More Scrutiny of Stenting for Profit Industry

Evelyn Pringle August 2007

The stenting for profit industry hit a major snag on March 1, 2007, when the US House Oversight and Government Reform Committee, ordered Johnson & Johnson and Boston Scientific to turn over documents related to their sales and marketing activities for drug-eluting stents.

Drug-eluting stents (DES) are mesh tubes used in patients with heart disease to keep arteries open after a procedures called angioplasty to remove blockage. The new drug-eluding stents were developed to address the problem of restenosis, which prevents renarrowing of the artery. The relative benefits of DES when compared to bare metal stents was supposed to be a reduction of death, heart attack and vessel revascularization.

“Since the new DES arrived on the market, stenting has evolved into a multi-billion dollar industry for the stent makers and doctors and hospitals alike. According to the May 17, 2007 Wall Street Journal, “Americans spent at least $14 billion on coronary-stent procedures last year, including surgical and hospital fees.”

Both J&J and Boston have received letters from Committee Chairman, Henry Waxman (D-CA), requesting documents to include correspondence with the FDA. The Committee also wants to know whether the companies used marketing funds to conduct clinical trials and how much researchers were paid and seeks information related to any adverse events revealed in the pre-approval clinical trials, as well as in post-approval use of the products.

In May 2007, after J&J announced that it would withdraw the Conor Medsystem’s heart stent from the Indian market after the device failed to complete clinical trials in the US, the Drug Controller General of India raided the company’s distributor’s office in New Delhi and seized all existing stock of the heart stent, India’s drug controller general M Venkateswarlu told the Economic Times on May 10, 2007.

The exact number of Conor stents currently on the market was still being assessed but the Times reports that thousands of patients in India could be at risk because an estimated 8,000 Indian patients have be implanted with the device.

Also the recent “Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE),”study published online on March 26, 2007, by the New England Journal of Medicine showed patients who received stents fared no better than patients who did not.

For the study, led by Dr William Boden of Buffalo General Hospital in New York, half of the roughly 2,300 patients underwent stenting procedures, took heart drugs, and were counseled to make lifestyle changes, such as losing weight, exercising, and giving up smoking and the other half received only lifestyle counseling and drugs to lower cholesterol, relax blood vessels, slow heart rate, and prevent blood clots. After an average of four and a half years, the study found a similar rate of death, heart attack, and stroke in both groups.

In an editorial accompanying the NEJM study, Dr Judith Hochman and Dr Gabriel Steg wrote: “The COURAGE trial should lead to changes in the treatment of patients with stable coronary artery disease, with expected substantial health care savings.”

Experts note that there are massive profits at stake. In 2006 alone, combined J&J and Boston earned $3 billion from the devices. On December 4, 2006, Bloomberg News reported that in 2005, the new stents accounted for 52% of total sales for J&J and 43% for Boston.

In July 2007, the stent makers announced their second-quarter earnings and J&J revealed that sales of the Cypher in the US have dropped 41% from this time last year, while Boston released sales figures for its Taxus showing a drop of 42%.

In December 2006, an FDA Advisory Panel determined that off-label use, or using a stent for a purpose outside the device’s approved label, is associated with an increased risk of stent thrombosis, death or heart attack compared to approved uses.

Some examples of off-label stenting include use in previously stented patients, patients with diabetes, patients who have stents placed immediately after a heart attack or patients who have stents placed in two arteries which branch off from each other.

Experts say that in the majority of cases the devices are being implanted in patients who could potentially be harmed. According to the FDA, over 60% of DES are being implanted in patients with more complex heart problems than the conditions for which the devices were approved.

With a priced tag of $10,000 to $38,000, as many as 85% of the stenting procedures are non-emergency and are being performed on people with only partially blocked arteries for the relief of recurrent chest pain, according to March 23, 2007 Associated Press.

The first DES was approved in April 2003, and by December 2006, at a hearing on the “Prospective on Drug eluting Stents: Balancing Risks and Benefits,” the Advisory Panel reported that 3 out of 5 implants were for unapproved uses.

Dr Ron Waksman presented the results for Contemporary Registries of Washington Hospital Center and reported that the rates of stent thrombosis were almost doubled in cases of off-label use compared to on-label use at 30 days and at 12 months.

He also said that in general, when they looked at on-label and off-label use, “the drug eluting stents are more thrombogenic than bare-metal stents.”

For both on-label and off-label use, Dr Waksman said, “over time, late stent thrombosis is seen more in the DES versus the bare-metal stents.”

Dr Peter Smith of Duke University told the panel that stenting is being performed on patients with high severity coronary problems such as 3 vessel disease who should be undergoing coronary bypass grafting surgery.

He presented data that showed in these types of cases, 1 out of every 20 patients who died after treatment with stenting would have survived if coronary bypass grafting would have occurred and that DES use in patients with 3 vessel disease results in about 3,600 premature deaths annually in the US.

In the end, the panel did recommend that a warning be added to the DES labels stating that off-label use may increase the risk of thrombosis, myocardial infarction, and death, and several members recommended that a black box warning be added. However, Dr Brian Zuckerman, director of the FDA’s division of cardiovascular devices, quickly quashed that idea, saying there would be no black box warning, according to MedPage Today on December 8, 2006.

But as usual, investigations have shown that the FDA was aware of the DES problems for years. Within 6 months of the approval of the first DES, the FDA had already identified 50 cases of allergic reactions and agency records show that a few months after the Cypher arrived on the market, the FDA received a cluster of sub-acute thrombosis reports and the FDA and J&J issued a letter notifying doctors of the initial reports in July 2003.

The Tarus was launched in March 2004, and on July 16, 2004, Boston announced a major recall of 85,000 of the devices after a death and serious injuries were linked to the DES, just two weeks after 200 were recalled following reports of malfunctions during implant procedures. At the time of the announcement, the company also said that it was recalling 11,000 bare metal stent systems, which the FDA found to be linked to two deaths and 25 serious injuries.

Two years later on October 23, 2006, Bloomberg reported that 2.9% of DES patients could develop clots within three years and said, “More than 4 million people have received such stents since 2001, which means clotting related to drug-coated devices may have caused as many as 20,000 heart attacks and 10,000 deaths worldwide.”

The American College of Cardiology posted an editorial online by Dr Sanjay Kaul, director of the cardiology fellowship training program at Cedars-Sinai Medical Center and a colleague on October 11, 2006, that warned that blood clots in drug-coated stents may be causing an extra 2,160 deaths in the US alone each year.

The next month, on November 29, 2006 analysis by researchers at the Cleveland Clinic found the risk of blood clots was increased as much as 5-fold in patients who receive drug-coated stents compared to patients implanted with the old bare-metal stents.

“There are hundreds of thousands of Americans who are currently getting stents placed who do not need it as initial therapy,” according to Dr Raymond Gibbons, professor of medicine at the Mayo Medical School and president of the American Heart Association, in a United Press International article.

