Conflicts of interest in international human drug research and the insufficiency of international protections.

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. …