Annual direct and indirect costs attributable to nocturia in Germany, Sweden, and the UK

Individuals who awaken one or more times at night to void, with each void being preceded and followed by sleep, are considered to have nocturia [1]. However, those who experience less than two voids per night are generally not regarded as having clinically significant nocturia that warrants diagnostic investigation and treatment. In contrast, people who experience two or more on a regular basis are perceived to be experiencing a significantly bothersome and clinically meaningful condition [2‐4]. One consequence of persistent nocturia is associated sleep fragmentation, suggested by some to be more bothersome than nocturnal voiding frequency per se [5]. Sleep fragmentation affects the most restorative stage of sleep (slow-wave sleep), which could have potentially deleterious impact on daytime alertness, health, and well-being [6, 7].

While nocturia is usually defined as awakening two or more times at night to void [2, 3], nocturnal polyuria is defined as “abnormally excessive urination during the night (>33 % of urine production in 24 h in elderly individuals)” [8]. Pathophysiologically, nocturia is frequently attributed to nocturnal polyuria (nocturnal urine overproduction) [9], which is often due to an altered endogenous production of arginine vasopressin hormone. Nocturia can also be a consequence of a range of causes, such as congestive heart failure, cirrhosis of the liver, obstructive sleep apnea, nephrotic syndrome, chronic renal disease, advanced age, side-effects from drugs or low anatomical or functional bladder capacity (e.g., due to bladder-wall fibrosis, overactive bladder syndrome, or benign prostatic enlargement/bladder outlet obstruction) [1, 10].

The consequences of nocturia and associated poor sleep include daytime fatigue, reduced quality of life (QoL), mood disturbance, reduced productivity at work, poorer overall health, and increased falls and fractures [11]. Notwithstanding, nocturia is a relatively underreported condition, and the true extent of the problem in the population is difficult to estimate. Additionally, nocturia is often under- or misdiagnosed by the treating physician [12, 13]. These factors may contribute to the challenge of identifying patients for whom investigation and corresponding treatment would be indicated.

Prevalence estimates in the published literature vary and are affected by the population studied, the age range considered, and the definition of nocturia used. There have been previous attempts to estimate the costs associated with nocturia in Europe. However, they have generally focused on individual components of healthcare or indirect societal costs arising from lost productivity [14]. High-quality articles on the cost of illness associated with nocturia are generally lacking. Accordingly, the objectives of this study were to estimate the prevalence-based cost of illness imposed by nocturia (≥2 nocturnal voids per night) in Germany, Sweden, and the UK in an average year. Sweden was selected as it was considered to be representative of the Nordic countries. Germany and the UK were selected as they were considered to be representative of Western European countries. However, Germany’s healthcare system allows patients to contact specialists directly without prior referral from a family practitioner, whereas the UK’s healthcare system employs a primary-care gatekeeper system.

This study estimated the economic burden that nocturia imposes on healthcare systems and society as a whole in three typically different European countries: Germany, Sweden, and the UK. The total annual direct healthcare cost of £1.4 billion attributable to managing nocturia in the UK is comparable with the annual National Health Service (NHS) cost of managing dementia (£1.5 billion at 2013–2014 prices) [38]. The total annual direct healthcare cost of €2.3 billion attributable to managing nocturia in Germany is comparable with the total annual direct healthcare cost of managing diseases of the thyroid gland and acute upper respiratory tract infections (€2.3 billion and €2.2 billion at 2014–2015 prices respectively) in Germany [39]. The total annual direct healthcare cost attributable to managing nocturia in Sweden (5.1 billion kr) is concordant with the total annual direct healthcare cost of managing overactive bladder syndrome (3.7 billion kr at 2014–2015 prices) in Sweden [40]. Comparable costs for managing overactive bladder syndrome in Germany and the UK were estimated to be €1.4 billion and £0.9 million, respectively [40].

The total annual direct healthcare cost of managing a nocturia patient in Germany (€186 per patient) and the UK [€205 (£157) per patient] were comparable. However, the corresponding cost in Sweden [€449 (4215 kr) per patient] was more than twofold greater that in the other two countries. The reason appears to be the unit cost of clinician visits and most hospital procedures in Sweden being higher than in the other two countries (Table 3).