In the March 28, 2007, Wall Street Journal Health Blog, Dr Andy Demajio wrote, “It has been distressing to see how interventional cardiologists have been happily stenting their patients to fatten their wallets.”

“This immoral practice should come to a stop,” he wrote. In May 2007, the Medicare Strike Force reported that one cardiologist had implanted 25 unnecessary stents in 2006 alone, with most procedures paid for by Medicare.

Legal experts are predicting that future lawsuits filed against Boston and J&J may well include the names of cardiologists and hospitals that helped turn the stenting for profit business into a billion dollar industry. Being there is no way to reverse the stenting procedure, patients face a life-time of worry because a blot clot in a stent can cause a stroke or heart attack without warning at any time.

Lawsuits against the stent makers continue to mount. On December 6, 2007, 46-year-old Sean O’Shea, a man who had five stents implanted, announced a lawsuit against J&J, alleging the company failed to warn him about potential blood clotting complications associated with the stents.

“Had I known there would have been this many complications,” he said in a news conference, “I would have chosen other options.”

On July 30, 2007, the Zimmerman Reed law firm announced the filing of a lawsuit against J&J by a Minnesota man who suffered a heart attack as a result of a blood clot at the site of his Cypher implant. According to the press release, it is estimated that over 50,000 patients have been implanted with the Cypher stent.

Investigations of Anemia Drug Profiteering Far from Over – Part I

Evelyn Pringle August 5, 2007

On July 20, 2007, the Centers for Medicare & Medicaid Services issued new reimbursement rules that limit the use and dosage for a class of anemia drugs known as erythropoiesis stimulating agents (ESA’s), in large part prompted by findings that the medications were being over-prescribed for profit under the current billing rules.

However, right about now, reimbursement rates are probably the least of the worries for the companies that market the drugs, Johnson & Johnson and Amgen. On May 10, 2007, Amgen received a subpoena from the New York attorney general seeking documents related to “promotional activities, sales and marketing activities, medical education, clinical studies, pricing and contracting, license and distribution agreements and corporate communications,” according to the firm’s May 22, 2007, SEC filing.

Also, a J&J spokeswomen said her company has also received a subpoena that covers the sales, marketing, medical education, and clinical trials of the ESA’s, according to the May 25, 2007, Cancer Letter.

The drugs are sold under the brand names Procrit, Epogen, and Aranesp, and Amgen manufactures all three, but Procrit is marketed by J&J.

On April 17, 2007, Newsday reported that the large for-profit dialysis chains like DaVita and Fresenius are negotiating volume discounts that allow them to buy ESA’s at a lower price than the reimbursement rate from Medicare, “making the drug a profit center.”

A June 2007 report on an investigation by the US Department of Health and Human Services Office of Inspector General found dialysis facilities could acquire the anemia drugs for as much as 10% below Medicare reimbursement levels. Acquisition costs varied substantially, the report notes, with chain-owned freestanding clinics often paying less than non-chain freestanding and hospital-based facilities, but all totaled, 99% of freestanding dialysis facilities could purchase ESA’s for less than the Medicare reimbursement rate.

On May 9, 2007, the New York Times reported that J&J and Amgen were paying “hundreds of millions of dollars to doctors every year in return for giving their patients anemia medicines.”

Federal law bars drug makers from paying doctors who prescribe drugs in pill form to be purchased at a pharmacy, but companies are allowed to offer rebates to doctors who buy drugs that are administered in their office.

Documents obtained by the Times show that, at just one practice in the Pacific Northwest, six cancer doctors received $2.7 million from Amgen for prescribing $9 million worth of its drugs last year.

Michael Sullivan, who worked as a business manager for the six doctors in the Pacific Northwest for 9 years, told the Times that the rebates inevitably encourage use of the drugs and that as result of the rebates from Amgen, the six doctors made about $1.8 million in net profit on the drugs they prescribed.

On May 10, 2007, the Wall Street Journal reported a review of documents provided by Dean McClellan, a former sales representative who filed a whistleblower lawsuit against J&J alleging that the company “offered excessive financial incentives for doctors” to prescribe Procrit and encouraged doctors to prescribe the drug at higher doses than were approved.

One document, cited by Journal, estimated that a doctor who purchased nearly $1 million worth of Procrit over 15 months would receive $237,885. Another program offered a discount for J&J’s product line for hospitals that used Procrit at least 75% of the time. J&J also developed a “Right of First Refusal” contract that required doctors to allow J&J to make a better offer if Amgen lowered the price of Aranesp, making it cheaper than Procrit.

Half of Amgen’s total revenue for 2006 was earned by Epogen and Aranesp, bringing in combined sales of $6.6 billion. Procrit was J&J’s second best selling drug last year at $3.2 billion, according to Forbes on March 21, 2007.

In the US, the majority of the profits are tax dollars, because Medicare pays for over 90% of services provided to patients with end stage renal disease (ESRD), and the anemia drugs cost approximately $2 billion a year, according to a report by the US House Ways and Means Committee which oversees spending by the Medicare and Medicaid programs.

The drugs are approved only for the limited use with patients who are anemic and undergoing dialysis due to chronic kidney disease, cancer patients who are receiving chemotherapy and patients who are scheduled to have major surgery to reduce the need for blood transfusions.

According to the FDA-approved labeling, before receiving ESA’s, patients should have a hemoglobin (red blood cell count) level of 10-12 grams per deciliter of blood, and the drugs are to be used only if the level drops below 10 grams.

Despite the FDA label, a 2006 report by the US Renal Data System, a large federally-funded registry of patients on dialysis, found that more than 40% of dialysis patients have a hemoglobin level greater than 12, and over 20% have hemoglobin levels above 13.

In the past year, investigations have shown that the drugs are being administered to patients who are not receiving dialysis or chemotherapy and in higher doses than approved. In fact, one study found that about 50% of dialysis patients had hemoglobin levels above what the FDA considers safe, and about 20% develop dangerously high levels that can lead to heart attacks and strokes, according to the November 17, 2006, medical journal Lancet.

A November 2006 Dialysis and Transplantation study found that the population with a red blood cell count above the guidelines also had higher costs of $3,100 per patient per year more for just the anemia drug.

Dr Laura Pizzi, a Research Associate Professor of Health Policy at Jefferson Medical College in Philadelphia who led the study, testified at a December 2, 2006 hearing before the House Ways and Means Committee and discussed how the study converted the difference in utilization to dollars amounts between actual usage versus recommended practice based on 2005 Medicare reimbursement rates and estimated that Medicare could have reduced the cost for the drugs by 36% if dialysis facilities adhered to the guidelines.

“If CMS spends $2 billion per year,” she said, “it is reasonable to say that several hundred million dollars could have been saved on the drug if providers followed the guidelines.”

On December 6, 2006, Dr Ajay Singh, clinical chief of the Renal Division and director of dialysis services at the Brigham and Women’s Hospital, testified at a hearing before the US House Ways and Means Committee and told lawmakers that patients in the higher hemoglobin group had a 34% higher risk of death and cardiovascular complications compared to patients in the lower level group.

