Shortages of cancer drugs continue to take a toll on patient care, increasing drug errors and costs, and leading in some cases to the purchase of short-supply products from “gray-market” suppliers, according to results of a new survey of oncology practitioners.
“We were expecting oncology drug shortages to be very common and we showed that, but I’m not sure I expected the extent of patient impact that we saw—93% of respondents reported a delay in chemotherapy administration or change to a different treatment,” said lead researcher James Hoffman, PharmD, MS, BCPS, a medication outcomes and safety officer in pharmaceutical sciences at St. Jude Children’s Research Hospital, in Memphis, Tenn. “Further, I was impressed that 16% of respondents reported an adverse patient outcome such as disease progression or an increase in adverse drug events.”
Dr. Hoffman said that although other investigators have looked at shortages of single-agent cancer medications, his research team’s study (Am J Health Syst Pharm 2013;70:609-617) is the first to focus on a wider range of chemotherapy regimens.
|Figure. Negative effects of ongoing|
“Cancer shortages are difficult in that there are few [alternative agents available],” commented Erin Fox, PharmD, the director of the drug information service at the University of Utah Hospitals & Clinics in Salt Lake City, who was not involved with the study. “This [research] is important because it demonstrates the broad impact and overall concern for future outcomes.”
The survey was distributed to 1,672 members of the Hematology/Oncology Pharmacy Association (HOPA). The Institute for Safe Medication Practices also distributed the survey, by various methods, to an undetermined number of recipients through the Association of Community Cancer Centers and the American Society of Clinical Oncology. Of the 243 survey respondents, the majority represented community hospitals (41%) and academic medical centers (39%), and 97% were pharmacists.
Ninety-three percent reported delays in chemotherapy administration or changes in treatment regimens related to drug shortages. Fluorouracil, leucovorin, liposomal doxorubicin and paclitaxel were most frequently reported as being in short supply.
Sixteen percent of those surveyed said therapy modifications caused near-miss medication errors, and 6% said the shortages had caused one or more medication errors. Wrong-drug errors, incorrect dosing conversions and the use of the wrong concentration of medication collectively accounted for 74% of near-miss errors. The majority of wrong-drug errors involved shortages of liposomal doxorubicin, and the majority of incorrect dosing conversions involved leucovorin shortages. Cytarabine shortages were the cause of the majority of wrong-concentration errors.
Near-miss errors included incorrectly converting IV etoposide doses to equivalent amounts of oral etoposide or etoposide phosphate, ordering liposomal doxorubicin in place of doxorubicin, mixing multiple concentrations of cytarabine, and incorrectly converting a prescribed dose of leucovorin to an equivalent dose of levoleucovorin. One institution linked a patient’s death to incorrect medication dosing of epirubicin, which replaced daunorubicin during a shortage.
At 34% of the surveyed institutions, the shortages added at least 1,000 hours of additional labor annually, which correlates to approximately 20 hours per week. Despite this increased workload, only 4% of respondents reported that their institution had hired additional personnel.
“Hospitals and pharmacies would definitely welcome [additional] resources to manage shortages; it’s time that is being taken away from other tasks that add much more value to patient care,” Dr. Hoffman said. “For example, inventory and purchasing [pharmacists] could be spending time looking for opportunities to save the hospital money and improving purchasing practices. Clinical folks could be writing another guideline or doing another performance improvement project. Dealing with shortages takes time away from direct patient care.”
The survey also revealed that drug shortages disrupted clinical trials at 44% of institutions, mainly by preventing patients from being enrolled (67%) or delaying patient enrollment (44%). Eighty-five percent of survey respondents reported that the treatment modifications increased costs, and 10% said they had difficulties getting reimbursed because of drug substitutions. Nearly one-third (28%) of survey participants admitted to purchasing products from the gray market, with 14% paying at least 100% over fair market value.
Gray-Market Purchasing Deemed a Risky Strategy
In a presentation at the recent annual HOPA meeting, Moe Schwartz, PharmD, BCOP, the senior director of clinical content and services at McKesson Specialty Health, said uncertain medication integrity and inflated costs are problems with the gray market. Questions arise about the production source, product handling throughout the life of the drug, storage conditions, accuracy of the expiration date, manipulation of the drug product, and whether the product is in fact counterfeit. The World Health Organization estimates that 10% of pharmaceuticals in the world are fakes, but this number is significantly lower in the United States, in part because the lion’s share of medications are bought from legitimate channels such as community pharmacies and mail order. (More than 50% of medications purchased from illegal Internet sites, in contrast, are counterfeit, according to the organization).
Despite the low overall incidence of counterfeiting in this country, it remains a vexing problem, Dr. Schwartz stressed. And it only promises to worsen, given the rapid rise in drug shortages, which have tripled in the past five years in the United States and in many countries around the world, she noted.
The shortages clearly are taking their toll. Dr. Schwartz said a survey of 1,322 directors of pharmacy who were members of the American Society of Health-System Pharmacists estimated labor costs associated with managing drug shortages in the United States to be $216 million annually (Am J Health Syst Pharm 2011;68:1811-1819). In this survey, respondents said the shortages increased work burden by 97%, increased costs by 93% and increased perceived frustration directed at pharmacy by 82%. Eighty percent of those surveyed thought shortages changed practice and 55% felt they compromised patient care.
Those survey results follow on the heels of a study published in The New England Journal of Medicine that also underscored the clinical price to pay when crucial drugs become scarce. The researchers documented a 13% drop in two-year event-free survival rates when pediatric patients with Hodgkin lymphoma were given cyclophosphamide in place of mechlorethamine because of a prolonged shortage of the latter agent (N Engl J Med 2012;367:2461-2463;Pharmacy Practice News, February 2013, page 1).
Dr. Fox said she is not surprised by the HOPA/ISMP survey statistics. “The numbers, unfortunately, aren’t a shock,” she said, “but I hope they will help people understand that drug shortages are a widespread problem.” The challenge, Dr. Fox noted, is that “this isn’t a problem easily fixed; these shortages are due [in large part] to manufacturing issues, and they are taking a long time to resolve.” She noted for example that supplies of electrolytes, common salts such as calcium and phosphate, and trace elements such as zinc continue to be in chronic short supply, creating “severe difficulties for clinicians and patients.”
For Dr. Hoffman, federal legislation passed in 2012 offers hope that at least some shortages may be checked before they get out of hand. The bill gave the FDA additional tools to prevent and ease the shortages, including requiring manufacturers to report anticipated supply problems of key medications.
But more work is ahead, he stressed: “While the FDA and others have worked diligently to address continuing shortages, additional action is needed to address this problem.”