Lynn Divers thought she had heard the worst of it when doctors told her that her daughter Alyssa had cancer. But the diagnosis was only the first in a series of emotional bombshells: Alyssa’s cancer, osteosarcoma, is rare, and in her case, aggressive, requiring a cocktail of different chemotherapy drugs. She didn’t respond well to the first regimen that doctors tried, which led to their adding three other punishing medications to her treatment. Because of the chemotherapy, Alyssa’s kidneys were in danger of failing, so she would need nightly infusions of phosphorous to keep her organs functioning.
Then came the truly heartbreaking news. In late February, when Divers called the hospital to confirm Alyssa’s upcoming chemotherapy treatment, the nurse informed her that there was a drug shortage. The hospital couldn’t be sure that there would be enough methotrexate — the cornerstone of therapy for some childhood cancers, including leukemia and osteosarcoma — to treat Alyssa, now 10. Divers was told she might have to reschedule the session; the hospital would let her know. “It made me sick to my stomach to hear that,” says Divers, a former chaplain from Palmyra, Va. “Alyssa was in treatment for over a year already, and the last thing you want to do is add unnecessary delays in treatment, which gives the cancer a chance to catch up.”
Divers explains that her daughter’s cancer doubles in tumor load every 34 days, “so you need to hit it again and again to eradicate it.”
The story was much the same for Rebecca Robinson, 37, a historical interpreter from Sturbridge, Mass., when she showed up for chemotherapy at the Dana Farber Cancer Center in Boston in July. Robinson had been diagnosed with angiosarcoma, a rare, blood-based soft-tissue cancer, in February 2010, and she had already had five rounds of chemotherapy with Doxil, a drug that seemed to be keeping her cancer in check. When she showed up at the hospital expecting a sixth dose, however, her doctor told her that there was no more Doxil available. There were alternatives, but her physician wasn’t sure if the other drugs would work as well or if Robinson would have bad reactions to them.
“I was just in shock,” says Robinson. “How is it possible that no one knew this was coming? It just seemed impossible that a fairly commonly prescribed drug, especially in cancer treatments where it’s important for people to get the doses of their medicine regularly, could run out.”
For patients like Alyssa and Robinson, the questions — but no satisfactory answers — keep coming. How did this happen? How could hundreds, perhaps thousands of cancer patients suddenly find themselves without the drug treatments that could save their lives? The shortfalls have forced major cancer centers to stop putting new patients on either therapy; Dana Farber is adding only a limited number of new patients on Doxil treatment because physicians aren’t confident they can continue to provide the patients with enough of the drug to complete a full course of treatment.
In February, the U.S. government stepped in to resolve the critical cancer-drug shortages, allowing shipments of drugs from India and Australia to fill the gap. The immediate threat for many cancer patients had passed, but as Dr. Hagop Kantarjian, chairman of the leukemia department at M.D. Anderson Cancer Center in Houston, says, “All of these [efforts] are Band-Aids, temporary measures that don’t address the key issues.”
The shortfalls aren’t limited to cancer drugs either — antibiotics, anesthetics, vaccines and even medications to treat ADHD are getting scarcer. According to the Food and Drug Administration (FDA), demand outstripped the supply of 178 drugs in 2010. The University of Utah Drug Information Service, which works with the American Society of Health System Pharmacists (ASHP) to track shortfalls, says the number was actually closer to 211. Last year, the ASHP and Utah group say, the number of drugs in short supply reached a record high of 267.
What accounts for the widespread shortfalls? And why now? The FDA says 54% of the shortages in 2010 were due to manufacturing problems that led to temporary or permanent plant shutdowns. Drugmakers, while acknowledging that quality-control issues contribute to supply interruptions, point the finger back at the FDA. The agency is responsible for overseeing drug manufacturing safety and quality, but it lacks adequate funding to hire reviewers to look at companies’ applications for new manufacturing facilities and processes or to send inspectors to existing plants in a timely way. Its bureaucracy adds to delays in approvals for new facilities or manufacturing processes, which can run a year long; meanwhile, lags in new drug approvals also continue, leaving the drug supply in jeopardy.
Others cite the government’s tight price controls on generic drugs — particularly those paid for with Medicare and Medicaid — which slim down profit margins for manufacturers. Neither the government nor drugmakers subscribe to this explanation, but the argument goes that diminishing profits motivate drugmakers to abandon generics in pursuit of more profitable, patented products and de-incentivizes them from investing in better manufacturing technologies for generics. Both problems mean production of important drugs can grind to a halt when the slightest quality issue or financial glitch disrupts the system.
Congress has launched several investigations of the drug-shortage problem, and last year President Obama issued an Executive Order directing the FDA to expand its authority to police drug shortages, including requiring all manufacturers to notify the agency of impending shortages; currently the FDA can only compel companies to alert them if they are the sole maker of a drug they plan to discontinue.
The Obama Administration also instructed the FDA to report any violations of the government’s price controls on generics, which some critics believe will serve only to inflame the problem rather than resolve it.
Meanwhile, the nation’s drug supply is growing increasingly unstable, leaving an unprecedented number of patients vulnerable to lapses in care. “There’s little question that it has never been like this, not just with cancer drugs but with drug shortages in general,” says Dr. Michael Link, president of the American Society of Clinical Oncology. “We have had shortages before, but they have been intermittent, and never anything as extensive both in terms of the breadth of drugs affected and the depths of shortages and how long they lasted.”
So who’s right — the FDA or the industry? Or neither?