By Celia Esteban Serna.
Already in the 90s, people began to insist on, not without naivety, the need to “change the paradigm” from “experience-based medicine” to “evidence-based medicine”, in an endeavour to improve the quality of medical attention, and reduce the misuse of medical resources and workforce (Muckart & Malbrain, 2017). But what happens when the “evidence” on which medicine intends to be based is biased? And who would be against truthful evidence-based medicine? We aim to explore the reasons behind publication bias, and the problems deriving from it in contemporary medicine. In particular, we focus on the overmedicalisation of female sexual interest/arousal disorder to illustrate how and why medical knowledge-creation becomes unethically distorted.
Also known as the “file-drawer bias” (Rosenthal, 1979), publication bias occurs when the results of controlled clinical trials evaluating the therapeutic benefits of a medical product, often funded by the pharmaceutical companies which manufacture said product, are not made public because they undermine its effectiveness (Pollack, Wopat, Muench & Hartung, 2009; Wood, et al., 2008; Hopewell, Loudon, Clarke, Oxman & Dickersin, 2009; Melander, Ahlqvist-Rastad, Meijer& Beermann, 2003). That is, only those findings which favour the entity producing and/or commercialising the compound are made available to the public, giving the false yet seemingly grounded impression that these are indeed useful. It is estimated that approximately between 40% and 50% of the studies undertaken are never published (Portalupi, et al., 2013; Easterbrook, Gopalan, Berlin & Matthews, 1991). By extension, meta-analyses, which are often viewed as a means to finding the most robust and sensible answer to whether or not therapeutic interventions should be included in regular practice or not (Mallet, 2012), are not exempt of this problem. Systematic reviews can further distort empirical evidence by applying a series of “exclusion criteria” (Rahman, 2016), through which specific articles are not included for analysis, on the grounds that they are “methodologically flawed”.
As problematic as publication bias is per se, it is also a link within a complex chain of phenomena of increasing magnitude which affect and subvert global public health and medical epistemology, such as disease and illness, overmedicalisation, overtreatment and overdiagnosis (Pollock & Jones, 2015; Chanska & Grunt-Mejer, 2016; Béhague, 2015; Brodersen, 2017; Carter, 2015; Buck, 2016; Lyu, Xu & Brotman, 2017), as well as, in many cases, unnecessary and preventable medical attention (Eveleigh et al., 2017).
Overmedicalisation, overtreatment and overdiagnosis can be included under the umbrella term “disease mongering”, which involves “trying to convince essentially well people that they are sick, or slightly sick people that they are severely ill” (Payer, 1992). The creation and promotion of female sexual interest/arousal disorder (FSIAD) could be a case study of disease mongering.
Previously known as female hypoactive sexual desire disorder (FHSDD), female sexual interest/arousal disorder (FSIAD) describes the absence of sexual desire and activity (Brotto & Yule, 2017). The mere change in diagnostic labelling and criteria is considered by some to be enough evidence of “disease mongering” tactics by the drug industry through an effort to match up a drug to some subcomponent of the DSM classification (Hartley, 2006; see figure 1). Indeed, the diagnosis of FSIAD is surrounded by method controversies, mostly because the tools used are often self-rated (e.g. Female Sexual Functioning Index; FSFI), rather than laboratory tests objective measures (Meston, 2003). It is also possible, asexual communities claim, that some asexual women are wrongly being diagnosed with FSIAD, which would perpetuate the pathologisation of their sexual orientation (Jones, Hayter & Jomeen, 2017).
These methodological issues and confounding factors could lead to both under- and over-diagnosis of FSIAD which might explain the disparities found in the literature on its prevalence rates, ranging from 10% to 60% (Hayes, et al, 2008). Two questions prevail, however (Katz, 2016, p. 235): how and who decides that female sexual desire is abnormally low, and can these “problems” really be solved using drugs?
Despite this, after three reviews, flibanserin (Addyi, Sprout Pharmaceuticals) was finally approved in 2015 by the US Food and Drug Administration (FDA) as the first, and so far only drug for the treatment of FSIAD for premenopausal women (US FDA, 2015). Flibanserin is an antidepressant which increases dopamine and norepinephrine, both responsible for sexual excitement, and decreases serotonin, responsible for sexual inhibition. However, its approval was controversial due to its marginal efficacy (Jaspers et al., 2016), but severe side-effects, which include 1) sudden and unpredictable hypotension, 2) syncope, and 3) central nervous system depression (i.e. drowsiness, sedation and fatigue). Why approve such a controversial drug for such a controversial disorder? And especially when, prior to 2015, testosterone compounds were already being prescribed off-label to treat FSIAD instead (Snabes & Simes, 2009; Achilli & Panay, 2017; Schwenkhagen & Studd, 2009)?
The truth is that while around one third of the agency’s funding comes from taxpayers, the FDA receives the majority of its drug-reviews funding from pharmaceutical companies, the very industries it should be regulating, which unarguably poses a considerable conflict of interest. Currently, in the US market, the price of Addyi is around $509 for a supply of 30 tablets, which represents a projected cost of $6,108 per year, or $30,504 per 5 years.
While the FDA guarantees post-approval trials to take “regulatory action as needed” (Joffee et al., 2016), existing evidence, biased towards and by pharmaceutical companies, is enough to convince physicians of the benefits of the medical product which, in turn, stimulates the demand for it. It is worth mentioning, nevertheless, that off-label prescription is discouraged by medical regulatory agencies across the globe. As such, it seems like practitioners become, unknowingly, a pawn following Big Pharma’s interests, often to the detriment of patients.
In conclusion, publication – and more specifically, sponsorship – bias instigates off-label prescription and, and through, disease mongering and overmedicalisation, which affect and subvert medical epistemology and practice. The solution is, unfortunately, tautological: to move from profit- towards patient- oriented published biomedical knowledge.
Celia Esteban Serna is currently an MSc Psychology and Language Sciences and Events and Welfare Officer at the UCL Bioethics and Medical Law Society.
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