What evidence for a cholera vaccine? Jaime Ferrán's submissions to the Prix Bréant.

This article analyses how the French Academy of Sciences assessed Jaime Ferrán's cholera vaccine submitted for the Prix Bréant in the 1880s. Ferrán, a Spanish independent physician, discovered the treatment in 1884 and tried it on thousands of patients during the cholera outbreak in Valencia the following year. His evaluation sparked a controversy in Spain and abroad on the vaccine's efficacy. The Bréant jury did not see any evidence for it in Ferrán's submission, a decision usually interpreted in terms of French scientific nationalism (or simple chauvinism): an outsider from the scientific periphery could not be awarded the Bréant. Drawing on the archival records of the award, we suggest that Ferrán failed instead to provide data that the Academy could consider unbiased, according to the contemporary standards for data presentation. We will illustrate these standards at work in the assessment of another submission from Spain, by Philip Hauser, who received the Bréant for the thoroughness of his statistical endeavour.

Placebo trials without mechanisms: How far can they go?

In this paper, I suggest that placebo effects, as we know them today, should be understood as experimental phenomena, low-level regularities whose causal structure is grasped through particular experimental designs with little theoretical guidance. Focusing on placebo interventions with needles for pain reduction -one of the few placebo regularities that seems to arise in meta-analytical studies- I discuss the extent to which it is possible to decompose the different factors at play through more fine-grained randomized clinical trials. My sceptical argument is twofold. On the one hand, I argue that experiments alone are not enough to standardize interventions, and that it is necessary to include theories. On the other hand, I argue that the social interactions that seem to be part of placebo effects are difficult, if not impossible, to blind. Therefore, the measurement biases arising from the participants' reactivity to the experimental setup cannot be controlled for. Further decomposition of placebo effects requires a theoretical account of the existing experimental regularities that may guide further tests.

Disease-mongering through clinical trials.

Our goal in this paper is to articulate a precise concept of at least a certain kind of disease-mongering, showing how pharmaceutical marketing can commercially exploit certain diseases when their best definition is given through the success of a treatment in a clinical trial. We distinguish two types of disease-mongering according to the way they exploit the definition of the trial population for marketing purposes. We argue that behind these two forms of disease-mongering there are two well-known problems in the statistical methodology of clinical trials (the reference class problem and the distinction between statistical and clinical significance). Overcoming them is far from simple.

On the impartiality of early British clinical trials.

Did the impartiality of clinical trials play any role in their acceptance as regulatory standards for the safety and efficacy of drugs? According to the standard account of early British trials in the 1930s and 1940s, their impartiality was just rhetorical: the public demanded fair tests and statistical devices such as randomization created an appearance of neutrality. In fact, the design of the experiment was difficult to understand and the British authorities took advantage of it to promote their own particular interests. I claim that this account is based on a poorly defined concept of experimental fairness (derived from T. Porter's ideas). I present an alternative approach in which a test would be impartial if it incorporates warrants of non-manipulability. With this concept, I reconstruct the history of British trials showing that they were indeed fair and this fairness played a role in their acceptance as regulatory yardsticks.