He testified to a study that found there were 52 deaths in the higher group versus 36 in the lower hemoglobin group, or a 48% higher risk and a 41% higher risk of hospitalizations for heart failure and more cardiovascular adverse events.

Dr Singh also said the study found no benefits for patients who received the drugs and, therefore, “the conclusion was there was both increased risk and no substantive incremental quality of life benefit in raising the hemoglobin among patients with chronic kidney disease not on dialysis.”

An editorial in the April 18, 2007, Journal of the American Medical Association, by Dr Daniel Coyne, a professor at Washington University School of Medicine, estimated that it costs the Medicare program $1,700 more for each patients on the higher dose. “Physicians need to challenge industries,” he wrote, “that appear to be using patients as profit centers based on bad science.”

In February 2007, the FDA notified health care professionals of the results from a large clinical trial evaluating the use of Aranesp to treat cancer patients not receiving chemotherapy in which patients received either Aranesp according to the approved dosing regimen or a placebo.

Patients treated with Aranesp, the FDA reported, had a higher death rate and no reduction in the need for transfusions compared to those treated with placebo. The FDA warned that the finding showed that treating anemic cancer patients not on chemotherapy with an ESA may offer no benefit and may cause serious harm.

In a March 9, 2007, safety alert, the FDA reported that an analyses of four new studies in patients with cancer found a higher rate of serious and life-threatening side effects and/or death with the use of ESA’s. The studies were evaluating an unapproved dosing regimen, a patient population for which ESA’s are not approved, or a new unapproved ESA.

According to the FDA, as of March 2007, there were five clinical trials that demonstrated decreased survival time in cancer patients receiving ESA’s compared with those receiving blood transfusions.

In addition, the agency reported a higher rate of blood clots, strokes, heart failure, heart attacks and death in patients with chronic kidney failure when ESA’s were given to raise hemoglobin levels higher than 12.

The FDA advisory also noted that a higher risk of blood clots was reported in patients who were scheduled for major surgery and received ESA’s.

The FDA also warned of an increased rate of tumor growth in patients with advanced head and neck cancer receiving radiation therapy and metastatic breast cancer patients receiving chemotherapy, when ESA’s were given to maintain levels of more than 12.

There was also a higher rate of death reported, the agency said, but no fewer blood transfusions when ESA’s were given to patients who were not receiving chemotherapy.

In March 2007, the FDA revised the product labeling for the drugs to include updated warnings, a new boxed warning and modifications to the dosing instructions. The boxed warning advises doctors to use the lowest ESA dose to gradually increase the hemoglobin level to a concentration sufficient to avoid the need for blood transfusions.

The label revisions, the FDA said, were based on recently completed trials that described an increased risk of death, blood clots, strokes and heart attacks in patients with chronic kidney failure when ESA’s were given at doses that resulted in higher than recommended hemoglobin levels.

The revisions also addressed the trial findings for cancer patients, both when ESA’s were given at doses intended to result in higher than recommended hemoglobin levels, and when ESA’s were given to cancer patients whose anemia was not chemotherapy-related.

The revised label also summarizes the information from the trial that showed an increased risk for deep venous thrombosis in patients following orthopedic surgery when ESA’s were administered without the blood clot prevention measures listed on the product label.

On May 8, 2007, the FDA released a report by agency scientists that said there was no evidence to support that ESA’s improved the quality of life in patients or extended their survival, while several studies show the drugs can shorten lives when used at high doses.

On June 26, 2007, Robert Vito, Regional Inspector General for Evaluation and Inspections in Philadelphia at the US Department of Health and Human Services’ Office of Inspector General, testified at a hearing before the House Ways and Means Committee and described cases where dialysis centers have been found to be submitting false claims for payment to Medicare involving the anemia drugs.

This year, he said, Dialysis Clinic, Inc., which provides services to Medicare beneficiaries with ESRD with clinics located in more than 30 States, agreed to pay $1.8 million to resolve liability under the False Claim Act, with the majority of the settlement associated with the administration and billing of ESA’s when it was medically unnecessary.

Investigations of Anemia Drug Profiteering Far from Over – Part II

Evelyn Pringle August 7, 2007

According to US Renal Data System and the Medicare Payment Advisory Commission, Medicare spends about $64,000 annually for each person on hemodialysis for all medical services, and the anemia drugs Procrit, Epogen and Aranesp are the single largest drug expense for Medicare.

In 2005, Medicare spent $2 billion on the drugs, and from 1991 to 2004, the cost of the medications to Medicare increased 716% from $245 million to $2 billion, according to a report by the US House Ways and Means Committee.

Amgen produced the synthetic epoetin in 1989 and sold it under the brand name Epogen as a treatment for anemic kidney patients and HIV related anemia. Shortly after Epogen came on the market, Amgen entered into an agreement to allow J&J to sell the same drug under the brand name Procrit, as long as it stayed out of the dialysis market, which basically helped the young company raise capital.

In 1993, J&J received approval to sell Procrit as a treatment for cancer patients with chemotherapy-related anemia, and a few years later, Amgen gained FDA approval for the long-lasting version of the drug, Aranesp, to treat both renal and chemotherapy related anemia.

Recent investigations have shown the drug makers are providing incentives to encourage the over-prescribing of ESA’s to Medicare patients by charging less for the drugs than the Medicare reimbursement rates.

A March 2006 government report entitled “Medicare Reimbursement for New End Stage Renal Disease Drugs,” found freestanding dialysis facilities on average were able to acquire Aranesp for between 14 and 27% below the Medicare reimbursement amounts in 2005.

On May 10, 2007, due to reports of rampant over-prescribing of the drugs for uses and doses not approved by the FDA and the deaths and injuries to patients as a result, the Oncology Drug Advisory Panel (ODAC) voted 15-2 in favor of adding new restrictions on the use of the drugs and voted 17-0 in favor of requiring the drug makers to conduct new clinical trials.

However, experts say the recommendations come about ten years and probably tens of thousands of deaths and injuries too late, because the FDA was made aware of the serious health risks associated with ESA’s in a report on the Amgen sponsored Normal Hematocrit Study back in 1996, and the FDA did little more than revise the product labeling a wee bit.

The 1996 study was designed to evaluate whether patients with chronic renal failure undergoing dialysis had fewer cardiovascular complications if the ESA was administered to attain a higher hematocrit level as compared to a lower level. The trial was terminated early because of a finding of more deaths and non-fatal myocardial infarctions in the patients randomized to the higher hematocrit target level.

The labeling revision recommended that the ESA’s not be used to achieve hematocrit in excess of 36%, or a hemoglobin level of 12 g/dL and was accompanied by the sponsor’s agreement to conduct a study to further examine the risk for blood clots among patients receiving ESA’s because an increased thrombotic risk was suspected to be one of the causes for the risks detected in the study, according to the FDA.

