Patient characteristics and PAGE-B score
A cohort of n = 607 patients with positive serum HBsAg were identified during the year 2018, who underwent laboratory work up and regular HCC screening during a total n = 1.210 visits per year. Patients with confirmed cHB receiving second-generation NA for a minimum of one year (n = 227) were eligible for HCC risk assessment by the PAGE-B score. This led to the identification of patients of high (n = 33), intermediate (n = 100) and low (n = 94) HCC risk, respectively (Table 1). Throughout the year, three patients of the total cHB cohort died, whereas no mortality was observed in the low HCC risk subpopulation. Patients with low HCC risk did also not develop any HCC during this time period. The patient numbers with a low risk PAGE-B score (≤ 9 points) were applied to calculate cost reduction by PAGE-B adapted HCC screening.
Time requirements of sonographic HCC screening
The examiner and assistant staff were occupied for a median total exam time of 12.4 min (IQR 9.2–17.2 min) during liver ultrasound. This included a hands-on time of 5.4 min (IQR 4.1–7.8 min) for the examiner. The remaining time span was used for room preparations and documentation of the findings. The total exam time of the liver ultrasound was selected for subsequent work cost calculations during HCC screening. An administrative time of 30 seconds were estimated for the out-patient clinic as well as the endoscopy ward, respectively.
In parallel, patients were involved in HCC screening during a median total turnaround time of 45.0 min (IQR 34.0-59.8 min). The median total turnaround time was applied for calculation of external opportunistic costs for sonographic HCC screening.
Full cost calculation of sonographic HCC screening
Full cost calculation for sonography included costs for instruments, software, technical services, facilities and consumables (Table 2). Average personnel costs expenses for administration (0.346 €/min), medical assistance (0.418 €/min) and physicians (0.574 €/min) were adjusted to the median total exam time and administration time as outlined above.
Table 2
Expenses for the sonography unit
Facility expenses#
|
Euro/m2/year
|
Euro/room#/year
|
Facility fee
|
67.8
|
10,712.4
|
Facility services
|
62.76
|
9,916.08
|
Energy supply
|
4.98
|
786.84
|
Water supply
|
3.68
|
581.44
|
Consumable expenses
|
Amount/exam
|
Euro/exam
|
Paper cover (n)
|
1
|
0.08
|
Paper towels (n)
|
6
|
0.08
|
Desinfection towel (n)
|
1
|
0.05
|
Sonography gel (g)
|
4.9 g
|
0.01
|
Disposable gloves (n)
|
(2)
|
0.07
|
Print out (Paper/Toner) (n)
|
1
|
0.01
|
Fixed costs
|
Amount
|
Cost (Euro)
|
Computer§
|
1
|
625.94
|
Printer hardware
|
1
|
143.72
|
Administration workplace license
|
1/year
|
1904
|
Viewpoint workplace license
|
1/year
|
500
|
#Facility expenses were calculated on basis of the sonography room (15.8 m2). Consumable spendings and IT-support costs were derived from the institutional listed prices. §Including operating system software license.
|
Full costs calculation for HCC screening eventually resulted in a total of 22.82 €/exam (Table 3). A capacity utilization of 75% was applied for the diagnostic sonography unit, as our institution runs two additional work places, used as back up for diagnostic or interventional sonographies. The capacity utilization grade was applied to correct for fixed costs, whereas consumable costs and personnel costs were purely based on exam numbers. A yearly interest rate was applied to account for general price increases as well as personnel expenses. The approximated yearly inflation rates were obtained from the German federal office for statistics survey [12].
