Bisphosphonates include drugs such as Actonel, Boniva, Fosamax, Reclast, and Zometa. These are among the most commonly prescribed to patients who have been diagnosed with the bone-thinning condition osteoporosis or its precursor, osteopenia.

They work by slowing cells responsible for the natural cycle of bone breakdown called resorption. As a result however, a patient may be left with old bone that would normally breakdown then be reformed as part of the normal lifetime cycle of bone. Messing with the natural cycles through the long-term use of bisphosphonates may actually leave bones weaker causing atypical femur fractures, osteonecrosis or a weakening of the jaw, and esophageal cancer. These are rare but serious adverse events.

The FDA review, “Bisphosphonates for Osteoporosis – Where Do We Go from Here?” published in the New England Journal of Medicine found that Fosamax offered little if any benefits after long-term use of three to five years. And the downside may not be worth the risk. Researchers estimated that up to 70 percent of users could come off the drugs after three to five years, particularly those women who have been diagnosed with the less serious osteopenia.

Watch this video on YouTube.

The American Society for Bone and Mineral Research (ASBMR) is on record saying the benefits of this class of drugs still outweigh the risks, but it adds that each individual patient should be evaluated on a case-by-case basis.  Stopping the drug might not be the best option either, the group concludes, and more research is critically needed to guide doctors and their patients about what to expect when someone discontinues the long-term treatment.

According to a May article in the Journal of Bone and Mineral Research, when bisphosphonate use is discontinued there is a gradual reduction in bone turnover markers and a slow return to pretreatment levels within three to 60 months.

As it’s been two years since the FDA notified the public about atypical femur fractures associated with this class of drugs, 400 lawsuits have been filed in federal court in New Jersey and about 2,000 individual cases have been filed.

With more than 150 million prescriptions dispensed to treat osteoporosis between 2005 and 2009, one in two women and one in four men over the age of 50 need answers now whether the treatment is worse than the disease.  The answers are long overdue for the 10 million Americans with osteoporosis and another 34 million at risk for it.

A British Medical Journal (BMJ) researcher, Deborah Cohen, who in February published a history of metal-on-metal (MoM) hip implants and what’s gone wrong, has raised the ire of J&J, the parent company of the DePuy MoM hip.

J&J sent a letter to the BMJ this week accusing the researcher of factual errors in reporting on the safety of MoM hip implants. We have expected those arguments would become part of the defense groundwork as DePuy is facing thousands of complaints that its metal hip implants caused devastating injuries from metal particles getting into the bloodstream.

With a high failure rate, it’s estimated about one in eight patients with an ASR (Articular Surface Replacement) will have to have corrective surgery within five years after the initial implant. Because of those unusually high odds, about 93,000 DePuy ASR hips were recalled in August 2010.

Interestingly, that fact doesn’t stop J & J from calling the BMJ report ‘unnecessarily alarmist.’

In the February BMJ study, Cohen reports hundreds of thousands of patients around the world have been implanted with the defective hips made by DePuy, Smith & Nephew, and Zimmer and therefore have been exposed to toxic metal substances, all due to poor development, evaluation and regulation.

Cohen asks in the BMJ letter why no clinical studies were carried out before the Pinnacle MoM hip system was put on the market?

DePuy’s response is that all hips wear and that subsequent reviews showed the MoM hips were successful long term. The question, of course, for unfortunate MoM patients is, what exactly is “long term”?

After being called ‘unnecessarily alarmist,’ Cohen shot back, “We do think it is necessarily alarming rather than ‘unnecessarily alarmist’ that design changes to implants that were already known to release potentially toxic metal ions passed through the regulators without any need for clinical studies.”

J & J is facing class action defective product lawsuits as well as multidistrict litigation which should begin to be heard in the beginning of next year in what’s known as bellwether trials. Searcy Denney has taken on three new ASR implant cases just this week to be added to MDL No. 2197 which were transferred to U.S. District Court in the Northern District of Ohio which currently has consolidated 3,600 lawsuits with more expected to join.

In December, 2012 in Las Vegas, Nevada some individual cases, which are not part of the MDL, should begin to be heard and in January 2013, three more cases should be heard in Maryland.

