A new study documents that oncology drug shortages occur frequently and have serious consequences for patients. The study, a survey of 1,672 members of the Hematology/Oncology Pharmacy Association (HOPA) and published in the American Journal of Health-System Pharmacy (2013;70:609-617), is the first to focus on oncology specifically and is a good snapshot of the problems pharmacists and clinicians faced at the time the survey was done in 2011, said Lisa M. Holle, PharmD, BCOP, HOPA, Assistant Clinical Professor at the School of Pharmacy at the University of Connecticut and HOPA's Immediate Past President.
The survey (first author is Ali McBride, PharmD, MS, BCPS, of the James Cancer Hospital and Solove Research Institute and Ohio State University) also shows the potential harms of drug shortages to cancer patients, she said. Shortages can cause delays and changes to chemotherapy that could have a negative impact on outcomes and increase the risk of medication errors and cost. Additionally, shortages can impact clinical trial design and enrollment.
Chemotherapy drugs are difficult to substitute, unlike pain medications, for example, where alternatives are readily available and the transition from one drug to the other is relatively smooth, noted James M. Hoffman, PharmD, Medication Outcomes and Safety Officer and Associate Member in the Pharmaceutical Sciences Department at St. Jude Children's Research Hospital. “There's often no evidence base for alternatives for chemotherapy.”
Asked for his opinion for this article, James B. Fahner, MD, Division Chief for Pediatric Hematology/Oncology at Spectrum Health's Helen DeVos Children's Hospital in Grand Rapids, Michigan, called the survey “a welcome and timely summary of the real dangers being created for patients due to unpredictable rolling drug shortages.
“Certainly, those of us on the ground in clinical oncology experience this problem as part of daily practice, and it's beyond frustrating,” he said.
The investigators conducted a 34-item online survey that was completed by 243 participants, mostly pharmacists who were HOPA members, between September 28 and October 28, 2011. The majority of respondents were from either community hospitals or academic medical centers. A total of 98 percent of respondents reported experiencing at least one oncology drug shortage in 2011, and 93 percent said they had had a delay in chemotherapy administration or a change in treatment due to these shortages.
A total of 220 participants said the shortages occurred mostly in patients with ovarian cancer (52%), colorectal cancer (51%), breast cancer (49%), and acute myeloid leukemia (35%). Liposomal doxorubicin, fluorouracil, leucovorin, paclitaxel and cytarabine were the most difficult agents to obtain.
About 34 percent of respondents reporting spending at least 1,000 or more personnel hours handling oncology drug shortages during the year. Eighty-five percent noted that shortages increased drug costs to their institution, resulting in problems with reimbursement for replacement medications.
Medication errors that occurred due to the drug shortage but that did not affect patients were reported by 16 percent of respondents and included wrong-drug errors, incorrect dosing conversions, and the wrong medication concentration. An additional six percent of participants reported errors that reached patients, with one respondent attributing a patient death to incorrect medication dosing due to a drug conversion.
LISA HOLLE, PHARMD, BCOP
Adverse events attributed to drug shortages were reported by 16 percent of survey participants and included increased toxicity, disease progression, cardiac events, and emotional stress.
To manage drug shortages, 28 percent of participants reported using the gray market. In other cases, respondents said they changed protocols. For example, to contend with a shortage of liposomal doxorubicin, 34 percent of respondents said they used an alternative therapy, 27 percent used conventional doxorubicin, and 17 percent omitted liposomal doxorubicin from treatment without a substitute.
According to the respondents, 44 percent of institutions said that drug shortages affected clinical trials, with 44 percent mainly experiencing delays in patient enrollment and 67 percent choosing not to enroll patients.
“This survey is very much representative of what we have dealt with at the University of Pennsylvania,” said Donna L. Capozzi, PharmD, Associate Director of Ambulatory Services in the Department of Pharmacy at the Hospital of the University of Pennsylvania and Perelman Center for Advanced Medicine (PCAM). “We expend a great deal of time managing these shortages.”
Shortages affect clinical as well as non-clinical staff members, she noted, explaining that, for example, the purchasing staff works to find drugs during shortages, and clinical personnel work with physicians to adjust guidelines as needed and communicate those changes to information technology colleagues so that electronic standardized templates can be updated.
