Briefly summarize the case, identify the ethical nature of the problem, along with the essential elements and factors involved.

Answer each of the questions at the end of the case and explain those answers.

>> THE ETHICS OF OFFSHORING CLINICAL TRIALS

The process of offshoring (outsourcing an organizational function overseas) is being applied to clinical drug trials with the same speed and enthusiasm as major U.S. corporations transplanting their customer service call centers to countries such as Ireland, India, and increasingly further eastern locations. In a report released in June 2010 by Daniel R. Levinson, the inspector general of the Department of Health and Human Services, 80 percent of the drugs approved for sale in 2008 had trials in foreign countries, and 78 percent of all subjects who participated in clinical trials were enrolled at foreign sites. Ten medicines approved in 2008 received no domestic testing at all.

For U.S.-based pharmaceutical companies, the rush is driven by both attractive options and practical realities:

• Pursuing the same cost advantages as other U.S. corporations, drug companies are now discovering that trials in countries in such regions as Eastern Europe, Asia, Latin America, and Africa can produce the same quality of data at a lower cost and often in a shorter time frame.
• After safety concerns over drugs like the anti-inflammatory Vioxx, which was withdrawn from sale in 2004, regulators such as the Food and Drug Administration (FDA) are now requiring even more data as a prerequisite for the approval of a new drug. That equates to more trials enrolling more people for longer periods of time-sometimes many thousands of patients over 12 months or longer.
• Patients in North America are increasingly unwilling to participate in phase 1 experimental trials, preferring instead to participate in phase 2 or 3 trials where the effectiveness of the drug has already been established and the trials are focused on identifying appropriate dosage levels or potential side effects.
• In contrast, these new overseas trial sites offer "large pools of patients who are 'treatment naive' because the relatively low standard of health care compared with Western countries means they have not had access to the latest and most expensive medicines."
• In North American trials, each doctor may only be able to offer a handful of patients who are willing and able to participate, whereas in populous nations such as India and China, a single doctor may see dozens of patients a day who would be willing trial participants, allowing faster recruitment from a smaller number of sites.

However, pharmaceutical companies don't have everything their own way. Developing countries or not, restrictions are in place either to directly prevent trials or, at the very least, to ensure the professional and ethical management of those trials:

• Many developing countries have laws against "first in person" trials to prevent the treatment of their citizens as guinea pigs in highly experimental drug trials.
• Russia and China have both limited the export of blood and patient tissue samples in recent years, partly out of concern over illegal trafficking in human organs.
• The FDA recently set up an office in China to increase inspections of the rapidly growing number of clinical trials.
• The World Medical Association's 2004 Helsinki declaration called for stringent ethical practices in drug trials, but these remain voluntary practices.

 In addition, the rush to take advantage of these cost savings and practical benefits has produced some problems ranging from questionable data to patient deaths:

• In 2003, several patients with AIDS died after an experimental drug trial in Ditan Hospital in Beijing. Viral Genetics, a California biotechnology company, was criticized for failing to explain adequately to participants that they were taking part in a drug trial rather than receiving a proven medicine.
• Further criticism was levied at Viral Genetics for an issue that has become a greater concern for clinical drug trials in general-specifically the use of a sugar pill or placebo as a comparative measure of the efficacy of the drug. In the Ditan trial questions were raised as to why an antiretroviral treatment-the most effective treatment for AIDS in the West-wasn't used as a comparative treatment.
• The lack of education and lower standards of care in these developing countries also raise questions about patient eligibility for participation in these trials. While they may qualify by diagnosis, do they really understand the concept of informed consent, and, more importantly still, do they realize that once the trial has ended, it may be months or years before they have access to the drug for a prolonged treatment regimen for their condition?

In the end, it is likely that basic economics will win out. Increasingly stringent standards in North America, driven, some would argue, by the litigious nature of our society, will only serve to increase the attractiveness of overseas trials. Without a suitable regulatory framework to oversee these trials and ensure that patients are treated in an ethical manner, the feared picture of uneducated citizens from developing countries being used as guinea pigs in experimental trials that citizens from developed nations are unwilling to participate in will become a reality.

1. Identify three factors that are driving pharmaceutical companies to host clinical drug trials overseas.

2. What regulations are in place to oversee the professional and ethical management of these trials?

3. If patients lack the language skills or education to understand the significance of informed consent or the use of a placebo, is it ethical to allow them to participate in the drug trial? Why or why not?

4. What proposals would you offer to make the offshoring of clinical drug trials a more ethical process for all the stakeholders involved?