Intended for healthcare professionals

Feature Essay

Clinical judgments, not algorithms, are key to patient safety—an essay by David Healy and Dee Mangin

BMJ 2019; 367 doi: (Published 02 October 2019) Cite this as: BMJ 2019;367:l5777
  1. David Healy, professor1,
  2. Dee Mangin, professor2
  1. 1Department of Psychiatry, Bangor University, Wales
  2. 2Department of Family Medicine, McMaster University, Ontario
  1. Correspondence to: david.healy54{at}

When it comes to detecting harms related to drugs, clinicians’ and patients’ judgment trumps trials, say David Healy and Dee Mangin. Failure to realise this is the greatest threat to the safety of medicines

Immediately on taking a selective serotonin reuptake inhibitor (SSRI), most people have some genital anaesthesia.1 This may be aggravated on withdrawal of the drug and can remain for years after treatment has stopped, constituting post-SSRI sexual dysfunction (PSSD).2 The first case of PSSD was reported to regulators in 1987, even before fluoxetine was approved. While sexual dysfunction features in the labels of SSRIs, neither genital anaesthesia nor PSSD does. The fluoxetine label states that “there are no adequate and well-controlled studies examining sexual dysfunction with fluoxetine treatment.” The citalopram label acknowledges “some evidence suggests that SSRIs can cause such untoward sexual experiences.”

A standard refrain is that randomised clinical trials of short duration and small size have limited ability to detect rare effects of drugs, implying that longer trials are all that’s needed. But as indicated by the sexual effects of SSRIs, which are more common than their mood effects,1 a possibly greater problem lies not in whether we can detect rare adverse events but in our limited ability to detect common ones. Fetishising RCTs as medicine’s only true tool for establishing drug-effect relations may be one reason for this problem.

The gold standard way to miss adverse events

In 1962, in the wake of the thalidomide disaster, RCTs—a then poorly understood technique brought into the mainstream by the English epidemiologist Austin Bradford Hill—were adopted in amendments to the US Federal Food, Drug, and Cosmetic Act to buttress the safety of medicines by keeping ineffective drugs off the market, even though Bradford Hill’s landmark RCT of streptomycin offered less information on the drug’s benefits and side effects than prior clinical …

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