Meanwhile the DePuy Pinnacle, a predecessor to the ASR, is facing a MDL consolidating more than 1,100 lawsuits in the U.S. District Court for the Northern District of Texas.

In all, J & J has phased out 11 dangerous drugs and medical devices in the past few years because of the harm to patients.

Where is the needed FDA regulation of these devices and what has happened to manufacturers’ responsibility for consumer safety?

On Tuesday, May 8, a House subcommittee unanimously voted to approve its version of the Medical Device User Fee Act (MDUFA) which funds the U.S. Food and Drug Administration’s oversight of medical devices for the next five years.

The device makers actually fund about 20 to 30 percent of the FDA’s budget to hire the scientific researchers who review medical devices for safety before they are approved.

Industry has been pressuring Congress to get MDUFA reauthorized as soon as possible.

Even though the budget is about $595 million in medical device user fees, almost doubling the budget from the last five years, industry wants something in return. The medical device makers, through their lobbying organizations, will require the FDA to adhere to tighter approval times and less stringent rules for approval. The money sounds good until you consider that industry wants to increase the actual number of medical devices that make it to the market, so tripling the work of the FDA is not compensated by a doubling of its budget.

Seeing the writing on the wall, Rep. Edward Markey (D-MA) introduced the Sound Devices Act. H.R. 3847, proposed to close a major loophole in the device approval by giving the FDA the authority to stop the approval of a medical device that names as its “substantial equivalent,” an earlier devices that’s been found defective or has been recalled.

Watch this video on YouTube.

Naming a substantial equivalent is the way thousands of medical devices make it to U.S. consumers every year. No science required, just a predicate device selected and named.

Would the auto industry have used the Ford Pinto as a model car upon which to design a generation of cars to follow?  Of course not, but that is exactly what happened with synthetic surgical mesh. The ProteGen mesh made by Boston Scientific was recalled in 1999 after it was found to be defective. Regardless, because a generation of meshes used in women to treat pelvic organ prolapse and incontinence named as a predicate the ProteGen mesh.

And the FDA has no authority to stop it.

Rep. Markey expressed his disappointment when the Sound Devices Act was rejected by his fellow lawmakers in their markup of MDUFA. Without giving the FDA the ability to reject devices that are modeled after defective devices, the safety of untested devices will continue to be a question that is only answered by the ultimate clinical trial – using U.S. consumers as the guinea pig.

Patients have suffered irreparable and avoidable harm from metal-on-metal hips (approved based on a predicate), as well as synthetic surgical mesh, and defective defibrillator leads among the 3,000 medical devices fast-tracked onto the marketplace with no assurances required of the manufacturers for patient safety.

It was a safety loophole that Rep. Markey tried to close.

Instead, the MDUFA contains no mention of patient safety but plenty about the growth of jobs in the industry and bringing medical devices to the marketplace quicker. That does not square with what the American people say they want.

Consumers Union found in its recent poll that 82 percent of respondents believe preventing harm to consumers is a more important role for the FDA than encouraging innovation by limiting safety testing on devices.

Unfortunately, now the FDA is legally obligated to clear a new medical device if it’s similar to an earlier model, even if that model was recalled for serious safety problems. The industry exerts its control and the FDA limps ahead with its hands tied.

The MDUFA and PDUFA (prescription drug funding) approvals are part of the Food and Drug Administration Reform Act H.R. 5651 which now moves onto the full House and Senate for approval and on to the president for his signature likely to happen before the summer recess.

• December 15, 2009 – Original New Drug Application (NDA) filed by Boehringer Ingelheim with the FDA seeking approval of Pradaxa (dabigatran exteliate), a direct thrombin inhibitor, for the prevention of strokes in patients with atrial fibrillation not caused by valvular heart disease.
•  February 12, 2010 – FDA issues a Refusal to File Letter due to data integrity issues in the RE-LY trial, the primary data utilized by Boehringer Ingelheim to substantiate its claims of Pradaxa’s superiority over Coumadin (also known as warfarin) for the prevention of strokes in patients with atrial fibrillation.
•  April 19, 2010 – Boehringer Ingelheim resubmitted its New Drug Application for Pradaxa along with a Medication Guide which is supposed to provide important drug-related safety information directly to patients.
•  August 24, 2010 – The New Drug Application for Pradaxa was amended to include a REMS strategy.  The FDA Amendments Act of 2007 gave the Agency the authority to require a Risk Evaluation and Mitigation Strategy (REMS) in hopes of improving drug safety, the adequacy of warnings given to patients, and ensuring that the claimed benefits for risky medications are well substantiated.   A REMS program can include production of a medication guide, a communications plan, or other safeguards intended to protect patients.  The FDA ruled, inexplicably, that a communications plan was not required in connection with the approval of Pradaxa.
•  September 20, 2010 – The Cardiovascular and Renal Drugs Advisory Committee to the Food & Drug Administration conducted a hearing regarding approval of Pradaxa for sale in the United States.  The panel voted unanimously in support of approval of the drug for use in stroke prevention in patients with atrial fibrillation.
•  October 19, 2010 – Pradaxa was approved for sale and marketing in the United States by the FDA after only six months of review by the Agency.

