Many medicines developed for the rich are tested on poor people from developing countries. This is a failure in the allocation of scientific resources and, worse, a threat to the public health of the entire world.
Never before have drug-makers lavished so much attention upon the world's poor. Boehringer Ingelheim's sparkling test labs in
But they are not there to cure the impoverished sick who line up at their shiny research clinics. Drug companies have migrated to developing countries to carry out experiments. In 2006 more than half GSK's drug trials took place outside western markets, mainly in "low cost" countries like
The companies built these laboratories to produce medicines aimed at wealthy westerners with age-related conditions such as heart disease, arthritis, hypertension and osteoporosis. With the average American bringing home 10 prescription drugs every year, the
The more drugs Americans enjoy, the less willing they seem to enrol in the clinical trials required to develop new ones. Each new drug requires over 4,000 patients enrolled in clinical trials, which in turn means that over 100,000 people must be enticed into test clinics for initial screenings (2).
Why so many? It doesn't take many test subjects to prove the effectiveness of, say, insulin for people in diabetic comas, because the drug's effect is so dramatic. But it is far more difficult to prove the effectiveness of new drugs for heart disease, arthritis, hypertension and other chronic conditions: and, despite the industry's best efforts, most new drugs aimed at these illnesses are only marginally effective. Some are hardly better than a placebo. "You usually have to struggle to find a difference" between treated and untreated patients, said one veteran clinical researcher.
The industry's need for experimental subjects is therefore vast. Yet fewer than one in 20 Americans can be bothered to take part in clinical trials. To short-circuit this problem, drug-makers often run tests comparing their new drug's effect against that of a placebo. Fewer subjects are needed for such trials and proving that a new drug works better than nothing is all that the FDA requires.
Pressing need for trials
The only trouble with placebo trials is that they require sufficient numbers of people who are willing to participate in an experiment where they may get no active treatment at all - an increasingly difficult task, especially in the drug-marinated West where it is difficult to find "treatment-naÃ¯ve" patients (sick people too poor to get medical treatment) and where ethics demand the accustomed minimum standard of care. As a result, 80% of the drug industry's clinical trials fail to meet their recruitment deadlines. Each day that a drug remains locked up in development, drug companies haemorrhage some $1m in lost sales, while their rivals beat them to market.
The sicknesses endemic in poor countries are a low priority when a $200m market is the bare minimum to elicit industry interest. But the populations of developing countries do not suffer only from malaria and tuberculosis. According to the World Health Organisation (WHO), 80% of deaths from chronic non-communicable diseases now occur in developing countries. Ninety percent of the world's cases of type 2 diabetes occur in
According to the WHO, the public health implications of this phenomenon are "staggering and are already becoming apparent". Patients being treated for these conditions inevitably suffer more complications than do those in the West. This presents an opportunity for industry trials. To prove that a heart drug works, for example, one needs to show that people who take the drug suffer fewer "events" (heart attacks and deaths) than those who do not. Trials in poor countries can therefore be completed much faster. As an executive from a clinical trials company noted during a conference presentation on the desirability of poor countries for clinical trials: "If you don't have enough events, you'll never finish your trial."
Clinical trials companies (also called contract research organisations or CROs) specialise in conducting clinical trials in foreign countries on behalf of the major pharmaceutical companies. Quintiles, Covance, Charles River Laboratories and PPD (see graph below) have offices and facilities in many developing countries. Quintiles, for example, has clinical sites in
In 25 years the number of therapeutic trials has multiplied by seven. Clinical trials companies are operating on every continent. The sector's turnover is growing by nearly 20% a year and reached $15.4bn in 2006.
Source: Thomson CenterWatch analysis of company reports, 2006.
The main attraction of poorer countries is rapidity. It can take months and even years to recruit sufficient numbers of test subjects in trials in western countries. In
Covance says it can run trials at 25,000 separate medical sites in over a dozen countries. The trade press of the clinical trials industry brims with enthusiastic articles. "Ski where the snow is," recommends one ad from a CRO. "Conduct clinical trials where the patients are."
Win-win, for some
Defenders claim that this is a win-win situation. Clinical trials offer better care than local clinics where patients can wait for entire days to see overworked, under-resourced staff. Poor patients should consider themselves lucky - and their alacrity to participate suggests that they know it. Clinics and hospitals in poor countries get access to the latest technology and frequently capitalise on the new equipment supplied by drug companies for the trials. "We got some equipment," said one clinical researcher in
Being a human guinea pig may be work that westerners no longer want to do, but that doesn't rule it out as a good deal for the poor, who benefit from the best care and get paid for it. If factories can be relocated to take advantage of lower salaries or less rigorous environmental constraints, why not clinical trials? "They said [I was] taking advantage," complained an industry researcher criticised for conducting trials in poor countries. "But without that trial, those children would be dead." "I think it is usually good for people to be in clinical trials," said FDA medical director Robert Temple. "Half of the people [get an active drug] and better care. The other half...[get] better care."
