The Challenges of Drug Shortages

Christan M. Thomas, PharmD BCOP
Clinical Pharmacy Specialist, Oncology
James H. Quillen VA Medical Center
Johnson City, TM

Marc Geirnaert, BSc Pharm
Director of Provincial Oncology Drug Program
CancerCare Manitoba
Winnipeg, Manitoba, Canada

Drug shortages have created significant challenges for oncology pharmacists over the past few years. In 2014, Fox and colleagues reported that the financial effect of drug shortages is estimated to be hundreds of millions of dollars annually for health systems across the United States.¹ At the time, the authors also reported more than 15 documented deaths from lack of available drugs or suitable alternatives.¹

Unfortunately, manufacturing issues, allocations, and unavail­ability have become a reality in pharmacy practice. Dealing with these shortages continues to be a hot topic within institutions and has spurred much discussion in the oncology pharmacy community.

The American Society of Health-System Pharmacists (ASHP) defines a drug product shortage as a supply issue that affects how the pharmacy prepares or dispenses a drug product or influences patient care when prescribers must use an alternative agent.² The U.S. Food and Drug Administration (FDA) defines a drug shortage as a situation in which the total supply of all clinically interchange­able versions of an FDA-regulated drug are inadequate to meet the current or projected demand at the patient level. Some of the differences between the FDA and ASHP drug shortages websites are listed in Table 1 (see PDF).³

When a drug shortage occurs, it is important for pharmacies to develop action plans that clearly identify the drug shortage and the impact it will have on patients’ treatments and the pharmacy operations. ASHP describes a process for decision making in the management of drug product shortages (Figure 1 - See PDF).²

The ASHP decision-making process outlines a systematic approach to drug shortages. Initially, a thorough evaluation of the situation should be performed—including both an operational and a therapeutic assessment. Operationally, there should be a review of the details of the shortage (e.g., the reason for the shortage and when it will be resolved), stock on hand, and ability to obtain additional product.² Each institution should review usage and the supply of any alternative products that may be substituted.

Table 1: Contrasting the FDA and ASHP Drug Shortage Websites

Parallel to the operational assessment, practitioners must evaluate the broad patient population and individual patients affected by the shortage as well as possible therapeutic alternatives.²

Once both of these areas have been reviewed, the true impact on patient care can be assessed, and a plan can be created and implemented.² This plan may involve stratification of patients by curative versus palliative intent or other factors as well as identi­fication of appropriate alternative therapies. All of this must be operationalized for the individual institution (i.e., changes to order sets and compounding guidelines).

One key factor is communication with all involved parties. Communication to physicians, nurses, pharmacists, pharmacy assistants, and purchasing agents should begin when the date the shortage takes effect is known. Alternative prescribing practices and temporary guidelines must be clearly outlined and passed along to the multidisciplinary team.

One recent shortage—bleomycin—has left practitioners scram­bling for options and provides a real-world example of the ASHP decision-making process. Assessment of the situation reveals that the bleomycin shortage is a result of manufacturing issues.⁴ Of three manufacturers, one has stopped making bleomycin complete­ly, one has the product on back order because of a shortage of the active ingredient, and the third is on shortage due to increased demand and has placed the product on allocation. Anticipated resolution dates are September 2016 for one active manufacturer and the second quarter of 2017 for the other.⁴

Two major populations affected include testicular cancer and Hodgkin lymphoma patients. If clinicians cannot obtain enough bleomycin for all patients from usual suppliers or through alloca­tion for specific patients, they will be forced to find a plan B. This leaves pharmacists and other providers to decide when it is appro­priate to switch regimens entirely—such as choosing EP instead of BEP for testicular cancer patients. If this is not possible, stratifying patients—either by age, therapy intent, or other factors—has become necessary.

Alternatively, clinicians look to any available literature to guide treatment. In the case of bleomycin for Hodgkin lymphoma patients, several centers report using information from the RATHL study—presented by Johnson and colleagues at the 2015 13th International Conference on Malignant Lymphoma—to omit bleomycin after 2 cycles of ABVD if adequate response is seen on PET scans. Others are substituting brentuximab for bleomycin in ABVD. Two trials were presented at the same conference in 2015 that added brentuximab to AVD (one was sequential in elderly patients and one included brentuximab plus AVD with or without radiation). A phase 1 study that compared ABVD plus brentuximab or AVD plus brentuximab also was published in Lancet Oncology.⁵ Though it was a small trial (51 patients), complete response rates in each arm were statistically equal (95% for ABVD group and 96% for AVD; 95% confidence interval 77.2–99.9 and 79.7–99.9, respectively).⁵

Regardless of the agent, strategies employed during this particular challenge can be translated to the larger problem of drug shortages. The management of drug shortages will continue to challenge oncology pharmacists on a daily basis. Implementing a drug shortage management strategy and ensuring communication to all affected individuals will help in effectively managing such shortages.

References

1. Fox ER, Sweet BV, Jensen V. Drug shortages: a complex health care crisis. Mayo Clin Proc. 2014;89(3):361-373.

2. ASHP Expert Panel on Drug Product Shortages, Fox ER, Birt A, James KB, Kokko H, Salverson, S, Soflin DL. ASHP guidelines on managing drug product shortages in hospitals and health systems. Am J Health Syst Pharm. 2009;66(15):1399-1406.

3. Contrasting the FDA (CDER) and ASHP drug shortage websites: what are the differences? www.ashp.org/DocLibrary/Policy/DrugShortages/ FDA-versus-ASHP.pdf Accessed June 25, 2016.

4. ASHP Drug Shortages Resource Center www.ashp.org/menu/DrugShort­ages.aspx Accessed June 30, 2016.

5. Younes A, Connors JM, Park SI, et al. Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed Hodgkin’s lymphoma: a phase 1, open-label, dose-escalation study. Lancet Oncol. 2013;14(13):1348-1356.