Why a pediatric cancer drug shortage has persisted for decades

Doctors told Laura Bray that she was “lucky” because her 9-year-old daughter’s leukemia was curable.

Abby had a 90% chance of beating the blood cancer if she followed a three-year treatment. There was just one problem.

Doctors told Bray the key drug that kicked off Abby’s chemotherapy in 2018 was hard to find. She had to figure out a way to tell her daughter.

“I had no answers for her when she asked me if she was going to die if she didn’t have her medicine,” said Bray, 47, from Tampa, Florida. “All I could say is that, ‘We’re going to try to find it. Sometimes, extraordinary things happen when you try.’”

The family eventually found that medication. Later, two others Abby needed were hard to find. The Brays, like thousands of families across the country, got a firsthand education in the widespread shortage of children’s cancer drugs.

Experts say this backlog for an array of pediatric cancer drugs has existed for decades. Advocacy groups have tried to get manufacturers, wholesalers and hospitals on the same page and create a reliable supply chain.

Bray, who founded the national nonprofit Angels for Change to address these drug shortages, said everyone involved in that chain should be thinking about the children.

“In the end, it’s someone’s life,” she said.

Which cancer drugs are in shortage and why?

Several pediatric cancer drugs are in shortage and others have been discontinued, according to the Food and Drug Administration.

The most widely used of them is injectable methotrexate sodium, a chemotherapeutic often used for acute lymphoblastic leukemia, brain tumors, non-Hodgkin lymphoma and osteosarcoma, according to St. Jude Children’s Research Hospital. The FDA shortage list also includes leucovorin, a drug used to reduce the side effects of methotrexate.

These drugs, which tend to be sterile injectables, are particularly susceptible to shortages because few companies make them, said Prashant Yadav, a medical supply chain expert and professor of INSEAD, a graduate business school in France.

Making generic sterile injectables is complicated and requires strict quality control. These medications are fairly cheap and manufacturers often exit the market because they can’t turn as much of a profit as they would with other medications, Yadav said.

The few remaining companies operate in the U.S. and in China and India, where FDA officials struggle to enforce and maintain the high standards of quality they expect from domestic manufacturers.

If the FDA detects a quality issue, which Yadav says happens fairly often, the agency shuts production down until the problem is resolved. A drug shortage like this reverberates across the market as other manufacturers try to keep up with increased demand.

“All it takes is a glitch at one company for (the drug) to go into a national shortage,” said Dr. Gwen Nicols, executive vice president and chief medical officer of The Leukemia and Lymphoma Society. “It’s terrifying for families and it’s incredibly hard for the doctors who are looking at these families and saying, ‘I can’t find the therapy anywhere.’”

It can take months for a pharmaceutical company to resolve a quality issue and resume production, and the impact of these shutdowns and shortages on patients can last for years, Yadav said.

Yadav sees this as “heartbreaking,” Yadav said, noting that medical practices are “state of the art in how we progressed in biological medicines, but we can’t get pediatric oncology drugs.”

How providers handle cancer drug shortages  

Hospital staff have grown accustomed to scrambling when a pediatric cancer drug is in shortage.

They call other hospitals to see if they have medication in stock they can ship or dip into their adult stash and prepare doses appropriate for children.

If all else fails, doctors may use a different treatment. But these alternatives are not usually as effective as the first-choice drug in shortage, said Dr. Gwen Nichols, executive vice president and chief medical officer of The Leukemia & Lymphoma Society.

“It’s a terrible waste to treat someone with second best when you’re talking about a child,” she said. “It’s so inefficient and so crazy and so dangerous and it just shouldn’t happen.”

There are ways to mitigate delays, but part of the problem, experts say, is that hospitals, wholesalers and drugmakers aren’t in sync.

Rather than working in silos, Yadav said, these institutions should be working together. This means opening up lines of communication and being transparent about product supply and the risk of a drug shortage.

Other solutions to cancer drug shortages

The best way to address the root causes of the cancer drug shortage is to make these medications more profitable, which will motivate manufacturers to enter the pediatric oncology market, experts say.

This could mean bumping up the price of these generics in what Yadav calls a “market resiliency premium.” He emphasized that this extra cost shouldn’t be passed down to patients. Wholesalers, hospitals and insurance companies should cover it.

The federal government could also create incentives for new drugmakers, attracting more companies to increase the supply and providing alternatives if something goes wrong in the supply chain.

“It’s a big piece of the puzzle,” said Brooke Bernhardt, chief pharmaceutical officer at St. Jude Children’s Research Hospital. “We have to start with having drugs available in the first place.”

Another way to mitigate shortages is to build up a rotating stockpile, Yadav said. Wholesalers or manufacturers can save up to six months’ worth of medications to ensure a backup supply is available in the event of a shortage.

This will minimize any interruption to care and providers won’t have to scramble to find medications, like they did during Abby’s treatment.

Since Bray’s daughter rang the cancer-free bell in February 2021, she has continued the fight to end drug shortages for pediatric cancers through her nonprofit, Angels for Change.

“I know what it’s like being a parent or caregiver watching your child fight for their life,” Bray said. “You want them to have the best ability to fight.”

Adrianna Rodriguez can be reached at adrodriguez@.com.