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Clinical Trials Offshored: On Private Sector Science and Public Health

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Abstract

This article addresses the offshoring of clinical trials to middle- and low-income countries, and the complicated ways in which they have become integral to public health and quality of care in these contexts. I focus on the operations of United States-based contract research organizations (CROs), which make up a specialized global industry focusing on the recruitment of human subjects and investigators; they are key players in an outsourced world of clinical development ‘service providers’. To get an on-the-ground understanding of the offshored clinical trial, I worked with regulators, health services administrators, and research clinicians in Eastern Europe and Latin America, two clinical trial market ‘growth regions’. By addressing the strategies of evidence-making that inform clinical trial offshoring, this article identifies the context-specific calculations by which experimental groups are being identified. It also addresses aspects of the clinical trial operational model, in which the failure to predict safety outcomes or a paradigm of expected failure is being exported along with the offshored trial. By highlighting the uncertainties of clinical research, this article points to gaps in systems of human protection as it considers new forms of accountability in private sector science and public health.

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Notes

  1. 1 This work draws from a larger book project, The human subjects research enterprise (Princeton UP, forthcoming). Estimates of the current number of clinical trials differ dramatically. The 50,000 number comes from the Boston-based Thomson CenterWatch, which provides intelligence services to the drug industry. To arrive at 50,000, researchers used FDA (US Food and Drugs Administration) estimates of the number of trials initiated annually on the basis of US submissions, the number of drugs currently in development and the average length of trials. One CenterWatch research team member told me that 50,000 is a ‘guesstimate’—‘very conservative’, in his words—in part because of the FDA drug reviewers’ lack of knowledge of the number of experiments informing a new drug application. Ambiguity in numerical estimates suggests a global field of experimental activity whose true scope is largely unknown. Estimating the number of clinical trials is an inexact science, to say the least. Dickersin and Rennie suggest major barriers to a comprehensive repository of clinical trials, including ‘industry resistance, the lack of a funding appropriation for a serious and sustained effort, lack of a mechanism for enforcement of policies, and lack of awareness of the importance of the problem’ (2003: 516).

  2. 2 Among the 10 leading global pharmaceutical markets, the United States ranks first and holds a 60.5 percent share. Germany, France, Italy, the UK, Spain and Belgium also rank among the top 10. Combined, they hold a 21 percent share, followed by Japan (15.1%), Canada (2.4%), and Australia (1.1%) (www.imshealth.com). The Office of Inspector General, Department of Health and Human Services, states that ‘among the countries that have experienced the largest growth in clinical investigators [for commercially sponsored trials] are Russia and countries in Eastern Europe and Latin America’ (2001: i).

  3. 3 For critiques of the United States system for developing, testing, and using prescription drugs, see (Abramson 2004), Angell (2005), Avorn (2004), Goozner (2004), Kassirer (2004); Moynihan and Cassels (2005).

  4. 4 According to CenterWatch, an investigator is:

    A medical professional, usually a physician but may also be a nurse, pharmacist or other health care professional, under whose direction an investigational drug is administered or dispensed. A principal investigator is responsible for the overall conduct of the clinical trial at his/her site.

    A study monitor is:

    [a] person employed by the sponsor or CRO who reviews study records to determine that a study is being conducted in accordance with the protocol. A monitor's duties may include, but are not limited to, helping to plan and initiate a study, and assessing the conduct of studies. Monitors work with the clinical research coordinator to check all data and documentation from the study.

    Reference: www.centerwatch.com/patient/glossary.html#5

  5. 5 On this point see Angell (2005).

  6. 6 The drug is used to treat peptic ulcers, gastritis, and esophageal reflux.

  7. 7 This estimate is given by the Association for Clinical Research Organizations (www.acrohealth.org/trends.php). ACRO is the main lobbying and trade organization for the world's largest CROs.

  8. 8 For an assessment of the commercialization of ethical review boards, see Lemmens and Freedman (2000).

  9. 9 When I refer to clinical trials in this article, I am mainly referring to Phase III trials.

