As illustrated in Fig. 1, out of 5301 invited women, 1010 were eligible and included in the final analyses. The total of 1010 individuals had an ID diagnosis with a diagnostic test within the last 2 years, they had specific symptoms of ID and they were not pregnant, not suffering of a chronic disease or had no operation in the last 8 weeks. Patient characteristics are shown in Table 1. The mean age of the included women was 33.5 years, and only 3.5% reported that they were not working.
In 96.4% of cases, “being tired or exhausted” led to the decision to consult a medical doctor, followed by reduced physical energy level (41.0%) and headache (27.7%). In the mean, it took 28.3 weeks until a medical doctor was consulted due to the named symptoms (median: 12 weeks, range: 0 weeks n – 1040 weeks). In total, 700 (69.3%) of all women mentioned a history of repeated ID diagnosis (mean number of diagnosis: 3.2; median: 2.0).
ID diagnosis and costs of misdiagnoses due to similar symptoms
In the mean, patients had to visit a medical doctor for 1.7 times (within a time span of 8.5 weeks) until ID was diagnosed. Most of the ID diagnoses (77.8%) were confirmed by general practitioners (GPs) followed by gynecologists (17.9%) and the hospital (0.9%).
Misdiagnosis (initial diagnosis)
A misdiagnosis was assumed in case of an initial diagnosis other than ID, in which case the prescribed treatment other than iron therapy showed a lack of efficacy and in which iron therapy improved symptoms. Table 2 shows the frequency of other diagnoses such as depression, burnout, anxiety state, chronic fatigue and others. In total, 354 (35.0% of the total sample) patients received an initial diagnosis other than ID. Of those, 46.8% were treated prior to the ID diagnosis with a medical therapy or psychotherapy (16.9% of the total sample). The mean duration of the therapy ranged between 34 and 104 weeks.
Comparing patients with a misdiagnosis and without a misdiagnosis shows a statistically significant difference regarding the mean number of consultations (3.0 versus 1.3, p-value: < 0.001) and the mean duration of sick leave (9.6 days versus 2.0 days, p-value: < 0.001). This fact would also have an impact on the health care costs but was not incorporated in our analysis.
Costs of misdiagnoses
Based on the numbers of patients with an initial diagnosis other than ID and the fraction of patients receiving treatment for the respective disease, the total cost for all misdiagnosed patients within our sample population was determined. The per-patient costs for depression (CHF 5085), burnout (CHF 1424), anxiety state (CHF 1318) or chronic fatigue (CHF 946) were multiplied with the number of misdiagnosed patients within our sample [17, 18]. The total costs of all treated patients ranged between CHF 18,471 for chronic fatigue and CHF 357,385 for depression (Table 2). This would yield in CHF 110 per patient with ID within our sample population. The costs for depression were the major driver (80.2%) of the health care costs in our sample.
In order to estimates costs to the Swiss health care system (budget impact), the number of potential patients was identified based on the size of the Swiss female population aged 18–50 years old (n = 1,867,768 in 2014) . Based on our sample (1010 women diagnosed with ID during 2 years, of 5301 screened for eligibility), we assumed an annual incidence of ID diagnosis of 9.5% (range for sensitivity analysis, +/− 20%: 7.5–11.5%). This leads to a population-level estimate of N = 177,438 diagnosed cases per year (range: 140,083-214,793) [3,4,5]. According to our observations, a fraction of 14% would receive a misdiagnosis and an underlying therapy for depression, burnout, anxiety state and chronic fatigue (“others” were not taken into account).It is thus expected that 19,545 to 29,969 Swiss female patients per year may be potentially misdiagnosed (Table 3). The direct medical costs resulting therapies would be CHF 78 million (range: CHF 62 million and CHF 95 million; Fig. 2).
Economic burden of ID due to symptoms (measured as absence from work)
Absence from work due to symptoms
Within the sample, 291 (28.8%) women mentioned that they were not able to comply with their daily business (e.g. work, studies, household) due to the named symptoms (mean: 11.8 days; median: 5 days). Within those participants in the workforce, who mentioned that they were not able to comply with their daily business (N = 287, 28.7%), they had in the mean 5.2 missed work days over 2 years (hence 2.6 days within 1 year) (Table 4). Within this sub-sample, there were also women with zero missed work days. If only women with ≥1 missed work days due to ID symptoms were taken into account, the mean missed work days were 10.8 (n = 138, 14.2% of the total sample). Among housewives, external help was required for 1.2 days (mean).
Economic burden of ID (measured as absence from work)
In our sample, 974 participants were either full-or part-time workers (96.5%). Currently, the fraction of Swiss female in the workforce is 88.9% among 25 to 54 years old . Hence, in our sample, the proportion of Swiss women working was slightly higher.
Extrapolating these numbers to the Swiss female population between 18 and 50 years (n = 1,867,768), we would assume that 177,438 (range: 140,083 to 214,793) are potentially suffering from ID each year (based on an incidence of ID diagnosis of 9.5%, range: 7.5 to 11.5%). If we only consider women in the work-force, the number would be 157,742 (range: 124,533 to 190,951). In total, we would assume that 45,430 (range: 35,866 to 54,994 depending true incidence) patients would take on an average 2.6 days of sick leave due to debilitating symptoms of ID per year, yielding a total of 118,117 (range: 92,251 to 142,984)days per year.
Based on an incidence rate of 9.5% (range: 7.5 to 9.5%), the estimated societal economic burden would be CHF 33 million (range: CHF 26 million to CHF 40 million), if calculated with the human capital approach and CHF 26 million (range: CHF 21 million to CHF 32 million) with the friction cost method, respectively (Fig. 3).
Impact on quality of life
To determine the societal burden, patients were asked to rank various aspects of their life into five categories and their energy level (0–100%) before any ID therapy. Being exhausted and impaired concentration appear to be the most important factors impacting daily living negatively and hence quality of life (Fig. 4).
Associations between energy level (before ID diagnosis) and present misdiagnosis or sick leave were assessed by Spearman’s correlation coefficient. A positive, weak correlation between patients without misdiagnoses and mean energy level was shown (rho: 0.14; p-value: < 0.001). Furthermore, the analysis indicates a further, but weak correlation between duration of sick leave and lower energy level (rho: − 0.19; p-value: 0.01).