The FDA has several timetables that it follows for approval of New Drug Applications (which has cut the average time period for drug approvals from 27.2 months to 13.8 between 1993 and 2003):

• Fast Track  – 60-day review process for drugs that treat serious disease and fill an unmet medical need or show some advantage over other available treatments (such as greater efficacy, fewer side effects, or improve the ability to diagnose a disease);
•  Accelerated Approval  - permits the Agency to approve drugs based upon surrogate endpoints (essentially looking only for signs that a drug may cure a disease) rather than clinical outcomes (actually proof that it does cure the disease); and
•  Priority Review – allows drug manufacturers to be placed ahead of other pending applicants if their new drug would provide a major advance in treatment for a particular condition or a completely new treatment option.

The emerging litigation over Pradaxa will be focusing closely on this approval process and whether short-cuts were taken as well as whether the FDA was provided accurate and complete information about the special risks that patients taking Pradaxa are facing and whether those risks are truly outweighed by the claimed benefits of the drug. Discovery in these individual lawsuits brought on behalf of patients who have suffered catastrophic or fatal bleeding episodes as a result of their use of Pradaxa will seek to answer a number of fundamental questions:

• Did Boehringer Ingelheim deserve an expedited approval of Pradaxa?
• Was approval of the drug even appropriate in light of other pending drug applications for medications that have the same benefits as Pradaxa but also have an available reversal agent or antidote, one of the critical defects in Pradaxa?
• What factors led to the unanimous decision by the Advisory Committee? Were those committee members biased? Did they have financial ties to Boehringer Ingelheim?
• Does Pradaxa meet an unfilled need in the medical community?
• Does Pradaxa provide a greater benefit over warfarin, a drug whose safety profile has been documented and understood for more than 50 years?

It will likely be several years before the litigation process answers these questions, and far too late to make a difference for the thousands of patients who have already suffered harm.

Bard is a unit of New Brunswick, New Jersey-based Johnson & Johnson. Hundreds of cases are still being filed in state courts around the country. In Atlantic City, New Jersey, Superior Court Judge Carol Higbee has set a November 5 trial date for the first bellwether litigation to be heard against Ethicon, a unit of Johnson & Johnson, over its Gynecare Prolift vaginal mesh.

The women claim injuries such as mesh erosion and shrinkage, pelvic and nerve pain, organ perforation, and infection, among other complications, and that Bard sold a defective and dangerous medical device and has been doing so since 2005.

Watch this video on YouTube.

The outcomes of these early cases, which represent similar complaints by other plaintiffs, will indicate how future cases will be tried and may serve as the basis for a settlement.

There are three other mesh manufacturers named in the multidistrict litigation or MDL consolidated before Judge Goodwin – American Medical Systems, Boston Scientific Corp. and Ethicon Inc. Bard has been in the same court since 2010.

An early version of synthetic mesh, used in women to treat prolapse and incontinence, was the ProteGen mesh by Boston Scientific; however that was recalled from the market for being defective.  That did not stop most of today’s transvaginal mesh manufacturers to name it as a ‘predicate device’ to serve as the model for the others to follow that are on the market today. Rep. Edward Markey has legislation pending that devices cannot name a recalled predicate medical device as a basis for approval.

Synthetic vaginal mesh remains on the market even though an expert panel recommended it be reclassified as Class III or high-risk last fall because of the number of adverse reports coming forward to the agency. Just short of a recall, in January the FDA ordered mesh manufacturers to begin studying the rate of complications after implant surgery. The surveys must continue for three years. Unfortunately, the evaluations are being done after surgery and not before.

