Survey on Oncology Drug Shortages

Chicago—According to a survey, most oncologists and hematologists have faced drug shortages in recent years and have had to deny, delay, or modify treatment regimens for cancer patients. Although the scarcity of these drugs has received national attention, the majority of doctors indicated they had no guidance on how to deal with the problem and decide the best course of action.

Keerthi Gogineni, MD, the study’s lead author, presented the data during a clinical science symposium session at the ASCO meeting. The research was supported in part by Pfizer Inc.’s Medical and Academic Research Fellowship in Bioethics program. ASCO had no role in conducting or analyzing the survey.

Dr. Gogineni said manufacturing drugs is a long and complicated process and depends on a consistent supply of raw materials, adequate manufacturing capacity, and contracting with wholesalers and distributors to deliver drugs to the hospitals and pharmacies. Any interruptions along the way can lead to drug shortages.

The reported number of drug shortages in the United States increased from 70 in 2006 to 211 in 2010. Most shortages occur in sterile injectables and generic drugs. Oncology drugs are especially susceptible to shortages, too, according to Dr. Gogineni. However, she noted that most of the information about shortages on agents used to treat and cure cancer patients is based on anecdotal evidence rather than quantifiable data.

Researchers at the University of Pennsylvania and the University of Massachusetts-Boston developed the survey. Between September 2012 and March 2013, the authors contacted a random sample of oncologists and hematologists in the United States from the 2012 ASCO membership list and asked them about their experience with drug shortages in the previous 6 months. Of the physicians contacted and eligible for inclusion, 55% (n=250) responded and completed the survey. The authors analyzed the responses from 214 of those physicians. The other 36 respondents were not medical oncologists or hematologists. The data included information from March 2012 to March 2013.

The baseline characteristics of the physicians analyzed were representative of practicing oncologists and hematologists in the United States, according to Dr. Gogineni: 65% were white, 72% were male, 61% worked in community-based private practices, and 91% described their jobs as mainly clinical and saw a mean of 72 patients per week. Approximately two thirds of respondents worked in community-based private settings, while the rest practiced in university-based academic settings.

Of the respondents, 83% said they could not prescribe the preferred chemotherapy drug because of shortages in the previous 6 months. In addition, 94% of physicians who could not prescribe the drugs because of shortages said that their patients’ care was affected.

Nearly 70% of physicians said they received no formal guidance on deciding how to manage drug shortages. Oncologists at academic centers were significantly more likely to have received guidance compared with community-based doctors, although only 30% of academic-based oncologists said they had access to guidelines or oversight to help make decisions.

The most common drugs reported in short supply were leucovorin and liposomal doxorubicin, with 66% and 62% of physicians saying those drugs were in short supply, respectively. Leucovorin is used for colorectal cancer and to reduce the toxicity of lymphoma and leukemia, while liposomal doxorubicin is used in many cancers, including breast, ovarian, and multiple myeloma, according to Dr. Gogineni. Other drugs in short supply were 5-fluorouracil for colorectal cancer (19%), bleomycin for Hodgkin’s lymphoma and testicular cancer (17%), and cytarabine for leukemia (16%).

When generic drugs were in shortage, nearly 60% of doctors substituted them with more expensive brand-name drugs. For example, they substituted levoleucovorin for leucovorin, capecitabine for 5-fluorouracil, and nab-paclitaxel for paclitaxel. The brand-name drugs are much more expensive than the generics, according to Dr. Gogineni. Levoleucovorin costs nearly 30 times more than leucovorin, while capecitabine costs 140 times more than 5-fluorouracil for 1 cycle of colon cancer treatment. She noted that there are also hidden costs such as paying staff to manage the shortages.

Asked how they responded to the shortages, 78% of physicians said they changed their patients’ drug regimens, 77% substituted a different drug, 43% delayed treatment, 37% had to choose among patients to receive the drug in shortage, 29% omitted doses, 20% reduced doses, and 17% referred their patients to a different cancer center that had more of the drugs available.

Dr. Gogineni said a bivariate analysis found that oncologists who saw more patients per week were significantly more likely to have a drug shortage regardless of practice setting (P=.002). There was no difference in the frequency of shortages at community-based private practices compared with university-based academic practices. She noted that large institutions with more buying power were less likely to have shortages, but the authors in this survey only included individual oncologists and did not ask them about how they purchased the drugs. There was also no difference in shortages based on the region of the United States.

Further, the drug shortages affected clinical trials. In more than 11% of trials, shortages prevented or delayed enrollment, delayed administration of the study drug, or suspended involvement in the trial.

The study had some limitations, according to Dr. Gogineni. Although the authors found that thousands of patients had their treatment regimens changed because of drug shortages, they could not determine the extent to which the changes affected clinical outcomes. The design of the cross-sectional survey was also a potential issue.

“The nature of the drug shortage problem is, by definition, a moving target,” Dr. Gogineni said. “The severity of a shortage varies with time.”

However, she added that the shortages have been persistent and pervasive since 2006 and have affected the treatment of curable malignancies and added to healthcare costs. She noted that the shortages have affected curable and common cancers. The combination of leucovorin and 5-fluorouracil is commonly used in the treatment of colon cancer, which is the third most common cancer death in the United States, according to Dr. Gogineni. Meanwhile, doxorubicin and paclitaxel are typically prescribed for locally advanced breast cancer, which is the second most common cause of cancer death among women in the United States. She also mentioned that there is no substitute for cytarabine, which is important in treating patients with acute leukemia.

The authors did not ask how the physicians will prepare and compensate for future shortages, but Dr. Gogineni said they are aware that wholesalers may be hoarding drugs and creating artificial shortages.