And yet offering one's body to science is not the same as a day job at the factory. Even a sweatshop job, in the usual course of things, will offer quantifiable benefits to the individual, however slim. The clinical trial can make no such promises. This uncertainty, of course, is part of the reason why an experiment is called for in the first place.
The cornerstone of ethical research on humans, as encoded in a myriad of documents (notably the Nuremberg Code, adopted while Nazi doctors were on trial in 1947, and the World Medical Association's Declaration of Helsinki, agreed in 1964 and updated in 2004) is that research subjects should give informed and voluntary consent. The notion of coercion should include over-generous compensation packages. When Aids activists demanded that researchers guarantee lifelong HIV treatment for subjects who became infected in the course of experimental vaccine trials, researchers argued that such a requirement violated the principle of voluntary consent. The deal was just too good: even uninfected people might enrol just for the sake of the free drugs.
And yet a growing body of evidence suggests that experimental subjects in developing countries are not voluntarily consenting to be experimented upon. Bioethicists track the number of people who refuse to participate in or drop out of trials as a sort of after-the-fact indicator: by refusing to participate or dropping out, subjects show that they understand that their participation in trials is voluntary. Refusal and drop-out rates in western trials can run up to 40% or more. But many clinical investigators in developing countries stated that potential subjects never refused to participate in trials. The great speed of recruitment in these trials is another indication of this geographical discrepancy (5).
In some trials up to 80% of the subjects were unaware that they were free to leave - evidence of coercion that was used as a reason to conduct more trials. According to an article in the magazine Applied Clinical Trials, Russian subjects "don't miss appointments, they take all their required pills... and only very rarely do they withdraw their consent.... Russian subjects do what their doctors tell them to do. What a phenomenon!" A Centerwatch story on trials in
Oversight is minimal. Data from overseas trials are accepted by American and European regulatory authorities, but neither requires that drug-makers alert them before they start their overseas trials. The sole requirement is that the Declaration of Helsinki or local rules, whichever afford more protection, are observed. If these trials fail - and 90% of drugs entering clinical trials do fail - the results simply vanish without a trace.
Lucrative income stream
Local ethics committees and regulators are supposed to ensure that subjects' rights are protected: this would probably be fine if they were up to the task. Government officials in
According to The Economic Times, the country's leading business newspaper: "The opportunities are huge, the multinationals are eager, the Indian companies are willing. We have the skills, we have the people, and we have an advantage which
In almost every area of medical practice and research in
Not surprisingly, there has been a whole series of scandals. During the 1970s an unapproved antimalarial drug, quinacrine, was distributed to hundreds of thousands of illiterate women, triggering permanent sterilisation. In the 1980s an injectable contraceptive, that had been withdrawn from the market when it was found to cause tumours in rats, was tested on villagers who later said they had "no idea they were participating in a trial".
In the late 1990s government researchers purposely withheld treatment from over 1,100 illiterate women with precancerous lesions on their cervices, in order to study the progression of the disease. These subjects (like those involved in the notorious
Unethically conducted clinical trials also undermine the legitimacy of western medicine among people in the developing world. To give just two examples:
This argument is rarely so baldly stated, but it is a common undercurrent. It may be true that the quality of care in clinical trials is often superior to regular care, and that clinicians involved in trials get access to the latest technology and tools and to desperately needed income that they can divert to caring for patients. But the data itself cannot be equated with medical progress, as anyone who has seen cutting-edge vaccines rotting in tropical warehouses can attest.
Basic justice demands that subjects in trials should get eventual access to the medicines whose approval they have helped to secure. Too often, new drugs developed via experiments on people in poor countries are not licensed for use in those countries, are priced prohibitively, or are unusable there because the drug isn't relevant from a clinical perspective.
Such moves may close down some trials. But as the bioethicist Jonathan Moreno said, that's part of the price we pay for recognising that there is a difference between a laboratory rat and a human being. ________________________________________________________
Sonia Shah is a Canadian journalist and the author of The Body Hunters: How the Drug Industry Tests its Products on the World's Poorest Patients (New Press,
(1) See Jean-Philippe Chippaux, "Pharmaceutical colonialism in
(2) See for example Stan Bernard, "The Drug Drought: Primary causes, promising solutions", Pharmaceutical Executive, November 2002.
(3) For a thorough study of the role of "nutritional transition" in the development of some diseases, see Benjamin Caballero and Barry M Popkin eds, The Nutrition Transition: Diet and Disease in the Developing World (Academic Press,
(4) Rapid and voluminous enrollment figures feature prominently on CRO's websites: see, for example, www.quintiles.com
(5) See "Ethical and Policy Issues in International Research: Clinical Trials in Developing Countries", National Bioethics Advisory Commission, April 2001.
(6) The Economic Times, Mumbai, 10 March 2004.
(7) During the US Public Health Service's