So ten years later, two clinical trials and an editorial finally appeared in the New England Journal of Medicine in November 2006, to report the risks associated with the use of ESA’s in the treatment of anemia from chronic renal failure.

The Correction of Hemoglobin and Outcomes in Renal Insufficiency (CHOIR) study showed increases in serious and potentially life-threatening cardiovascular events when Procrit was administered to reach higher hemoglobin levels, and the Cardiovascular Risk Reduction by Early Treatment with Epoetin Beta (CREATE) study trended toward more cardiovascular events in a pattern similar to the CHOIR study, thus strengthening the findings of the CHOIR study, the FDA said.

On June 26, 2007, Dr John Jenkins, Director of the FDA’s Office of New Drugs Center for Drug Evaluation and Research, testified at a hearing before the House Ways and Means Committee and said the study findings “underscore the importance of the warnings previously described in the labeling for Procrit, Epogen, and Aranesp regarding cardiovascular risks that include thrombotic events and increased mortality in hemodialysis patients who participated in the Normal Hematocrit Study.”

He told the Committee that the new studies, combined with the findings from the Normal Hematocrit Study, showed that patients with anemia due to chronic renal failure, whether or not receiving dialysis, “were at increased risk for serious cardiovascular complications when ESA’s were administered to attain hemoglobin levels in excess of the 12 g/dL level recommended in the ESA product labels.”

Dr Jenkins also said the FDA became aware of safety concerns about the use of ESA’s in cancer patients receiving chemotherapy between 2001 and 2003, when the agency received reports from two trials (BEST and ENHANCE) that demonstrated higher mortality and more rapid tumor growth when the ESA’s were given to maintain hemoglobin levels of greater than 12 g/dL and the findings were discussed at a May 2004 meeting of the ODAC.

He said the new safety data was added to the labeling for ESA products shortly after that meeting and that the advisory panel recommended additional data be gathered to further evaluate the new safety concerns about patients with cancer.

However, according to Dr Jenkins, it was not until late 2006 and early 2007 that the FDA was informed of several new trials in cancer patients that raised additional safety concerns.

In December 2006, the ESA makers informed the FDA of the interim results of the Danish Head and Neck Cancer Study Group trial (DAHANCA 10), a trial that compared radiation therapy alone to radiation therapy plus Aranesp in the treatment of advanced head and neck cancer.

The trial assessed whether treating anemia to achieve and maintain a hemoglobin concentration of 14.0-15.5 g/dL during radiotherapy would improve local-regional disease control.

The data monitoring committee for this trial found that 3-year local-regional control in patients treated with Aranesp was worse than for those not receiving Aranesp. Overall survival time also favored those not treated with Aranesp, he said, and the monitoring committee recommended the ESA treatment be stopped in the experimental arm on December 1, 2006.

Dr Jenkins said the FDA was notified in January 2007 of the results of a 989 patient trial of Aranesp in cancer patients with anemia who were not receiving chemotherapy when the target hemoglobin in the Aranesp treatment group was 12 g/dL.

The FDA’s analysis of the study data, he told the Committee, demonstrated that Aranesp did not significantly reduce the need for red blood cell transfusions and showed an increase in mortality in patients receiving Aranesp compared to those receiving placebo.

He said the FDA was also notified in February 2007 of the final results of a double-blind, placebo-controlled study that was designed to evaluate whether Epoetin alpha improved the quality of life for patients with non-small cell lung cancer who were not receiving chemotherapy with the dose titrated to maintain a hemoglobin level of 12 to 14 g/dL.

However, according to Dr Jenkins, this study was closed down in December 2003 after enrolling only 70 patients because its data monitoring committee found higher mortality rates in patients treated with Epoetin alfa.

Dr Jenkins informed the panel that the median time to death in patients treated with Epoetin alfa was 68 days and significantly shorter than the median time of 131 days in those treated with placebo. Also, he noted, treatment with Epoetin alfa did not significantly reduce the need for red blood cell transfusion or improve quality of life.

Dr Jenkins also explained that in 1996, the FDA approved the indication for use of ESA’s to reduce the need for blood transfusions in patients with hemoglobin values between 10 and 13 g/dL scheduled to undergo non-vascular, non-cardiac surgery.

Here, too, the approval was accompanied by a commitment to complete a post-marketing study to evaluate the risk for thrombotic events among patients who were not receiving preventive therapy with anti-thrombotic drugs.

In this case, according to Dr Jenkins, the FDA only received the results of this post-marketing study in 2007. Specifically, he said, the FDA was notified in February 2007 of the preliminary results of a trial with Procrit compared to the standard of care in patients undergoing spinal surgery.

“In this trial,” he said, “the frequency of deep venous thrombosis in patients treated with Procrit was 4.7 percent (16 patients), a rate more than twice that of patients who received usual blood conservation care (2.1 percent, seven patients).”

On June 26, 2007, Robert Vito, Regional Inspector General in Philadelphia at the US Department of Health and Human Services’ Office of Inspector General, testified at a hearing before the House Ways and Means Committee subcommittee and described cases where dialysis centers have been found to be overbilling Medicare for the anemia drugs.

He discussed a 2004 audit of payments to DaVita for ESA services provided at one Philadelphia dialysis center, which found that 44 of the 143 claims reviewed did not meet Medicare payment requirements.

In some cases, he said, they identified inconsistencies between the number of units prescribed in the physician order and the number billed to Medicare and also identified instances in which the drug was still administered to the patient after the doctor had ordered its discontinuation.

As another example, he told the committee that, in 2005, Gambro Healthcare, owner and operator of over 500 dialysis centers, agreed to pay over $350 million to resolve civil and criminal fraud allegations in the Medicare, Medicaid and TRICARE programs. To resolve its civil liability, he noted, Gambro paid $310.5 million for submitting false claims to Medicare and paying doctors improper remuneration related to their medical director services.

The new CMS reimbursement rules stipulate that cancer patients receiving chemotherapy should only use ESA’s if their hemoglobin levels fall below 10 and also limit the duration of therapy to a maximum of eight weeks after the completion of chemotherapy. They also limit the starting dose to match the FDA recommendations and limit the levels by which doses can be raised and Medicare will not cover treatment for anemic cancer patients who are not receiving chemotherapy or radiation.

The subpoena from New York Attorney General is just the tip of the iceberg when it comes to Amgen’s legal woes. The company’s failure to disclose the results of a Danish study in head and neck cancer has resulted in an inquiry by the SEC and several shareholder lawsuits.

According to the SEC filing, a class-action lawsuit was filed on May 11, 2007, in California, alleging that Amgen and its executives “made false statements that resulted in a fraudulent scheme and course of business operated as a fraud or deceit on purchasers of Amgen publicly traded securities.”

On May 14, 2007, the company was also served with a shareholder demand on the board of directors to establish a “special litigation committee” to investigate potential breaches of fiduciary duties by current or former officers and directors of the company, according to the filing.

