Week 10 Summary: CROs and Offshore Clinical Trials

In the article ‘The Contract Research Organization and the Commercialization of Scientific Research’  by Philip Mirowski and Robert van Horn, the authors examine the arising of contract research organizations (CROs) as often ignored initial sources of the globalization and commercialization of scientific research beginning in the 1980s, especially within the pharmaceutical industry. The authors commence by describing the creation of CROs, and then proceed to evaluate the roles of CROs in the commercialization of pharmaceutical research with respect to at least research on human subjects, disclosure and confidentiality, publication and authorship, and the feedback of ends upon means. The authors describe the arising of CROs in the following manner: in the USA, the Food and Drug Administration (FDA) regulates the drug development process of pharmaceutical companies. First, a pharmaceutical company will initiate a preclinical stage of drug development involving animal testing, and then after filing an Investigational New Drug (IND) application with the FDA and receiving preliminary approval from the FDA, the company will begin a clinical stage of drug development involving four standardized phases of suitably informed human subject testing. While an institutional review board (IRB) oversees the procedures and protocols of the clinical trials, investigators at academic institutions and hospitals administer the trials. Finally, if the clinical trials are promising, then the pharmaceutical company files a New Drug Application (NDA) with the FDA, and if the FDA approves the NDA, then the company may commence marketing of the drug in question. However, for many pharmaceutical companies, their clinical development cycles of drugs were overly prolonged, due primarily to the former academic nature of drug testing. So pharmaceutical companies began desiring novel research entities that would be less academic and more corporate-minded about drug testing, and which could also administer clinical trials with always-increasing patient populations. These new research entities were the CROs, and so in the 1980s, pharmaceutical companies began outsourcing their research and development and drug testing trials to CROs, not only for CROs’ increased efficiency and cost savings (relative to the previously used academic health centres or AHCs), but also because CROs were more adept at coordinating international clinical research, and reaping the advantages of new technological innovations in drug testing.

Given this account of how CROs arose in the 1980s, the authors now consider the influence of CROs on the commercialization of pharmaceutical research, with respect to the areas listed above. Essentially, the authors contend that CROs have created new research practices (by transforming older ones) that more effectively agree with privatized corporate science rather than individual academic scientists. First, the authors consider CROs and their relation to research on human subjects. Since 1974, the USA has required every pharmaceutical institution accepting federal funding to possess an IRB to monitor the treatment of human subjects in drug testing. So, until 1981, local IRBs at universities and non-profit institutions monitored human clinical trials of drug companies, but such IRBs were neither efficient nor cost-considerate, had uncertain legal status, and imposed strange testing protocols. In 1981, the FDA therefore allowed for independent IRBs, which were ultimately employed by CROs and were more efficient and flexible than local IRBs. With respect to human subjects, CROs are also not generally limited to specific geographical areas, and so can use foreign human patients in foreign drug trials that suffer from fewer legal restrictions, thus shortening and rendering more efficient the drug development cycle. Concerning disclosure and confidentiality, once regulatory pharmaceutical agencies demanded to review all drug development data from pharmaceutical companies rather than only some, pharmaceutical companies began employing CROs for clinical drug testing, since CROs will report mostly (if not only) positive data back to the companies for transmittal to the regulatory agencies. The authors also note that conflicts of interest that may exist in the researchers of CROs are not significantly problematic, since such researchers are mere employees of the pharmaceutical firms employing such CROs, and hence the motives of these researchers will be subjected to the directives of the firms. In terms of publication and authorship, the authors note that there has been a recent increase in guest and ghost authorship in medical literature due to the significance of CROs in pharmaceutical research. Since CROs are ultimately not directed towards academic authorship, in that most of the researchers employed by CROs are not interested in such authorship, it follows that many medical papers produced by CROs on behalf of pharmaceutical companies will feature guest or ghost authors. Finally, the authors suggest that the commercialization of scientific research has fundamentally changed the output of pharmaceutical research due to the influence of CROs. CROs facilitate the approval process for new drugs in the pharmaceutical industry, but despite the quantities of FDA-approved drugs increasing over the years, smaller and smaller proportions of these new drugs are actually distinctly innovative. In fact, most of these new drugs are mere ‘copycat’, ‘me-too’, or ‘recycled’ drugs, and CROs have allowed for the proportional increase in these kinds of new drugs because while academic researchers in AHCs typically avoided studying these unoriginal drugs due to their insignificance and lack of scientific interest, researchers in CROs lack such disinclinations. In this way, with respect to research on human subjects, disclosure and confidentiality, publication and authorship, and the feedback of ends upon means, the authors have illustrated how CROs have influenced and facilitated the commercialization of scientific research in at least the pharmaceutical industry.

