The claims of randomized controlled trials (RCTs) to be the gold standard rest on the fact that the ideal RCT is a deductive method: if the assumptions of the test are met, a positive result implies the appropriate causal conclusion. This is a feature that RCTs share with a variety of other methods, which thus have equal claim to being a gold standard. This article describes some of these other deductive methods and also some useful non-deductive methods, including the hypothetico-deductive method. It argues that with all deductive methods, the benefit that the conclusions follow deductively in the ideal case comes with a great cost: narrowness of scope. This is an instance of the familiar trade-off between internal and external validity. RCTs have high internal validity but the formal methodology puts severe constraints on the assumptions a target population must meet to justify exporting a conclusion from the test population to the target. The article reviews one such set of assumptions to show the kind of knowledge required. The overall conclusion is that to draw causal inferences about a target population, which method is best depends case-by-case on what background knowledge we have or can come to obtain. There is no gold standard.

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.

The complex ways in which technical challenges of trial design provoke, and are provoked by, ethical, commercial and political factors are considered. It is suggested that the quality of the drug trial evidence base greatly depends on the how ethical, commercial and political priorities are set, and not merely on standardized techniques of data processing. Whether such standardized techniques are raising or lowering the quality of safety information about new drugs, and the protection of patients on clinical trials is explored. It is revealed that these international standards, intended to define valid evidence-based medicine for drug trials, are not themselves robustly evidence-based. It is argued that the internationalized regulatory standards developed to frame the evidence base for drug safety and efficacy are frequently inconsistent with furthering patients’ well-being and public health. Rather, those standards reflect a regulatory culture of neoliberal corporate bias, and have been powerfully shaped by the commercial and political interests of the pharmaceutical industry and regulatory institutions. It is questionable that regulatory agencies are thoroughly and robustly scrutinizing the claims that pharmaceutical firms make about their products. New political and regulatory arrangements that could facilitate more ethical drug trials in the interests of patients and public health are proposed.

This article concerns the challenges faced by pharmaceutical researchers seeking to develop novel antidepressants. Based on ethnographic and documentary research into the drug development process, it shows how researchers try to manage the problem of the placebo response in antidepressant trials. The high rate of placebo response in these trials makes it difficult to demonstrate efficacy and often leads to trial failure. According to researchers, a major reason for high placebo response rates is the inability of standardized rating scales to define a coherent group of ‘drug responders’. They have developed alternative means of classifying patients in order to circumvent this problem and thereby improve the chances of trial success. In their search for ‘the right patients for the drug’, pharmaceutical researchers also provide an incisive critique of the epistemological assumptions underlying the clinical trial process.

Who controls indeterminacy in the doctor–patient encounter defines the nature of professional power. Evidence-based medicine (EBM) is one such control strategy claiming to reduce uncertainty by identifying effective (and efficient) interventions and by removing ineffective treatments from clinical practice. EBM, however, as a means of keeping some autonomy for a profession beset by increasing government control, has had to compete with other professionalizing strategies within medicine. And, despite its promise, EBM is shown not to have reduced indeterminacy but to have shifted the problem into a wider policy arena that involves interpreting evidence. Moreover, in an era of concern for patient safety, EBM is proposed as part of a solution (through its claim to reduce uncertainty about the effect of interventions) but remains itself a potent source of danger and increased indeterminacy.

This article considers the complex construction of randomized controlled trials that lies behind the rhetoric of the gold standard. Drawing on insights from Science and Technology Studies and empirical material, I argue that trials in the field of cardiovascular disease prevention are constituted as ‘research’ rather than ‘science’. In these examples, control emerges out of a dual concern with practices of purification and involvement of aspects of the world outside the experiment, as the designers of trials aspire to relevance as well as rigour. Such strategies of ‘contextualization’ mean that trials are more like alchemy than assay, proceeding by complex moves to transform ‘base’ matters rather than distilling elements of clinical practice.

Evidence-based medicine emerged in connection with struggles for clinical authority in the second half of the twentieth century, as patient-centred medicine and community-oriented medicine presented challenges to laboratory-oriented medicine. The renowned medical researchers Alvan Feinstein and Archie Cochrane helped to develop the new models of patient-centred and community-oriented medicine respectively. They made important contributions to methodological reflections in medicine, and also contributed to social theories about clinical medicine and health care, challenging and criticizing in different ways dominant ontological medical understandings (such as essentialist conceptions of disease and illness). The medical ontologies of patient-centred and community-oriented medicine comprise different (partly incompatible) perspectives on what constitutes standards of evidence, something reflected, for example, in Feinstein and Cochrane’s contrary views on the importance of controlled trials. The analysis of their work in this article illuminates the connection between medical ontologies, standards of evidence and the political in general, reminding us of the need to explore the role of politics in discussions of evidence-based medicine.