You Tested A Drug. It's Been Approved. Now ... Try And Get It
When a new drug is up for FDA approval, trials may be held not only in the U.S. but other countries too. A study looks at global availability after approval. Big Pharma disagrees with the findings.
It can be genuinely thrilling when a new drug is approved for use in the U.S. It may be a big step forward in treating folks with, say, HIV or diabetes or breast cancer.
But sometimes the very people who took part in the trials to determine if the drug is effective and safe may not be able to benefit.
That's the conclusion of a new study published in JAMA Open Network.
The study looked at drug trials necessary to gain approval from the U.S. Food and Drug Administration. The trials take place in the United States but in other countries as well — sometimes in countries classified as lower- and lower-middle income. It's cheaper to run trials there. And the potential test subjects can add to the diversity of the overall test population.
The study authors wanted to see if this international group of volunteers get access to the drug once it's approved.
They looked at FDA approvals of novel drugs made by large companies in the years 2012 and 2014, including drugs for infectious diseases such as HIV and hepatitis C, chronic conditions including diabetes, and cancers such as breast cancer and colorectal cancer.
Five years after FDA approvals of 2012 and 2014, they checked to see the status of the 34 drugs. Only five of them had been approved in all the countries where they were tested. And the drugs were less frequently available in the poorer countries included in the study.
"The people subjecting themselves to experimentation are mostly outside the U.S.," says Peter Bach, a co-author of the study and director of the Center for Health and Policy Outcomes at Memorial Sloan Kettering Cancer Center. "The volunteers in other countries don't get back what we get, which is the products when they're actually effective."
Pharmaceutical companies vigorously dispute the study. But global health advocates say it confirms what they'd always suspected. "These findings didn't really come as a surprise," says Junaid Nabi, a New Voices fellow at the Aspen Institute who grew up in Kashmir. Nabi, a physician who writes about global health and bioethics, says many practitioners on the ground in low resource countries have had their suspicions about equity and access to drugs. "I think what this study has done is provide the numbers and some evidence to what a lot of global health thinkers as well as practitioners on the ground intuitively understood," he says.
Bioethicist Jennifer Miller of the Yale School of Medicine headed the study, working with seven other researchers. They checked FDA data to see where the 34 drugs had been tested and checked those countries' regulatory websites to see if the drugs were currently being marketed. Then they compared the results from high income countries such as Germany and Canada to upper-middle-income countries such as Hungary and South Africa and lower-middle-income countries such as Guatemala and Vietnam.
After five years, the FDA-approved drugs were available in nearly half of the high income countries where they were tested, but only 9% of the upper-middle-income countries and 22% of the lower-middle-income countries.
Here's what the situation looks like for one particular drug: Pfizer tested leukemia drug Bosulif in 23 high-income countries and was marketing it in all but four of these countries within two years. It tested Bosulif in 10 upper middle-income countries and was marketing it in two of those countries in two years. And it tested the drug in two lower middle-income countries, India and Ukraine; the JAMA data show it's still not available in either place.
"You could argue that this is the marketplace, that the pharmaceutical industry is an amoral industry that seeks returns," says study co-author Bach. "This is the failing of the free market – it doesn't benefit everyone equally, it doesn't even benefit everyone efficiently, it just benefits those who have capital."
John LaMattina disagrees. LaMattina is former head of Pfizer's global research and development division, and worked at the company for 30 years before leaving 13 years ago. Since then he's served on a variety of biotech boards and is a senior partner at a drug development firm. He doesn't question the JAMA data but says the conclusions are contrary to what he saw in his years at Pfizer. "It doesn't make sense that you would go through all the trouble of getting drugs manufactured and approved and then not sell them in these countries," he told NPR.
LaMattina cited 2020 sales figures for Bosulif published by the company. Overall, they show $4 million in sales in emerging markets in the fourth quarter of 2020. But that's not nearly as much as in the rest of the world — $23 million in Western Europe, Scandinavia and Finland, and $14 million in Australia, Canada, Japan, New Zealand and South Korea.
He says Pfizer never failed to market drugs in countries where they were tested when he was there, and despite the JAMA numbers he doesn't think it's happening now.
Asked to comment by NPR, a Pfizer spokesperson emailed back: "I understand that you already spoke with [industry trade group] PhRMA regarding this flawed study. We are going to let PhRMA speak on behalf of industry on this one."
Pfizer did not respond to a follow-up request for more information on Pfizer drugs.
In answer to written questions, PhRMA roundly panned the report. "This JAMA Open Network study is based on incomplete and inaccurate data that severely bias the results. In fact, actual sales data show that these products launched in nearly all countries where they were tested, including most countries where the authors claim they have not launched. Furthermore, the study authors did not take into account approval delays that biopharmaceutical companies encounter in many markets around the world based on local regulatory requirements, delaying medicine availability for patients by years."
Miller and her colleagues do note in their paper that some drug lags may be due slow approval processes in other countries, but they're sticking by their numbers and their conclusions.
Others who are part of the global health field agree that equity remains a pressing issue. Manuel Martin, a physician who works with MSF (Doctors Without Borders) on access to medical technology in low resource countries, points to COVID-19 vaccines, which were not in the JAMA study, as another example.
"A lot of testing for some of the vaccines was done in developing countries, which are now at the back of the queue in gaining access," he says. "Patients quite literally put their bodies on the line to test these vaccines and now these same patients are being told they have to wait and they can't have access as a priority."
And even when pharmaceutical companies provided access to FDA approved products, individuals on the ground still may not be able to obtain them – the price may be unaffordable to many people.
Companies are making some attempts to make products available where they're tested. Sanofi, for example, is providing a drug for a rare genetic disease included in the study to four of the five people in Egypt on whom it was tested, although not to the general public. And Regeneron, which recently had success with a drug for Ebola, is providing it for free in the Democratic Republic of the Congo, which has had recent outbreaks.
But MSF's Martin isn't satisfied with the Regeneron effort. "It's only available through an incredibly resource-intensive process that requires all sorts of approvals and a dedicated principal investigator," he says.
The JAMA Open Network study itself has not sparked a reckoning in the global health community yet, suggests physician Junaid Nabi, but he thinks that may be because current conversation revolves around the COVID-19 vaccine.
But he expects the study will be much discussed in the years to come: "I can assure you of that, because of the extent of the problem."
Joanne Silberner, a former health policy correspondent for NPR, is a freelance journalist living in Seattle.
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