Drug shortages are multifactorial in nature. These shortages impact the supply of many types of medications. Drug scarcity can be especially distressing when it impacts oncology care, leading to diminished patient safety and poorer outcomes. Chemotherapy shortages force oncology providers into a situation where difficult decisions need to be made regarding who receives that particular drug versus one that may be less effective or more toxic, creating an ethical dilemma. In an effort to have a deeper understanding of drug shortages, it is important to explore why shortages happen and how shortages are being approached by providers in an ethical and equitable manner.
Drug shortages are defined by the US Federal Drug Administration (FDA) as “a period of time when the demand or projected demand for the drug within the U.S. exceeds the supply” DSTF_Full_ Report.pdf (fda.gov). The FDA has determined that drug shortages are increasing in frequency and duration over time. There are three root causes for drug shortages. First, there is a lack of incentive for drug producers to invest in older, generic medications due to diminished profit margins. As the drugs get cheaper over time, there is increased price competition, decreased opportunity for revenue, and a higher investment requirement, leading to decreased profitability DSTF_Full_ Report.pdf (fda.gov).
The second root cause of shortages of medications is related to a lack of reward for manufacturers to invest in updating or maintaining mature quality management systems. There are regulatory requirements to which drug manufacturers must adhere in order to be able to sell their product in the US marketplace. However, there is little oversight regarding quality management systems. It is difficult for buyers to obtain information regarding the quality of the manufacturers’ practices. Furthermore, it is difficult for buyers to even discern at which factory specific drugs are produced. Due to this lack of information, there is no incentive for manufacturers to invest money in updating quality management systems, which eventually leads to quality and safety issues, ultimately causing drug shortages DSTF_Full_ Report.pdf (fda.gov).
The third root cause of drug shortages is that logistical and regulatory issues make it more difficult to recover after a disruption in supply. Over the past years, the drug supply chain has become longer and more fragmented due to more production occurring overseas. This makes it challenging for drug manufacturers to increase production and for new manufacturers to enter the market because they have to obtain approval from multiple regulatory bodies which can be a lengthy process consisting of application and waiting for approval DSTF_Full_ Report.pdf (fda.gov).
It is likely that most patients are not even aware drug shortages are occurring and could negatively impact cancer care. Currently, there are 124 drug shortages that have been reported to the FDA. Included in that list of 124 drugs, there 23 oncology drugs that are either in shortage, or have been discontinued by the manufacturer. Regulatory bodies, such as the FDA, cannot force a manufacturer to continue making a drug if they decide to discontinue production. Discontinuations often occur due to low profitability (FDA Drug Shortages).
Oncology drug shortages may result in treatment delays, dose reductions, or missed doses (McBride et al. 2022). These shortages present an ethical dilemma for oncology providers, forcing them to make a decision regarding who receives medications in shortage and who does not. Patients trust oncology providers to keep them safe. It is important that providers are ensuring that care decisions, when faced with drug shortages, remain safe and fair. Providers must work with a multidisciplinary team within their organization to develop and follow guidelines that allow for effective and acceptable management of drug shortages.
Multiple oncology organizations, including American Society of Clinical Oncology (ASCO), have developed bioethical recommendations for clinicians to follow that allow oncology practice to remain as close to evidence based as possible, when facing chemotherapy shortages (Hantel et al., 2024). ASCO listed principles of allocation to guide clinicians in fair decision making. The goals of these principles are to promote patient wellbeing, avoid unnecessary harm, ensure responsible use of scarce resources, maintain transparency and communication, respect the patient’s right to make their own healthcare decisions, and to ensure the fair distribution of risk and benefit across a population (Hantel et al., 2024).
The ASCO allocation principles have benefits and limitations associated with each principle. Each principle includes ethically justifiable reasons for allocating scarce oncology medications in that manner. It is the provider’s and the organization’s responsibility to determine the appropriate application of the principles to rationing scarce medication (Hantel et al., 2024). The ASCO allocation principles ask providers to consider the following approaches to prioritizing certain patients:
1. Lives saved; life years saved. Prioritize by curative intent and expectation of long-term survival.
2. Worst off. Prioritize those with medically contraindicated alternative treatments.
3. Youngest first. Prioritize children and young adults.
4. Lottery. Random choice.
5. First come, first served.
6. Reciprocity. Prioritize a group if they have previously provided some type of altruism.
7. Instrumental value. Prioritize of the basis of future usefulness.
8. Duty to care for established patients within the organization (Hantel et al., 2024).
Additional oncology organizations, such as Society for Gynecologic Oncology (SGO), have issued recommendations that overlap with the ASCO principles, albeit this list is more specific to the gynecologic oncology population. The SGO recommendations addressed the platinum shortages in 2023. Carboplatin and cisplatin, in combination with other chemotherapy agents, are both standard of care treatment options for ovarian, fallopian tube, peritoneal, endometrial, cervical and vulvar cancers. The SGO recommendations for managing carboplatin and cisplatin shortages include:
1. Minimizing ordering non-essential platinum. If an alternative agent is equally efficacious and safe it should be used instead of the platinum.
2. Increase the interval between cycles and reduce the total platinum dose when clinically acceptable to do so.
3. Consider minimizing or omitting cisplatin or carboplatin for recurrent platinum-resistant ovarian and other cancers.
4. Round dose down to the nearest vial size as a first step to ensure efficient use. If the shortage becomes more critical, consider reserving carboplatin and cisplatin for curative intent treatment or when prolonged clinical benefit is anticipated.
5. Consult with your oncology pharmacy to determine your healthcare system’s current supply of these platinum agents and escalate any shortages promptly along the supply chain and to your clinical teams.
6. If adequate supplies are unavailable, select an alternative, evidence-based regimen and consider a consultation with oncology/hematology colleagues (https://www.sgo.org/news/drugshortage).
Drug shortages are going to continue to be an ongoing challenge in healthcare, and specifically in oncology care. Chemotherapy shortages can be distressing for both patients and providers due to the need to prioritize who receives potentially lifesaving or life prolonging medication. On the federal level, the FDA has gathered a task force with the goal of mitigating drug shortages in the US. On the organizational level it is imperative that multidisciplinary groups work together to develop strategies that allow for fair and safe allocation of scarce medications. Trust and communication within the organization and between the provider and patient is paramount. Currently, it is difficult to know the downstream impact of oncology drug shortages. If efforts are made to educate patients regarding the reasons for the shortages, as well as methods for risk reduction, using alternative dosing, treatment schedules, or alternative agents, trust will remain intact and fears will be reduced.
Sources
3. Ali McBride et al., National Survey on the Effect of Oncology Drug Shortages in Clinical Practice: A Hematology Oncology Pharmacy Association Survey. JCO Oncol Pract 18, e1289-e1296(2022).
DOI:10.1200/OP.21.00883
4. Andrew Hantel et al., ASCO Ethical Guidance for the Practical Management of Oncology Drug Shortages. JCO 42, 358-365(2024). DOI:10.1200/JCO.23.01941
5. https://www.sgo.org/news/drugshortage/ Assessed and Endorsed by the MedReport Medical Review Board