Why do kids with cancer in the Global South have such low survival rates?

Every year, an estimated 400,000 children worldwide develop a form of cancer.

Five-year survival rates in high-income nations are typically over 80%, with an expected cure rate of near 100% for some cancers like retinoblastoma — a malignant eye tumor that strikes about 8,000 children annually.

The picture in low- and middle-income countries is far bleaker. The average five-year survival rate for children in these countries is less than 20%. That figure comes from a a 2023 study in The Lancet Oncology journal compiled by specialists from St. Jude Children’s Research Hospital and seven other academic institutions in the U.S., Canada, Mexico, Chile and Guatemala.

This was an issue raised at the Union for International Cancer Control congress in Geneva this fall.

While there are plenty of medicines with a track record of effectiveness at curing children with cancer, many countries struggle to afford them. So they rely on cheaper copies called generics often made by manufacturers in India or China. But evidence compiled by academics in the U.S. and Canada as well as government institutions such as Colombia’s health authorities is increasingly showing that some generics are of dubious quality, contaminated or outright fake.

“There is a penalty which low- to middle-income countries face,” says Luke Thomas, CEO of the charity World Child Cancer. “They often get access to lower quality medicines or medicines without enough of the active ingredient, so effectively what’s being prescribed to children is hope and a death sentence, and that is just not acceptable.”

A distressing reaction to a drug

Consider folinic acid, otherwise known as leucovorin. It’s one of the most common medicines prescribed for childhood leukemia, which is diagnosed in more than 67,000 children yearly. The drug has two benefits: It can make chemotherapy more effective and can also reduce its side effects.

Yet with a month’s supply of leucovorin costing nearly $2,500, many underfunded hospitals turn to generic versions that cost as little as $139 per month.

In the U.S., generic drug companies must submit to regulators evidence that all ingredients in their products are acceptable. But in many countries, there is no such evaluation. And while the generic market has been credited by the World Economic Forum as having a key role in boosting access to life-saving drugs, local doctors often have no way of knowing the quality of what they receive.

Dr. Ndella Diouf, a pediatric oncologist who treats cancer patients at Dalal Jamm Hospital in Senegal, recalls receiving a new batch of leucovorin earlier this year from a manufacturer in India. After she administered it to a group of children with leukemia undergoing chemotherapy, she says they began vomiting and violently shaking. Because these symptoms began suddenly, her immediate thought was that the drug was contaminated with a virulent bacteria, although she had no means to prove her suspicion.

Within an hour of taking the drug, the children developed a high fever, she says, another indication of possible drug contamination — and a dangerous turn of events since chemotherapy weakens the immune system. Since a fever is often a reaction to infection, she administered antibiotics.

In this case, the children recovered, she says — although they had to cease chemotherapy until their fever ended. One boy’s family subsequently paid for him to continue cancer treatment in Spain; the remaining children were given emergency supplies of branded leucovorin when they resumed chemotherapy, purchased at a higher price from a company in France.

Diouf and her colleagues reported this incident to Senegal’s national pharmacy, which orders medications for the country’s hospitals and monitors drug safety. She claims that her complaint was swiftly glossed over and forgotten. NPR made repeated phone calls to the national pharmacy for comment but was not able to reach anyone to address our questions about this incident.

“We often suspect issues with drugs, but we don’t have the proof,” says Diouf.

According to Diouf and surgical oncologist Dr. Dior Ndiaye Niang at the Children’s Hospital of Diamniadio in the capital Dakar, the national pharmacy orders all drugs for hospitals. So doctors do not have a way of getting in touch with the manufacturer to raise concerns.

“We don’t have a laboratory to test these products and confirm our suspicions,” says Diouf. “And with the politicians in our country, it doesn’t seem to compute that one clear safety incident is an incident too many.”

The incident involving leucovorin is just one of many examples of problems related to generic drugs, says Diouf. She claims that Senegal’s national pharmacy is mandated by the government to seek out generics for the lowest possible prices. (NPR was unable to reach any source in the pharmacy to confirm.) As a result, she says that sometimes the hospital receives only adult doses of a particular cancer medication rather than customized child-sized doses, which are more expensive to buy. So doctors take the adult dose and break it into child-sized doses themselves. It’s not a safe solution because being precise is difficult, says Diouf.

A global problem

The problem exists across the Global South. In late 2019, epidemiologists from Colombia’s National Institute of Health began investigating a case of suspected drug contamination, after approximately 100 children with leukemia across more than a dozen clinics developed high fevers after receiving a generic form of the chemotherapy drug methotrexate, which had arrived from a Mumbai-based manufacturer. Four of them died from complications which were found to be related to a bacteria called pseudomonas aeruginosa. Colombia’s health authorities tested three batches of methotrexate received from the company. All were found to be contaminated with pseudomonas aeruginosa.

Sometimes the problem is not contamination but suboptimal quality. Researchers from the University of Notre Dame and Addis Ababa University in Ethiopia teamed up to examine the quality of samples of generic cisplatin, a chemotherapy drug imported from manufacturers in India by a local hospital in the Ethiopian capital. They found it contained only 40-70% of the key ingredient, rendering it useless.

Yet without foreign aid to help finance such testing, doctors across Africa are often left wondering whether a patient’s deterioration is a consequence of the disease itself — or the medication.

The U.S. Food and Drug Administration has previously raised concerns about quality control and manufacturing slippages from India’s $50 billion pharmaceutical industry. In a 2020 report, the FDA described how ‘India had a lower percentage of acceptable outcomes than other countries and regions.’ Last year, FDA investigators reported safety and quality violations in 11% of India’s generic manufacturing plants, the most of any country studied.

