Pharmaceutical Research, Democracy and Conspiracy

International Clinical Trials in Local Medical Institutions

Edison Bicudo

• Publisher: Routledge
• Year: 2016
• ISBN:
  9781317081364
• Edition: 1
• Topic: Business
• Subtopic: Pharmaceutical, Biotechnology & Healthcare Industry
• Index: Business

Clinical trials used to be conducted overwhelmingly in the US and Europe but for a range of economic, technical and ethical reasons, the number of multicentre studies recruiting subjects in different regions of the World has grown exponentially. New medicines are tested in vast research networks involving several countries, hospitals and other medical institutions, and hundreds of individual subjects. In Pharmaceutical Research, Democracy and Conspiracy, Edison Bicudo examines the connections between global and local scales, exploring how it is possible for social actors as different as global companies and patients of local hospitals to come together and establish social relationships that may last many years. He also identifies the implications of these global-local relationships for the financial, technical and cultural structures of the participating hospitals. His study draws on fieldwork conducted in five countries: the UK, Spain, France, Brazil and South Africa. Shining a light on the social mediations that enable the encounter between these rationalities, the author concludes that this has the practical effect of subjecting countries hosting trials to institutional engineering. Hospitals and research agencies create new, sometimes surprising, institutional arrangements to cope with international research projects, which change relations between physicians and patients, as they acquire new roles as clinical investigators and research subjects. Frequently, such shifts deviate the institutional structures of medical institutions away from democratic, and towards conspiratorial, schemes. The book reviews the concept of mediation in sociological thought, proposes further developments in Habermas' theory of communicative action, and offers some political reflection about the role of institutions in contemporary democracies.

PART ONE
Global Trials in Medical Institutions

1
Infrastructure: The Indirect Privatization of Hospitals

In multicentre trials, the international reach of CROs and pharma companies requires the establishment of several types of standards, so that activities and outcomes can be normalized and compared. Hospitals are turned into sites; patients into research subjects; individual sufferings into cases. We are dealing with the sociological phenomenon of ‘commensuration’, as defined by Espeland and Stevens (1998, p. 316): ‘Commensuration transforms qualities into quantities, difference into magnitude. It is a way to reduce and simplify disparate information into numbers that can easily be compared.’

As Lakoff (2005) pointed out, standardization and commensuration are typical to medical thought, which frames diseases as stable phenomena existing outside the body. In clinical trials, this abstract approach is reinforced because there must be a vast range of standards ruling procedures and ways of measuring events. Clinical protocols ‘standardize a set of practices, actors, and situations. They intervene in a specified situation and prescribe a set of activities that should be performed in a similar way in order to achieve results comparable over time and space’ (Timmermans and Berg 2003, p. 63).

The first and most general manifestation of standardization in trials is the emergence of international rules that submit several countries to the same clinical and regulatory procedures. In 1964, the Declaration of Helsinki mandated broad ethical parameters (Fisher 2009), and was subsequently reshaped by the interests of multinational companies (Shah 2006).

Petryna (2009) provides us with many other examples of how regulatory standardization advanced in clinical trials: in the early 1990s, pharmaceutical companies formulated a new set of guidelines through the creation of the International Conference on Harmonization, launched in tandem with the Trips Agreement;¹ many systems and institutions have mushroomed all over the world, as is the case of ethics committees; the Food and Drug Administration (the United States regulatory agency) has audited sites in many countries, thereby enforcing the global diffusion of some standards; in 1995, the world witnessed the creation of GCP: ‘The GCP (Good Clinical Practice) is a set of World Health Organization guidelines for the design, conduct, performance, monitoring, auditing, recording, analysis, and reporting of clinical trials’ (Petryna 2009, pp. 107–108).

As a result of this process, the field of clinical trials has turned into an internationalized regulatory environment (Rozovsky and Adams 2003; Abraham 2007, 2009). The trend is reinforced because in many countries ‘the pharmaceutical industry was, and is, permitted to have privileged strategic access to, and involvement with, government regulatory policy over and above any other interest group’ (Abraham 2009, p. 58).

The goal of this chapter is not to analyse the occurrence of standardization in clinical trials, as this has already been successfully carried out (Gray 1975; Timmermans and Berg 2003). Here, I try to unravel the impacts of standardization and commensuration upon particular hospitals involved in global trials. We shall see that standards can have both positive and disturbing outcomes, depending on how, and by whom, they are installed. Moreover, we shall see that the proliferation of standards ends up creating series of regulatory loopholes, which open up some leeway for hidden negotiations in multicentre trials. Slowly, research activities conducted in medical institutions become less and less subject to decisions taken in state agencies, and the trials industry seems to take over these responsibilities, fostering a process of indirect privatization of hospitals.

