Large pharmaceutical companies test drugs in dozens of foreign countries but often don't bother to make the drugs available to those nations once the drugs are approved in the U.S. — a significant bioethics issue involving people the industry calls "partners in research."
A new study published May 5 in JAMA Network Open found that 34 novel drugs approved by the U.S. Food and Drug Administration in 2012 and 2014 were tested in 70 countries — and within five years, only 22 countries had access to drugs tested on people from those countries. The countries with the lowest access to drugs tested on their residents were African countries; meanwhile, the five countries that got access within a year were all high-income countries.
Drugs were tested in a median of 25 foreign countries.
When it comes to equity in clinical research, "a lot of attention has gone towards looking at demographic representation in clinical research — do we test drugs on the patients who actually will end up using the medicines or vaccines, or do we tend to test drugs on healthy, young, white males, as has been shown in the past?" said Jennifer E. Miller, an assistant professor at the Yale School of Medicine and the lead author of the paper. "Less attention has gone to the equitable distribution or access to research benefits. … One important piece of equitable access to research benefits is whether the countries who are participating in research — helping develop drugs or test drugs — whether they actually ever get access to medicines and vaccines they helped develop."
The study looked at foreign marketing approval of drugs and vaccines made by large pharmaceutical companies at one year to five years after the drug was approved in the U.S. — pharmaceutical companies have to apply for marketing approval separately in other countries. Miller noted that market access is a crude but critical measure: Without a company's intent to sell, it doesn't matter whether the drug is affordable or accessible in other ways. Although the researchers did share their findings with pharmaceutical companies and ask whether any relevant drugs were missing from the publicly available databases, only one company provided information, which did not change the results.
Miller and her co-authors looked at only the 34 new drugs made by large companies, assuming that large companies would have more resources for timely marketing in other countries.
They found stark disparities: Although the rates of marketing approval were low across the board, they were much higher in high-income countries. Five years after FDA approval, 46% of the 39 high-income countries had access to the drugs tested there; only 9% of upper-middle-income countries had access, and only two of nine lower-middle-income countries had access. In high-income countries, the median approval time was at eight months; in upper-middle-income countries, it was 11 months; and in lower-middle-income countries, it was 17 months. Over half the drugs were tested in at least one lower-middle-income country, and 32 of 34 were tested in at least one upper-middle-income country.
Notably, the researchers also found that drugs for rare diseases were less likely to be approved in foreign countries compared with drugs for more common diseases.
Moving forward, governments in countries hosting trials could stipulate that pharmaceutical companies must submit a marketing-approval application within a certain time frame; companies could also adopt this policy themselves. Miller said streamlining the approvals process in some regions would help — the European Union, for example, has the European Medicines Agency covering member states.
Moreover, the study's findings add to the ethical debate over how clinical trials are conducted. "The risks and benefits have to be balanced," Miller said.
Among ethicists, "the responsiveness camp says access to the medicine or vaccine has to be included among the benefits," Miller said. "The [fair benefits] group says to let the country or population decide in negotiations with the company through a collaborative engagement, a collaborative transparent process. The responsiveness framework says to that fair benefits group, 'That's ridiculous. It's very unlikely that a poor country can negotiate with a huge multinational company what it needs.' Regardless of which camp you find yourself in, neither is happening."
The study, "Evaluation of drug trials in high-, middle-, and low-income countries and local commercial availability of newly approved drugs," published May 5 in JAMA Network Open, was authored by Jennifer E. Miller, Joshua D. Wallach, Emily M. Gudbranson, Joseph S. Ross and Cary P. Gross, Yale University; Michelle M. Mello, Stanford University; Blake Bohlig, Brigham and Women's Hospital; and Peter B. Bach, Memorial Sloan Kettering Cancer Center.