- Ondis Eardensohn and Gregory Sanford
Like most Americans, Ondis Eardensohn didn’t know the U.S. had a prescription drug shortage — until she experienced it firsthand.
On August 8, the retired postmaster drove two hours from her home in Plainfield to New Hampshire’s Dartmouth-Hitchcock Medical Center for an infusion of Doxil, one of the only viable treatments for her stage-4 breast cancer.
Eardensohn was waiting for the medicine when her physician walked in. “I’m sorry,” the doctor told her, “but we don’t have enough Doxil to treat you.”
“I drove home with no treatment. I was in shock,” recalls Eardensohn, 58, a warm and resolutely optimistic mother of two. “When you are at stage 4, your options get more and more limited. If you have one option taken away, it may have been your last.”
Eardensohn does not fit the stereotypical image of a wasted cancer patient. She laughs easily, and her soft white curls have grown back after 16 years of on-and-off radiation and chemotherapy treatments. Nonetheless, she says, “I am not the same person I used to be.”
A week after Eardensohn’s frustrating trip to Dartmouth-Hitchcock, a hospital staffer called her at home, where she lives with her longtime partner, state archivist Gregory Sanford. The hospital still hadn’t located any Doxil; the rescheduled treatment would also have to be canceled.
Dartmouth-Hitchcock isn’t alone in lacking a number of life-saving and -sustaining drugs. Nor is it the only health-care institution that has turned to the “gray market” — the legal, but sometimes shady network of secondary suppliers — to find them.
Doxil, manufactured by Johnson & Johnson, is one of some 200 drugs that critically ill patients and their providers are discovering may be unavailable, rationed or scalped for stratospheric prices. The list of hard-to-find drugs ranges from chemotherapy agents to anesthesia and morphine. According to a survey by the American Hospital Association, 99.5 percent of U.S. hospitals reported at least one drug shortage in the first six months of this year, while 44 percent reported shortages of more than 20 drugs.
Vermont Health Commissioner Harry Chen says drug shortages “have been a way of life for some time,” and the problem is getting worse. Five years ago, the U.S. Food and Drug Administration (FDA) reported 55 drugs in short supply. By 2010, there were 178 drugs on that list; this year there will be 350, predicts North Carolina-based Premier Inc., a major hospital drug-purchasing cooperative. The majority of those are generics, but brand-name pharmaceuticals are also affected, especially anesthesia and chemotherapy products. Premier Inc. spokeswoman Amanda Forster says pharmacists all over the country “are scrambling and desperate.”
Vermont health care providers are no exception. Karen McBride, Fletcher Allen Health Care’s director of Pharmacy Services, says scrounging for hard-to-find meds is a weekly occurrence. Several months back, one patient was nearly put at risk when a critical antibiotic called Bactrim ran out. After working the phones for several hours, McBride finally located a supply of Bactrim at another New England hospital — four hours away — and arranged for a courier to drive it to Burlington.
“It’s 10 times more work than it used to be,” McBride says, adding, it helps that her buyer is on it “like a junkyard dog.”
Drug shortages cost hospitals $200 million a year owing to the additional staff time required to source supplies, inflated prices and the cost of treating side effects caused by alternate products. In February, the Wall Street Journal wrote about a Maryland oncologist who was desperately seeking hard-to-find leucovorin. He found the cancer treatment for $177 per dose; the normal cost is $7.41.
But there is a deeper price — namely “adverse patient outcomes,” including death. The American Hospital Association survey revealed that shortages have resulted in negative outcomes at one in every five facilities. Eighty-two percent of hospitals reported delaying patient treatment due to drug shortages, and more than half were not always able to provide the patient with the recommended treatment. Three out of four hospitals report rationing or implementing restrictions for drugs that are in short supply.
A 2010 survey of physicians by the nonprofit Institute for Safe Medication Practices found that drug shortages resulted in delayed surgeries, dosage errors and interrupted drug studies, as well as deaths linked to the use of substitute antibiotics to which patients were resistant.