We begin this analysis with a brief overview of recent regulatory renewals experienced by the five countries included in my study. We move on to focusing on the global standards that CROs implement and comply with. Subsequently, the so-called feasibility studies are analysed. Then, we begin to focus on the impacts of global standards on the organization of hospitals, starting this analysis with the rhythms of work imposed by the industry. We continue by addressing the quantitative concerns promoted in multicentre trials. After discussing the ways in which hospitals equip themselves for the arrival of international trials, we focus on the hospitals’ human resources. Then, the partnerships between hospitals and the trials industry are studied. Finally, I stress the deep association between private companies and state hospitals, as well as the emergence of a new reality in medical institutions.

1.1 National Regulatory Renewals

In all of the five countries we are studying here (the UK, Spain, France, Brazil and South Africa), it is possible to identify approximately the same regulatory structures: national laws of clinical research, regulatory agencies, and ethics committees, among others. To be sure, there are differences pertaining to the pace of the regulatory process and the internal organization of institutions, but the fundamentals of these national systems do not vary substantially.

In South Africa, ethics committees² have appeared sparingly, because many hospitals delegate the review of their studies to other sites (Bicudo 2012). It is the only country in our ‘sample’ where private ethics committees are of important weight.³ In 1996 South Africa published the National Policy on Medicines, whose guidelines were addressed in detail by the 2003 Act 59, in which national legislation was brought into line with international rules. Today the Medicines Control Council is the regulatory agency responsible for authorizing clinical trials, whereas the National Health Research Ethics Council is the principal ethics body, responsible for registering and certifying ethics committees.

The Brazilian regulatory framework was also changed in 1996, when the National Commission for Research Ethics (Comissão Nacional de Ética em Pesquisa) was created as one of the measures mandated by Resolution 196, which addressed ethical and practical procedures of clinical research. The Resolution fostered the proliferation of ethics committees in several hospitals and, as a result, Brazil has today more than 600 ethics committees. The National Agency for Sanitary Surveillance (Agência Nacional de Vigilância Sanitária) is the main regulatory body.

The situations of the UK, Spain and France can be studied together, for these countries have participated in a regional effort of regulatory harmonization. In 2001, the European Parliament approved the Directive 2001/20, which created regional rules for the conduct of clinical trials. As Marchal (2007) explains, the Directive aims to both encourage the implementation of good clinical practices and harmonize the procedures mandated by the different countries. As a consequence, national procedures to process research applications are slowly becoming similar, enabling, for instance, the approximation of the timelines followed by ethics committees and regulatory agencies.

In 2004, the Directive was transposed to the British, Spanish and French laws. In the UK, the shift was realized by the Medicines for Human Use Regulations; in Spain, the transposition happened through a Royal Decree; France adopted the Directive’s rules by means of a Law of Public Health that was complemented by a 2006 decree. While the UK and Spain have ethics committees attached to research sites, France holds a system of regional committees, whose number amounts to only 40.

Thus the trials industry is aware that in spite of some differences, these five countries are operating under the same basic conditions. The modernization of national regulatory frameworks creates a sort of international language that is more than suitable for companies such as global CROs. In the next section, we analyse how they have been implementing global standards of work and therefore producing a type of abstract space of their own.

1.2 The Global Space of Multinational CROs

In 2011 the Brazilian government began to renew its regulations pertaining to clinical trials. The initiative would imply, in a first moment, shifts in the so-called Regulation 196, which guides the conduct of clinical studies. In the UK, I interviewed a CRO’s Global Manager who was aware of the changes in Brazil. According to him, ‘we’re lobbying and we’re working with the Brazilian Ministry of Health to be able to make it more competitive in being involved in clinical trials’. This interest is understandable, for the more similar national legislations the more appropriate the operational field of multinational actors becomes. As a result of such globalizing trends, a regulatory framework tends to be globally constructed and as Espeland and Stevens (1998) claimed, it becomes difficult to sustain the force of local rules.

If shaping national rules is a tricky aim for multinational companies to achieve, the formulation of global procedures to be followed within a company is much simpler. In an interview in Madrid, a CRO’s Director of Clinical Operations summarized the tenets of global companies:

We work with global procedures. Theoretically, the vast majority of our work procedures are global ones and valid all over the world. Then there is a set of procedures that are specific to regions (Europe, America, Asia or Africa) and then there are a few procedures that are specific to the country … Because, of course, there are some procedures that depend on local regulations. But I would say that 90 per cent or more of our work is of global procedures; they are the same all over the world.