What’s wrong with this picture?

Judge Katz’s court is located in Toledo, Ohio, but he also holds hearings in West Palm Beach, Florida during the winter months.  At a hearing last week in Florida, Judge Katz indicated that he would soon be selecting the first cases to be scheduled for trials in the MDL as a part of the bellwether process.  These first trials may involve either plaintiffs from Ohio or perhaps even litigants from Florida.  Judge Katz is expected to announce the individual cases selected for the first bellwether trials as well as the trial plan and schedule at the next MDL status conference, which will be held on June 5^th in Philadelphia. At that time, Judge Katz will be speaking on a panel at a Mass Tort Litigation Conference.  We anticipate that the first DePuy ASR trials should be conducted in the first half of 2013.

The recall of the DePuy ASR hip implants in August of 2010 came as a shock to surgeons and patients who were unaware of the significantly elevated failure rate associated with the defective design of these implants.  Data from patient registries in Australia and New Zealand led, in part, to the recall and will be an important piece of the liability evidence presented at trial.  These cases are also significant in that each patient was required to undergo painful revision surgeries and protracted physical therapy and rehabilitation only a few years after the initial surgery due to the development of metallosis. Metallosis is a breakdown of the metal surfaces of the implant which leads to an inflammatory response, fluid around the implant, pseudotumor formation, and dangerously elevated serum levels of cobalt and chromium.

These latest filings by the Searcy Denney law firm involve plaintiffs from North Port, Florida; Avon Park, Florida; and Lexington, South Carolina.  Each of these patients was implanted with a DePuy ASR metal-on-metal hip implant, which was represented as being a superior product to other implants on the market, especially implants with ceramic or plastic/polyethylene liners.

The New Jersey coordinated bisphosphonate proceedings before Judge Higbee now include approximately 2,000 individual lawsuits. The state court cases before Judge Higbee all involve some use of the brand name version of Fosamax.

The MDL, also pending in New Jersey, has grown from less than 100 cases a few months ago to nearly 400 pending lawsuits.  A recent order from the MDL judge expanded the scope of this federal court coordination to include cases involving Boniva and Reclast.  It is anticipated that the MDL might be expanded further to include use of other bisphosphonate drugs, such as:

• Alendronate
• Zometa
• Aredia, Didronel
• Skelid
• Aredia
• Aclasta
• Bondronat
• Fosavance
• Atelvia

The expansion of the MDL has given plaintiffs yet another option for pursuing atypical femur fracture cases, and it is anticipated that the number of cases pending in the MDL could increase significantly.  There are also cases pending in state court in California, which utilizes a mass tort coordination process much like that used in New Jersey and in the MDL.

Judge Higbee has selected 9 cases involving local plaintiffs for trial preparation. The first trial is tentatively scheduled to begin in September of 2012, which means that there is a lot of work that needs to be completed in the coming months with regard to the development of case-specific and generic liability, scientific, and causation evidence.  Six cases involving New Jersey plaintiffs have also been selected in the MDL proceedings for case-specific discovery and trial preparation.  The first MDL trial is expected to occur in New Jersey in April of 2013.

The scheduling of these trial dates is an important step forward in the national litigation efforts. The general liability and causation evidence that is developed with these first trial cases will be available to all of the plaintiffs in the coordinated state and federal litigation and will streamline the prosecution of their individual lawsuits.

At this time, it is too soon to know whether settlement negotiations are likely, although Judge Higbee is well known for being a resolution-oriented judge and will certainly encourage conclusions in the best interests of all concerned. Merck has been successful in obtaining defense verdicts in several recent trials involving Fosamax-induced jaw osteonecrosis, so we anticipate that Merck will be resistant to global settlement talks. Judge Higbee, however, was one of the judges instrumental in orchestrating Merck’s landmark $5 billion Vioxx settlement program, which resolved nearly 50,000 pending state and federal court lawsuits several years ago.

In order to better inform patients and the doctors who treat them, the FDA then needs to create a publicly available document so the public can understand what risks they are really taking when prescribed a drug, without which you cannot have a true informed consent. That analysis of the drug should continue over its lifetime, says the IOM study.

