May Offer Example for U.S. Debate
July 21, 2000
By STEPHEN D. MOORE
Staff Reporter of THE WALL STREET JOURNAL
As the drive to rein in the price of prescription drugs in the U.S. builds, one of the side effects of capping what drug manufacturers charge can be seen in a growing battle over cancer care in Europe.
European governments, which pick up most of their citizens' health-care tab, need to keep drug prices down because state budgets are tight. But the system, according to patients and physicians from Berlin to London, has led to rationing of, and delayed access to, new anticancer drugs.
In some places, drug availability depends on whether the local health authorities are willing to pay their share. In other places, the introduction of a new medicine can be held up as drug makers spend months haggling with individual European governments over reimbursement prices. Elsewhere, the state bans altogether drugs it deems too costly.
The outcry in Europe over cancer drugs adds a crucial talking point to the debate in the U.S. over high drug prices. At the heart of the matter is the question of whether elderly Medicare recipients should have prescription-drug coverage. U.S. drug makers fear that such a move would lead to government-imposed price controls similar to those in Europe. Critics of the U.S. pharmaceutical industry cite Europe's low drug prices as an example of how drug makers overcharge Americans.
The debate drew fresh fuel from the Senate's approval Wednesday of an amendment that would allow American pharmacists and wholesalers to import drugs made outside the U.S. in facilities approved by the Food and Drug Administration. The assumption is that Europe would become a major source of cheaper prescription drugs. The amendment faces other legislative hurdles, but its easy passage through the Senate amid fierce lobbying by drug makers reflects the issue's political firepower.
An Ailing System
While no such concerted effort on high drug prices exists in Europe, the pockets of protest over drug availability are growing stronger, and more change is emerging in an old and ailing system. Much of Europe's postwar recovery came with a social safety net that offered the citizenry almost blanket health care at little cost. In recent years, though, demographics and budgetary pressures have torn holes in that net. Shrinking birth rates and a growing pool of elderly are pinching tax rolls and squeezing pension funds. As governments look to cut costs wherever possible, state health-care officials try to control prices in the one area where they consistently rise: prescription drugs.
Demographics also underpin the cancer-drug debate. Experts predict that the incidence of cancer will rise relentlessly among Europe's aging populations. This will boost demand for a spate of revolutionary anticancer medicines expected to reach the market during the coming decade. At the same time, the current generation of Europeans is more savvy and demanding than its postwar predecessors when it comes to health care.
"Europeans have tended to say the doctor knows best," says John Rees, a professor of hematology at the University of Cambridge, England. "Now, with the Internet, they're knocking on every door they can to get the medicines they want."
In Europe's prescription-drug war, Belgium and Norway have emerged as particular trouble spots. They were cited in a recent report by the U.S. Trade Representative's office for extreme delays in approval of pricing and reimbursement of new drugs. U.S. drug giant Merck & Co. has filed complaints against both countries with the European Free Trade Association's surveillance authority over delays besetting Singulair, a new antiasthma drug that has piled up sales in the U.S.
Innovative cancer drugs have gotten bogged down even earlier in the system. Herceptin, a new breast-cancer medication from San Francisco-based Genentech Inc., was approved two years ago by regulators in the U.S., where it benefited from an accelerated review offered to novel cancer therapies. It is still awaiting regulatory approval in most of Europe, where the drug will be marketed by Genentech's parent, Roche Holding Ltd.
Many European countries also attempt to restrict demand after new medicines reach pharmacy shelves. Drugs can be saddled with tight prescribing rules to limit consumption. Patients across Europe are fighting for improved access to older drugs like Taxol, the world's top-selling anticancer drug, from Bristol-Myers Squibb Co.
Sometimes governments simply refuse to raise state-hospital budgets enough to cover the cost of an expensive new drug, forcing physicians to prune costs elsewhere or deny treatment when their money runs out. Herbert Pinedo, an oncologist at University Hospital in Amsterdam, says he has exceeded his budget for pharmaceuticals during the past three years because of liberal prescribing of so-called "taxanes" -- either Taxol or Taxotere, a similar anticancer treatment from Aventis SA, the Franco-German company. But outside of big-name university hospitals, Dr. Pinedo says, use of taxanes is tightly controlled. "Patients who really want treatment with a taxane can ask to be referred to an academic hospital," he adds, "but most patients don't know that."
A recent industry-funded study by U.S. consulting firm Lewin Group Inc. examining prescribing patterns between 1996 and 1998 suggests that the curbs have been effective. While 99.9% of patients with advanced breast cancer in the U.S. received treatment with a taxane, the comparable figure was 48% for the Netherlands and only 25% for Britain.