The shareholders allege that these individuals violated core fiduciary duties, causing Amgen to suffer damages, and seek to recover damages resulting from their breach of fiduciary duties, monies and benefits improperly granted to them, insider trading proceeds and all costs associated with the inquiry by the SEC.

No Preemption for J&J against Charite Spine Surgery Victims

Evelyn Pringle April 25, 2007

According to Johnson and Johnson’s SEC filings, as of December 31, 2006, there were 100 lawsuits pending against the company involving the Charite artificial spinal disc, seeking “substantial compensatory and, where available, punitive damages.”

The J&J subsidiary, DePuy Spine, has marketed the Charite since the disc was FDA approved for sale in the US in October 2004, to treat patients who have degenerative disc disease at one level in the spine.

In a nutshell, the lawsuits allege that the Charite is defective, it was improperly marketed, and J&J failed to adequately warn doctors and consumers about the dangers of the disc.

In March 2006, J&J filed a motion for summary judgment in attempt to have 4 lawsuits dismissed in the Superior Court in Bristol, Mass, using a legal defense known as preemption where a device maker cannot be sued if the FDA has approved the device.

Its ironic that J&J would try to use this argument when experts say the fault lies with the FDA for approving the Charite to begin with based on one 2-year noninferiority trial that sought only to show that it worked as well as the Bagby and Kuslich (BAK) cage used in spinal fusions, which had already been abandoned due high failure rates.

And even when compared to the outdated surgery, the disc worked no better in relieving pain and most Charite patients were still taking narcotic pain drugs 2 years later.

On April 11, 2007, Judge Susan Garsh denied J&J’s motion and noted that the plaintiffs alleged that DePuy made specific performance claims to obtain FDA approval that the device failed to achieve and “there is evidence to support the device does not perform in the manner which DePuy represented to the FDA that it must perform,” she wrote.

According to the lawsuits, Charite patients were provided materials by DePuy that stated: “The Charite Artificial Disc has a clinical history spanning 17 years. Its safety, efficiency and remarkable durability have been proven through thousands of implants worldwide.”

DePuy also promoted the disc with the phrase: “Natural Motion is Back.”

J&J claims that replacement surgery will alleviate chronic back pain, permit natural movement and improve the patient’s ability to function under the premise that segmental mobility of the spine will improve, as has been the case with hip and knee replacement.

J&J’s main selling point is that disc replacement is more effective than lumbar spinal fusion surgery, where the damaged disc is removed and the vertebrae are joined together using bone grafts, metal screws and/or cages and motion can no longer occur in that area.

However, critics point out that in many of the surgeries listed as successes, the Charite only worked after the auto-fusing of bones together, similar to spinal fusion surgery, which eliminates the possibility of natural motion that leads patients to chose the costly replacement surgery to begin with.

A long line of studies show the odds for revision surgery in Charite patients are high. Back in 1996, Cinotti, David et al, analyzed the follow-up on 46 patients and eight patients had undergone subsequent fusion surgery. “The main cause of poor outcomes appear to be an inappropriate selection of patients undergoing disc replacement,” the authors concluded.

In 1997, Lemaire, Skalli, et al, reported on 105 patients with average follow-up of 51 months and found that fifty patients or 48% had undergone at least one operation.

A 1999 study by Zeegers, Bohnen et al in the Netherlands reported the 2-year results for 50 patients and found 12 patients, or 24%, needed re-operation.

In a more recent study from the University Medicine in Berlin (2005), Putzier, Funk et al evaluated 71 patients who received implants between 1984 and 1989, and of the 53 patients available for examination, 12, or 23%, had undergone surgical fusion.

But there were warnings that the Charite was not all it was cracked up to be even before it was approved. In April 2003, the Spine Journal published the paper, “Total Disc Replacement for Chronic Low Back Pain: Background and a Systematic Review of the Literature,” that stated: “There is no evidence that disc replacement reliably, reproducibly, and over longer periods of time fulfils the three primary aims of clinical efficacy, continued motion, and few adjacent segment degenerative problems.”

Some experts say the Charite itself is the problem. On October 23, 2006, the reported that researchers at the University of California at Irvine claim the device maker made a crucial mistake when designing the disc that explains why the replacement surgery has resulted in repeated failures with “catastrophic consequences” for patients.

“They’ve based their center of rotation on a disc space that is in front of the spinal canal,” Dr Charles Rosen, a Cal-Irvine spine surgeon, told the Street.

According to Dr Rosen, the makers overlooked the spine’s normal function by creating an “artificial center of rotation” in a space that lies in front of the spinal canal instead of behind it and has compromised the body in the process.

“You have a center of rotation that’s normally there, and they falsely impose another,” he told the Street. “You can’t have two because they will neutralize each other. Something has to give.”

“To give,” he says, “either the back part of the device breaks or the front part dislocates.”

J&J has a lot of money riding on the Charite and if it turns out that Dr Rosen is right, its January 1, 2006, projection the total spine market will bring the company $9 billion by 2010 will go right down the tubes.

Spine surgery is a multi-billion dollar industry. According to the August 5, 2006 LA Times, at least $3.2 billion was spent in the US on spinal fusion in 2005, and Medicare payments to hospitals for implant surgery have risen about 40%, in the past 2 years, from $10 billion to $14 billion, according to the September 26, 2006, New York Times.

However, serious questions are being raised about whether doctors and hospitals are practicing surgery for profit, especially since the revelation that surgeons are investing in companies that make the devices and hardware used during spine surgery.

On December 30, 2006, Reed Abelson reported in the New York Times that over the past couple of years, about 30 start-up companies have begun selling spine devices and hardware and about a dozen have doctors investors.

“Because most of the companies are private and the relationships are not publicly disclosed,” he wrote, “there is no way to know how many spine surgeons around the country are partial owners of device makers.”

Stan Mendenhall, editor of the newsletter, Orthopedic Network News, told the Times that the spine device market has doubled in the last 3 years and there are now about 100 companies and doctors have ownership in some of the newest firms. And there are apparently plenty of profits to spread around because the report says a single screw sells for around $1,000 or 10 times the cost of making it.

Back on June 28, 2006, the Times revealed another funneling scheme set up by doctors and device makers when it reported that, “doctors in private practice have set up tax-exempt charities into which drug companies and medical device makers are, with little fanfare, pouring donations — money that adds up to millions of dollars a year.”

“The tax-exempt money also sometimes flows to the for-profit medical groups affiliated with the charities,” the Times wrote, “sometimes covering business expenses or even paying parts of the salaries of doctors.”

For example, the Times revealed that the tax-exempt, “Blue Ridge Bone and Joint Research Foundation,” headed by Dr Joseph Moskal, an orthopedic surgeon, received $75,000 from DePuy in the year ending July 31, 2004, and then paid $30,000 of that money to the for-profit Roanoke Orthopaedic Center, where Dr Moskal practices, to defray the costs of a fellowship program there.

