To Sell Pricey Drug, Eli Lilly
Fuels a Debate Over Rationing
It Rallies Doctors, Patients to Speak Out
For Xigris, Even as Some Hospitals Balk
By ANTONIO REGALADO
Staff Reporter of THE WALL STREET JOURNAL
In the war over how health care should be allocated in the U.S., one of the big new battlegrounds is an expensive drug called Xigris.
A committee of doctors and academics was convened this year to study "ethics and rationing" in intensive-care units after debate erupted over who should get Xigris. The drug, used to treat severe sepsis, a deadly syndrome associated with severe infections, costs $6,800 per treatment. Some doctors and patients, concerned about reluctance to prescribe the drug, are questioning whether patients are dying because of tight-fisted hospital policies.
"It's amazing. This is a new, lifesaving technology that works," says Jay Steingrub, director of Baystate Medical Center's medical intensive-care unit in Springfield, Mass., who has begun speaking out on the issue. "Yet it's been rationed without the American public being aware of it."
Behind the scenes, an unconventional campaign by Xigris's maker, Eli Lilly & Co., is fueling the debate. With Xigris's sales far below expectations, Lilly is stoking a controversy over who should get expensive treatments in times of limited resources.
It gave a $1.8 million grant for the study of health-care rationing practices. It successfully lobbied for a special reimbursement of half the drug's cost for Medicare patients. It hired public-relations firms that helped the drug maker shape a rationing-debate strategy. And it has rallied patients and doctors who believe in the drug.
Dr. Steingrub, for instance, occasionally travels and speaks on behalf of Lilly, and is paid per diem consulting fees by the company. He says he began speaking out about rationing after becoming concerned that patients weren't being informed of their options. "I talk about the academic aspects" of the drug's use, he says. "I don't push the product."
Lilly's campaign for Xigris reflects the unique way in which health care is rationed in America. In other countries, for better or worse, government bureaucracies set guidelines for what drugs cost and who gets them. But in the U.S., these decisions are made every day by a vast array of gatekeepers, from doctors, to government employees to insurance officials. And all of these people are targets for a big company that wants to influence the process.
Xigris was approved in late 2001 to treat severe sepsis, which kills about 250,000 people a year. Lilly had counted on Xigris -- the first new treatment for sepsis in years -- to be a blockbuster, and some analysts were predicting sales would reach $1 billion a year. Lilly launched a giant marketing blitz; doctors arriving at one conference found Xigris's name emblazoned on the key cards to their hotel rooms.
But rising costs have forced hospitals and doctors to make hard decisions. Many expensive treatments and procedures are being scrutinized, with medical benefits closely weighed against cost. Xigris hasn't fared well in those calculations: According to Lilly, an estimated 750,000 suffer from severe sepsis each year. Sales figures suggest doctors wrote fewer than 15,000 prescriptions for Xigris in 2002. Total sales were only $100 million.
'Underutilized'
Lilly marketing executives declined to be interviewed for this article. In a prepared statement, Lilly said it believes its drug is "underutilized" because doctors don't always recognize severe sepsis and because of inadequate reimbursement from insurers and the government. Lilly says its goal is "to make sure that all patients who meet the eligibility criteria for the use of Xigris receive the treatment."
The company says it won't lower the price of the drug. Xigris's price is based on the benefit it gives patients, as well as the high cost of discovering and manufacturing the drug, Lilly says.
A recent survey published by the Society of Critical Care Medicine, a professional group, found intensive-care doctors said they were withholding treatments because of cost, even though they believed it was unethical to do so. According to the 620 doctors who answered the survey, Xigris was the most widely rationed drug: 27% said they had withheld Xigris, and 43% said they might. The survey wasn't funded by Lilly, but it was conducted by a doctor who consults with Lilly.
Some experts say the drug isn't widely used because doctors simply aren't convinced it works. In a clinical trial of 1,690 patients, 25% of Xigris patients died, compared with 31% of those on standard treatment. (Standard treatment involves putting patients on antibiotics and medicines to increase blood pressure, which typically cost less than $50 a day.) Last year, a group of scientists published a critical assessment of Xigris in the New England Journal of Medicine, arguing that another study was needed in order to "justify the use of the drug."
Lilly rebutted the published criticisms as "without merit" and says denying Xigris to desperately ill patients is "unethical." The company's clinical trial showed Xigris saves about 1 in 16 people who would otherwise die of sepsis if given only standard treatment. The rate is 1 in 8 among severe cases, Lilly says.
In March 2002, Sandra Tiffany was in a coma, suffering from sepsis. When the doctor treating her, Daniel Dea, of Providence Saint Joseph Medical Center in Burbank, Calif., prescribed Xigris, a hospital pharmacist came to the intensive-care unit to double-check the diagnosis.
Ms. Tiffany, a state senator from Nevada, got the new drug and lived.
Dr. Dea has used Xigris about 15 times since. He's had to explain his decision each time, he says, to the hospital pharmacy and other doctors. In some cases he's agreed not to use it. "We have been under pressure from the pharmacy and hospital to almost ration it," he says.
Teresa Lee-Yu, pharmacist at Saint Joseph, says that for every Xigris use, there is "a significant loss," of $3,000 or more for the hospital. "It would be a budget-buster if it was not used appropriately, or used indiscriminately," she says. Xigris is "an expensive drug with side effects," says Myron Berdischewsky, chief medical officer at the nonprofit Catholic hospital. While doctors have the ultimate say in which drugs are used, he says, "today cost is part of the equation. It's not so much rationing drugs, but using them rationally."