Adriana Petryna’s article ‘Clinical Trials Offshored: On Private Sector Science and Public Health’ discusses the offshoring of clinical drug trials to middle- and low-income countries and the roles of CROs in this phenomenon. The author reports that at the time of the paper’s writing, 40% of the world’s clinical drug trials (most of them commercially funded) occurred in nontraditional research areas, or countries with declining health resources that enjoy an insignificant share in the world pharmaceutical market. The demand for larger groups of (foreign) human subjects for clinical drug testing derives from a number of causes, some of which are listed as follows: the large number of drug trials being administered (especially for blockbuster drugs and copycats thereof), US regulations that require large-scale testing for the long-term safety of drugs, the rapid expansion of drug categories whose new constituent drugs require clinical testing, and finally the simple creation of truly new drugs to be tested. Specific to the demand for more foreign human subjects is the consideration that the number of available human subjects in Western pharmaceutical markets is decreasing, since in such markets there is a phenomenon of treatment saturation that renders Western subjects increasingly unsuitable for drug testing (essentially, many Westerners already consume multiple drugs and so their bodies will not be very likely to demonstrate specific drug effectiveness). Also, in 1980, pharmaceutical companies were prohibited from utilizing US prison populations for drug testing, although these populations had constituted large portions of the drug testing populations of many pharmaceutical companies. As a result, such companies were compelled to search internationally for substitute drug testing populations.

However, the author indicates that the global expansion of pharmaceutical testing (especially in Eastern Europe and Latin America, the two fastest-growing regions for international clinical drug trials) is encouraged not only by industry motives but also by attractive testing properties of certain foreign regions. For example, CROs perceive Eastern Europe as an especially viable subject recruitment area, because its postsocialist healthcare institutions have remained centralized and enjoy appropriate scientific infrastructure for drug testing, so that they can administer efficient clinical trials. Moreover, patient enrollment is also attractively swift in Eastern Europe because of the region’s unsatisfied demand for specialized medical care. Eastern European subjects are also desirable because they are generally literate and hence can provide more meaningful informed consent. Large Latin American cities are also considered to be excellent drug testing sites because of their large populations contained in small areas, so that travel costs for CROs are reduced. Some foreign regions are attractive pharmaceutical testing sites because they feature treatment naïveté, or populations that have not been diagnosed or treated for a certain medical condition. Such populations are valuable, because they minimize the number of factors (linked to previous treatments) potentially affecting drug trial results. Third World regions are also advantageous drug testing areas, at least because their populations are poor and legally disadvantaged and so will have minimal legal recourse in case of harm during clinical trials. Finally, in order to attract pharmaceutical investments, the regulatory agencies of many countries signed up for the International Conference on Harmonisation, which entailed that these countries would begin creating agencies to standardize and monitor the administration of clinical trials in their countries, as well as ethical review boards to guarantee the rights and protections of testing subjects. Consequently, the subjects of international clinical trials increased substantially in the late 1990s, with the largest increase in international clinical trial participation occurring in Eastern Europe and Latin America. But despite this swift creation of protective agencies in foreign regions, scandals have still arisen with respect to international clinical trials, for example the scandal concerning the antibiotic Trovan that caused the deaths of 11 Nigerian children in a 1996 trial for the drug. Therefore, this article discusses not only the causes and motivations for increased international drug testing since at least the 1980s, but also the potentially negative consequences that such drug testing has imposed on its patients.

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