The Department of Justice made it known that J&J’s relationships with doctors are under investigation in June 2006, when it served subpoenas and search warrants on DePuy, demanding copies of consulting contracts, professional services agreements, and documents that evidence the company’s arrangements with orthopedic surgeons.

Lawmakers go after Amgen and J&J Over Off-Label Sales of Anemia Drugs

Evelyn Pringle April 22, 2007

To increase profits, drugs used to treat anemia in patients covered by Medicare are being given at higher doses and for conditions not approved by the FDA, due to reimbursement policies adopted by the Centers for Medicare and Medicaid Services under the leadership of top officials appointed by the Big Pharma-friendly Bush Administration.

At a December 6, 2006 hearing of the House Ways and Means Committee, then chairman Bill Thomas (R-CA), told Leslie Norwalk, acting commissioner of the CMS, “we have a payment policy that perhaps is killing people; and we are using $2 billion, the highest price paid in a relatively narrow area for the use of the drug through the payment policy, that may in fact be doing that.”

Studies have shown that the massive off-label marketing of these drugs has definitely resulted in many deaths, but the question that remains is how many.

The drugs at issue include Aranesp, the brand name for darbepoetin, and Epogen and Procrit, the brand names for epoetin. Amgen manufactures all three drugs, but Ortho Biotech Products, a Johnson & Johnson subsidiary markets Procrit.

They are top money-makers for both companies. In 2006, ESA’s combined had sales of nearly $10 billion, and Aranesp and Epogen accounted for $6.63 billion, or 48% of Amgen’s total $14.3 billion revenue in 2006.

The drugs belong to a class known as Erythropoiesis Stimulating Agents (ESAs), which are man-made versions of a hormone normally produced in the kidneys to stimulate bone marrow cells to produce hemoglobin which is the main component of red blood cells.

The severity of anemia is determined by a patient’s hematocrit, the proportion of red blood cells in whole blood, which should remain at between 33% and 36%, according to the FDA. The labeling for ESAs specifies that patients should have a hemoglobin level no higher than 12 grams per deciliter of blood.

ESAs are approved only to treat anemia and reduce the need for blood transfusions in patients with chronic kidney failure undergoing dialysis, patients with cancer who are receiving chemotherapy, patients scheduled for major surgery, and HIV patients with anemia due to zidovudine therapy.

However, they are being administered off-label to kidney patients who are not receiving dialysis, cancer patients who are not undergoing chemotherapy and in doses that result in higher levels of hemoglobin than are approved by the FDA as safe and effective.

On March 9, 2007, the FDA announced that all ESAs must carry black box warnings on their labels about the increased risk for serious side effects, including death, and advised doctors that they should use the lowest dose necessary to avoid the need for blood transfusions caused by anemia.

Several recent reports have shown that dialysis centers are administering higher doses of ESAs which has resulted in an increased rate of stroke, heart attack and death in dialysis patients. The dosage received by the typical dialysis patient in the US has nearly tripled since the early 1990s, according to the November 16, 2006, New York Times.

A paper presented at the annual conference of the American Society of Nephrology[,] reported that 37% of patients at Davita clinics, the second largest provider of dialysis in the US, had hemoglobin levels higher than 14 grams at least one time in a 9-month period.

Dialysis patients in the US are dying at a higher rate due to this drugging-for-profit scheme. In Europe, where lower doses of ESAs are given, the Times reports that, about 15% of dialysis patients die each year compared to 22% in the US.

Dialysis centers are also boosting profits by administering the drugs intravenously instead of by injection. According to the Boston Globe on October 24, 2006, clinics would use 30% less ESAs, at a potential savings of $375 million each year, if ESAs were injected because the method require a lower dose and they stay in the system longer.

Critics blame the over-use on the financial incentives in Medicare reimbursement policies. Medicare covers medical care for patients with End Stage Renal Disease, and between 1998 and 2003, spending for ESRD patients increased nearly 50%. About $64,000 a year is spent for each dialysis patient, according to US Renal Data System.

Medicare guarantees dialysis centers a 6% profit for administering ESAs, and in April 2006, the CMS drew fire from Capitol Hill when it adopted a policy allowing payment for the administration of ESAs until hematocrits reached 39%.

The Ways and Means Committee chairman, Rep Thomas, sent a letter chastising Mark McClellan, the CMS Administer at the time, asking why CMS had not developed a policy to deal with the out-of-control dosing of patients at a higher levels. “I cannot understand why CMS would knowingly contradict FDA findings,” he wrote.

The CMS did not respond to the letter, so in November 2006, incoming chairman of the Committee, Rep Pete Stark (D-CA), and Rep Thomas sent a another letter to acting CMS Administrator Leslie Norwalk, describing the CMS policy as “a reimbursement incentive for providers to continue to increase doses” past the approved level.

Ms Norwalk did not respond to that letter either, but on December 6, 2006, Ms Norwalk and specific experts were called to testify at a Committee hearing due to “growing concern about unsafe and questionable treatment for Medicare’s coverage for kidney failure, also known as End Stage Renal Disease,” Rep Thomas said.

Through the current rules which endorse expanding reimbursement to allow hematocrit to be targeted to any level, Thomas said, CMS has implemented a policy harmful to its beneficiaries that will cost hundreds of millions of dollars in additional expenditures.

During the questioning of Ms Norwalk, it was revealed that the Monitoring Policy Group, created by the CMS, approved the higher hematocrit guidelines, and two-thirds of the members had financial ties to either Amgen, Johnson & Johnson or the dialysis clinics that profit by selling more of the drugs.

“Now what troubles me is that of the 24 members,” Rep Stark told Ms Norwalk, “18 of them disclosed financial associations with Amgen or Johnson & Johnson.”

It was also noted that the National Kidney Foundation guidelines had raised the hemoglobin limit to 13. However, a clue as to how that came about surfaced a few months later on March 21, 2007, when the New York Times reported that the president of the Foundation, Dr Allan Collins, was also the director of the Minneapolis-based Medical Research Foundation and in 2004, the year he was made president, Amgen underwrote more than $1.9 million worth of research and education programs led by Dr Collins, and paid him at least $25,800 in mostly consulting and speaking fees in 2005.

Dr Laura Pizzi, a professor at Jefferson Medical College, testified as lead author on a study in the November 2006, Dialysis and Transplantation journal, conducted to determine to what extent health care providers were adhering to clinical guidelines for patients receiving dialysis.

She said the study found significant overuse of the drugs, and although the researchers were not surprised to see that providers were not strictly adhering to the guidelines, they were surprised by the extent to which ESA use deviated from the recommendations.

When converting the increased use to dollar amounts based on Medicare reimbursement rates in 2005, Dr Pizzi said the population with a red blood cell count above industry guidelines had higher drug costs of $3,100 per patient each year.

“We estimate that CMS,” she told the panel, “could have reduced expenditures for these drugs by 36 percent if dialysis facilities adhered to the guidelines.”

If CMS spends $2 billion a year, she said, “it is reasonable to say that several hundred million dollars could have been saved if the providers followed the guidelines.”