  10. 10 As Hein Besselaar recounted to me in 2004, ‘That was really the situation that set the regulators on their course to make the whole process of drug approval and therefore the regulatory affairs business much more rigid than it was before.’ And in the wake of that scandal, there was a dearth of regulatory-minded drug development experts. Besselaar had organized his postgraduate medical studies to fill this vacuum as a contract researcher: ‘I learned a lot about how to organize the human phase of drug development, and not the animal phase, and I thought maybe there is a business there.’

  11. 11 On ‘irrational’ treatment uses, see Etkin (1999). On the circulation of pharmaceuticals within the lifeworlds of the urban poor in Delhi, see Das and Das (2006).

  12. 12 For different perspectives on this controversy, see Angell (1988, 1997, 2000), Bayer (1998), Botbol-Baum (2000), Crouch and Arras (1998), de Zulueta (2001), Farmer (2002), Lurie and Wolfe (1998, 2000), Rothman (2000).

  13. 13 In the trial business, a placebo is an inactive treatment made to appear like real treatment; it amounts to no treatment.

  14. 14 Marcia Angell (2000), for example, said that practices like the use of a placebo arm were reminiscent of the Tuskegee experiment, in which, for decades, African-American men were followed to observe the natural course of their untreated syphilis.

  15. 15 Variability is not meant to evoke the notion of cultural relativism here, although variability has been considered in such terms (Christakis, 1992). Reliance upon culture to explain differences in global health practices has been a central project in the field of medical anthropology for decades. Knowledge of such differences as translated into the health-care arena tends to focus on ‘unbridgeable’ moral divides between Western and non-Western cultures. In the ethical imperialism vs relativism debate (see Macklin, 1999), anthropologists working in health arenas have been faulted for an alleged blind defence of local culture. See Geertz on the ‘moral and intellectual consequences that are commonly supposed to flow from relativism—subjectivism, nihilism, incoherence, Machiavellianism, ethical idiocy, esthetic blindness, and so on’ (2000: 42). Medical anthropologists more recently contend that a focus on cultural and moral difference in health care has become dangerous to the very people and practices anthropologists have sought to explain, particularly in the contexts of massive epidemics and debates over treatment access. As anthropologist-physician Paul Farmer (1999) and others point out, culture has been used to explain ‘why’ the poor are somehow less responsible regarding treatment regimes. The alarmingly slow development of the anti-HIV drug market in Africa, for example, has been attributed to the allegedly unreliable medical and economic behaviors of that continent's desperately poor HIV sufferers. These characteristics are said to heighten investment risk that, in turn, justifies limited access to low-cost drugs. Anthropologist-physician Jim Yong Kim (Kim et al., 2003) has exposed the way moral assumptions in health planning can further entrench inequality, justifying some interventions while disallowing others. Other medical anthropologists have shown how the local trajectories of pandemics are influenced by the logic of international policy and choices (Biehl, 2001; Cohen, 1999; Das, 1999). This latter body of work explores how differences in the organization of institutions authorized to deal with health problems (state bureaucracies, welfare agencies, insurance companies, medical facilities, and religious and humanitarian organizations) result in distinct programs and policies. These not only differ greatly in form and content, they also can shape different courses of health and disease and influence the outcomes of both (see Petryna and Kleinman, 2006). These works move beyond an emphasis on difference in the health arena, and point to the kinds of empirical work that are required to address the moral, ethical and cultural realities of emergent global drug markets.

  16. 16 The Helsinki Declaration has been modified five times since its first edition in 1964. It deals with ‘all aspects of human biomedical research, providing guidelines for investigators to follow in research involving human subjects’ (Guess et al., 2002: 19).

  17. 17 Another researcher echoed the sense that concerns have shifted from justice to efficiency-based standards in global research when he told me that ethics is a ‘workable document…. Equivalent medication in Eastern Europe is not the same as equivalent medication in Western Europe, so you could work the Helsinki Declaration.’

  18. 18 A recent review (Kent et al., 2004) found that ethical guidelines that specify best proven therapy are routinely being violated, regardless of decisions made by local or international scientists and regardless of funding sources.

  19. 19 An NDA is an application to the FDA to obtain a license to market a new drug in the US.