“No patient care has been compromised at Fletcher Allen” because alternatives to unavailable drugs are found, says Bruce Leavitt, head of the hospital’s Pharmacy and Therapeutics Committee.
Chen says he has not heard reports of compromised patient care due to drug shortages. As for solutions, Chen says fundamental fixes must originate at the federal level, though he adds, “We should look for ways to create a system in Vermont that would lessen the effect.”
Eardensohn was supposed to be protected from Doxil shortages. In June, Johnson & Johnson warned hospitals: No new patients should start on Doxil, but current ones would be given priority for the life-extending chemotherapy. After their attempts to secure the drug proved unsuccessful, Eardensohn’s doctors apparently lost faith in the company’s ability to deliver a steady supply. On August 26, three weeks after they sent her home without treatment, Dartmouth-Hitchcock switched Eardensohn to a different medicine.
What’s causing the drug shortages currently plaguing America’s hospitals? Quality problems, including potentially deadly microbial contamination, caused more than half of the recent shortages in injectable drugs, according to the FDA. Other factors impacting the supply chain, according to government and nonprofit researchers, as well as pharmaceutical trade publications, include: cost-cutting manufacture, lack of raw ingredients, just-in-time production, Medicare price controls, discontinuation of less lucrative products, domestic and foreign outsourcing, substandard ingredients, and so-called “pay to delay” deals, in which makers of brand-name drugs with patents about to expire pay generic drug makers to delay marketing of generic versions.
Johnson & Johnson insists that the Doxil shortage is not due to “quality” or “safety” problems. Instead, company spokeswoman Monica Neufang blames “manufacturing issues,” “capacity constraints” and “production delays.” Neufang says that a program to ensure Doxil to continuing patients such as Eardensohn has been “very successful,” but she also acknowledges that some patients are on a waiting list. The number and other details are “proprietary,” she says.
Although Doxil bears the Johnson & Johnson brand, it is produced by a third-party contract manufacturer called Ben Venue Laboratories. Based in Ohio, BVL is a division of Germany-based Boehringer Ingelheim, and also produces pharmaceuticals for Pfizer, Takeda and Bristol-Myers Squibb. The company is part of a $46 billion global contract-manufacturing industry.
How does BVL explain the Doxil shortage? Without elaboration, the company lays blame on “manufacturing capacity constraints.” But the FDA’s Canadian counterpart, Health Canada, banned importation of some BVL drugs on August 17 for what it called “quality deficiencies.” Health Canada spokeswoman Olivia Caron describes the problem as “shortcomings in Good Manufacturing Practices ... including product sterilization and quality oversight.” Europe has also imposed restrictions on BVL’s product.
Within days of the Canadian ban, the company announced it would no longer do contract-manufacture work for larger drug companies.
As supplies become less reliable, a network of gray marketers is stepping in to fill the gap. These wholesalers operate outside normal pharmaceutical distribution channels but, for the most part, within the law.
Gray marketers buy drugs in bulk at discount prices and resell them to other wholesalers who may sell them again, with prices hikes and profits accumulating like undercarriage dirt in mud season. The San Antonio Express-News recently reported a gray market drug sale that carried an “astounding markup of 6213 percent.”
By monitoring recalls, plant closings, trade and government websites, the gray marketers can anticipate the market in order to stockpile and hoard potentially scarce drugs. And providers often feel they have no choice but to buy them: Some 52 percent of respondents to the Institute for Safe Medication Practices survey reported buying drugs on the gray market in the last two years.
“When faced with the situation that you know a patient will die without it, you really don’t want to buy from the gray market, but it is an option of last resort,” explains Joseph M. Hill, director of federal legislative affairs at the American Society of Health System Pharmacists. “What are you going to do?”
Hill goes on, “We’d like to get an answer to where they are getting their supply. Large national wholesalers say they don’t supply to the secondary market. That may be a policy, but [products] could also could come from sales reps trying to make their quarterly numbers.”