The anemic U.K. result partly reflects a form of rationing called postal-code prescribing. Under this practice, access to treatment in virtually every disease can vary, depending on where a patient lives and the will and ability of the local health authority to pay.
Laurie Allford was battling breast cancer in the Northamptonshire district, where the health authority refuses to pay for Taxotere. She was denied treatment with the drug until irate letters to British Prime Minister Tony Blair and her local member of Parliament won her a transfer to the neighboring Leicestershire health authority, which does pay for Taxotere. After several months of treatment, the drug seems to be working, Mrs. Allford says, "but I had to fight for this. A terrible fight it was."
Judith Ainge, a 54-year-old housewife from Desborough, England, was diagnosed with breast cancer and had a mastectomy in 1996. When new tumors appeared last year, Mrs. Ainge had more surgery and her oncologist suggested follow-up treatment with Taxotere.
But Mrs. Ainge is also covered by the Northamptonshire district health authority. Initially, she had to settle for older anticancer drugs, which failed: New tumors have appeared in recent months. Mrs. Ainge is convinced that Taxotere is her last chance to keep the disease at bay. "But the oncologist wouldn't give it to me straightaway. He still had to pick and choose who he's giving Taxotere to," she says.
Her fight ended last month when a National Health Service panel recommended that the taxanes be adopted as the standard therapy for ovarian and advanced breast cancer. The recommendation follows a succession of moves by the Labor government to upgrade cancer care as part of a five-year, multibillion-pound overhaul of the NHS. During an appointment with her oncologist this week, Mrs. Ainge learned she will be able to begin treatment with Taxotere as soon as arrangements can be completed with her local hospital.
Willing to Travel
Often, the quest for the latest treatments leads west across the Atlantic. Prodded by Internet-savvy patients, European specialists are racing to join trials of promising new drugs developed in the U.S., says Jose Baselga, a Spanish oncologist who spent more than a decade in the U.S. before returning to his native Barcelona four years ago. "If we can't bring the drug they want here," he adds, "people are willing to travel to New York or wherever necessary to get it."
For European patients and pressure groups, the biggest breakthrough so far has come in Germany. Maverick cancer specialists have exploited a loophole in German law to treat hundreds of breast-cancer patients with Herceptin, which hasn't been approved by EU drug regulators. "Approval in Europe is two years behind the U.S. -- but usage in Germany certainly isn't," boasts Wolfgang Eiermann, a cancer specialist at the Frauenklinik vom Roten Kreuz in Munich.
The first time many German women heard about Herceptin was in late 1995, when Dr. Eiermann appeared on a popular TV talk show. The anchorwoman was one of his patients and had invited him to talk about research under way in breast cancer. Dr. Eiermann was a scientific adviser to Genentech at the time and saw an opportunity to boost recruitment to ongoing clinical trials of Herceptin. Talking up an experimental drug on TV irked some peers, Dr. Eiermann says, but he remains unrepentant. "To be successful with a study, you have to market it," he says.
Herceptin has been heralded as a breakthrough for about a third of all breast-cancer patients because they carry a genetic mutation that triggers a particularly aggressive form of the disease. It works by targeting tumors caused by that genetic glitch without harming healthy tissue. The drug isn't a cure. But in clinical trials that earned approval from the FDA, Herceptin significantly slowed tumor growth and increased one-year survival rates in women with advanced breast cancer.
Moreover, by using diagnostic tests to pinpoint women with the type of tumor most likely to benefit from Herceptin treatment, physicians have been able to achieve positive responses in up to 60% of patients treated in clinical trials, an unusually high level for an anticancer therapy. Screening also helps prevent waste in use of Herceptin, which is a crucial consideration for payers since a year's therapy costs roughly 60,000 German marks, or about $28,600.
A Different Source
Dr. Eiermann and several other German cancer specialists enrolled patients in the pivotal clinical trial that earned Herceptin FDA approval, and Genentech continued to supply the drug to those patients after the trial ended. But new German patients who were candidates for Herceptin treatment had to find a different source.
The solution was a little-known German law that allows pharmacists to import any drug that has been approved by regulators anywhere in the world. Several pharmacies offered to import Herceptin from the U.S., and a few oncologists began prescribing it. Gerhard Schaller, a cancer specialist in Berlin, sees patients from as far away as Hamburg and Heidelberg "because they couldn't find doctors willing to treat them with Herceptin," he says. Many oncologists, Dr. Schaller adds, remain wary of potential side effects associated with Herceptin, but he says his experience suggests that most side effects can be controlled.