  20. 20 I am grateful to Veena Das for pointing me to the theory of incomplete contracts.

  21. 21 This point was made publicly by the owner of a small US-owned clinical trials company at an industry-sponsored conference in December 2004.

  22. 22 This is a pseudonym.

  23. 23 Quality was measured by Poland's low ‘finding per FDA inspections ratio’.

  24. 24 Complexity is reflected in the number of different subject inclusion and exclusion criteria, I was told,

    The patient has to be like that, but can't be like that; he has to meet certain parameters and have certain symptoms.… Sometimes the patients are non-existent. Pharma companies want to prove something for non-existing patients. I don't know why. But I think they are driven by trends in the pharmaceutical market, by competition to prove … that one medication is better than others.

    As his director put it: ‘The industry is pushing towards this selectivity in order to maximize signs of drug benefit. As a result, the experiment is too difficult to control on the ground.’

  25. 25 The quote continues: ‘the inclusion of an independent endpoints committee should be the rule, and exceptions to this rule should be justified (2004:2025).’

  26. 26 Indeed, the notion that adversities stemming from the drug can be obscured by ‘normal’ background risks in a given context was precisely the argument the FDA used to explain why it failed to flag Vioxx as risky: ‘The national adverse event reporting system that helps the FDA flag dangerous side effects was of little use in this case because the ailments possibly caused by Vioxx—heart attacks and strokes—are so common’ (Masters and Kaufman, 2004: A01).

  27. 27 Indeed, there has been a shift since the 1980s with the integration of desperate patients suffering from cancer and AIDS into ‘fast-track’ research. Acknowledging this group of special patients called for flexibility within medical institutions with regard to the process of evaluating the effectiveness of therapies through clinical trials. In terms of drug access Brazil's free dispensation of combined anti-retroviral treatments has been hailed as a model of AIDS intervention in a low-income country.

References

  • Abramson J. (2004). Overdosed America: The broken promise of American medicine. New York: HarperCollins.

    Google Scholar 

  • Angell M. (1988). Ethical imperialism? Ethics in international collaborative clinical research. New England Journal of Medicine, 319, 1081–1083.

    Article  Google Scholar 

  • Angell M. (1997). The ethics of clinical research in the Third World. New England Journal of Medicine, 337, 847–849.

    Article  Google Scholar 

  • Angell M. (2000). Investigators’ responsibilities for human subjects in developing countries. New England Journal of Medicine, 342, 967–968.

    Article  Google Scholar 

  • Angell M. (2005). The truth about the drug companies: How they deceive us and what to do about it. New York: Random House.

    Google Scholar 

  • Angell M. (2006). Your dangerous drugstore. New York Review of Books, 53(10). URL (accessed February 2007): www.nybooks.com/articles/19055

  • Avorn J. (2004). Powerful medicines: The benefits, risks, and costs of prescription drugs. New York: Knopf.

    Google Scholar 

  • Bayer R. (1998). The debate over maternal-fetal HIV transmission prevention trials in Africa, Asia, and Caribbean: Racist exploitation or exploitation of racism? American Journal of Public Health, 88, 567–570.

    Article  Google Scholar 

  • Biehl J. (2001). Technology and affect: HIV/AIDS testing in Brazil. Culture, Medicine and Psychiatry, 25, 87–129.

    Article  Google Scholar 

  • Biehl J. (2006). Pharmaceutical governance. In Petryna A. Lakoff A. & Kleinman A. (Eds), Global pharmaceuticals: Ethics, markets, practices. Durham, NC: Duke University Press.

    Google Scholar 

  • Botbol-Baum M. (2000). The shrinking of human rights: The controversial revision of the Helsinki Declaration. HIV Medicine, 1, 238–245.

    Article  Google Scholar 

  • Christakis N. (1992). Ethics are local: Engaging cross-cultural variation in the ethics for clinical research. Social Science and Medicine, 35, 1079–1091.

    Article  Google Scholar 

  • Cohen L. (1999). Where it hurts: Indian material for an ethics of organ transplantation. Special issue on ‘Bioethics and beyond’, Daedalus, 128, 135–165.

