For a child with cancer, where they live has a major impact on their survival.

A child undergoing cancer treatment. Childhood cancer survival rates in countries of the Global South are often lower than in wealthier countries.

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

Five-year survival rates are typically more than 80% in high-income countries, with expected cure rates of nearly 100% for some cancers such as retinoblastoma – a deadly eye tumor that affects 8,000 children annually.

For a child with cancer, where they live has a major impact on their survival.

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

The issue was raised at the Union for International Cancer Control Congress in Geneva this fall.

While there are plenty of drugs with a track record of effectiveness in curing children with cancer, many countries struggle to afford them. So they rely on cheaper copies called generics made by manufacturers in India or China. But evidence compiled by academics in the US and Canada, as well as government bodies such as health authorities in Colombia, shows that some generic drugs are of questionable quality, adulterated or outright counterfeit.

“Low- and middle-income countries face penalties,” says Luke Thomas, CEO of the charity World Child Cancer. “They often use drugs that are of poor quality or do not contain enough active ingredients, so they are effectively prescribing children a death sentence and a death sentence, and that is unacceptable.”

Tragic drug reaction
Consider folinic acid, also known as leucovorin. It is one of the most common drugs prescribed for childhood leukemia, which is diagnosed in more than 67,000 children each year. The drug has two advantages: it can make chemotherapy more effective and it can also reduce its side effects.

Although a month’s supply of leucovorin costs about $2,500, many underfunded hospitals are turning to generic versions that cost as little as $139 per month.

In the U.S., generic drug companies must provide regulators with evidence that all the ingredients in their products are acceptable. But in many countries, no such assessment takes place. And while the World Economic Forum has credited the generic market with playing a key role in increasing the availability of life-saving drugs, local doctors often have no way of knowing the quality of the drugs they receive.

Dr. Ndela Diouf is a pediatric oncologist who treats children at the Dalal Jam Hospital in Guediawe, Senegal. Earlier this year, he was giving chemotherapy to children suffering from leukemia, giving them this drug; he says he suddenly started vomiting and shaking violently.

Dr. Ndela Diouf, a pediatric oncologist who treats cancer patients at Dalal Jam Hospital in Senegal, remembers receiving a new batch of leucovorin from a manufacturer in India earlier this year. After a group of children with leukemia received chemotherapy, they began vomiting and shaking violently. Because the symptoms came on suddenly, she immediately suspected the drug was contaminated with dangerous bacteria, although she had no way to prove her suspicions.

She says that within an hour of taking the drug, the children developed high fevers, another sign of possible drug contamination — and a dangerous turn of events because chemotherapy weakens the immune system. Since fevers are often a response to infection, she gave antibiotics.

In this case, she says the children recovered — although they had to stop chemotherapy until their fevers subsided. One boy’s family then paid for her to continue cancer treatment in Spain; The remaining children were given an emergency supply of branded leucovorin while they resumed chemotherapy, which they had purchased at a higher price from a French company.

Diouf and her colleagues reported the incident to Senegal's national pharmacy, which orders drugs for the country's hospitals and monitors drug safety. She claims her complaint was quickly covered up and forgotten. NPR repeatedly called the national pharmacy for comment but was unable to reach anyone to answer our questions about the incident.

"We often suspect problems with the drugs, but we don't have proof," Diouf says.

According to Dr. Dior Ndiaye Niang, a surgical oncologist at Diamniadiona Children's Hospital in the capital, Dakar, the national pharmacy orders all the drugs for hospitals. So doctors have no way to contact the manufacturer to express concerns.

Dr. Dior Ndiaye Niang, a surgical oncologist at Diamniadiona Children's Hospital in Senegal, says Senegalese doctors have no way to contact drug manufacturers to express concerns.

“We don’t have a lab to test these products and confirm our suspicions,” Diouf says. “And with our country’s politicians, it doesn’t seem like one clear safety incident is too many incidents.”

The incident involving leucovorin is just one of many examples of problems with generic drugs, Diouf says. She claims that Senegal’s national pharmacy has been ordered by the government to find the lowest-priced generic. (NPR was unable to reach any sources at the pharmacy to confirm.) As a result, she says, hospitals sometimes receive only adult doses of a particular cancer drug instead of children’s doses, which are more expensive to buy. So doctors take adult doses and divide them into children’s doses. That’s not a safe solution because it’s hard to be precise, Diouf says.

