Profitable failure: antidepressant drugs and the triumph of flawed experiments

Abstract

Drawing on an analysis of Irving Kirsch and colleagues' controversial 2008 article in PLoS [Public Library of Science] Medicine on the efficacy of SSRI antidepressant drugs such as Prozac, I examine flaws within the methodologies of randomized controlled trials (RCTs) that have made it difficult for regulators, clinicians and patients to determine the therapeutic value of this class of drug. I then argue, drawing analogies to work by Pierre Bourdieu and Michael Power, that it is the very limitations of RCTs -their inadequacies in producing reliable evidence of clinical effects -that help to strengthen assumptions of their superiority as methodological tools. Finally, I suggest that the case of RCTs helps to explore the question of why failure is often useful in consolidating the authority of those who have presided over that failure, and why systems widely recognized to be ineffective tend to assume greater authority at the very moment when people speak of their malfunction.

Do general practitioners and psychiatrists agree about defining cure from depression? The DEsCRIBE™ survey

“…This idea has been mooted previously in the published literature [4,20] and has been stated particularly elegantly by Linsey McGoey of the Said Business School, University of Oxford: "Never before have the inadequacies of RCTs been so apparent to so many. Yet equally, never before have those in positions of authority - from regulators, to NICE policy makers, to doctors - relied so extensively on RCT evidence" [21]. Our data are indeed an illustration of the previous statement since endpoints in RCTs and endpoints in physicians' view seem to be very different.…”

The logic of strategic ignorance

“…In practice, a number of factors restrict the ability of most RCTs to determine a drug's clinical usefulness, such as the fact that RCTs are often tested in populations which are unlikely to receive the drug clinically, and the fact that most RCTs have too few participants to reveal adverse risks that often appear once a drug is on the market (Healy ; Lakoff ; McGoey ). Despite widespread awareness of the limits of RCTs for determining clinical effects, the status of RCTs as the perceived gold standard has led to situations where if an adverse drug effect does not appear on a randomized trial, regulators tend to view it as less alarming or worthy of immediate action.…”

“…Such rationalizations have led to two curious paradoxes. One is that RCTs have never been more powerful in drug regulation than today, when observers increasingly acknowledge their limitations in practice (McGoey ). A second is that those who have most vocalized concerns with RCTs have tended to face more negative professional consequences than those who deliberately ignore concerns.…”

Non-strategic ignorance: Considering the potential for a paradigm shift in evidence-based mental health

“…Partly because of the regulatory and clinical dependence on RCTs, problems within individual RCTs are rarely seen as indictments of the methodology as a whole: instead, they are used as evidence of the need to refine and perfect the methodology further. (McGoey, 2010) McGoey hones in on Kirsch's conclusion that the summed effect of antidepressants has a Cohen's d of 0.32, below NICE's threshold of 0.5, itself an arbitrary marker. She points out that in using an argument derived from EBMH principles in order to unseat pharmaceutical claims, Kirsch further reifies the paradigm and its principles:…”