    Google Scholar 

  • Crouch R.A., & Arras J.D. (1998). AZT trials and tribulations. Hastings Center Report, 28, 26–34.

    Article  Google Scholar 

  • Das V. (1999). Public good, ethics, and everyday life: Beyond the boundaries of bioethics. Special issue on ‘Bioethics and beyond’, Daedalus, 128, 99–134.

    Google Scholar 

  • Das V., & Das R.K. (2006). Pharmaceuticals in urban ecologies: The register of the local. In Petryna A. Lakoff A. & Kleinman A. (Eds), Global pharmaceuticals: Ethics, markets, practices. Durham, NC: Duke University Press.

    Google Scholar 

  • de Zulueta P. (2001). Randomised placebo-controlled trials and HIV-infected pregnant women in developing countries: Ethical imperialism or unethical exploitation? Bioethics, 15, 289–311.

    Article  Google Scholar 

  • Dickersin K., & Rennie D. (2003). Registering clinical trials. Journal of the American Medical Association, 290: 516.

    Article  Google Scholar 

  • Epstein S. (1996). Impure science: AIDS, activism, and the politics of knowledge. Berkeley: University of California Press.

    Google Scholar 

  • Etkin N. (1999). The rational basis of ‘irrational’ drug use: Pharmaceuticals in the context of development. In R.A. Hahn (Ed.), Anthropology in public health: Bridging differences in culture and society, 165–182. New York: Oxford University Press.

    Google Scholar 

  • Farmer P. (1999). Infections and inequalities: The modern plagues. Berkeley: University of California Press.

    Google Scholar 

  • Farmer P. (2002). Can transnational research be ethical in the developing world? The Lancet, 360, 1301–1302.

    Article  Google Scholar 

  • FDA (Food and Drug Administration) (2004). Innovation/stagnation: Challenge and opportunity on the critical path to new medical products. March. Washington, DC: Dept of Health & Human Services.

  • Geertz C. (2000 [1984]). Anti anti-relativism. In Available light: Anthropological reflections on philosophical topics, 42–67. Princeton, NJ: Princeton University Press.

    Google Scholar 

  • Goozner M. (2004). The $800 million pill: The truth behind the cost of new drugs. Berkeley: University of California Press.

    Google Scholar 

  • Gorman J. (2004). The altered human is already here. New York Times, 6 April: F1.

  • Guess H.A., Kleinman A., Kusek J.W., & Engel L.W. (Eds) (2002). The science of the placebo: Toward an interdisciplinary research agenda. London: BMJ Books.

    Google Scholar 

  • Harkness J.M. (1996). Nuremberg and the issue of wartime experiments on US prisoners: The Green Committee. Journal of the American Medical Association, 276, 1672–1675.

    Article  Google Scholar 

  • Healy D. (2003). Lines of evidence on the risks of suicide with selective serotonin reuptake inhibitors. Psychotherapy and Psychosomatics, 72, 71–79.

    Article  Google Scholar 

  • Juni P., Nartey L., Reichenbach S., Sterchi R., Dieppe P.A., & Egger M. (2004). Risk of cardiovascular events and rofecoxib: cumulative meta-analysis. The Lancet, 364, 2021–2029.

    Article  Google Scholar 

  • Kahn J.P., Mastroianni A.C., & Sugarman J. (1998). Beyond consent: Seeking justice in research. Oxford: Oxford University Press.

    Google Scholar 

  • Kassirer J.P. (2004). On the take: How medicine's complicity with big business can endanger your health. Oxford: Oxford University Press.

    Google Scholar 

  • Kent D., Mwamburi M., Bennish M., Kupelnick B., & Ioannidis J. (2004). Clinical trials in sub-Saharan Africa and established standards of care: A systematic review of HIV, tuberculosis, and malaria trials. Journal of the American Medical Association, 292, 237–242.

    Article  Google Scholar 

  • Kim J.Y., Mukherjee J.S., Rich M.L., Mate K., Bayona J., & Becerra M.C. (2003). From multidrug-resistant tuberculosis to DOTS expansion and beyond: Making the most of a paradigm shift. Tuberculosis, 83, 59–65.