We were unable to stratify our findings according to patient age. However, younger patients may experience more troubled sleep and associated problems than older patients [41]. Irrespective of whether sleep interruptions are caused or exacerbated by nocturia, these may affect the general state of health and well-being of sufferers. Furthermore, the negative effects of nocturia may be particularly difficult for younger patients because they are more likely to have more active lifestyles and demanding work schedules than older patients [42]. As proportionally more younger than older adults are expected to be employed, nocturia is seen as having a disruptive economic impact that is disproportional to the prevalence of this condition relative to that of older adults. Indeed, we estimated that the total annual indirect societal cost attributable to nocturia ranges from €20.8 billion in Germany to 19.7 billion kr in Sweden to £4.3 billion in the UK. Notwithstanding, others have reported that older patients with moderate to severe nocturia (≥3 nocturnal voids) incur significantly higher total medical costs, greater number of hospitalization days, higher inpatient medical costs, and higher outpatient medical costs than younger patients [43]. Furthermore, our analysis suggests there is no absenteeism from work as a direct result of nocturia in Germany and Sweden. By way of comparison, this would not appear to be the case for patients with overactive bladder syndrome in these countries [40]. Hence, the annual indirect societal cost attributable to overactive bladder syndrome has been estimated to be €441.3 million in Germany, 726.4 million kr (€77.38 million) in Sweden, and £199.0 million (€259.84 million) in the UK at 2014–2015 prices [40].

This analysis has several limitations: it is based on a systematic review of published literature and clinician experiences. Accordingly, the models were constructed by combining data from numerous, and in many instances non-European, countries with assumptions derived from the clinical authors. Additionally, patient-level data were not available for the study. As the clinical basis of the models was diverse studies, patient populations may not be identical in all of them. Consequently, the modelled patient populations may not necessarily reflect patients who are managed in clinical practice in Germany, Sweden, and the UK, and the observed clinical outcomes may not necessarily reflect those observed from patient cohorts in clinical practice.

The models were based on many assumptions pertaining to prevalence, incidence, mortality, and remission rates. The effect of all these limitations and the uncertainty surrounding the results underwent sensitivity analyses. Nevertheless, the results may be subject to unknown confounders.

The published literature describes various comorbidities that might be associated with nocturia. However, there is no clear evidence on the causal relationships between these comorbidities and nocturia [26]. Consequently, it was decided to exclude the cost of managing those comorbidities where there was any ambiguity regarding their relationship with nocturia. Nevertheless, the analysis can be updated once additional evidence becomes available. Notwithstanding, a scenario analysis estimated the impact of including the cost of depression, which was reported in a systematic review [34] to have a bidirectional association with nocturia.

Healthcare resource use was not collected prospectively but was estimated retrospectively from surveys and the clinical authors. Consequently, resource use for the “average clinician” may not be the same as for clinicians who participated in this study and may not be indicative of the entire populations of Germany, Sweden, or UK. The models incorporated resource use values for an “average patient” and did not take into account disease stage and patient characteristics such as age, gender, and comorbidities. In addition, the possibility of changing treatments (i.e., varying the number of different drug prescriptions) within a year was excluded from the analysis due to scarce applicable data; similarly, resource use and corresponding costs of managing patients in remission were excluded.

The study was performed from the perspective of the health service in each country and society as a whole. However, direct costs incurred by patients (including any co-payments), families, and/or caregivers were excluded (except for over-the-counter medication in Germany) due to the paucity of data. Inclusion of all missing costs (e.g., patient co-payments, cost of managing patients in remission) may affect study results and warrant further investigation. Therefore, generalizing results of this study to other healthcare systems would be challenging. Although healthcare systems in these three countries differ from each other, they could be viewed as being representative of similar types of healthcare structures. Hence, study results for Germany could be generalized to other Western European countries where patients can visit a specialist without a prior referral from a family practitioner. Conversely, study results for the UK could be indicative of other Western European countries with a primary-care gatekeeper system. Furthermore, results for Sweden could be representative of other Nordic countries.

In conclusion, nocturia appears to impose a substantial socioeconomic burden in Germany, Sweden, and the UK. Clinical and economic benefits could accrue from an increased awareness of the impact that nocturia imposes on patients, health services, and society as a whole.