IRB: Ethics & Human Research

Offshoring Science: The Promise and Perils of the Globalization of Clinical Trials

Research ethics is often said to have been born of scandal. The field is regularly accused of having developed in response to particular cases and transgressions. Whether or not this is true of the field in general, it does seem to be the case for much of the literature on the ethics of international research. InWhen Experiments Travel: Clinical Trials and the Global Search for Human Subjects, the anthropologist Adriana Petryna sets out to portray not scandal or crisis, but the routine offshoring of clinical trials. Through a series of gripping interviews and detailed case studies, Petryna follows the lifecycle of international research and traces its connections to health systems, legal systems, and entitlement programs. She also provides a glimpse into the complex social relations on which the research process depends. In particular, the reader sees the way that the labor is divided, the responsibilities delegated, the risks shifted, and decisions with far-reaching social consequences shaped by a spectrum of market, regulatory, and cultural influences.

The first chapter provides some background about patent law, the history of drug regulation in the United States, and other social and economic dynamics that make offshoring an attractive opportunity for pharmaceutical companies. The second chapter takes the reader inside the world of contract research organizations (CROs), site management organizations (SMOs), and the other corporate entities that play an increasingly crucial role in the conduct of clinical research. Through a detailed conversation with Dr. Hein Besselaar, the person Petryna describes as “widely regarded as the founder of the clinical-research outsourcing industry” (p. 53), the reader sees how members of these organizations view both scientific success and regulatory oversight as obstacles to drug development that have in turn created the niche in which their organizations flourish.

Petryna is at her best in such interviews, unobtrusively allowing her interlocutors to reveal themselves and their worldview with sometimes surprising frankness. In many cases, these vignettes manage to convey an element of life that is often lost in philosophical or ethical discourse—namely, the degree to which ethically problematic conduct can grow naturally and incrementally out of routine activities or relations. The problem in these cases is seldom a discrete point at which a single agent makes a decision to cross a line. It is many agents making many decisions—dividing labor, creating incentives and opportunities, delegating responsibility, and otherwise doing one’s part in an organization—that ultimately entails morally problematic acts.

Chapter three takes Poland for its setting to explore the “lifecycle” of international research. In the first stage, the “gold rush,” pharmaceutical companies and CROs flock to a country where physician-researchers will accept comparatively low remuneration in return for recruiting large numbers of treatment-naive subjects into trials that are shaped almost entirely by the preferences of the research sponsor. The second stage, the “peak moment,” arrives when this process becomes regularized and the social, legal, and regulatory structures of the host community begin to catch up to these new social practices. Finally, as demand for their expertise grows, local researchers raise the prices they charge and become more selective about which protocols they accept. Researchers become “too choosy” (p. 130), regulations become more meaningful, and the pool of highly prized, treatment-naive subjects begins to dwindle. At this point, countries reach the final stage of “exhaustion.”

The mantra of pharmaceutical companies, CROs, SMOs, and researchers in these chapters is that the offshoring of clinical research represents a faster and economically more efficient means of generating socially valuable information. But Petryna’s narrative casts a critical and at times deeply skeptical eye on the social value of the information that emerges from such offshoring. In particular, the globalization of clinical research now makes it possible for CROs to shop around for populations of research participants with very specific disease characteristics. This makes it possible to execute in practice trials that generate information that may have little relevance to the populations likely to be end users of the interventions being evaluated. As a result, side effects or complications associated with a new intervention may only be detected long after it has left the rarified population of carefully screened trial participants and has been used on a widespread basis by patients in the target community, who may have a very different clinical profile.

The ability to shop from among a wide range of potential trial participants also makes it possible for sponsors to spend ever-greater amounts on trials of so-called me-too drugs—interventions that are similar enough in function that they can compete with highly profitable treatments for common medical conditions, but sufficiently different in composition to generate unique patent protection and intellectual property rights. Petryna adds her voice to those who have argued that an increasingly singular focus on capturing a share of lucrative markets for these “blockbuster” drugs has resulted in a decline in genuine innovation within the pharmaceutical industry. Because the globalization of clinical research makes this process easier and more feasible in practice, it enables what amounts to a stagnation of medical innovation.

Chapter four moves to Brazil to explore the impact of international research on the health systems of host communities. Here we see that host communities are not simply temporary homes for transient research projects; they are emerging markets for new interventions. We also learn how clinical trials are not merely exercises in scientific inquiry; they are powerful tools for shaping the opinions, preferences, and behavior of physicians, patients, and a nexus of other actors—such as lawyers, judges, and politicians—who administer or oversee entitlement programs or other mechanisms by which citizens make claims on shared health resources.

