Pulse
Running Short
Dwindling supplies of some medications are affecting treatment regimens for many patients—with few long-term solutions on the horizon.
By Jeanne Mettner
For Marjorie Swedberg, playing the waiting game is getting uncomfortably risky. After being diagnosed with fallopian tube cancer and undergoing a complete hysterectomy in February 2010, the 72-year-old Webster, Wisconsin, resident learned that the cancer had spread to her lung. After three different therapies proved ineffective in lowering the levels of the cancer marker CA125 in her blood, her doctors recommended that she try Doxil, a low-cost drug that has long been considered a mainstay therapy for ovarian cancer, multiple myeloma, sarcoma, and some breast cancers. Doxil brought Swedberg’s CA125 levels down from 1,125 to 600 U/mL, moving her closer to a normal range, in just four months.
But by August of 2011, production challenges had created unexpected shortages of the drug, and its manufacturer, Johnson & Johnson warned that supplies would be only “intermittently available in the coming weeks.” Within 10 days of the announcement, Minnesota Oncology in Minneapolis, where Swedberg received treatment, had gone through its supply of Doxil, ending treatment with the drug for Swedberg and others. Although Johnson & Johnson attributed the shortage to production delays, the reasons matter little to Swedberg, who continues to worry whether Doxil will be available. “I feel fine right now, but I wait and wonder how long it will be before they call and say that I can finally get the treatment that’s working for me,” she says.
Cancer Drugs in Short Supply
The FDA recently notified hospitals and pharmacies of shortages (or potential shortages) of the following drugs:
Cytarabine • for acute myelogenous leukemia in children and adults
Doxil • for breast cancer, ovarian cancer, sarcoma, multiple myeloma
Leucovorin • for colon cancer Fluorouracil (5FU) • for colon cancer
Cisplatin • for testicular cancer
A complete listing is available on the American Society of Health- Care Pharmacists website, www.ashp.org/DrugShortages/Current/.
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Swedberg’s case illustrates a disturbing trend: an increasing number of drugs are in short supply. In 2010, the FDA reported a shortage of 178 medications—triple the number that were in short supply in 2005. The causes are myriad—raw materials shortages, plant contaminations, inspection failures, drug company mergers, and glitches in manufacturer production capabilities.
But in the minds of many, the real problem revolves around profitability. “The profit margins on these drugs are very small, and because the pharmaceutical industry has become this globalized monster, there are fewer and fewer drug makers out there now,” says Joseph Leach, M.D., a medical oncologist with Minnesota Oncology. “For some of these generic drugs, there is not only one company manufacturing them but literally only one plant in the entire world that makes the world supply; if they have a problem, there is no way to pick up the slack.”
Putting Lives on Hold
Patients in Minnesota and throughout the United States have felt the brunt of the diminished supply. Although providers have seen shortages of pain relievers, anesthetics, and heart medications, the majority of drugs that are currently in short supply are cancer therapies (see p. 10). At Children’s Hospitals and Clinics of Minnesota, Minnesota Oncology, and a number of other oncology practices, shortages of cytarabine, a drug used to treat acute leukemia in children and adults, have sent providers scrambling for solutions. “Acute leukemia is a very aggressive cancer that can be curable but needs to be treated immediately,” Leach says. “At one point last spring, we went day-to-day not knowing if we would have enough to give treatment at the hospital.”
Although supplies eventually trickled in (suppliers say they are still experiencing shortages of cytarabine), Leach and his team began to discuss what they would do if they had to resort to “rationing.” “Ultimately, the decision we came to was that we would administer the medication on a first-come, first-served basis,” he says. “Ethically, we didn’t feel that we could prevent a person from getting treatment if we had it on hand.”
At Children’s, the shortage of cytarabine affected patients on a three-drug regimen for acute leukemia that included intrathecal cytarabine. Because of the shortage, the drug was excluded from the regimen for a number of patients. “We have been able to get by so far, but we have had to make modifications for some of our patients,” explains Bruce Bostrom, M.D., a pediatric hematologist and oncologist. “Whenever you have to change therapy, you don’t know for sure what the outcome will be. Most malignancies are treated with a combination of drugs, so we think we will do O.K. by trying to substitute out or eliminate one of the drugs from the combination, but obviously we don’t know for sure.”