Table 3
Full cost calculation for a single liver sonography (75% capacity utilization)
|
Costs per exam
|
|
|
2018
|
2019
|
2020
|
2021
|
2022
|
Factor
|
Consumables costs
|
|
|
|
|
|
|
Paper cover
|
0.080
|
0.081
|
0.082
|
0.082
|
0.083
|
1.01
|
Paper towels
|
0.080
|
0.081
|
0.082
|
0.082
|
0.083
|
1.01
|
Desinfection towel
|
0.050
|
0.051
|
0.051
|
0.052
|
0.052
|
1.01
|
Sonography gel
|
0.010
|
0.010
|
0.010
|
0.010
|
0.010
|
1.01
|
Disposable gloves
|
0.070
|
0.071
|
0.071
|
0.072
|
0.073
|
1.01
|
Print out (Paper/Toner)
|
0.010
|
0.010
|
0.010
|
0.010
|
0.010
|
1.01
|
Fixed costs
|
Sonography instrument
|
3.755
|
3.755
|
3.755
|
3.755
|
3.755
|
1.00
|
Instrument Service
|
0.747
|
0.747
|
0.747
|
0.747
|
0.747
|
1.00
|
Computer hardware
|
0.134
|
0.000
|
0.000
|
0.000
|
0.000
|
1.00
|
Printer hardware
|
0.031
|
0.000
|
0.000
|
0.000
|
0.000
|
1.00
|
SAP workplace license
|
0.406
|
0.406
|
0.406
|
0.406
|
0.406
|
1.00
|
Viewpoint workplace license
|
0.107
|
0.107
|
0.107
|
0.107
|
0.107
|
1.00
|
Facility fee
|
2.285
|
2.308
|
2.331
|
2.355
|
2.378
|
1.01
|
Facility services
|
2.115
|
2.137
|
2.158
|
2.180
|
2.201
|
1.01
|
Energy supply
|
0.168
|
0.171
|
0.175
|
0.178
|
0.182
|
1.02
|
Water supply
|
0.124
|
0.125
|
0.127
|
0.128
|
0.129
|
1.01
|
Personnel costs
|
Administration (out-patient clinic)
|
0.209
|
0.213
|
0.218
|
0.222
|
0.226
|
1.02
|
Administration (endoscopy ward)
|
0.137
|
0.140
|
0.142
|
0.145
|
0.148
|
1.02
|
Procedure (medical staff)
|
7.116
|
7.258
|
7.404
|
7.552
|
7.703
|
1.02
|
Procedure (assistent staff)
|
5.187
|
5.291
|
5.397
|
5.505
|
5.615
|
1.02
|
Total costs
|
22.820
|
22.961
|
23.271
|
23.587
|
23.908
|
|
Full cost pricing of diagnostic liver sonographies was based on a total median exam time of 12.4 minutes as identified for liver sonography. The full costs were calculated on basis of n = 6250 sonographies per year at a capacity utilization of 75%. Factor, inflation rate.
|
Opportunistic expenses for sonographic HCC screening
Opportunistic costs result from patients lost income and lost productivity during HCC screening. The income calculation is based on the assumption, that cHB patients are typically fully integrated in the employment market. This particularly holds true for cHB patients without disease activity and no impairment of liver function, as observed in our cohort (Table 1).
German federal office income statistics were applied and adjusted to the median age of male patients (32.7 years, IQR 31.1–35.2 years) and female patients (49.9 years, IQR 38.9–56.4 years) from the cHB cohort [13]. According to available data (year 2014) an average gross income of 19.13 €/hour for men and 17.08 €/hour for women was extrapolated. The resulting income loss was 17.5 €/exam for male patients and 15.6 €/exam for female patients for the year of assessment. Finally, German unemployment rates of 4.1% for men and 3.3% for women as well as an annual wage increase of 2% were taken into account (Table 4).
