Diabetes drug maker hid test data on risks, files indicate

In the fall of 1999, the drug giant SmithKline Beecham secretly began a study to find out if its diabetes medicine, Avandia, was safer for the heart than a competing pill, Actos, made by Takeda. Avandia’s success was crucial to SmithKline, whose labs were otherwise all but barren of new products. But the study’s results, completed that same year, were disastrous. Not only was Avandia no better than Actos, but the study also provided clear signs that it was riskier to the heart.

But instead of publishing the results, the company spent the next 11 years trying to cover them up, according to documents recently obtained by The New York Times. The company did not post the results on its Web site or submit them to federal drug regulators, as is required in most cases by law.

“This was done for the U.S. business, way under the radar,” Dr. Martin I. Freed, a SmithKline executive, wrote in an e-mail message dated March 29, 2001, about the study results that was obtained by The Times.

The heart risks from Avandia first became public in May 2007, with a study from a cardiologist at the Cleveland Clinic who used data the company was forced by a lawsuit to post on its own Web site. In the ensuing months, GlaxoSmithKline officials conceded that they had known of the drug’s potential heart attack risks since at least 2005.

But the latest documents demonstrate that the company had data hinting at Avandia’s extensive heart problems almost as soon as the drug was introduced in 1999, and sought intensively to keep those risks from becoming public. In one document, the company sought to quantify the lost sales that would result if Avandia’s cardiovascular safety risk “intensifies.” The cost: $600 million from 2002 to 2004 alone, the document stated.

Mary Anne Rhyne, a GlaxoSmithKline spokeswoman, said that the company had not provided the results of its study because they “did not contribute any significant new information.” The company said that Avandia was safe and that Dr. Freed no longer worked for GlaxoSmithKline.

A panel of experts will meet Tuesday and Wednesday to decide whether Avandia should still be sold and whether it is ethical to test Avandia directly against Actos. Whether to withdraw Avandia is a question that has split the FDA, with some officials arguing that the drug is useful despite its risks and others insisting that it must be withdrawn.

According to the documents, Dr. John Jenkins, director of the agency’s office of new drugs, who has argued internally that Avandia should remain on the market, briefed the company extensively on the agency’s internal debate.

“It is clear the office of new drugs is trying to find minimal language that will satisfy the office of drug safety,” a top company official wrote in an e-mail message after he spoke with Dr. Jenkins, according to a sealed deposition obtained by The Times.

In the deposition, Dr. Rosemary Johann-Liang, a former supervisor in the drug safety office who left the FDA after she was disciplined for recommending that Avandia’s heart warnings be strengthened, said of Dr. Jenkins’ conversations with GlaxoSmithKline, “This should not happen, and the fact that these kind of things happen, I mean, I think people have to make a determination about the leadership at the FDA.”

An FDA spokeswoman said the agency would not comment on the contents of the deposition. Members of Congress, where the Avandia case has led to legislative changes, said they were outraged at GlaxoSmithKline’s behavior. Besides the trial comparing Avandia with Actos, the company also conducted trials comparing Avandia with glyburide, a cheaper and older diabetes medicine.

When Rhona A. Berry, a company official, asked about publishing two of the trials, Dr. Freed responded in an e-mail message dated July 20, 2001, that referred to Avandia by the abbreviation of its generic name, rosiglitazone: “Rhona — Not a chance. These put Avandia in quite a negative light when folks look at the response of the RSG monotherapy arm,” the message said. “It is a difficult story to tell and we would hope that these do not see the light of day.”

With Avandia, GlaxoSmithKline has done more than hide trial data. An FDA reviewer who closely examined a landmark Avandia clinical trial called “Record,” found at least a dozen instances in which patients taking Avandia suffered serious heart problems that were not counted in the trial’s tally of adverse events, mistakes that further obscured Avandia’s heart risks.

The company’s conduct of the Record trial has received sharp criticism from medical leaders for other reasons as well. To compare Avandia and Actos in 1999, researchers at SmithKline measured Actos’s effects in patients in the same way that they had conducted earlier trials of Avandia so that the results for the two drugs could be compared. When the results of the study suggested that Avandia was more dangerous than Actos, the company decided against further comparisons. Visit the New York Times for the article. title=http://www.imakenews.com/eletra/gow.cfm?z=kcprofessional%2C161639%2C0%2C462787%2Cb11

Kimberly-Clark Professional launches Kimtech One-Step Germicidal Wipe to kill organisms that cause HAIs

Kimberly-Clark Professional announced today the North American launch of KIMTECH One-Step Germicidal Wipe at the 37th Annual Educational Conference & International Meeting of the Association for Professionals in Infection Control and Epidemiology (APIC), July 11–15 at the Ernest N. Morial Convention Center in New Orleans, LA.

