For this article about the Medtronic recall last year, Mr. Snowbeck uses as his starting point a "Perspective" piece by William H. Maisel, M.D., M.P.H., which was published in the March 6, 2008 edition of The New England Journal of Medicine (NEJM), "Semper Fidelis — Consumer Protection for Patients with Implanted Medical Devices", which he describes as follows: 

Dr. William Maisel, an expert on medical device safety at Boston's Beth Israel Deaconess Medical Center, writes in today's edition of the New England Journal of Medicine that the Medtronic recall is the latest example of how manufacturers and the U.S. Food and Drug Administration have failed to provide the public with timely, critical information about device malfunctions....

Maisel said that five months before Medtronic recalled the Sprint Fidelis lead wire, the company submitted an application to the FDA to change the product's design and manufacturing.

That request was not publicized to physicians or patients, Maisel wrote, even though doctors had received letters from Medtronic in February 2007 stating that there could be a problem with the lead. He noted that after FDA approved the design changes, old versions of the Sprint Fidelis lead remained on hospital shelves for use in patients.

"Often, a flawed product continues to be marketed while the manufacturer submits a revised marketing application to the FDA and awaits approval of the amended product design and manufacturing plan," Maisel wrote. "Manufacturers have repeatedly and knowingly sold potentially defective devices without public disclosure."

Mr. Snowbeck then permits Medtronic an opportunity to respond to these contentions by Dr. Maisel:

Rob Clark, a Medtronic spokesman,... maintained Maisel's editorial omits key details in describing how the company handled the Sprint Fidelis matter.

"The narrative is incomplete and omits facts that are essential to any full accounting or analysis of the events and their ramifications," Clark said.

.. Clark said the Sprint Fidelis design change sought by the company in May had nothing to do with the problems that ultimately led to the recall. Manufacturers regularly make such design changes as they improve products, Clark said, and those changes don't indicate earlier versions are flawed.

Finally, Mr. Snowbeck goes beyond the NEJM article dispute to get the insight and opinion of a man who helped bring the Sprint Fidelis problem to light. In July 2007 Dr. Robert Hauser, of the Minneapolis Heart Institute, published a medical journal article that suggested patients with implantable defibrillators which had Sprint Fidelis lead wires were being needlessly and repeatedly shocked because those lead wires were fracturing at an unusually high rate. Here's what Dr. Hauser told Mr. Snowbeck as he prepared his March 2008 story:

"When you stand back and look at this, what's so disturbing is that physicians started implanting this lead because it was FDA-approved — they thought, 'Well, it's a nice, small lead, and it's FDA-approved so it must be OK,'" said Hauser. "Just because a device is FDA-approved does not necessarily mean it is safe."

Unfortunately for us, however, Medtronic and other makers of medical devices like implantable defibrillators are now immune from legal liability any injury or death their product might cause as long as it was FDA-approved.  This situation is the result of an opinion issued by the U.S. Supreme Court on February 20, 2008, in the case Riegel v. Medtronic Inc. (No. 06-179).

As explained by New York Times reporter in her February 21, 2008 article, "Justices Shield Medical Devices From Lawsuits":

The 8-to-1 decision [in the Riegel v. Medtronic case] was a victory for the Bush administration, which for years has sought broad authority to pre-empt tougher state regulation.

In 2004, the administration reversed longstanding federal policy and began arguing that "premarket approval" of a new medical device by the F.D.A. overrides most claims for damages under state law. Because federal law makes no provision for damage suits against device makers, injured patients have turned to state law and have won substantial awards.

The Bush administration will continue its push for pre-emption in another F.D.A. case that the court has accepted for its next term, on whether the agency’s approval of a drug, as opposed to a device, pre-empts personal injury suits. Drugs and medical devices are regulated under separate laws.

The prescription drug injury case referred to in that last paragraph is Wyeth v. Levine and in that case the Supreme Court will decide whether a patient should be able to sue a pharmaceutical company when there is a serious side effect that the company did not fully disclose, amongst other scenarios where currently the patient does have access to the court system here in the U.S.

The short of it is, as seen by this March 5 article about the defective Sprint Fidelis lead wire, just because a medical device was approved by the FDA does not mean it is a safe product.

P.S.  A well-written Opinion article from attorney Thomas R. Kline, "Immunity is a bad medicine for Americans' well-being", was published by The Philadelphia Inquirer on March 7, 2008.  It begins with this paragraph:

On Feb. 20, the U.S. Supreme Court granted legal immunity to manufacturers of medical devices that secure "pre-market approval" from the Food and Drug Administration for their products. The 8-1 decision in Riegel v. Medtronic guarantees medical-device manufacturers will have no financial accountability for their mistakes when their products are simply made according to FDA minimum specifications. Those standards are, in the words of noted Harvard pharmaco-epidemiologist Jerry Avorn, so minimal they "would be unacceptable anywhere else in research."...

Patient Lawsuits Against Pharmaceutical Companies For Drug Injuries Might Be Prohibited In U.S.

Our Tort System Provides A Needed Means Of Accountability; Law Professor: "A lot is lost without these lawsuits."