The implementation of global standards of work has to do with the economic efficiency sought by multinational companies, which would incur high costs if they were to realize drastic adjustments in different countries. As a CRO’s Vice-President for Global Patient Recruitment claimed: ‘it doesn’t make a lot of sense to be doing … one system in Asia and another system in North America and a different system in Europe’. The search for rationality and efficiency may lead to extreme examples of standardization, such as the layout of CROs’ offices, which must have the same appearance and functionality regardless of the country.

However, such details are nothing but expressions of more fundamental issues relating to the CROs’ organization of work, such as the formation of departments and teams. As long as the most decisive and strategic operations (such as the financial management of studies) remain centralized in global headquarters, the constitution of globally widespread teams can be economically interesting. Indeed, CROs’ employees are often selected from different countries, or even continents, to form a team dealing with specific matters. As a British Vice-President for Clinical Management explained to me: ‘most of the communication on running a study is international rather than national’. Technologies such as email or teleconferences are of paramount importance for people who can be in more frequent touch with their counterparts in distant countries than with other people working on a different floor of the same building. In Johannesburg, for example, I interviewed a Contract Specialist who spends about 50 per cent of her work time dealing with contracts to be signed in Europe. Such phenomena enhance the international flow of personnel between different units of a company. According to a Director of Clinical Management interviewed in São Paulo:

I’ve already had monitors transferred to the office in Canada, the office in the United States, some managers were also transferred, and they leave here and the following day they are working there … And it is like exactly the same procedures, exactly the same training, the adaptation is immediate.

For these nomadic workers, language is not an issue. I interviewed a British Director of Clinical Management who spent some years in China; and a South African CEO who lived in Brazil for three years. Both persons did not become able to communicate in the local languages, for they used English in their everyday tasks. Indeed, the field of multicentre trials witnessed the emergence of a global vocabulary not only because of the globalization of procedures, standards and schemes; because the flow of data and information between various countries must be rapid and precise, a global language is in need, and English has been elected to play this role.

As Santos (1979) pointed out, multinational companies tend to have few relationships in the places they are based in. By analysing the case of CROs, one might even have the impression of floating companies for which the surrounding situation would be of minimal relevance. For those who are engaged in the everyday tasks of CROs, an eventual feeling of geographical indifference may be experienced. This is, for instance, the declaration of a Director of Clinical Operations interviewed in Madrid:

The geographical location is almost meaningless. As our studies are international, a monitor who is based in Spain has a clinical study manager who may be in Belgium, the project manager may be in the United States and the person who is responsible for regulatory issues may be in Sweden and the physician who is responsible for the trial may be in another country.

As we shall see,⁴ such impressions of geographical indifference are not underpinned by careful analyses that can reveal the strong dependency the trials industry has toward local actors and creations.

Obviously, the proliferation of international standards has its implications. On the one hand, the global organization of CROs leads to economic and technical efficiency. On the other, it provokes misconceptions and a dearth of knowledge. For instance, professionals who are responsible for overseeing global operations are sometimes likely to ignore national particularities that are crucial to the conduct of a study. One example was given by a CRO’s Contract Specialist interviewed in São Paulo. She told me that in some cases, the global legal department cannot help her team to deal with specific legal issues:

Apart from the support you get from the legal department, do you sometimes have to look for any external support?⁵

Yes, because the legal department of our company, which serves Latin America, is based in the United States. So they basically know the legislation of the United States. So when we need some support relating to the local legislation, either of Brazil or other countries (because we are also responsible for other Latin American countries), then we contact some local lawyers, which are law offices that offer services to us.

Thus CROs have created, through their operations, a sort of abstract global space that, being continuously reiterated and revisited, is sometimes more real than the concrete locations of their offices. On the one hand, we are dealing with companies whose global organization prevents a full commitment to the dynamics of the places in which they are installed. On the other hand, these very same companies are many times dictating procedures to be complied with by local actors. In Johannesburg, for instance, I visited a local CRO, a small company in the first years of its existence. According to its managing director, the company must strive to apply standards and procedures similar to those of multinational CROs. This is so ‘because pretty much the [pharma] companies expect the same standard and there is no excuse if you’re a small company or a large company’. Imitating the procedures of multinational CROs becomes a requisite for small CROs’ survival. For research sites and whole countries, the weight of global standards can be even stronger, as we shall see in the following sections.

1.3 What are Feasibility Studies?

In global pharmaceutical research there are initial questions to ask: where are trials meant to be conducted? In what regions, countries and cities? Under the auspices of what institutions and professionals? In order to address these questions, CROs have developed an ingenious system called ‘feasibility study’. The process, which often takes one month to be concluded, can be either sold by CROs as a separate service or included into the package of services that pharma companies buy. Three procedures belong to this process.

First, as a Feasibility Manager working in Paris explained to me: ‘The goal of feasibility [studies] is first of all to know what the best countries are to participate in a study.’ To be se...