Using Evidence to Combat Overdiagnosis and Overtreatment: Evaluating Treatments, Tests, and Disease Definitions in the Time of Too Much

While a large part of the world’s population faces the problems of underdiagnosis and undertreatment, it is apparent that a ‘‘modern epidemic’’ of overdiagnosis afflicts high-income countries [1], with tangible human and financial costs of the unnecessary management of overdiagnosed diseases [2,3]. While there is ongoing debate about how to best describe the problem, narrowly defined, overdiagnosis occurs when increasingly sensitive tests identify abnormalities that are indolent, non-progressive, or regressive and that, if left untreated, will not cause symptoms or shorten an individual’s life. Such overdiagnosis leads to overtreatment when these ‘‘pseudo-diseases’’ are conventionally managed and treated as if they were real abnormalities; because these findings have a benign prognosis, treatment can only do harm. More broadly defined, overdiagnosis happens when a diagnostic label is applied to people with mild symptoms or at very low risk of future illness, for whom the label and subsequent treatment may do more harm than good [3]. Among the drivers of overdiagnosis are technological developments producing ever more sensitive imaging and biomarker tests, and changing disease and treatment thresholds that medicalize more people [4]. For example, detection of indolent breast lesions is now recognised as an established risk of mammography screening [5]; widened definitions of chronic kidney disease label many asymptomatic seniors as diseased [6]; lowered thresholds increase concerns about overdiagnosis of attention deficit hyperactivity disorder [7]; and more sensitive imaging methods are causing the treatment of large numbers of potentially benign pulmonary emboli [8]. It’s important to note there is a complex interrelationship between overdiagnosis and overtreatment—which can occur for many reasons other than overdiagnosis. If we consider the narrow definition of overdiagnosis—where someone is diagnosed with a ‘‘disease’’ that will not progress or harm them—overdiagnosis generally leads to overtreatment. Writing about overdiagnosis in 1998, Black described the cycle of increasingly sensitive tests causing more ‘‘pseudo-disease’’ to be diagnosed and conventionally treated [9]. Because prognosis of ‘‘pseudo-disease’’ is generally benign, there is a perception that patients do well on treatment, reinforcing belief in the value of treatment to the widened patient pool, and in turn fuelling further overtreatment [9]. In other situations, inappropriate overtreatment can occur where there is a legitimate clinical diagnosis, and in some circumstances a degree of overtreatment may be warranted, for instance, the early use of parenteral antibiotics in someone suspected of having bacterial meningitis.