Govind Persad, JD, PhD
During the COVID-19 pandemic, many medical specialties became familiar with supply chain interruptions resulting in drug, equipment, and personnel scarcity. Intensive care unit beds, staff, and essential medicines were at times in short supply. The federal government, individual states, and localities all developed plans for distributing these limited-resource medical necessities.
Unfortunately, medical scarcity has returned again—this time in the form of cancer drug shortages. According to the U.S. Food and Drug Administration, as of May 2023, 14 cancer drugs were in short supply, including the chemotherapy agents carboplatin (used as a first-line treatment of breast, ovarian, head/neck, and lung cancers, among others) and cisplatin. According to the National Cancer Institute, up to 20% of patients with cancer rely on platinum-based chemotherapy drugs such as cisplatin and carboplatin.1 The shortage has caused medical groups to issue guidance on how to ration the existing supply. Needed contrast agents for computed tomography scans have also sometimes been hard to find.
What, if anything, can oncology practices learn from the COVID-19 pandemic regarding how to manage shortages in cancer medicines? There are both legal and ethical dimensions of properly addressing the problem.
Ensuring Fair Distribution of Scarce Drugs
Two of the most important values in fairly distributing drugs in short supply, including cancer drugs, are:
1) To deliver drugs where they can prevent the most harm
2) To promote health equity and mitigate health inequities.2
Delivering drugs where they can prevent the most harm typically involves considering both how seriously ill patients are likely to become without the scarce drug and how much they are likely to benefit if they can receive the drug. Patients may be less likely to have negative outcomes without the drug for multiple reasons. For example, some patients may be less likely to experience cancer progression without the drug and can wait for the agent to be back in supply, whereas others may have alternative medication options available.
Multiple factors can affect the likelihood of benefit if patients receive the drug as well. Some patients may have a lower predicted benefit from a given therapeutic agent, because they have already tried that drug or similar ones and their cancer progressed. Others may have a cancer that is less likely to respond to the chemotherapeutic agent or a type of cancer that is likely to be incurable even if it responds temporarily to treatment. Still others may have other co-occurring conditions that are likely to cause death even if a chemotherapy response is successful.
Mitigating health inequities sometimes runs parallel to preventing harm, but sometimes it conflicts with it. Preventing harm and mitigating health inequities may align when someone who is likely to benefit greatly from a drug in short supply would also experience particularly great disadvantage without it. One example involves childhood cancers. If not successfully treated, these cancers will likely mean early death for young patients. At other times, however, those who have experienced health inequities may also be more difficult to protect from harm because treatment may be less effective for them. For instance, a patient whose cancer is advanced because of a delayed diagnosis stemming from lack of access to health services may no longer have as much expected benefit from chemotherapy, compared with a patient whose cancer was caught earlier, at a stage when chemotherapy presents better prospects of cure.
Setting Institutional Priorities
Medical allocation issues are a permanent feature of our health-care system, and popular remedies to combat such issues as drug shortages or effective but expensive treatments are often focused on the patient level. For example, the “God Committee,” created in the early 1960s to determine which patients with kidney failure should receive dialysis, is a classic example of an allocation system directed at patients. But medical allocation is also sometimes addressed at the institutional or governmental level.
Ideally, institutions can learn from their experience with hospital load-balancing frameworks during the COVID-19 pandemic and develop processes to share drugs across institutions.3 They can also advocate for state and federal action to facilitate cross-site collaboration and simplify billing, insurance, and interoperability challenges. It can be valuable to allow sites to share drugs easily without having to deal with red tape related to reimbursement and billing. States should also align incentives to share supply and disincentivize hoarding of scarce drugs or their overuse for lower-priority patients.
Within hospitals and health systems, priorities should similarly be set in a coordinated fashion. If different services are all using the same scarce drug, they should work out a hospital-wide prioritization approach. The same is true if different hospitals within a system are drawing on a limited supply of the scarce drug.