(Posted by Tom Lamb at DrugInjuryWatch.com)

On March 3, 2008 the U.S. Supreme Court issued its ruling in the Warner-Lambert v. Kent case and, in so doing, declined the invitation of pharmaceutical companies -- and the Bush administration -- to prohibit drug injury lawsuits from being filed by patients who have suffered serious side effects caused by unsafe prescription drugs.

The tie vote by which the Supreme Court arrived at its decision in Warner-Lambert v. Kent, however, means that this ruling does not set any precedent on the federal preemption issue that is the increasing focus of products liability lawsuits that involve FDA-approved prescription drugs and medical devices.   

From the March 4, 2008 article, "Court Allows Suit Against Drug Maker", by New York Times reporter Linda Greenhouse:

This case, Warner-Lambert Co. v. Kent, presented a narrow slice of the broad pre-emption issue that the court will take up in its next term. In that new case, Wyeth v. Levine, the question is whether the Food and Drug Administration’s approval of a drug’s label precludes individual damage suits based on the claim that the label failed to include sufficient information or adequate warnings.

In essence, if the answer is yes, most individual lawsuits for damages caused by approved drugs would be pre-empted. Last month, in Riegel v. Medtronic Inc., the court interpreted a federal law, the Medical Device Amendments, as barring most individual lawsuits against manufacturers of approved medical devices....

The Bush administration, which has embraced a broad theory of federal pre-emption of individual tort suits, entered the case on the manufacturer’s behalf. It argued that “permitting lay juries to second-guess” the adequacy of a drug application would interfere with the agency’s “exercise of its expert judgment.”

In more detail, the Bush administration will be arguing in Wyeth v. Levine (No. 06-1294) that the Food, Drug and Cosmetic Act of 1938 -- under which the FDA regulates prescription drugs -- has "implied preemption" due to the structure of this statute, i.e., the law's text does not include any preemption clause. 

The Levine case involves a Vermont woman who lost a hand and forearm to gangrene after being improperly injected with the drug Phenergan. At the trial of this lawsuit, Wyeth argued that its drug had met FDA labeling requirements and, accordingly, the drug company should face no liability under state law.  The trial court judge disagreed, and the jury in that case awarded $6.8 million in legal compensation to Levine for her injury.

According to some critics, federal preemption of drug injury cases may have some merit in an ideal world where the FDA was performing its drug-safety regulatory functions at 100%.  But that has not been the situation in the past, nor is it the case today.

In his March 3, 2008 article, "Patients' ability to sue at risk", Los Angeles Times reporter Daniel Costello presented these facts which tend to show why federal preemption of drug injury cases is a bad idea:

The FDA "doesn't have the ability at this time to oversee in a comprehensive fashion everything it regulates," said David A. Kessler, a former FDA chief and a professor at UC San Francisco.

A trio of recent reports, including one by the FDA's own advisory committee, has raised serious questions about the agency's recent performance.

Last fall a yearlong study by the FDA's advisory committee found "the agency is so underfunded and understaffed that it's putting U.S. consumers at risk in terms of food and drug safety."

In an unusual public departure from the view of the Bush administration, the current FDA commissioner, Andrew C. von Eschenbach, said in an interview last week that the agency needed a systemic overhaul that could take years....

Some legal experts and attorneys are concerned that without such lawsuits, regulators and the public may never hear of evidence that manufacturers knowingly marketed products they knew were unsafe.

In recent years, documents and e-mails uncovered in court cases have shown that some companies kept safety issues involving their products from the FDA.

"Without the tort system, what reasonable assurance do we have we will learn about the bad actors?" asked David Vladek [sic], a law professor at Georgetown University.

"A lot is lost without these lawsuits."

Oral arguments in the Levine case are scheduled for October 2008.  Sometime thereafter the Supreme Court will decide whether FDA approval of a prescription drug prohibits the filing of personal injury and wrongful death lawsuits against drug companies.

No doubt we will continue to hear a lot about this important policy issue in the months to come.

P.S.  Dr. David A. Kessler, Dean and Vice Chancellor for Medical Affairs at the University of California San Francisco and former FDA Commissioner, and David C. Vladeck, Professor of Law at Georgetown University Law Center, explore the legality and wisdom of this continuing effort by the FDA and the Bush administration to persuade lower courts, including the Supreme Court, to preempt most failure-to-warn claims asserted by patients against drug companies in this recent law review article:

David A. Kessler & David C. Vladeck, A Critical Examination of the FDA’s Efforts To Preempt Failure-To-Warn Claims, 96 GEO. L.J. 461 (2008).

Dean Kessler and Professor Vladeck explain how the FDA’s position, if ultimately adopted by the Supreme Court, would effectively eliminate a significant incentive for the drug company to ensure that its drug labels reflect accurate and up-to-date safety information, i.e., the possibility of failure-to-warn product liability litigation.  The authors explain, also, why the FDA’s view that the agency, alone, is capable of regulating the safety of prescription drugs in the U.S. is unrealistic. 

This 35-page scholarly article is compelling and insightful as to why federal preemption of drug injury cases is a bad idea.  (3/5/08)