KIMTECH One-Step Germicidal Wipe is an EPA registered product that features a new chemistry to quickly and effectively clean and disinfect environmental surfaces, killing MRSA in 30 seconds and C. difficile spores in 6 minutes, versus 10 minutes, as required by other environmental surface disinfectants.

Eliminating infection-causing organisms, some of which can survive on environmental surfaces for up to 5 months, is a top concern for infection control and environmental services professionals according to a recent survey conducted by Kimberly-Clark Professional. In fact, more than 78 percent of survey respondents stated their greatest surface cleaning challenge was maintaining proper contact times to kill the largest number of organisms, while more than 55 percent of respondents were concerned about the effectiveness of their current surface cleaning products and processes for killing pathogens that cause healthcare-associated infections (HAIs).

KIMTECH One-Step Germicidal Wipe combines the power of peracetic acid and hydrogen peroxide with a proprietary wiper treatment, which keeps the solution active over time allowing it to kill a broad spectrum of organisms. The peracetic acid breaks into the outer membrane or coat of the target spore, bacteria or virus. Then, the hydrogen peroxide oxidizes and destroys its internal components. This dual action quickly kills 35 organisms.

The pre-moistened KIMTECH One-Step Germicidal Wipe is dispensed as ready-to-use individual sheets. The single-use wipe means less cross-contamination between rooms and surfaces. Compared to traditional cleaning methods, such as disinfectant sprays and bucket systems, the risk of spills and dilution errors are eliminated, and inhalation-related issues are reduced.  This groundbreaking chemistry is non-corrosive and is not damaging to most surfaces. The KIMTECH One-Step Germicidal Wipe active ingredients also decompose into water, oxygen and vinegar.

The recent Kimberly-Clark survey revealed that both infection control and environmental services professionals recognize the importance of removing and killing microbes on surfaces, with more than 90 percent of respondents stating environmental surface cleaning is extremely important in controlling infection in the healthcare environment. In fact, more than 64 percent of environmental services professionals stated they collaborate at least quarterly with their infection control team to evaluate surface cleaning products and protocols.

Today, Clostridium difficile infections (CDI) account for 15-25 percent of all antibiotic-associated disease (AAD).[1] In fact, a recent survey by Duke University revealed that C. difficile has surpassed MRSA as the most prevalent healthcare-associated infection among patients in the southeast U.S. There are 3 million new cases of CDI annually, with 500,000 hospitalizations for C. difficile Associated Disease (CDAD) each year. The infection results in some 15,000 deaths and an in-hospital mortality rate approximately 4.5 times higher than average. A comprehensive and coordinated approach to preventing infection in the healthcare setting includes surface disinfection and hand hygiene as well as the appropriate application of barrier precautions. For more information and/or a free sample of KIMTECH One-Step Germicidal Wipe, contact your Kimberly-Clark representative or visit www.kimtech.com/usgermicidalwipe.

Knowledge is Power: Search and Destroy - Eliminating Pathogens in the Patient Care Environment

The Kimberly-Clark Knowledge Network will host in-booth educational sessions on environmental cleaning and effective elimination of pathogens such as C. diff, MRSA and VRE. Each session earns participants two hours of continuing education credit. Sessions are held every hour, starting on Monday, July 12, at 12 p.m., and Tuesday and Wednesday, July 13 and 14, starting at 10:15 a.m. CDT. To learn more, visit Kimberly-Clark at APIC booth #1234. Visit www.kcprofessional.com.

Federal agents seize Bee-Shield Hand Sanitizer from Puerto Rican company

At the request of the U.S. Food and Drug Administration, U.S. Marshals on July 8, 2010, seized $230,000 worth of hand sanitizing gel made by Puerto Rico Beverage Inc. of Maunabo and distributed by Lord Pharmaceutical, LLC, doing business as Bee International Distributors. The hand sanitizer is distributed only in Puerto Rico.

The product Bee-Shield Hand Sanitizer with Aloe Vera (10 fl. oz. or 1 gallon bottles) is an unapproved new drug and in violation of federal law. The seizure warrant was issued in the U.S. District Court for the District of Puerto Rico by U.S. District Senior Judge Salvador E. Casellas.