Delaying Discoveries
In some cases, the paucity of certain medications is also affecting research. At Minnesota Oncology, patients enrolled in clinical trials for colon cancer often take an inexpensive drug called leucovorin as part of their treatment or as a prerequisite to study participation. After weeks of being without the drug, Leach, who directs Minnesota Oncology’s research program, says the practice has had to “literally shut down” certain studies. “Not only is this shortage affecting people who are getting treatment right now; it’s slowing down investigations for better treatments because it’s throwing a monkey wrench into these research protocols,” he says.
Similar problems are occurring with research trials involving cytarabine in pediatric patients. According to Bostrom, clinical trials of new treatments for acute leukemia in children typically require that patients first receive intrathecal cytarabine. Because cytarabine is not available, many patients have been disqualified from the clinical trials. “That obviously concerns us because advances over the last 50 years improved the cure rate of childhood acute lymphoblastic leukemia from under 10 percent to 80 or 85 percent today—thanks largely to clinical trials,” he says. “If patients cannot be in a clinical trial, we will, of course, give them the best therapy available, but that’s not going to contribute to the knowledge base needed to improve the state of pediatric cancer treatment in the future.”
A Short-term Solution
To U.S. Sen. Amy Klobuchar, the stories of drug shortages and their negative effect on patient care were a sign that something needed to be done as quickly as possible. “I see Minnesota as the canary in the coal mine when it comes to health care issues such as this,” Klobuchar explains. “We tend to find out about problems in our state before they take hold nationally.” Talking to hospital administrators, pharmaceutical groups, clinicians, and patients revealed many possible solutions to the problem of shortages, including reimportation of the drugs from countries where there are surpluses, which Klobuchar says is “not the law of the land” and would take time that some patients frankly don’t have.
Klobuchar has proposed legislation that is based on fairly simple, short-term measures that helped the Food and Drug Administration (FDA) prevent supply shortages of 38 drugs in 2010. Known as the Preserving Access to Life-Saving Medication Act, the legislation requires prescription drug manufacturers to notify the FDA immediately when an incident occurs that could result in a drug shortage—such as a merger, a change in raw material supply, or the closing of or delayed production within a facility. In addition to allowing the FDA to coordinate efforts to prevent shortages from affecting patients—perhaps by helping to direct supplies to areas of need—the bill directs the FDA to notify the public about shortages and the actions the agency would take to address them. It also requires the FDA to include “prevalence of use” as a factor in determining whether a drug is medically necessary.
Introduced last February, the bill is currently in the hands of the Committee on Health, Education, Labor, and Pensions. It has the support of the Minnesota Hospital Association, the American Hospital Association, Fairview Health Services, the American Society of Clinical Oncologists, the Institute for Safe Medication Practices, the American Society of Health-System Pharmacists, and the American Society of Anesthesiologists.
“The legislation will be helpful because we don’t know if there is going to be a drug shortage sometimes until literally a few days before there is no drug; but the larger problem is incredibly complex,” Leach says. “This is not something that Congress can just legislate; you cannot force multinational companies to produce a drug for which there is little profit.”
Meanwhile, Swedberg can only wait. If a shipment does not arrive soon, she says her oncologist plans to recommend a different treatment regimen. “I haven’t asked my doctor if I can miss a month or so, but I imagine it can’t be good to be putting things on hold,” she says. “I don’t want to lose progress in my battle with this cancer, but at this point, the only thing I really can do is remain optimistic.”
There’s an App for that (Drug)
As part of “Pharma 3.0,” a pharmaceutical industry effort to encourage people to take the drugs they manufacture, drug companies have increased their investment in mobile technologies, particularly smart phone apps. In 2006, 11 percent of Pharma 3.0 initiatives were smart phone apps. In 2010, 41% were.
Some of the apps are aimed at patients; others at physicians. They do tasks ranging from helping patients manage medication schedules to providing physicians with an easy a way to contact a drug’s manufacturer. Pfizer, for example, worked with Epocrates to include a feature that allows physicians to contact the company to ask questions or report adverse events.