    Article  Google Scholar 

  • Lasagna L. Prisoner subjects and drug testing. Fed Proc 1977 Sept 36(10): 2349–2351.

    Google Scholar 

  • Lemmens T., & Freedman B. (1997). Ethics review for sale? Conflict of interest and commercial research ethics review. Milbank Quarterly, 78, 547–584.

    Article  Google Scholar 

  • Lexchin J., Bero L.A., Djulbegovic B., & Clark O. (2003). Pharmaceutical industry sponsorship and research outcome and quality: Systematic review. British Medical Journal, 326, 1167–1170.

    Article  Google Scholar 

  • Lurie P., & Wolfe S.M. (1998). Unethical trials of interventions to reduce perinatal transmission of the human immunodeficiency virus in developing countries. New England Journal of Medicine, 337, 853–855.

    Article  Google Scholar 

  • Lurie P., & Wolfe S.M. (2000). Letter to the National Bioethics Advisory Commission regarding their report on the challenges of conducting research in developing countries (HRG Publication #1545). URL (accessed January 2007): www.citizen.org/publications/release.cfm?ID=6746

  • Macklin R. (1999). Against relativism: Cultural diversity and the search for ethical universals in medicine. Oxford: Oxford University Press.

    Google Scholar 

  • Marks H. (1997). The progress of experiment: Science and therapeutic reform in the United States, 1900–1990. Cambridge: Cambridge University Press.

    Google Scholar 

  • Marks H. (2000). Where do ethics come from? The role of disciplines and institutions. Paper presented at the Conference on ‘Ethical Issues in Clinical Trials’, University of Alabama at Birmingham, 25 February.

  • Marks H. (2002). Commentary. 3rd Annual W.H.R. Rivers Workshop, ‘Global Pharmaceuticals: Ethics, Markets, Practices’, Harvard University, 19– 21 May.

  • Masters B., & Kaufman M. (2004) Painful withdrawal for makers of Vioxx. Washington Post 18 October, A01.

  • Moynihan R., & Cassels A. (2005). Selling sickness: How the world's biggest pharmaceutical companies are turning us all into patients. New York: Nation Books.

    Google Scholar 

  • Office of the Inspector General, Department of Health and Human Services (2001). The globalization of clinical trials: A growing challenge in protecting human subjects. Boston, MA: Office of Evaluation and Inspections.

  • Petryna A. (2002). Life exposed: Biological citizens after Chernobyl. Princeton, NJ: Princeton University Press.

    Google Scholar 

  • Petryna A. (2005). Ethical variability: Drug development and the globalization of clinical trials. American Ethnologist, 32, 183–197.

    Article  Google Scholar 

  • Petryna A. (forthcoming) The human subjects research enterprise. Princeton, NJ: Princeton University Press.

  • Petryna A., & Kleinman A. (2006). The pharmaceutical nexus: An introduction. In A. Petryna A. Lakoff & A. Kleinman (Eds), Global pharmaceuticals: Ethics, markets, practices. Durham, NC: Duke University Press.

    Chapter  Google Scholar 

  • Rothman D. (2000). The shame of medical research. New York Review of Books, 47(19), 60–64.

    Google Scholar 

  • Sim I., & Detmer D.E. (2005). Beyond trial registration: A global trial bank for clinical trial reporting. PLoS Medicine, 2, e365.

    Article  Google Scholar 

  • Temple R. (2002). Placebo-controlled trials and active controlled trials: Ethics and inference. In H.A. Guess A. Kleinman J.W. Kusek & L.W. Engel (Eds), The science of the placebo: Toward an interdisciplinary research agenda, 209–226. London: BMJ Books.

    Google Scholar 

  • Wardell W., & Lasagna L. (1975). Regulation and drug development. Washington, DC: American Enterprise Institute for Public Policy Research.

    Google Scholar 

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Petryna, A. Clinical Trials Offshored: On Private Sector Science and Public Health. BioSocieties 2, 21–40 (2007). https://doi.org/10.1017/S1745855207005030

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