Shortly after treating Sen. Tiffany, Dr. Dea says he received a phone call from Perry Communications Group Inc., a public-relations firm in Sacramento, Calif., which was seeking Xigris success stories on behalf of Lilly. Sen. Tiffany, 54, has since worked closely with the agency, giving TV interviews to describe her near-death experience. She's been given a "second chance to live" she says, and her aim is to "lift awareness" of the Xigris treatment.
Dr. Dea says he has begun work on a new study of Xigris funded by Lilly and has become a member of Lilly's speakers bureau. He gets a fee from Lilly, but Dr. Dea says it doesn't influence his use of the drug.
Lilly pays doctors speaking fees of $1,000 or more, depending on their seniority and expertise.
Rationing isn't part of the talking points and slides Lilly gives to its lecturers, who focus on sepsis and the drug's application. But the issue often comes up. At one educational roundtable he attended, doctors were asked which issue most affected their use of Xigris. "Everyone said the cost," Dr. Dea says.
Xigris's slow sales are a sore disappointment after Lilly invested nearly two decades and, the company says, "hundreds of millions" of dollars into development of the drug. Sepsis is an inflammatory response that can follow infection brought on by pneumonia or major surgery. But because it's a syndrome, not a single disease, the condition is tricky to diagnose -- and difficult to develop treatments for. Promising drugs tested by several companies during the 1990s failed.
Lilly's drug is a version of a molecule produced by the human body that blocks inflammation and clotting. The protein is complex and not easily made. But in 2000, the company's effort appeared to be rewarded. Lilly said its key study showed the drug was saving lives. The study was halted early and the company applied for government approval to market the drug.
Lilly expected Xigris to provide a much-needed boost after the loss of patent protection, in 2001, of its blockbuster antidepressant Prozac. Xigris was also important because it was a first-of-a-kind treatment for serious disease. "No medicine better symbolizes our mission than Xigris," Sidney Taurel, Lilly's chairman, president and CEO, wrote in the company's 2001 annual report, calling it "one of our industry's genuine breakthroughs."
The Food and Drug Administration's advisory panel split 10-10 on whether to recommend approval for Xigris, with some saying another clinical trial was needed. After studying Lilly's data, the FDA approved the drug in November 2001 -- but only for a subset of the sickest patients. The study indicated Xigris worked best in patients with the most severe form of the disease.
The limited definition of who can get the drug has contributed to its slow sales, Lilly says. It has several other continuing trials of the drug, hoping to win approval for other patient groups.
Worried about the drug's high cost and side effects, hospitals quickly began writing guidelines for its use. Many adopted the criteria used in Lilly's key trial -- which excluded several types of patients, including those with cancer, pregnant women and people over 80.
Falling Short
By the spring of 2002, it was clear sales were falling far short of expectations. Lilly shook up its external public relations, putting the contract for Xigris out for bid. It had been held by Edelman Worldwide, a large New York firm, but the winning proposal came from Belsito & Co., a small shop in Manhattan. Its pitch for the Lilly contract was titled, "The Ethics, The Urgency and The Potential." Marybeth Belsito, the ad company's president, says "the premise was that it was unethical not to use the drug."
Lilly put Ms. Belsito in contact with Mitchell Levy, head of the medical ICU at Rhode Island Hospital in Providence. Dr. Levy had previously conducted the survey of ICU doctors who said Xigris was the most widely rationed drug.
Ms. Belsito proposed that Dr. Levy lead a study of Xigris rationing. Dr. Levy insisted the study take a broad look at the rationing issue. It was "an opportunity to study something that would never otherwise get funding," he says.
Eventually Lilly agreed to provide $1.8 million for a comprehensive study of ICU rationing practices. The 20-person group, called the Values, Ethics & Rationing In Critical Care Task Force, has yet to present any findings, and its efforts aren't specifically aimed at Xigris. However, the task force includes many leading ethicists, hospital directors and ICU specialists who are in a position to influence views on the drug.
Dr. Levy, who is also a member of the faculty at Brown University's Medical School, hopes the rationing task force will help ground physician's decisions more firmly in medical evidence. "Lilly funded the consortium because they know the data behind their drug is damn good. They don't direct the task force, but they know we are going to prioritize treatments based on evidence-based data."
At their first meeting, at a Scottsdale, Ariz., spa in January, the group laid plans for a paper outlining the rationing phenomenon and a more comprehensive survey of how ICU doctors withhold treatments.
Dr. Levy says his initial rationing survey was motivated by his concern that the drug was being used inconsistently, including at the network of four nonprofit hospitals where he works, Lifespan Health Systems Corp. Dr. Levy's ICU was starting to use Xigris frequently, but the ICU at Miriam Hospital, another member of the network, used it rarely, leading to a noticeable difference in their pharmacy budgets.
Paul Yodice, head of Miriam's ICU, says the difference may be because of chance, given that each ICU sees different patients. But he adds that Xigris is "extraordinarily expensive." The expenditures are hard to warrant given his doubts over whether the drug really works, Dr. Yodice says.
Lilly has had some success in its effort to clear the way for wider use of the drug. Lilly won a new federal diagnostic code for severe sepsis, so hospitals would begin reporting how many patients they see who have the condition -- and might be eligible to receive the drug. The company has also encouraged state legislators to introduce legislation designed to promote the drug's use by mandating that sepsis cases be tracked by hospitals and reported to the state government.
Lilly successfully petitioned the Centers for Medicare and Medicaid Services for "new technology" status for Xigris, winning a special dispensation for 50% reimbursement from the federal government, up to $3,400. It was the first time such approval has been given. In most cases, hospitals are reimbursed for the cost of treating a disease or condition, rather than for a specific drug.
Sen. Tiffany says she personally called Health & Human Services Secretary Tommy Thompson's office to lobby for the approval. |