As it stands now, the public marketing of a drug is really the final clinical trial. Almost all drugs have some sort of side effect and in a diverse and large population these complications begin to show up. However, if you are not looking for them, many people will be injured before something is done.

That’s what happened to Merck’s painkiller Vioxx, which remained on the market while about 27,000 patients suffered heart attacks or strokes. It took five years to track the problem enough to pull Vioxx from the market. This was as totally preventable pharmaceutical injury if only someone was watching.

The Institute of Medicine provides scientific expertise when called upon to produce a report. The FDA does not have to follow the recommendations and Reuters reports they are not binding.  A spokeswoman for the FDA said the agency supports “the general concept of enabling the public to be able to clearly monitor relevant safety issues for all drugs.”

Without additional funding, the agency which is already way over its head in terms of the monitoring of our food, drugs and medical devices, will never be able to implement this recommendation.

The current regulation is for the FDA to check on a drug’s safety after it’s been on the market for 18 months or 10,000 patients have taken the drug, whichever comes later.  And how does the FDA ever know about ‘adverse events’? That is up to the doctors, patients or drugmaker to submit any reports it gets of complications to the agency. Imagine the incentive a drugmaker has to report on itself?

Until 2007 there was nothing the FDA could do to force compliance of reporting regulations. But that year a law was passed to give the FDA some muscle to compel manufacturers to conduct post-approval safety trials or to change a label when safety concerns arise.

Reuters reports on a FDA report issued last month that said the agency now spends as much money tracking a drug after it is on the market as during the pre-approval process.

To make the point, the FDA says it ordered 385 post-market studies over the last four years and to force a label change 65 times.

Remember- reports coming into the FDA represent just a fraction of what is occurring in the real world.

An online report from Adverse Events Inc., an independent company that analyzes the FDA’s database of Adverse Event Reporting System (AERS), has just issued its Top Ten list of Dangerous Drugs for the second quarter Q2 of 2011.

Compared to the first quarter of 2011 (Q1), the second quarter saw an increase in the number of adverse events or complications attributed to drugs – 161,784 compared to 152,871 for Q1 of 2011. Looking back even further, Q1 in 2010 saw 120,517 complications reported.

Adverse event reports appear to be steadily trending upward as the reporting goes back to Q1 in 2008 where there were about 90,000 reports.

Among the Top Ten drugs reported for Q2 2011 there were 21,355 deaths, 7,778 reports of disability, and 51,309 cases of hospitalization.

So which drugs made the Top Ten?

1. Tysabri, a treatment for multiple sclerosis and Crohn’s disease had more than 6,000 reports with the Top Adverse Event – Fatigue. A relapse of MS and headache were reported, as well as 174 deaths.
2. Nexium, a treatment for gastroesophageal reflux disease, difficulty digesting and peptic ulcers, had 4,833 reports, the Top Adverse Event being drug dose omission and ineffective drug, and 61 deaths.
3. Reglan treats vomiting, nausea and there were 4,316 reports with the Top Adverse Event – Tardive dyskinesia, as well as 217 deaths.
4. Clozaril reduces symptoms of schizophrenia. The drug had 3,240 reports with Top Adverse Event – 1,395 Deaths
5. Pradaxa used to treat atrial fibrillation by thinning the blood had 3,071 reports with the Top Adverse Event- Dyspepsia, dizziness and gastrointestinal hemorrhage, as well as 201 deaths.
6. Yaz, a contraceptive, had 3,058 reports with the Top Adverse Event – Pain, there were also 58 deaths reported.
7. Remicade, a treatment for Crohn’s disease saw 2,192 reports with the Top Adverse Event – Infusion related reaction, dyspnea and pyrexia, and 174 deaths.
8. Chantix, a smoking cessation drug, had 2,003 reports with the Top Adverse Event reported – Depression and 103 deaths.
9. Avandia, a treatment for type 2 diabetes, which the FDA announced would be pulled from the market beginning in November 2011, saw 1,507 reports with the Top Adverse Event – Myocardial infarction and 839 deaths.
10. Yasmin, an oral contraceptive had 1,345 reports with the Top Adverse Event – Pain and 25 deaths.