The gel was marketed as a product that could kill 99.99 percent of viruses, bacteria, and fungi. However, its safety and effectiveness have not been established. Additionally, the active ingredient, benzalkonium chloride, is not recognized as safe and effective for over-the-counter (OTC) antifungal use, making it noncompliant with FDA’s final monograph for OTC topical antifungal drug products.

The hand sanitizing gel is an unapproved new drug under the Federal Food, Drug and Cosmetic Act and is therefore not permitted to be introduced into interstate commerce. Additionally, the product is subject to the final monograph for Topical Antifungal Drug Products because its labeling contains antifungal treatment claims. The product also represents that it prevents the disease caused by the H1N1 influenza virus, that it is effective against viruses and provides extended antimicrobial efficacy. The FDA is unaware of any scientific evidence to support these claims.

Moreover, the product, which is not labeled correctly, is misbranded under the law because its packaging does not list all inactive ingredients, and its label fails to contain the place of business of the manufacturer, packer, or distributor.

The FDA inspected the product manufacturing facility between Aug. 19, 2009, and Sept. 28, 2009, and found numerous violations of U.S. current Good Manufacturing Practice requirements including failure to have a Quality Control Unit; failure to maintain a clean and sanitary processing, packing and holding area; failure to conduct appropriate lab tests; and many other violations.

Following that inspection the firm had agreed to recall and destroy its products but has continually failed to follow through on its commitments. This failure on behalf of the company led the government to request a seizure of the products. On March 3, 2010, the FDA warned consumers not to use this product because it contained high levels of a bacterium, Burkholderia cepacia, that can cause serious infections in humans. Visit FDA for more information.

Efficiency comes to the hospital

Two years ago, the supply system at Seattle Children’s Hospital was so unreliable that Susanne Matthews, a nurse in the intensive care unit, would stockpile stuff — catheters in the closet, surgical dressings in patients’ dresser drawers and clamps in the nurse’s office. And she wasn’t the only one. This, in turn, made the shortages more acute.

On a busy day last month in the I.C.U., it took Matthews just a few seconds to find the specialized tubing she needed to deliver medicine to an infant recovering from heart surgery. The tubing was nearby, in a fully stocked rack, thanks to a new supply system instituted by the hospital early last year following practices typically used in manufacturing or retailing, not healthcare.

There are two bins of each item; when one bin is empty, the second is pulled forward. Empty bins go to the central supply office and the bar codes are scanned to generate a new order. The hospital storeroom is now half its original size, and fewer supplies are discarded for exceeding their expiration dates.

The system is just one example of how Seattle Children’s Hospital says it has improved patient care, and its bottom line, by using practices made famous by Toyota and others. The main goals of the approach, known as kaizen, are to reduce waste and to increase value for customers through continuous small improvements.

Manufacturers, particularly in the auto and aerospace industries, have been using these methods for many years. And while a sick child isn’t a Camry, Seattle Children’s Hospital has found that checklists, standardization and nonstop brainstorming with front-line staff and customers can pay off. The program, called “continuous performance improvement,” or C.P.I., examines every aspect of patients’ stays at the hospital, from the time they arrive in the parking lot until they are discharged, to see what could work better for them and their families.

Last year, amid rising healthcare expenses nationally, C.P.I. helped cut Seattle Children’s costs per patient by 3.7 percent, for a total savings of $23 million. And as patient demand has grown in the last six years, he estimates that the hospital avoided spending $180 million on capital projects by using its facilities more efficiently. It served 38,000 patients last year, up from 27,000 in 2004, without expansion or adding beds.

Similar methods are now in place at other hospitals and health systems, including Beth Israel Deaconess Medical Center in Boston, Park Nicollet Health Services in Minneapolis and Virginia Mason Medical Center, also in Seattle. So many others have called for advice that Seattle Children’s put together a two-day workshop, presenting it to more than 200 medical workers and health care leaders from the United States and Europe.

“Some people think they have to choose between quality of care and saving money,” said Dr. David Chand, who attended the training and now uses C.P.I. methods at Akron Children’s Hospital in Ohio. To increase the number of surgeries the hospital could perform, Dr. Chand’s team spent about $20,000 overhauling the process to sterilize instruments, avoiding a $3.5 million expenditure to expand that department. More efficient scheduling in the M.R.I. department reduced the average waiting time for non-emergency M.R.I.’s from 25 days to 1 to 2.