Finding someone willing to pay for Herceptin treatment was tougher than finding a physician to prescribe it. But Dr. Eiermann proposed guidelines for treatment with Herceptin in discussions with private insurers and funds that provide health-care coverage for the vast majority of Germans. The guidelines follow U.S. practice, and in many cases physicians are required to seek specific authorization before beginning treatment. The funds and insurers went along with the proposal, saying, Dr. Eiermann recalls, that "if there isn't anything else for these patients, in this special situation, we'll pay."
As long as the number of women seeking treatment remains small, he doesn't
anticipate problems with access to Herceptin. But he frets about a possible
crackdown by payers if, as expected, Herceptin is approved by EU regulators
later this year and thousands of new breast-cancer patients clamor for
the drug. "Nobody is willing to discuss who will pay for this at the moment,"
Dr. Eiermann says. "It's all wait and see. Politicians always are years behind developments in science."
Britain's Poor Showing
In Britain, politicians largely ignored cancer until international studies of cancer survival highlighted the poor showing of patients treated in Britain's state-financed health system. An EU study that followed up 3.5 million cancer patients in 17 countries through 1994 found that the five-year survival rate for breast cancer in England was 66.7%. That was well behind Sweden and France, where survival was over 80%, and also lagged behind the European average of 72.5%.
The British government took the first step toward addressing the problem five years ago when medical directors from England and Wales issued a report urging an overhaul of cancer care to eliminate inequities in treatment and drug access. "There was both patient and professional dissatisfaction with the way our cancer services were organized. We really didn't have any all-embracing policy on cancer," says Robert Haward, medical director at the Northern and Yorkshire Cancer Registry and head of a group that issues national guidelines for cancer care. "Our most pressing problems have been access to bona fide teams of specialists" with proper training and equipment.
The resulting overhaul has been buoyed by the government's promise of a 17 billion pound ($25.7 billion or 27.5 billion euro) funding injection over the next five years. A big chunk of that money will go to improving access to new cancer drugs. A bipartisan All Party Group on Cancer from Parliament noted in a 1998 briefing paper that Britain spent only 95 pence ($1.40) per capita on chemotherapy in 1997, compared with 776 pence per capita in the U.S., 624 pence in Germany and 381 pence in Italy.
Crucial decisions about access to new drugs have been assigned to a newly created NHS unit called the National Institute for Clinical Excellence, or NICE. The role of NICE is to conduct cost-effectiveness studies for the health service. And at a time when virtually every European country is struggling to steer scarce funds toward the most cost-effective medicines, many NHS officials believe the NICE model will be widely emulated. However many patient-advocacy groups dismiss NICE as a sophisticated new rationing tool.
So far, the agency's track record is mixed, but it has won praise on cancer drugs. NICE recommended use of Taxol as standard therapy for ovarian cancer and both Taxol and Taxotere as standard therapy for advanced breast cancer for patients who have failed a previous course of chemotherapy.
Earlier this month, the government asked NICE to review more than a dozen additional anticancer drugs by next summer. They include: Herceptin; Gemzar, a treatment for pancreatic cancer from Eli Lilly & Co.; and two new treatments for colorectal cancer, irinotecan from Aventis and Pharmacia Corp., and oxaliplatin from Sanofi-Synthelabo SA. The government has ordered health authorities to adopt any NICE recommendations on new therapies.
Robert Glynne-Jones, a colorectal-cancer specialist at one of Britain's biggest cancer centers, Mount Vernon Hospital in Middlesex, knows well the problems with postal-code prescribing. His hospital treats patients from nine different health authorities, and each decides independently which drugs it will pay for. Last year, he was forced to tell roughly 20 of his patients that "they couldn't have the drug that would help them because the health authority wouldn't pay for it."
The squabbling escalated in recent months when fresh clinical studies showed irinotecan and oxaliplatin are more effective than previously believed. Swayed by those trial results, four health authorities now allow Dr. Glynne-Jones to treat appropriate patients with the new drugs. The remaining five authorities still refuse to pay.
"But we've got cracks in the system now, and once the first health authority goes, it's only a matter of time until the others follow," Dr. Glynne-Jones says. Of course, a positive recommendation from NICE on irinotecan and oxaliplatin would break the current impasse, and he's upbeat about prospects of change. "I think NICE is going to be friendlier than many of us had thought," he adds.
Write to Stephen D. Moore at firstname.lastname@example.org