It is widely believed that the FDA’s database for reporting is woefully inadequate with about 10 percent of actual real-life complications ever making their way to be officially reported.

Recently, some forward-thinking members of the Senate and House of Representatives introduced a bill to address the problems created by the United States Supreme Court in the Pliva v. Mensing decision last year. This controversial decision granted virtual immunity to the manufacturers of generic drugs for the safety of their products.  This decision should be troubling to consumers and taxpayers, as they will be the ones who ultimately bear the costs of injuries and harm caused by these manufacturers and their defective products.

The injured plaintiffs in the Mensing case developed tardive dyskinesia after taking the popular drug Reglan (also known as metoclopramide) for a prolonged period of time.  The antiquated labeling did not provide sufficient information about the likelihood of serious safety issues when metoclopramide was used for more than a few months.  Despite knowing that the drug was likely to cause tardive dyskinesia when used long-term, it was aggressively marketed by generic drug companies for use in the treatment of chronic conditions such as gastroesophageal reflux (GERD).

The companies that originally developed Reglan and published the first warning labels for the drug had essentially stopped marketing the medication by the 1970s as generic formulations became available.  The warning labels for the generic versions that were heavily marketed since the 1970s, however, did not reflect the current state of scientific knowledge over serious safety issues associated with the drug, especially when used long-term by patients.  Over the years, scientific studies have shown that as many as 29% of patients taking Reglan or metoclopramide develop tardive dyskinesia, a severe and debilitating neurological disorder that involves facial tics, involuntary limb movement, impaired ability to walk, and other serious physical limitations.   Sadly, this information did not reach most patients until 2009 when the FDA (rather than the drug companies) published a safety alert for prescribing physicians and patients to discourage continued long-term use of Reglan and metoclopramide.

While the history is quite complex, the issue behind the Mensing decision by the Supreme Court relates to the differing federal requirements for labeling of brand name versus generic prescription drugs.  Brand name manufacturers are required to update the warning label as new information emerges, while generic companies are supposed to copy the brand name label.  When the brand name drug is no longer marketed, however, federal drug labeling law fails to adequately protect consumers.   Obviously, generic drug companies could have asked the FDA for permission to update their labels or made certain that everyone knew of the latest safety issues, but that did not happen with Reglan (or other generic drugs being ingested by millions of consumers with inadequate safety warnings).  The Supreme Court’s decision did nothing to fill these holes, nor perhaps could they, but instead granted immunity to Pliva and other generic drug manufacturers. Mensing has also created serious safety issues for patients at a time when patients are being forced to take generic drugs by governmental and private health insurers.

The bill introduced in the Senate earlier this month  entitled “Patient Safety and Generic Labeling Improvement Act” (S. 2295) would restore sanity and require generic drug manufacturers to live up to the same standards as those required of brand name manufacturers, a simple concept that has vexed our legal system and federal government for years.  This legislative tweak would permit generic drug companies to update their own warning labels for their generic formulations of brand name drugs.  The Senate bill was introduced by Senator Patrick Leahy (D-VT) and is co-sponsored by Senator Al Franken (D-MN), Jeff Bingman (D-NM), Sheldon Whitehouse (D-RI), Sherrod Brown (D-OH), Christopher Coons (D-DE), and Richard Blumenthal (D-CT).

Representative Bruce Braley

A companion bill (H.R. 4384) was introduced in the House of Representatives by Rep. Bruce Braley (D-IA), who has long been a champion of patients’ rights, and Chris Van Hollen (D-MD).  Hopefully, we can count on other members of Congress who are strong advocates for patient safety and corporate responsibility to sign on as additional co-sponsors of these bills. Patients everywhere need to contact their members of Congress and request their support, as it is important that we hold generic drug makers responsible for the harm that they cause rather than shifting their burdens to taxpayers.

Public Citizen has also filed a petition with the FDA encouraging changes in the Agency’s guidelines as a solution to a problem that has been permitted to exist for too long at the expense of patients.  The FDA, as it is so prone to do, has promised to study the issue further.  Hopefully, they don’t want too long before doing the right thing.   The American Association for Justice has been strongly supportive of the efforts of both Congress as well as Public Citizen to level the playing field between generic and brand name drug manufacturers and to ensure that patients and taxpayers no longer suffer as a result of this drug regulatory blunder.