Petryna’s portrait of pharmaceutical research in Brazil reveals the extent to which clinical trials are not separate ecosystems from the local medical and public health systems of the communities in which such trials take place. Instead, she claims, they are, “operative environments that redistribute public health resources and occasion new and often tense medical and social fields” (p. 30). In part, this is because the lucrative remuneration available to those who carry out research can lure clinicians and other local talent away from clinical practice. But more fundamentally, clinical trials play a critical role in generating medical consensus and shaping patient demand in host countries. And when research carried out in these communities is driven by the health priorities of other populations, scarce social resources can be drawn away from prevention, primary care, and public health to fund access to expensive, on-patent medications for a highly limited pool of patients.

The most egregious instance of this disconnect occurs when developing countries are used to “salvage” compounds or entities whose therapeutic potential has been cast into doubt. In one particularly striking encounter, a Brazilian researcher, the pseudonymous “Dr. Santos,” recounts how she was tasked with the job of securing approval for a new antidepressant that had failed to show superiority to a placebo in a phase III trial. At first she planned to double the dose of the drug and combine it with a powerful hypnotic, but this possibility was foreclosed by the passage of a Brazilian law prohibiting such combined drug formulations. Although she reports being “happy” about the prospect of not having to do something that she now regards as “unethical,” she nevertheless worked to place the drug on the Brazilian market for the treatment of “a mild form of depression—a ‘made-up’ illness as she called it” (p. 124).

The cumulative effect of these vignettes is a portrait of pharmaceutical research that has come unhinged from the public good. Clinical trials are pursued in made-up populations to produce interventions for made-up diseases, yet they draw real resources from the health systems of both host and target populations in order to generate unbelievable profits for pharmaceutical companies.

At times, Petryna’s reflection on what might be called the strategic or the political use of clinical trials leads the reader perilously close to skepticism about the scientific paradigm of medicine and health care of which clinical trials represent a key element. But Petryna wisely resists this temptation and in chapter four explores how health technology assessment can be used in a way that is aligned with, and contributes to, the public health goals of a community. In this discussion, two things are palpable. The first is that when the scientific method is deployed in service of the health needs of host communities, clinical research has a valuable role to play in producing more effective and efficient health systems in low and middle-income countries. The second, however, is that there are powerful social dynamics that stand in the way of this process.

By the time the reader reaches the book’s final chapter, entitled “The Future of Global Medicine,” it is clear that there are no simple solutions to the problems that Petryna has uncovered. Although the final chapter touches on some small but hopeful efforts to harness the power of science in ways better aligned with public health priorities, nothing here seems to get to the heart of the problem. In fact, by the end of the book, it is not clear that any of the standard preoccupations and frameworks of research ethics are capable of dealing with these problems, either. The main ground for concern lies in the heavy focus of research ethics on a limited cast of characters (researchers and trial participants) and on issues that tend to arise in the course of their interactions (such as informed consent, having access to an adequate standard of care, and providing posttrial benefits). But many of the central problems illustrated in the book are problems of institutional design. They relate to disagreements about whatkindof good clinical research is: whether it is a private activity that produces a commodity for markets, or a public activity that should be focused on producing knowledge to advance important social goods. These questions require a focus on the way institutions divide labor and how to assure accountability for delegating and discharging a range of responsibilities and moral duties.

At its best,When Experiments Travel is enlightening and engrossing, and on the whole, the text is refreshingly clear and accessible. As a result, the periodic use of unnecessary jargon is unusually unnerving. For example, the term “experimentality” is introduced on p. 7 and used regularly without being clearly defined. Even though there is a section in chapter one with the heading “Experimentality,” I still have little idea what the term means or why it was introduced. One gets the feeling that it appears when Petryna is concerned about how an otherwise lucid and incisive narrative will be received by academic anthropologists.

When Experiments Travelis a provocative look inside the outsourcing of clinical trials. The issues that it raises are complex and profound. Hopefully, it will spawn further empirical work and influence the terms of the ongoing debate surrounding the ethics and regulation of international research.

Alex John London, PhD,is Associate Professor of Philosophy and Director of the Center for Ethics and Policy at Carnegie Mellon University, Pittsburgh, PA.

Alex John London, “Offshoring Science: The Promise and Perils of the Globalization of Clinical Trials,”IRB: Ethics & Human Research33, no. 1 (2011): 18-20.