All medical centers, especially larger ones, would have significant return on investment by using operations management techniques like C.P.I., says Eugene Litvak, president and chief executive of the Institute for Healthcare Optimization and an adjunct professor of operations management at the Harvard School of Public Health.

Techniques like C.P.I. may indeed be hard for many hospitals to put into effect, says Mark Graban, a senior fellow at the Lean Enterprise Institute, a nonprofit research, education and publishing company. The process takes a large amount of time and requires a culture shift that many hospitals may not be able to accommodate or sustain. “If the leadership tries to force new ways of doing things, the staff may chafe under the successive changes,” he says.

Standardization is also a C.P.I. cornerstone. Last year, 10 surgeons at Seattle Children’s performed appendectomies, and each doctor wanted the instrument cart set up differently. The surgeons and other medical staff members used C.P.I. to come up with a cart they all could use, reducing instrument preparation errors as well as inventory costs.

Dr. Lynn D. Martin, director of the anesthesiology and pain medicine department, says changes previously were instituted only when existing systems failed. Using C.P.I., teams can now make changes any time they think they can improve a process. When the operating room team saw that a tonsillectomy procedure involved filling out 21 separate forms, it sat down with the print vendor to remove duplications — and cut the number to 11.

Using C.P.I., the hospital has reduced the waiting time for many surgeries from three months to less than one. Recently, the bottleneck was not the surgeons’ time, but a lack of available inpatient beds for recovery. Examining the hospital’s census, administrators saw that there were empty beds on weekends. They realized that by scheduling more surgeries on Fridays, patients could recover over the weekend, when more beds were free. The change also benefited parents and patients who would miss fewer work and school days.

Lack of space in the recovery room was another logjam, and the hospital planned a $500,000 renovation to enlarge it. But a C.P.I. team saw that if a child’s parents went to a common waiting room during surgery, instead of an individual recovery room, more surgeries could be scheduled. Parents were given beepers to alert them when their child would arrive in the recovery room — and maps and colored lines on the walls helped point the way. Plans for the expensive renovation have been scrapped. Visit the New York Times for the complete article.

New government report raises questions about CT scans at Illinois hospitals

The information from the government shocked administrators at Edward Hospital. Their doctors were ordering so-called double CT scans — one using injected dye, one without — for patients at far higher rates than other hospitals in Chicago and across the nation. In the process, patients were getting large doses of radiation. The hospital launched an investigation, and physicians began to focus on curbing use of the scans.

This is just what the government hopes will happen as it publishes more information on the quality of healthcare in the U.S., including just-released, first-of-its-kind data about medical imaging. The data release is part of an ongoing effort to shine a spotlight on how well hospitals follow guidelines for care, meet patients' needs and end up saving lives. More than 4,600 hospitals across the U.S. submit information to the government, which posts it on a Web site called Hospital Compare.

Late last week, for the first time, information was made public about services provided in hospital outpatient settings, including emergency rooms, observation units and clinics. It showed that Illinois hospitals provided double chest CT scans twice as often as did hospitals nationally in 2008. In most cases, a single scan is all that's necessary. Illinois' rate of double CT scans of the abdomen also exceeded the national average.

The question is whether imaging procedures are being overused in Illinois, exposing people unnecessarily to potentially cancer-causing radiation. Although imaging tests help doctors make diagnoses and save lives, experts believe a significant number may be unwarranted.

At Edward Hospital, 70 percent of hospital outpatients who got chest CTs received double scans in 2008, compared with a national average of 5 percent. Similarly, 71 percent of patients with abdominal CTs got two scans instead of one at Edward, compared with a national average of 19 percent. The practice is potentially harmful; each double chest CT exposes patients to 700 times more radiation than a chest X-ray, while each double abdomen scan delivers 22 times more radiation. Recent research confirms a link between cancer and radiation exposure from diagnostic tests.

Until the government sent an advance copy of the data to Edward Hospital in February, the hospital had no idea its practices were out of line. It "made us realize we better look at this," said Ellen Stimac, director of performance improvement at Edward Hospital, affirming the medical center's commitment to addressing the issue.

The new data released by the government also examines follow-up mammograms for women screened for breast cancer. Dr. David Ansell, chief medical officer at Rush University Medical Center, questioned the usefulness of the information and the government's conclusion that follow-up mammogram rates under 8 percent may be too low, while rates above 14 percent may be too high. More meaningful would be information about how many cancers were detected per thousand women screened by various institutions, the size of those cancers, and whether women were referred to treatment within a reasonable time, he suggested. Visit the Chicago Tribune for the article.

