Prescription drugs kill some 200,000 Americans every year.
Will that number go up, now that most clinical trials are conducted overseas—on sick Russians, homeless Poles, and slum-dwelling Chinese—in places where regulation is virtually nonexistent, the F.D.A. doesn’t reach, and “mistakes” can end up in pauper’s graves?
The authors investigate the globalization of the pharmaceutical industry, and the U.S. Government’s failure to rein in a lethal profit machine.
More and more clinical trials for new drugs are being outsourced overseas and conducted by companies for hire. Is oversight even possible?
You wouldn’t think the cities had much in common. Iaşi, with a population of 320,000, lies in the Moldavian region of Romania. Mégrine is a town of 24,000 in northern Tunisia, on the Mediterranean Sea. Tartu, Estonia, with a population of 100,000, is the oldest city in the Baltic States; it is sometimes called “the Athens on the Emajõgi.” Shenyang, in northeastern China, is a major industrial center and transportation hub with a population of 7.2 million.
These places are not on anyone’s Top 10 list of travel destinations. But the advance scouts of the pharmaceutical industry have visited all of them, and scores of similar cities and towns, large and small, in far-flung corners of the planet.
They have gone there to find people willing to undergo clinical trials for new drugs, and thereby help persuade the U.S. Food and Drug Administration to declare the drugs safe and effective for Americans. It’s the next big step in globalization, and there’s good reason to wish that it weren’t.
Once upon a time, the drugs Americans took to treat chronic diseases, clear up infections, improve their state of mind, and enhance their sexual vitality were tested primarily either in the United States (the vast majority of cases) or in Europe.
No longer. As recently as 1990, according to the inspector general of the Department of Health and Human Services, a mere 271 trials were being conducted in foreign countries of drugs intended for American use. By 2008, the number had risen to 6,485—an increase of more than 2,000 percent.
A database being compiled by the National Institutes of Health has identified 58,788 such trials in 173 countries outside the United States since 2000. In 2008 alone, according to the inspector general’s report, 80 percent of the applications submitted to the F.D.A. for new drugs contained data from foreign clinical trials. Increasingly, companies are doing 100 percent of their testing offshore.
The inspector general found that the 20 largest U.S.-based pharmaceutical companies now conducted “one-third of their clinical trials exclusively at foreign sites.” All of this is taking place when more drugs than ever—some 2,900 different drugs for some 4,600 different conditions—are undergoing clinical testing and vying to come to market.
Some medical researchers question whether the results of clinical trials conducted in certain other countries are relevant to Americans in the first place. They point out that people in impoverished parts of the world, for a variety of reasons, may metabolize drugs differently from the way Americans do. They note that the prevailing diseases in other countries, such as malaria and tuberculosis, can skew the outcome of clinical trials.
But from the point of view of the drug companies, it’s easy to see why moving clinical trials overseas is so appealing. For one thing, it’s cheaper to run trials in places where the local population survives on only a few dollars a day. It’s also easier to recruit patients, who often believe they are being treated for a disease rather than, as may be the case, just getting a placebo as part of an experiment.
And it’s easier to find what the industry calls “drug-naïve” patients: people who are not being treated for any disease and are not currently taking any drugs, and indeed may never have taken any—the sort of people who will almost certainly yield better test results. (For some subjects overseas, participation in a clinical trial may be their first significant exposure to a doctor.)
Regulations in many foreign countries are also less stringent, if there are any regulations at all. The risk of litigation is negligible, in some places nonexistent. Ethical concerns are a figure of speech. Finally—a significant plus for the drug companies—the F.D.A. does so little monitoring that the companies can pretty much do and say what they want.
Consent by Thumbprint
Many of today’s trials still take place in developed countries, such as Britain, Italy, and Japan. But thousands are taking place in countries with large concentrations of poor, often illiterate people, who in some cases sign consent forms with a thumbprint, or scratch an “X.”
Bangladesh has been home to 76 clinical trials. There have been clinical trials in Malawi (61), the Russian Federation (1,513), Romania (876), Thailand (786), Ukraine (589), Kazakhstan (15), Peru (494), Iran (292), Turkey (716), and Uganda (132). Throw a dart at a world map and you are unlikely to hit a spot that has escaped the attention of those who scout out locations for the pharmaceutical industry.
The two destinations that one day will eclipse all the others, including Europe and the United States, are China (with 1,861 trials) and India (with 1,457). A few years ago, India was home to more American drug trials than China was, thanks in part to its large English-speaking population. But that has changed. English is now mandatory in China’s elementary schools, and, owing to its population edge, China now has more people who speak English than India does.
While Americans may be unfamiliar with the names of foreign cities where clinical trials have been conducted, many of the drugs being tested are staples of their medicine cabinets. One example is Celebrex, a non-steroidal anti-inflammatory drug that has been aggressively promoted in television commercials for a decade. Its manufacturer, Pfizer, the world’s largest drug company, has spent more than a billion dollars promoting its use as a pain remedy for arthritis and other conditions, including menstrual cramps.
The National Institutes of Health maintains a record of most—but by no means all—drug trials inside and outside the United States. The database counts 290 studies involving Celebrex. Companies are not required to report—and do not report—all studies conducted overseas. According to the database, of the 290 trials for Celebrex, 183 took place in the United States, meaning, one would assume, that 107 took place in other countries.
But an informal, country-by-country accounting by VANITY FAIR turned up no fewer than 207 Celebrex trials in at least 36 other countries. They ranged from 1 each in Estonia, Croatia, and Lithuania to 6 each in Costa Rica, Colombia, and Russia, to 8 in Mexico, 9 in China, and 10 in Brazil. But even these numbers understate the extent of the foreign trials. For example, the database lists five Celebrex trials in Ukraine, but just “one” of those trials involved studies in 11 different Ukrainian cities.
The Celebrex story does not have a happy ending. First, it was disclosed that patients taking the drug were more likely to suffer heart attacks and strokes than those who took older and cheaper painkillers. Then it was alleged that Pfizer had suppressed a study calling attention to these very problems. (The company denied that the study was undisclosed and insisted that it “acted responsibly in sharing this information in a timely manner with the F.D.A.”)
Soon afterward the Journal of the Royal Society of Medicine reported an array of additional negative findings. Meanwhile, Pfizer was promoting Celebrex for use with Alzheimer’s patients, holding out the possibility that the drug would slow the progression of dementia. It didn’t. Sales of Celebrex reached $3.3 billion in 2004, and then began to quickly drop.
One big factor in the shift of clinical trials to foreign countries is a loophole in F.D.A. regulations: if studies in the United States suggest that a drug has no benefit, trials from abroad can often be used in their stead to secure F.D.A. approval.
There’s even a term for countries that have shown themselves to be especially amenable when drug companies need positive data fast: they’re called “rescue countries.”