American Journal of Law & Medicine

Conflicts of interest in international human drug research and the insufficiency of international protections.(Globalization of Pharmaceuticals: International Regulatory Issues)

I. INTRODUCTION

The world relies largely on private firms for the development of new medicine, (1) and the system is efficient. Driven by the incentive to profit from sales of new pharmaceuticals, (2) drug companies risk millions of dollars and years of work to shepherd basic scientific discoveries through laboratory and human testing in the hope of developing a marketable drug. For example, it is estimated that in 2002 alone, pharmaceutical companies invested $45 billion the development of new medicine worldwide. (3)

While the profit incentive generates such enormous private investment in human drug development, it also encourages firms to pose inappropriate risks to the safety of human subjects when speeding a new drug to the market. The risks posed by financial conflicts of interest associated with human subjects research on new pharmaceutical products are notable examples, both in the U.S. and internationally. (4,5) Many physicians who conduct such research, and research institutions that house such research, have a financial interest in the outcome of the studies. Some own equity in the drug companies that own the products being tested and sponsor the studies to test those products on humans. (6) More often, researchers and their institutions are the principal owners of "faculty start-up" companies, which hold the rights to the scientific discoveries that are being further developed through human testing, and which have entered, or anticipate entering, into licensing agreements with drug companies for further development. (7) In both cases, researchers and their institutions have an incentive to see human testing go forward quickly and come to conclusions that tend to support the readiness of a new drug for market. The marketability of the drug increases the value of their equity holdings or the earnings that can be generated under a licensing agreement. Additionally, even when they do not have an ownership interest in the product being tested, researchers and research institutions have a financial incentive to serve the commercial interests of drug companies that sponsor human research because they rely on those companies to fund a substantial portion of their operating costs through the financial sponsorship of human drug research they conduct. (8)

Thus, for the sake of encouraging sponsorship of future human drug trials, researchers and their institutions are motivated to serve the interests of the drug companies sponsoring today's research. Moreover, financial conflicts of interest can be generated by paying researcher-physicians and third party physicians a fee for each human subject enrolled in a study, by paying fees to researchers for consulting with a drug company sponsoring a human drug trial conducted by those researchers, or by funding centers at the research institutions that house those trials. (9)

Although the U.S., the European Union (E.U.), and Japan are home to most of the world's private pharmaceutical developers, contain the largest consumer markets for human medicines, and operate the governmental agencies that approve or reject applications for new drugs to enter those markets, the conflicts of interest problems in human drug research span the globe. Drug companies increasingly test new drugs outside of the world's most industrialized countries, only to transfer back the test results to support applications in industrialized countries to market those new drugs. (10) Countries in Latin America, Eastern Europe, and Africa are just a few places that have become prime locations for privately sponsored human drug trials. (11) Those countries generally offer a larger population of potential human subjects than available in industrialized countries, and they pose fewer regulatory barriers that tend to slow the progress of human drug trials. (12)

As drug companies outsource their human research to developing countries, they also export the financial conflicts of interest problem. (13) For example, a December 2000 investigative report by the Washington Post revealed that drug companies often double or triple the annual incomes of health professionals in developing countries by paying salaries and human subject recruitment fees that are moderate under U.S. standards. (14) Similarly, the report established that governments in developing countries are eager to host human drug trials sponsored by pharmaceutical companies as a way of infusing their health care delivery systems with money. (15)

Financial ties among researchers, research institutions and the host country governments, on the one hand, and private firms sponsoring human drug research, on the other hand, create an incentive for researchers, institutions and governments to serve the commercial interests of the sponsoring drug companies. This conflicts with their interest to assure the safety of human subjects in those trials. For example, a researcher with a financial interest in conducting a quick and successful human trial has an incentive to enroll a subject even when the subject might not meet all of the clinical criteria for participation, or to underestimate the importance of a subject's adverse reaction to participation. Likewise, institutions with a financial interest in the studies they house have an incentive to permit those studies to go forward despite evidence of potentially inappropriate risks to human subjects. Similarly, governments eager to encourage drug companies to conduct future human trials in their countries have an incentive to encourage national and local committees designed to protect the safety of human subjects to be lenient in their oversight of the research.

Indeed, the Post investigation found that human subjects in trials conducted in foreign countries were exposed to inappropriate risks when researchers deviated from research protocols, adverse findings were not reported, potential human subjects were not adequately informed of the risks of participation, and enrolled human subjects whose conditions worsened were not moved from experimental to standard treatments. (16) Additionally, a 2001 report from the Office of the Inspector General of the U.S. Department of Health and Human Services found that ethics committees responsible for assuring human subject safety in foreign clinical trials often were too disorganized to sufficiently serve their purpose. (17) This is particularly troubling because international guidelines on human subject research and the laws in each of the world's major drug-producing markets rely heavily on researchers and ethics committees to protect the safety of human subjects. (18)

Thus, the problem of financial conflicts of interest in human subjects research is international in scope, and poses a substantial challenge for international regulation. This essay identifies international standards available to protect human subjects from the risks associated with financial conflicts of interest in human drug trials and assesses their adequacy. Given the rise in foreign drug trials--i.e, human drug research sponsored by a pharmaceutical company based in a highly industrialized country, but conducted in a developing country--such trials are the exclusive focus of the essay. …

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