Hospital woes show challenges of recovery

PORT-AU-PRINCE, Haiti — It was a simple problem with a novel solution. Doctors, nurses and technicians at Haiti's most important hospital had not been paid since before the earthquake — causing strikes and staffing shortages, and turning the facility into a dangerously inefficient, rat-infested mess. So in March, the American Red Cross volunteered to donate a small part of the $468 million it raised for earthquake relief toward supporting their salaries.

But the $3.8 million promised to the hospital is only now being delivered after four months of negotiations and red tape. While billions were spent on short-term projects, including medical assistance, doctors' strikes have continued and neglected patients at the city's main medical facility were left to suffer and die.

The breakdown at Haiti's State University Hospital is a prime example of the difficulty involved in trying to grind out a successful recovery. Six months after the magnitude-7 quake leveled much of the city and turned the hospital's courtyard into a grisly open-air morgue, promises to help Haiti become more self-sufficient have produced often frustrating results.

Sources involved with the project say the problem came down to clashing styles, needs and timetables. Haitian hospital administrators were trying to please government officials and satisfy extremely disgruntled employees while maintaining control of their institution.

The Red Cross, meanwhile, was trying something new: Disaster relief funds rarely go to fix up local institutions, especially ones run by the government. Doing so required heavy auditing and learning a new set of rules for operating.

Former U.S. President Bill Clinton, who is helping oversee reconstruction, said in a Saturday interview that his staff worked hard to see the agreement through — in large part because it might encourage other donors to support existing but foundering Haitian institutions.

"It took a while for it to get together, but we were working very intently on this," Clinton said by phone. "This is a little bit of a departure from what the Red Cross or other NGOs have done in the past. When you're trying to change all these cultures it's really something."

But at the hospital, frustrations are running high. Unpaid staff have little incentive to work — even passion for helping those in need can only take them so far. Cleanliness, thoroughness and efficiency fall by the wayside.

For a hospital in rundown Port-au-Prince, where public sanitation is nonexistent, that means horror-show conditions. The operating rooms are not sterile, and doctors say vermin sometimes run through during surgery.

With much of the building damaged from the earthquake, patients endure long waits for short-staffed doctors in hot, flimsy tents that offer little protection from the elements. Visit here for the article.

Diabetes drug Avandia has FDA split over new concerns about its safety

New federal analyses released Friday raised additional questions about the safety of the controversial diabetes drug Avandia. The analyses are among more than 700 pages of documents that were posted on the Food and Drug Administration's Web site in advance of a meeting next week of scientific advisers to once again consider whether Avandia should remain on the market. During a briefing for reporters Thursday, FDA officials cautioned that agency experts remained split over the drug.

"There's not complete unanimity within the FDA about interpretation of these data, and that's one of the reasons we're going to the advisory committee," said Janet Woodcock, director of the FDA's center for drug evaluation and research.

Among the new analyses are critiques of a study known as Record, which the company sponsored and touted as evidence that the drug is safe. Thomas A. Marciniak of the FDA's division of cardiovascular and renal products concluded the company's analysis was flawed and the data show the drug increases the risk for heart attacks. But another analysis by Ellis Unger, a deputy director in FDA's drug division, questioned Marciniak's findings. Critics said data provide convincing evidence that the drug increases the risk for heart attacks, strokes and death and should be removed from the market.

"What they were able to do in many ways was confirm my worst fears about the drug," said Steven E. Nissen, a Cleveland Clinic cardiologist who first raised questions about Avandia's safety and has campaigned to have it removed from the market. GlaxoSmithKline, which makes Avandia, disputed conclusions that the drug was unsafe, countering that many other studies have found it safe and effective.

"Together they show that this medicine does not increase the overall risk of heart attack, stroke or death," Murray Stewart, the company's vice president for clinical development, said in a statement.

Avandia, approved in 1999 to treat the most common form of diabetes, was once one of the world's most popular drugs. It controls blood sugar levels by sensitizing the body to insulin. But a series of studies has raised questions about whether it increases the risk for cardiovascular problems, a leading cause of death among diabetics. That prompted the FDA to issue a warning about the drug's safety, causing sales to plummet.

Deep divisions among FDA officials about Avandia led the agency in 2007 to decide to leave the drug on the market, and hundreds of thousands of diabetics still use it. Visit the Washington Post for the article.

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