“More complicated clinical implications arise when there is no substitution with evidence of activity for the same indication,” she said.
Ashley Chasick, PharmD, an Oncology Clinical Pharmacist at Ochsner Medical Center, said she and her colleagues closely monitor drug shortage bulletins from the American Society of Health-System Pharmacists and the Food and Drug Administration and hold weekly meetings with wholesalers to determine what medications will be in short supply. They then send an email to Ochsner oncologists to alert them to potential problems and work with them to develop different treatment plans, she said.
The medical team might substitute a drug that is similar to or in the same class as one that's not available, she said, noting, for example, that during a recent leucovorin shortage, Ochsner used levoleucovorin at half the dose as part of a regimen for colon cancer. After the change was communicated to the oncology staff, leucovorin was then removed from the electronic medical record as a treatment option.
Fahner and his colleagues discuss shortages on a daily basis and rate medication availability according to a color-coded system of red, yellow, and green. “We're actually very blessed as a regional referral hospital that is working in close collaboration with its pharmacy team to have averted some of the more negative endpoints mentioned in the [HOPA] study,” he said.
“There's a lot of discussion between the pharmacy team and clinicians about what supply should be guaranteed to particularly at-risk patients and what patients should receive changes in their protocols or order of drug cycles,” he continued, citing the methotrexate shortage of February 2012 as an example.
Supportive Drug Shortages Also Problematic
Chemotherapy shortages are especially problematic because pharmacologically similar medications may not exhibit the same degree of activity against a specific cancer type, Capozzi explained.
“Because chemotherapeutic agents have a narrow therapeutic index, differences in how the drugs may interact in multi-agent regimens can translate to unexpected differences in toxicity. Decreasing doses to conserve drug supply is also not an option.”
Supportive care agents can also be difficult to manage, she said. For example, shortages of ranitidine, mannitol, and bicarbonate can impact oncology patients and strain facility resources, she said.
Ochsner recently experienced a shortage of injectable electrolytes and had to resort to using oral supplementation, which was difficult for patients who cannot tolerate any medications by mouth, Chasick said. A recent antiemetic shortage was also challenging, although substitutions for supportive medications are easier and safer than with substitutions for chemotherapy drugs, she said.
In addition to electrolytes, lidocaine and heparin have also been in short supply and can interfere with cancer care, Fahner said.
While Executive Order 1358 (http://bit.ly/WhiteHouse-ExecOrder13588) to reduce prescription drug shortages and the FDA Safety and Innovation Act (http://1.usa.gov/114kcyM) have taken steps toward rectifying the problem, with fewer new drug shortages last year, active shortages are still a concern, Hoffman said, citing the University of Utah Drug Information Service. As of February this year, the service has tracked national and regional shortages of more than 320 drugs, which is the highest number since 2010.
Contending with drug shortages is a top priority of HOPA's advocacy efforts, Holle said. The organization encourages transparent communication among health care professionals, manufacturers, patient advocacy organizations, and government agencies to ensure the timely management or avoidance of drug shortages, she said.
Information from the organization notes that HOPA also encourages the FDA to:
- Develop better distribution options for drugs in short supply;
- Incentivize manufacturing redundancies for drugs vulnerable to shortages;
- Maintain adequate reimbursement for brand names and generics; and
- Develop evidence-based guidelines for using alternatives when the drug of choice is not available.
Holle noted that drug shortages have always existed, due to a multitude of factors, including difficulty in obtaining raw materials for manufacturing and a financial disincentive for making generics.
The manufacturing process for sterile generic injectables is also an issue, Hoffman said. “There are substantial manufacturing quality deficiencies, and once we address those, we can make a lot more progress to completely address drug shortages. It's a long-term proposition. A lot of manufacturers haven't seen major upgrades in quite some time.”
In the meantime, Chasick said, patients have to contend with a diagnosis that might take their life and then deal with not being able to access drugs that can help them. “This is frustrating because it's an aspect of care patients don't expect,” she said. “It can mean life or death.”
Coming Next Month
Article about the two surveys reported at the ASCO Annual Meeting of U.S. oncologists and hematologists showing that cancer drug shortages were common last year and affected patient care, with doctors reporting they often had to use more costly brand name drugs and had to delay or modify treatment.