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From our friends up north:

A Brief History of Placebos and Clinical Trials in Psychiatry
Edward Shorter, PhD, FRSC1

The history of placebos in psychiatry can be understood only in the context of randomized controlled trials (RCTs). Placebo treatments are as old as medicine itself, and are particularly effective in dealing with psychosomatic symptoms. In psychiatry, placebos have mainly been featured in clinical drug trials. The earliest controlled trial in psychiatry (not involving drugs) occurred in 1922, followed by the first crossover studies during the 1930s. Meanwhile the concept of randomization was developed during the interwar years by British statistician Ronald A Fisher, and introduced in 3 trials of tuberculosis drugs between 1947 and 1951. These classic studies established the RCT as the gold standard in pharmaceutical trials, and its status was cemented during the mid-1950s. Nevertheless, while the placebo became established as a standard measure of drug action, placebo treatments became stigmatized as unethical. This is unfortunate, as they constitute one of the most powerful therapies in psychiatry. In recent years, moreover, the dogma of the placebo-controlled trial as the only acceptable data for drug licensing is also being increasingly discredited. This backlash has had 2 sources: one is the recognition that the US Food and Drug Administration has been too lax in permitting trials controlled with placebos alone, rather than also using an active agent as a test of comparative effi cacy. In addition, there is evidence that in the hands of the pharmaceutical industry, the scientific integrity of RCTs themselves has been degraded into a marketing device. The once-powerful placebo is thus threatened with extinction.

Can J Psychiatry. 2011;56(4):193–197.

So for truly effective drugs, RCTs are probably not indispensable to licensing, especially given the staggering costs of such trials today; if the drug clearly works, vast and expensive trials would seem unnecessary, a way of keeping smaller players who cannot bankroll such trials out of the game.

Other scholars have argued that, in the hands of the pharmaceutical industry, RCTs themselves have become poisoned at the source. David Healy, Professor of Psychiatry at Cardiff University, has documented the degradation of clinical trials to a means of providing copy for pharmaceutical marketing. He notes that using P levels as measures of statistical signifi cance virtually guarantees that a large trial will churn up signifi cant findings, though the differences between drug and placebo may be clinically meaningless. Rating scales often obscure the heterogeneity within clinical populations, vastly expanding the potential market of a given agent (one thinks of the dubious term ajordepression). The proliferating so-called clinical guidelines, based on the findings of corrupted RCTs, become sluices for pharmaceutical sales rather than bulwarks of scientific integrity (which, I argue, they once were). Healy24 writes:

In the absence of compelling evidence, the
erection of guidelines that advocate one set of
agents over another, however well meaning, leaves
guideline makers open to being captured. Through
a combination of apparently novel indications
and publication strategies, companies can make
diseases fashionable, engineer the appearances
of comparative effi cacy and enlist academic
advocates for particular treatment options.p 31
Healy24 calls this process “guideline capture.”p 28

The poor old placebo, dragged down by bioethical strictures and the corruption of clinical trials that are randomly controlled with placebos, is thus threatened with extinction. This is a shame, in view of its being one of the most powerful treatments that psychiatry has to offer.

Full article:
https://journals.sagepub.com/doi/pdf/10.1177/070674371105600402