Dr Noshi Ishak, a kidney specialist who owns a dialysis clinic in Laconia, NH addressed the huge profits of administering ESA’s intravenously instead of by injections.

He said he switched to administering the drugs by injection in 1998 and usage dropped by more than 20%, or equivalent “to $3,120 savings per patient per year for Medicare.”

The FDA’s Oncology Drugs Advisory Panel is scheduled to meet on May 10, 2007, to review the safety and effectiveness of ESAs, and lawmakers have ordered Amgen and J&J to cease all direct-to-consumer advertising and physician incentives until the FDA determines whether measures need to be taken to protect the public from these products.

Amgen and J&J Funnel Tax Dollars Through Kidney and Cancer Patients

Evelyn Pringle April 17, 2007

Medicare has provided coverage for all patients with End Stage Renal Disease since 1972, and according to the House Ways and Means Committee, the government pays for 93% of services provided to dialysis patients, at a cost of about $2 billion a year.

In 2005, the drugs darbepoetin and epoetin, commonly used by patients who must undergo dialysis, accounted for almost 20% of the $13 billion spent on the Medicare Part B drug plan, and total sales for these drugs worldwide topped $9 billion.

Amgen manufactures and markets darbepoetin as Aranesp, and epoetin is sold under the names Procrit and Epogen. But Procrit is distributed by Ortho Biotech Products, a Johnson & Johnson subsidiary. There are no generic versions of these medications.

The drugs are among the top sellers for both companies. Amgen’s Epogen and Aranesp combined sales were $6.6 billion in 2006, nearly half of the company’s total revenues. Johnson and Johnson’s revenues were $3.2 billion in 2006, making it the company’s second-biggest-selling drug, according to on March 21, 2007.

The drugs are man-made versions of erythropoietin, a hormone normally produced in the kidneys, and belong to a class of drugs known as Erythropoiesis Stimulating Agents. ESA’s are used to treat anemia in raising hemoglobin levels by increasing the number of red blood cells in the body. Anemia’s severity is monitored by a patient’s hematocrit, the proportion of red blood cells in whole blood, which should stay between 33% and 36%.

According to the FDA, ESAs are approved to treat anemia in patients with chronic kidney failure, patients with cancer whose anemia is caused by chemotherapy, patients scheduled for major surgery to reduce potential blood transfusions, and for the treatment of anemia due to zidovudine therapy in HIV patients.

But Aranesp, Epogen, and Procrit are being administered “off label” for uses and in doses not approved by the FDA. For instance, an Amgen vice president recently estimated that about 10% to 12% of Aranesp sales are for the unapproved use of treating “anemia of cancer” in patients who are not undergoing chemotherapy.

A recent company study conducted to support FDA approval for using the drug to treat “anemia of cancer” in patients with cancer in remission who were not undergoing chemotherapy, revealed that Aranesp actually increased the risk of death in these patients.

The February 2, 2007, “Cancer Letter ,” a newsletter for cancer professionals, warns, “If the findings of the recently reported study hold up, more than one in 10 Americans getting Aranesp without chemotherapy has no chance of benefiting from the agent and could be harmed or killed by it, experts say.”

The report estimated that up to 12% of the use of ESAs in the US was for this condition.

After reviewing the results of this study and several others, on March 9, 2007, the FDA announced that black box warnings would be added to the labels for all ESAs and recommended using the lowest possible dose to raise the hemoglobin concentration to the lowest level.

The FDA-approved labeling for the drugs says patients should have a hemoglobin level of 10-12 grams per deciliter of blood, and patients are considered to need treatment if their levels fall below 10 grams.

During a press briefing, Dr Richard Pazdur, director of the FDA’s Office of Oncology Drug Products at the Center for Drug Evaluation and Research, said the black box warning was being added based on the results of several recently reported clinical trials.

Dr Karen Weiss, deputy director of the Office of Oncology Drug Products, said the FDA became concerned after receiving the results from several trials evaluating the aggressive use of ESAs to raise hemoglobin levels higher than listed on their approved labels.

In the March 10, 2007 Wall Street Journal, Dr Weiss was quoted as saying, the “bulk of the data that has raised concerns” came when patients were given higher doses, whether they were experiencing anemia from kidney disease or cancer treatment.

The evidence shows that “this type of strategy is not beneficial and, in fact, has some evidence of harm,” she said.

On March 9, 2007, the FDA also issued a public health advisory based on the results of a number of studies and warned doctors treating patients with kidney disease or cancer not to push hemoglobin levels over 12 grams per deciliter of blood.

The FDA noted a higher chance of death and an increased rate of tumor growth in cancer patients with advanced head and neck cancer receiving radiation therapy and in patients with metastatic breast cancer receiving chemotherapy, when ESAs were given to maintain levels of more than 12.
There was also a higher rate of death reported, but no fewer blood transfusions, when ESAs were given to patients with cancer and anemia who were not receiving chemotherapy.

A higher chance of death and an increased number of blood clots, strokes, heart failure and heart attacks were found in patients with chronic kidney failure when ESAs were given to raise hemoglobin levels of more than 12.
The Advisory warned that a higher risk of blood clots was also reported in patients who were scheduled for major surgery and received ESAs.

The FDA pointed out that ESAs are not approved for treatment of the symptoms of anemia, such as fatigue in patients with cancer, surgical patients and patients with HIV.

The drug makers have been using direct-to-consumer advertising to increase sales with cancer patients by claiming the drugs could restore energy and reduce fatigue in patients undergoing chemotherapy. But the FDA says there has never been any evidence to support claims that ESAs could increase energy or ease fatigue in patients undergoing cancer treatment.

In recent months, Congress has been investigating Medicare reimbursement policies that guarantee dialysis clinics a 6% profit for administering ESAs, since it became apparent that patients are being given higher doses than needed. Critics say any deal that allows for cost plus payments comes with a built-in incentive to provide unnecessary services.

On October 24, 2006, the Boston Globe reported that dialysis clinics are also increasing profits by administering ESAs intravenously instead of by injection, and about 95% of the patients receive the drugs intravenously.

Clinics could use 30% less, the Globe says, because when ESAs are injected they stay in the system longer and require a lower dose. A 2004 analysis found patients injected with the drugs were given 21% less, for a potential total savings of about $375 million.

The two clinic chains that dominate the dialysis industry are DaVita, with over 1,200 clinics, and Fresenius Medical Care, with about 1,500. According to the Globe, the clinics claim the intravenous method is more convenient because patients are already hooked up to IVs for dialysis.

Critics think differently. “The industry is incentivized to use intravenous because they make a profit margin on every unit they administer,” said Dr Peter Crooks, who oversees dialysis for 3,000 patients for Kaiser Permanente where most patients receive injections.

In an April 11, 2007 report, Bernstein Research estimates that dose volume in renal patients could fall as much as 25% if doctors abide by the new black box warning and insurers refuse to pay for the drugs in patients with hemoglobin levels over 12.