Dartmouth-Hitchcock has “been fairly successful in obtaining needed medications for our patients,” spokesperson Rick Adams says. “However, we have been forced at times to go to market to purchase some medications, and have been subject to gray market upcharges.”
Fletcher Allen has rejected that route, says McBride. “We get daily solicitations from gray marketers by telephone, fax and email, but we don’t buy from them because we can’t be assured of authenticity and integrity. Some are stolen or counterfeit, and there are ethical concerns about what they are doing: inflating the price hugely.” With a flash of outrage, she adds, “They are very shady, trying to capitalize on a bad situation. That is unethical. It’s disgusting.”
And potentially unsafe. Before reaching a hospital pharmacy, gray market drugs “can pass through five or six brokers, getting repackaged, relabeled and possibly stored under poor conditions,” says Premier Inc.’s Forster. Vermont is one of 39 states that requires pharmaceuticals sold in-state to have a drug “pedigree” — a paper trail that tracks the drug on every stop from manufacturer to final destination. New Hampshire does not.
But quality and safety problems also affect drugs obtained through normal channels. “The largest percentage of current shortages is caused by domestic quality problems,” says Mike Levy, acting director of the Drug Security, Integrity and Recalls division of the FDA’s Center for Drug Evaluation and Research.
Recently, Teva and Hospira — two of the U.S.’s largest makers of generics, including key chemotherapies — closed factories because of “manufacturing problems.” Johnson & Johnson units had to issue massive recalls, and the FDA placed three of its plants under consent decrees for persistent failures to meet quality standards.
Drug makers’ reliance on cheaper imported ingredients and finished products complicates the supply chain. Huascar Batista of the FDA’s Center for Drug Evaluation and Research says that 80 percent of all active pharmaceutical ingredients consumed in the U.S. are imported, mostly from India and China. Neither Johnson & Johnson nor BVL would answer questions about whether they source ingredients abroad, saying the information is proprietary.
According to the U.S. Government Accountability Office, the FDA inspects domestic pharmaceutical facilities only about once every two and a half years on average. It would take nine years to inspect the agency’s prioritized list of companies in the 150 countries that export drugs or ingredients into the U.S. Making matters worse, the FDA lacks authority to mandate recalls, require prior notification of impending shortages or force companies to continue manufacturing essential drugs.
Even when imports are found to have problems, the FDA can’t destroy poor-quality or dangerous drugs. It can only refuse them entry, after which importers can “port shop” the rejected products. “They try at several different ports, and sometimes they are successful [getting them into the U.S.],” says the FDA’s Batista.
No matter what the proximate cause of any particular shortage, profit considerations are almost always a factor. “Corporations look at profit margins,” says Fletcher Allen’s Leavitt, “and if a generic or other drug is not profitable, it is not a priority.”
While Doxil is a mainstay chemotherapy drug, it accounts for less than 1 percent of Johnson & Johnson’s annual revenues, which in 2008 were $24.6 billion.
Steven Kappel, who worked with William Hsiao to develop a blueprint for universal health care in Vermont, sees the profit motive of drug companies as a problematic component of the current system.
“It raises major ethical issues when making profits conflicts with saving lives,” Kappel says. As far as counteracting the shortages, Kappel says Vermont’s best bet is a reformed health care system that would allow the state to buy pharmaceuticals in bulk, “negotiating as a buyer as effectively as we can.”
But patients like Ondis Eardensohn can’t wait for single-payer health care. With Doxil no longer available, Eardensohn is being treated with Eribulin, a substitute that has left her feeling worse.
“Since I went off Doxil, I have developed a cough, and there has been a slight progression of the disease in my lungs,” Eardensohn reports. Also, Eribulin requires Eardensohn to make the 140-mile round-trip to Dartmouth-Hitchcock three times a month, while Doxil required just one visit a month.
“This shortage thing horrifies me, and not just for me,” Eardensohn says. “This is a kind of health care rationing. Why hasn’t something been done?”