Responding to Oncology Drug Shortages
One option for responding to oncology drug shortages is to offer alternative therapies that are also effective against a patient’s cancer but not typically used because they require lengthier or more complicated administration or have more side effects. For instance, ASCO has suggested that for patients with gastrointestinal malignancies, oxaliplatin could be used instead of cisplatin, and capecitabine could be used instead of fluorouracil.4
Another approach that was also used during the COVID-19 pandemic is fractional drug dosing and/or adjustment in dosing intervals. During the Mpox (formerly known as monkeypox) outbreak response, the Centers for Disease Control and Prevention authorized the use of one-fifth doses of the Mpox vaccine via a subcutaneous route to stretch a short supply of the vaccine.5
During the COVID-19 pandemic, many countries spaced vaccine doses at longer intervals than were used in clinical trials.6 Many health systems have similarly been rationing doses of cancer drugs in short supply.
Another option is to postpone treatment until the necessary drug is back in supply. In general, this is a last-resort option. However, prominent oncology centers have recognized that in some cases, drug shortages have necessitated treatment postponements.
All these approaches will sometimes require oncologists to make difficult decisions about how to treat their patients, including rationing drugs based on patients’ needs. As mentioned previously, some patients will receive drugs first, whereas others will have access postponed; still others will receive the therapy that would be used absent scarcity, whereas others will be offered alternative therapies or fractional rather than full doses.
Determining the Causes of Drug Shortages
The underlying causes of drug scarcities are also important to understand. Most of the currently scarce drugs are generics that have experienced manufacturing disruptions. Because the drugs are generic, they are typically sold near the cost of production as a result of competition. When one manufacturer stops producing a drug, it takes some time for others to ramp up production or enter the market. Many manufacturers may be disinterested in coming back online with a drug because the profit margins in the industry are small.
Some have suggested having federal or state governments, or nonprofit actors, manufacture generics to provide greater resiliency against supply shocks.7 This is likely to be most feasible for drugs that are widely used.
Although policy responses may help to alleviate drug shortages in the long run, cancer drug scarcity is likely to persist in the near term. The ethical values and approaches discussed here may help oncology practices manage the short supply of chemotherapeutics while continuing to provide effective patient care.
DISCLOSURE: Dr. Persad receives grant funding from the Greenwall Foundation.
REFERENCES
1. National Cancer Institute: The “accidental” cure—Platinum-based treatment for cancer: The discovery of cisplatin. May 30, 2014. Available at https://www.cancer.gov/research/progress/discovery/cisplatin. Accessed August 31, 2023.
2. Emanuel EJ, Persad G: The shared ethical framework to allocate scarce medical resources: A lesson from COVID-19. Lancet 401:1892-1902, 2023.
3. Mitchell SH, Rigler J, Baum K: Regional transfer coordination and hospital load balancing during COVID-19 surges. JAMA Health Forum 3:e215048, 2022.
4. ASCO: Gastrointestinal Cancer Guidance. Available at https://old-prod.asco.org/sites/new-www.asco.org/files/content-files/advocacy-and-policy/documents/2023-GI-ds-recs.pdf. Accessed August 31, 2023.
5. Centers for Disease Control and Prevention: Vaccination basics for healthcare professionals: Mpox. Updated May 5, 2023. Available at www.cdc.gov/poxvirus/mpox/clinicians/vaccines/vaccine-basics-healthcare.html. Accessed August 31, 2023.
6. Balch B: Canada took a risk delaying second COVID-19 vaccine doses. Now, its vaccination campaign is one of the best in the world. AAMC News, July 15, 2021. Available at www.aamc.org/news/canada-took-risk-delaying-second-covid-19-vaccine-doses-now-its-vaccination-campaign-one-best-world. Accessed August 31, 2023.
7. Brown D, Morten C: Public pharma is the best solution to the ongoing problem of drug shortages. STAT, August 9, 2023. Available at www.statnews.com/2023/08/09/drug-shortages-public-pharma-option/. Accessed August 31, 2023.
Editor’s Note: The Law and Ethics in Oncology column is meant to provide general information about legal topics, not legal advice. The law is complex, varying from state to state, and each factual situation is different. Readers are advised to seek advice from their own attorney.
Disclaimer: This commentary represents the views of the author and may not necessarily reflect the views of ASCO or The ASCO Post.
