Alice, a preteen with newly diagnosed leukemia, and her parents were understandably distraught when she was diagnosed with cancer. As I sat down to discuss treatment options with Alice’s parents, I was glad I had something positive to share with them: A recent clinical trial showed that adding the drug nelarabine to standard chemotherapy led to a significant improvement in survival for children with Alice’s form of leukemia.
Unfortunately, a national shortage of nelarabine meant that for Alice — I’ve used a pseudonym — the chances for a cure were suddenly less clear.
Approximately 85 percent of children with cancer in the United States are cured of their disease. This success rate isn’t due to new or cutting-edge medicines, but to decades-old and off-patent drugs for which there are no alternatives. But when it comes to treating childhood cancer, oncologists typically get just one chance at a cure.
Having cancer is hard enough without unnecessary and preventable impediments such as drug shortages, which represent a particularly vexing challenge. In the United States, shortages of drugs for cancer and other diseases over the past decade have become the new normal and the problem is getting worse. The Food and Drug Administration says that shortages are occurring with greater frequency and lasting longer, with significant effects on public health. The lack of available lifesaving chemotherapy drugs and supportive care agents represents a national crisis.
Some shortages stem from manufacturing and quality issues. But most experts agree that the primary driver for drug shortages is economic. At a recent drug shortage summit convened by the FDA and Duke University, Martin VanTrieste, a pharmaceutical executive and president and CEO of Civica Rx, acknowledged that “all drug shortages are the result of economics, financial and management decisions.”
We cannot continue to overlook the economic drivers that lead to shortages of older drugs costing just dollars per dose that offer cures for cancer while newer chemotherapy agents costing hundreds of thousands of dollars that may prolong life by just a few months are rarely, if ever, in short supply. Where is the logic?
Here’s a case in point. Acute lymphoblastic leukemia is the most common childhood cancer, accounting for nearly one-quarter of all cancers diagnosed in children. Thanks to the use of drugs that have been available for more than 50 years, the survival rate for those with acute lymphoblastic leukemia is close to 90 percent. Yet over the past decade, eight of the 10 drugs most commonly used to treat this type of leukemia have temporarily been unavailable.
At the height of the shortages, a survey of medical oncologists published in the New England Journal of Medicine found that a staggering 83 percent were unable to prescribe their preferred chemotherapy agent. The majority of them had to make a major change in treatment, such as choosing a different treatment regimen or substituting different drugs during the course of treatment. More than 40 percent reported having to delay the start of treatment while attempting to find the scarce drug. Imagine being diagnosed with cancer yet not being able to start treatment because there isn’t enough of a lifesaving medication or it isn’t available at all.
Even more worrisome, nearly 70 percent of the oncologists reported that their hospital or practice lacked any type of formal guidance for how to make decisions about which patients should get chemotherapy drugs that are in short supply. In two studies of childhood cancer specialists, one in 2015 and another in 2017, two-thirds of pediatric oncologists reported that their patients’ clinical care was compromised by drug shortages — exactly what Alice and her family were potentially facing.
Recognizing that some medications are more important than others, many countries throughout the world have adopted the World Health Organization’s essential medicines list. As defined by the WHO, essential medicines are those needed to treat the basic health care needs of the population. Medicines on this list are both clinically effective and cost-effective and should be available in functioning health systems at all times in adequate amounts and dosage forms, with assured quality and at affordable prices. The list underscores the idea that access to essential medicines is considered to be a basic human right.
The U.S. has neither adopted the WHO’s essential medicines list nor has it created its own.
The current WHO Essential Medicines List for Children (known as EMLc) includes 18 chemotherapy agents and four supportive care medicines. Over the past 30 months, nearly two-thirds of these essential medicines have been or are currently in short supply in the U.S. (today, four of the 18 are in short supply). During the same period, another nine chemotherapy agents not included on the EMLc have been or are currently in short supply in the U.S. As several colleagues and I wrote recently in JAMA Pediatrics, the U.S. should create an essential medicines list for pediatric oncology drugs.
Drug shortages are not unique to the U.S. and occur throughout the world. Over the past decade, though, drug shortages in the U.S. have occurred with greater frequency, lasted longer, and continued to negatively affect patients and the health system.
The single most important prognostic factor for a child with cancer is his or her country of residence when the disease is discovered and treated. It’s ironic that the U.S., a leader in medical breakthroughs and one of the most resource-rich countries in history, is also a leader when it comes to shortages of lifesaving chemotherapy and supportive care agents.
Workable solutions to prevent and mitigate drug shortages have been largely overlooked. Twice over the past five years, in 2013 and 2018, the FDA has considered establishing an essential medicines list to address drug shortages. While an important first step, solving the U.S. drug shortage crisis requires more than just creating an essential medicines list.
Reconciling drug shortages will ultimately require greater government involvement — like the federal government’s role in assisting the financial markets and the automotive and the housing industries. Congress should grant federal authorities the ability to ensure that patients in need have access to medications. Possible ways to achieve that include offering subsidies to pharmaceutical manufacturers to maintain production of critically important medications; providing incentives for high-quality manufacturing standards; and assuring equitable reimbursement practices.
To guarantee adequate supply and access, the government must also purchase and produce essential medicines. Ideally, this can be achieved through collaboration with motivated industry partners. For example, the government could join forces with a not-for-profit company like Civica Rx that is planning to produce generic drugs that are simultaneously affordable and readily available. The Department of Veterans Affairs has expressed interest in this approach.
Ultimately, through Herculean efforts, my pharmacy colleagues secured enough nelarabine for Alice’s first cycle of therapy. Whether enough will be available for her subsequent treatment courses isn’t clear.
I hope the recent FDA/Duke summit, “Identifying the Root Causes of Drug Shortages and Finding Enduring Solutions,” holds true to its name and objective. We must act to ensure that children with cancer, who are in an extremely vulnerable situation, are able to access basic and lifesaving medications.
Yoram Unguru, M.D., is a pediatric hematologist/oncologist at the Children’s Hospital at Sinai; chair of Sinai’s ethics committee; a core faculty member at Johns Hopkins Berman Institute of Bioethics; and an assistant professor at the Johns Hopkins School of Medicine.