A Global Problem
The problem exists across the Global South. In late 2019, epidemiologists at Colombia’s National Institutes of Health began investigating a case of suspected drug contamination, when nearly 100 children with leukemia developed high fevers at more than a dozen clinics after receiving a generic form of the chemotherapy drug methotrexate from a Mumbai-based manufacturer. Four of those children died from complications related to a bacteria called Pseudomonas aeruginosa. Colombian health officials 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 poor quality. Researchers from Ethiopia’s Notre Dame University and Addis Ababa University teamed up to examine the quality of samples of the chemotherapy drug, generic cisplatin, imported from manufacturers in India by a local hospital in the Ethiopian capital. They found that it contained only 40-70% of the key ingredient, rendering it useless.

Yet without foreign assistance for such testing, doctors across Africa often wonder whether a patient’s worsening condition is the result of the disease – or the drug.

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

“Many of our medicines come from India where there is a broad spectrum when it comes to quality,” says Professor Lorna Rayner, a consultant paediatrician at Korle Bu Teaching Hospital in Accra, Ghana. "When a child doesn't respond to treatment or experiences a relapse, you don't know what really happened. Was it a result of the cancer or was it a medication error?"

Thousands of children at risk
Cathy Pritchard-Jones, professor of paediatric oncology at the Great Ormond Street Institute of Child Health, University College London, has studied the production of generics. She explains that problems are particularly likely to arise in the case of drugs that require expensive and complex manufacturing processes. One notable example: asparaginase, an enzyme used to treat childhood acute lymphoblastic leukaemia, deprives cancer cells of essential nutrients.

Last year, a paper in the journal Paediatric Blood and Cancer described how at least 70,000 children with cancer in 90 countries around the world were 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 time,” says Ronald Barr, a professor of pediatrics at McMaster University in Canada. Barr is concerned that defective forms of asparaginase are being distributed by companies in India, and that these defective drugs are probably being re-directed from China without adequate quality controls.

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

“There is only one market, so the question is how do you handle it and really maintain quality control?” she says.

Moreover, it seems that the onus is increasingly on international collaboration to ensure this. Since 2000, the Franco-African Group for Pediatric Oncology (GFAOP) has been working with French-speaking African countries such as Senegal to develop and manufacture the drug in France. is supplying manufactured cancer drugs. However, with a budget of about $150,000 per year to purchase drugs for the pediatric oncology unit free of charge, the organization’s impact has been relatively limited.

“The impact is huge for the countries that receive these drugs, but as more people join our network, we don’t have the budget to meet all their needs,” says Leila Hessine, a pediatric oncologist in Morocco and current president of GFAOP.

According to Hessine, most NGOs have traditionally been reluctant to invest money in purchasing drugs for poor countries, for a variety of reasons. These barriers include complex regulatory processes in some African countries that can delay the drugs from reaching their target populations, 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 wants to use its vast 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 critical childhood cancer drugs to six countries: Ecuador, Jordan, Mongolia, Nepal, Uzbekistan and Zambia.

“We want to establish something that is truly transformative and sustainable, ensuring that quality medicines are available to all children and adolescents in need,” said Catherine Lam, a pediatric oncologist at St. Jude Children’s Research Hospital, while discussing the program at the UICC Congress.

Over the next few years, St. Jude representatives told NPR that the program will eventually expand to 40 to 50 countries. It aims to enroll six more countries by the end of 2025. St. Jude is donating $200 million of its own to the cause, having raised $2 billion in donations from wealthy individuals and large corporations in 2021. 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 the idea behind the program is to make it more viable for legitimate generic drug companies to manufacture complex drugs like asparaginase. “The idea with this new program is that if a company moves forward to make a generic version of this particular drug, they have this guaranteed demand, which allows them to invest in the facilities they need to make quality products,” she says.

Oncologists like Renner hope the WHO/St. Jude initiative will lead to a standardized list of drug manufacturers under WHO-monitoring.

“When the first generics of HIV antiretroviral drugs were made, all the companies had WHO pre-qualification, so each country knew they were getting the right drugs and that they were well-made,” she says. “We need the same thing for childhood cancer drugs. A database that national pharmacies across Africa can access and see if you buy from this particular manufacturer, it is certified according to WHO standards.”

Yet not every country supports the idea of ​​receiving donations through the WHO/St. Jude partnership. Some countries prefer to have equipment provided to them by international donors.

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