“Many of our medicines come from India where there’s a vast spectrum when it comes to the quality,” says Professor Lorna Renner, a consultant pediatrician at Korle Bu Teaching Hospital in Accra, Ghana. “When a child doesn’t respond to treatment or relapses, you don’t know what really happened. Was it the cancer itself or was the medication at fault?”

Tens of thousands of children at risk

Kathy Pritchard-Jones, a professor of pediatric oncology at University College London Great Ormond Street Institute of Child Health, has studied the manufacture of generics. She explains that problems are more likely to arise in cases of drugs which require a particularly expensive and complex manufacturing process. One notable example: asparaginase, an enzyme used to treat childhood acute lymphoblastic leukemia by depriving cancer cells of essential nutrients.

Last year, a paper in the journal Pediatric Blood & Cancer described how at least 70,000 children with cancer in 90 countries around the world are at risk of being treated with contaminated and low-quality asparaginase.

“The problem of defective forms of asparaginase has been known in the pediatric oncology community for some years,” says Ronald Barr, a pediatrics professor at McMaster University in Canada. Barr raises concerns that forms of defective asparaginase are distributed by companies in India and that these defective medicines are probably re-directed from China without adequate quality controls along the way.

Pritchard-Jones explained that one reason it is difficult to produce generic forms of asparaginase at a low cost is because it is a complex drug to manufacture and the volumes sold are relatively small.

“There’s only a small market, so the question is, how do you get a reputable supplier to take that on and really maintain quality control?” she says.

Increasingly, it seems that the onus to ensure this is falling on international collaborations. Since 2000, the Franco-African Group for Pediatric Oncology (GFAOP) has been supplying cancer drugs manufactured in France to French-speaking African countries like Senegal. However, with a budget of around $150,000 per year for purchasing drugs free-of-charge for pediatric oncology units, the organization’s impact has been relatively limited.

“The impact is huge for countries who receive these drugs, but with more joining our network, we don’t have the budget to cover all their needs,” says Laila Hessissen, a pediatric oncologist in Morocco and GFAOP’s current president.

According to Hessissen, most NGOs have been traditionally reluctant to put money into purchasing medicines for poorer countries due to a variety of reasons. These hurdles include complex regulatory procedures within some African nations that can delay drugs from reaching the target population and inadequate data collection systems to track and quantify the impact on public health.

A new WHO/St. Jude initiative

St. Jude Children’s Research Hospital is looking to use its ample resources to address this unmet need. Through a new partnership with the World Health Organization, St. Jude has launched a pilot program to identify suitable manufacturers and deliver effective generic forms of vital childhood cancer medicines to six countries: Ecuador, Jordan, Mongolia, Nepal, Uzbekistan and Zambia.

“We’re looking to set up something that will be truly transformative as well as sustainable, to ensure quality medicines for all children and adolescents who are in need,” Catherine Lam, a pediatric oncologist at St. Jude Children’s Research Hospital, said when discussing the program at the UICC Congress.

Over the next few years, representatives from St. Jude told NPR that this program will ultimately expand to between 40 and 50 countries. It aims to enroll a further six countries by the end of 2025. St. Jude is donating $200 million of its own money to the cause, having raised $2 billion in donations back in 2021 from wealthy individuals and large corporations. St. Jude has a history of addressing global disparities in childhood cancer, having previously created an initiative to help train doctors in 17 countries on the best ways to treat acute lymphoblastic leukemia.

Pritchard-Jones says that the program’s concept aims to make it more viable for legitimate generic drug companies to manufacture complex medicines such as asparaginase. “The idea of this new program is that if a company sticks their hand up to make a generic version of this particular drug, they have this guaranteed demand, which allows them to invest in the facilities required to make quality products,” she says.

Oncologists like Renner hope the WHO/St. Jude initiative will lead to a certified list of WHO-vetted drugmakers.

“When the first generics were produced of HIV antiretroviral medications, the companies all had WHO pre-qualification, so every country knew that they were getting the right drugs and they were made well,” she says. “We need the same thing for childhood cancer medicines. A database which national pharmacies across Africa can access and see that if you buy from this particular manufacturer, they’re certified as being WHO standard.”

Yet not every country supports the idea of receiving donations through the WHO/St. Jude partnership. Some countries would rather international donors give them the tools to create their own vetting process. Senegal, for example, is not on the initial list of nations set to receive drugs through the global access program, and while Dr. Niang, the surgical oncologist, is not doubting its effectiveness, she says there will always be countries in need that end up missing out.

As a result, she believes that the best approach would be for foreign donors to use their money to create a series of pharmacovigilance laboratories to screen cancer medicines on behalf of each African region. Asked to comment on this proposal, St. Jude sent an email statement asserting that “it is our intention to improve access to quality care and greater survival rates around the world through St. Jude Global and the Platform as it expands.”

“Why don’t we have a funded lab for neighboring African countries so we can do the testing and vetting ourselves?” Niang says. “My dream is to have one lab for all of West Africa, assessing the drugs which Indian companies sell to Senegal, Mali, Guinea, all the countries in this corner of the continent. That single laboratory could screen all the drugs being purchased for quality and contamination, and then we can decide which manufacturers to work with and which we should avoid.”

David Cox is a freelance health journalist who has written for publications around the world including NPR, The New York Times, Wired and The Guardian. He has a Ph.D. in neuroscience.