On November 17, 2006, the British journal Lancet reported that about half of all dialysis patients have hemoglobin levels above what the FDA considers safe, and about 20% of patients experience dangerously high levels, creating a risk for heart attack and stroke.

J&J Concealed Dangers of Ortho Evra Birth Control Patch

Evelyn Pringle April 16, 2007

Tens of millions of prescriptions have been written for Johnson & Johnson’s Ortho Evra birth control patch since it arrived on the market in 2002, and medical experts say the patch has harmed thousands of young women of childbearing age.

In September 2006, the FDA warned that use of the patch, made by the Ortho-McNeil division of J&J, increases the risk of blood clots, which can lead to heart attack and stroke.

Because the patch releases hormones directly into the blood stream, medical experts say, a much higher concentration of hormones enters the body than with birth control pills. A November 2005, FDA advisory reported that patch users were exposed to about 60% more estrogen than women on the pill.

A recent study in the February 2007, journal, Obstetrics and Gynecology, of 49,000 women who used the Ortho patch, and 202,000 who used oral contraceptives, found that blood clots or “venous thromboembolism” occurred in patch users at a rate of 2.2 times higher than with women on the pill.

Legal experts says proving causation in these cases will be easy because blood clots in young women are almost unheard of. No doubt due to the recognition of this fact, when the first lawsuits were filed, J&J quickly began settling cases out of court for substantial sums of money, trying to keep a lid on the news that women were being injured by the patch.

J&J has already settled lawsuits in state courts in New Jersey, Texas, and California, and federal courts in North Carolina and Pennsylvania, according to Bloomberg on April 2, 2007.

Texas attorney, Ray Chester, told Bloomberg that one settlement involved a 40-year-old woman with 2 children, who had a massive stroke after only 12 days on the patch and is now a quadriplegic with brain damage and requires around the clock medical care.

However, as the number of lawsuits multiplied, that strategy of quietly settling out of court could not continue for obvious reasons. J&J’s Annual Report filed with the SEC in February 2007, states that, as of December 31, 2006, “there were approximately 1,500 claimants who have filed lawsuits or made claims regarding injuries allegedly due to ORTHO EVRA.”

Documents revealed in litigation, prove that J&J knew about the high rate of blood clots because they show the company had been analyzing the FDA’s reports on injuries and deaths in women using the patch, and had even compiled charts showing the higher rates of clots and deaths when compared to women taking birth-control pills.

One memo from 2003, reveals that the company refused to conduct a study to compare the rate of adverse events with the patch to its Ortho-Cyclen pill because there was “too high a chance that study may not produce a positive result for Evra” and a “risk that Ortho Evra may be the same or worse than Ortho-Cyclen.”

Newly released documents show that, instead of warning consumers and prescribing physicians about the clot problems, Johnson & Johnson has been doing everything in its power to stop the negative information about the patch from becoming public.

Documents unsealed this month by Superior Court Judge, Bryan Garruto, in a New Jersey state court proceeding involving more than 300 lawsuits, reveal that J&J bought up dozens of internet domain names related to the Ortho patch in an attempt to stop negative information from appearing on the internet.

By using the standard trick of claiming the documents contained trade secrets, J&J had previously obtained a court order to keep them sealed so the public would not learn about the extent of the company’s damage control efforts.

But in granting a motion by the plaintiffs’ attorneys to unseal the documents, Judge Garruto said they were not entitled to a protective order because the information did not constitute trade secrets that, if revealed, would benefit J&J’s competitors.

One document released calls for, “Defensive actions to minimize impact of negative presence,” to include buying internet domain names, monitoring blogs and purchasing the top key words related to the patch that would be picked up by Google and Yahoo search engines.

Apparently, drug companies do this on a regular basis. According to Kent Jarrell, a spokesman for J&J, quoted by Bloomberg News on April 2, 2007: “The purchase of the domain names is a standard and accepted business practice for companies that are trying to prevent product disparagement and to safeguard the defendant’s reputation.”

Legal experts view the situation differently. According to Attorney, Derek Braslow, of the Conshohocken, Pennsylvania firm of Pogust & Braslow, “While J&J’s purchase of key internet search terms and domain names does not prove that the Ortho patch causes injuries,” he says, “J&J’s conduct, like the conduct of most drug companies, does show an intentional disregard for the victims of its deadly drug.”

He does not find the drug maker’s conduct surprising. “J&J has only taken the next step in the natural evolution of marketing,” Mr Braslow explains, “promote the drug at all costs during the life of the patent but eliminate all marketing and promotion after the money has been made and the victims start seeking answers and advocacy.”

“Purchasing the domain names has nothing to do with the merits of the litigation,” he says, “it has everything to do with damage control, protecting their drug at all costs and preventing victims from seeking and finding justice.”

After lives have been lost and families devastated as a result of using the patch, he states, the company is attempting to prevent the victims from finding legal counsel. “Instead of coming forward with the truth behind the patch,” he notes, “the company has gone to extraordinary measures to stop victims from finding attorneys to represent them.”

Attorney, Ted Chabasinski, who recently worked on a case involving the release of damaging Zyprexa documents that Eli Lilly had successfully kept hidden with a court order while settling out of court with about 26,000 litigants, agrees that J&J’s conduct is standard procedure when it comes to concealing damaging information about pharmaceutical products.

“What Johnson and Johnson is doing,” he says, “just reflects drug company practices in general.”

“None of them want the public to know that their products are dangerous and often ineffective as well,” Mr Chabasinski notes.

“America must wake up soon,” he warns, “to what these greedy corporations are doing to our health.”

“We need politicians,” he states, “who will stand up to the drug companies, and judges who will recognize that when drug company executives approve hiding the deathly effects of their drugs, thus killing thousands of people, they should be put in prison.”

“It isn’t enough,” he advises, “to make the companies pay damages.”

“Nothing will stop these practices,” he warns, “except holding the people who run these corporations personally responsible for their criminal behavior.”

According to FDA records obtained by the Associated Press with a FOIA request in 2005, in one 18-month period, there were 9,116 adverse events reported by women using the patch, a rate 7 times higher than women taking oral contraceptives.

A factor that must always be considered when assessing the number of people who may have been harmed by a product is that the FDA estimates that only 1% to 10% of adverse events are ever reported, which means the number of women harmed by the patch is definitely much higher. In 2005 alone, doctors wrote more than 9.4 million prescriptions for the patch, according to the pharmaceutical industry-tracking firm, IMS Health.

The review of records by the Associated Press revealed that the FDA knew that blood clots were at least 3 times more common with the patch before the device was approved.

The records show that in 2000, FDA doctors reviewing J&J’s clinical trials warned that clots could be a problem with the patch after finding that 2 women were treated for serious conditions where blood clots had traveled to their lungs.

One reviewer said, “The label should clearly reflect this reviewer’s safety concern about a potential increased risk.” But in the end, the label did not contain the warning, and there was no requirement for follow-up studies other than ordinary reviews of voluntary reports.