112 DEATHS LINKED TO SURGICAL STAPLERS FDA WILL ALERT DOCTORS TO WOES RATHER THAN RESTRICT USE

Pennsylvania - New Jersey - New York - Nationwide

By Alice Dembner, Globe Staff
November 8, 2003, Saturday, THIRD EDITION

A review by the Food and Drug Administration has linked 112 deaths and 2,180 injuries to surgical staplers, the same device implicated in the death of a Lawrence woman after gastric bypass surgery last month at Brigham and Women's Hospital.

In many cases, the staples failed to close around the patient's tissue, the apparent problem in the Brigham case, or the stapler failed to release the staples. Among the patients who died, the stapled tissue typically had begun leaking fluid or blood, leading to infection, an FDA official said.

The FDA plans to launch a website early next year to alert surgeons to the problems and ask for more complete reporting. An FDA committee formed in September 2001 has reviewed nearly 20,000 reports of problems with the devices from 1992 to mid-2001, and another thousand a year since. FDA epidemiologist Lori Brown said the agency believes the reports are "the tip of the iceberg."

"Because these [devices] are used so often, even if you have a very low rate of problems, it would affect a lot of patients," said Brown.

Staples are used in place of hand-stitches in at least 100,000 operations a year, ranging from gastric bypass to lung surgery to appendectomies. A surgeon uses the device to fire double lines of titanium staples and then to cut the tissue between the staples.

Tyco International, whose U.S. Surgical subsidiary made the device used in the Brigham surgery and dominates the stapler market, says that more than 500,000 surgeries have been performed since 1998 with its latest line of staplers. The FDA reports include more than 3,800 problems, including several deaths, linked to that Endo Gia brand.

Tyco spokesman Gary Holmes said the reports "do not necessarily signify that the product failed to perform as intended."

"When used in accordance with its instructions for use, every U.S. Surgical product is safe and efficacious," he said in a statement. "The company goes to great lengths to ensure our equipment is used in accordance with proper standards and regulations. We provide surgeons with technical training and support on the use of our products."

In the Brigham case, surgeon David Lautz initially used a laparoscopic technique, operating through small incisions. He said he noticed that staples in one row had popped out, so he switched to open surgery and hand-sewed a portion of the patient's stomach. Two days later, the patient, Ann Marie Simonelli, 37, died in her hospital bed without warning.

An autopsy showed another part of the stapled tissue had separated, allowing the contents of the stomach to leak, Brigham officials said. They are still investigating what caused her death and declined to comment on the FDA findings.

The reports to the FDA on earlier problems showed that some patients required colostomies, in which the intestine is connected to an artificial opening where wastes drain from the body into a bag. Brown, of the FDA, said the reports were not detailed enough to prove that the staplers caused the deaths or injuries. The problems may have resulted from design or manufacturing problems, mistakes by surgeons, or the condition of the patient, she said.

One of the most common problems reported was that the staple gun became stuck in the patients' tissue when it was fired, requiring surgeons to cut away tissue to remove the gun. The problems often prolonged surgery or forced doctors to switch from minimally invasive laparoscopic surgery to open surgery. Typically, open surgery entails more risk and a longer recovery.

Device manufacturers and hospitals are required to report problems to the FDA, but officials estimate that no more than one out of every 10 problems is reported. The FDA said it began its study because of the significant number of reported problems. Balancing the problems against the benefits of the devices, FDA officials said they decided on an educational campaign, rather than on more drastic action, such as pulling the devices off the market.

The FDA will not be the first to issue cautions. Emergency Care Research Institute, a nonprofit that investigates safety issues, printed cautions in its Health Devices newsletter in 2001 about deaths, tearing of tissue, and dangerous leakage of bowel contents. But the institute suggests many of the problems are caused by surgeons' misuse of the staplers.

"Certainly, devices fail," said Mark E. Bruley, vice president at the institute. "But at least 70 percent of medical device-related accidents are caused by the technique used. If you use the wrong size staples, it's going to come undone."

Many surgeons remain unaware of the extent of the problems.

"I haven't heard of serious problems," said Dr. Paul Wetter, chairman of the Society of Laparoendoscopic Surgeons. "I believe the vast majority of experience [with the devices] has been very good and very safe."

Wetter said the staplers are generally better for patients than hand-suturing and that a careful surgeon can spot most problems with the device while using it. "The row of staples can be applied in a matter of seconds, versus a half-hour or 45 minutes of suturing. It's much more precise than a human being can do by hand-sewing."

But Dr. Sidney Wolfe, director of the Health Research Group at Public Citizen, said he was concerned that the FDA was taking so long to act.

"If they were worried enough to launch an investigation two years ago, why haven't we heard anything?" he said. "They seem to be good at protecting industry, and not the public."

Dear Healthcare Professional:

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In March 2005, the WARNINGS; PRECAUTIONS, Drug Interactions; ADVERSE REACTIONS; ADVERSE REACTIONS, Post-Marketing Experience sections of the Prescribing Information; and the Medication Guide were updated to include this important new safety information. A copy of the revised full Prescribing Information and Medication Guide is enclosed. A summary of the changes is presented below.

WARNINGS

This section has been revised to include the following information:

Hepatic Injury

Severe hepatic injury, including cases of hepatic failure, has been reported rarely in patients taking AVONEX~. Asymptomatic elevation of hepatie transaminases has also been reported. and in some patients has recurred upon rechallenge with AVONEX®. In some eases, these events have occurred in the presence of other drugs that have been associated with hepatie injury. The potential risk of AVONEX® used in combination with known hepatotoxie drugs or other products (e.g. alcohol) should be considered prior to AVONEX® administration, or when adding new agents to the regimen of patients already on AVONEX®. Patients should be monitored for signs of hepatie injury (see Precautions: Laboratory Tests).

IMPORTANT DRUG WARNING

PRECAUTIONS, Drus Interactions

The section has been revised to include the following information: the potential for hepatic injury should be considered when AVONEX~ is used in combination with other products associated with hepatic injury, or when new agents are added to the regimen of patients already on AVONEX® (see WARNINGS: Hepatic Injury).

ADVERSE REACTIONS This section has been revised to include the following statement:

Hepatic injury, including hepatic failure and elevated serum hepatic enzyme

levels, has been reported in post-marketing experience (see WARNINGS:

Hepatic Injury).

The ADVERSE REACTIONS, Post-Marketing Experience section has been revised to add hepatic failure.

Additionally, the PRECAUTIONS, Information to Patients and Pregnancy sections of the Prescribing Information, and the Medication Guide were revised to include information regarding the AVONEX Pregnancy Registry. A summary of the changes is presented below.

PRECAUTIONS, Information to Patients and Pregnancy :

These sections have been revised to include the following statement:

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This new labeling will be included in packaging for AVONEX® (Interferon betala) manuthctured after April 18, 2005. All packaging will reflect the name change of Biogen Idec.

Healthcare professionals should report any serious adverse events in patients treated with

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FDA’s Med Watch reporting system by telephone (l-800-FDA-1088), facsimile (1-800-FDA- 1078), the Med Watch website at www.fda.gov/medwatch, or mailed to MedWatch, HF-2, 5600

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Enclosures:

AVONEX® (Interferon beta-la) Full Prescribing Information and Medication Guide 161023-1