Table 4
Opportunistic wage expenses by patient involvement
PAGE-B eligible cHB cohort (PAGE-B score ≤ 9 points)
|
|
2018
|
2019
|
2020
|
2021
|
2022
|
Patients (n)
|
94
|
91
|
87
|
83
|
81
|
Male patients (n)
|
27
|
27
|
25
|
25
|
23
|
Employed male patients (n)
|
26
|
26
|
25
|
25
|
23
|
Average gross income / hour
|
19.1
|
19.5
|
19.9
|
20.3
|
20.7
|
Average gross income / minute
|
0.32
|
0.33
|
0.33
|
0.34
|
0.35
|
including ancillary labor costs/ minute
|
0.39
|
0.40
|
0.40
|
0.41
|
0.42
|
Opportunistic wage expenses / exam
|
17.5
|
17.9
|
18.2
|
18.6
|
18.9
|
Total costs (male patients)
|
453.1
|
462.2
|
435.0
|
443.7
|
414.7
|
Female patients (n)
|
67
|
64
|
62
|
58
|
58
|
Employed female patients (n)
|
65
|
62
|
60
|
56
|
56
|
Average gross income / hour
|
17.1
|
17.4
|
17.8
|
18.1
|
18.5
|
Average gross income / minute
|
0.28
|
0.29
|
0.30
|
0.30
|
0.31
|
including ancillary labor costs/ minute
|
0.35
|
0.35
|
0.36
|
0.37
|
0.38
|
Opportunistic wage expenses / exam
|
15.6
|
15.9
|
16.3
|
16.6
|
16.9
|
Total costs (female patients)
|
1012.6
|
985.0
|
972.2
|
925.3
|
943.8
|
Total costs
|
1465.7
|
1447.2
|
1407.2
|
1369.0
|
1358.5
|
Opportunistic, age and gender adjusted costs of sonographic HCC screening during a median turnaround time of 45 minutes in PAGE-B eligible cHB patients with low HCC risk. All patients attended the infectious and liver disease out-patient clinic during the year 2018. Unemployment rates of 4.1% for men and 3.3% for women were considered. An annual income increase of 2% was applied.
|
Gross domestic product (GDP) per working hour was also considered, as wages do not directly reflect overall productivity. Therefore, the average GDP of 35.56 €/hour, from the year 2017, was adjusted to the total turnaround time (45 min), resulting in a GDP loss of 26.7 €/ exam [14].
Cost reduction by PAGE-B score adapted HCC screening
The annual cost reduction at our institution was calculated on the basis of the expenses for liver sonography and the number of cHB patients with a low risk PAGE-B score (≤ 9 points) receiving NA treatment. This assessment led to a cost reduction of 2,145 € for HCC screening during the year 2018 (Table 5). Given that only age is a time dependent variable of the PAGE-B score, whereas gender and thrombocyte count remaining unchanged, we extrapolated the number of annual HCC screens until a PAGE-B score of 10 points was reached. Based on these assumptions a median of n = 12 (IQR 6–12) postponed sonographies per person was calculated for our cohort, which makes a total of n = 1410 sonography screenings in total. A more restrictive calculation for a maximum 5-year follow-up, identified a total of n = 436 postponed HCC screenings. This resulted in a total cost reduction of 10,488 € for a 5-year period (Table 5).
Table 5
Annual cost reduction for PAGE-B tailored liver sonography
|
Total costs reduction for cHB patients
(PAGE-B score ≤ 9 points)
|
|
|
2018
|
2019
|
2020
|
2021
|
2022
|
Factor
|
Patients (n)
|
94
|
91
|
87
|
83
|
81
|
|
Consumables costs
|
|
|
|
|
|
|
Paper cover
|
7.52
|
7.37
|
7.13
|
6.81
|
6.72
|
1.01
|
Paper towels
|
7.52
|
7.37
|
7.13
|
6.81
|
6.72
|
1.01
|
Desinfection towel
|
4.70
|
4.64
|
4.44
|
4.32
|
4.21
|
1.01
|
Sonography gel
|
0.94
|
0.91
|
0.87
|
0.83
|
0.81
|
1.01
|
Disposable gloves
|
6.58
|
6.46
|
6.18
|
5.98
|
5.91
|
1.01
|
Print out (Paper/Toner)
|
0.94
|
0.91
|
0.87
|
0.83
|
0.81
|
1.01
|
Fixed costs
|
Sonography instrument
|
352.94
|
352.94
|
352.94
|
352.94
|
352.94
|
1.00
|
Instrument Service
|
70.19
|
70.19
|
70.19
|
70.19
|
70.19
|
1.00
|
Computer hardware
|
12.55
|
0.00
|
0.00
|
0.00
|
0.00
|
1.00
|
Printer hardware
|
2.88
|
0.00
|
0.00
|
0.00
|
0.00
|
1.00
|
SAP workplace license
|
38.18
|
38.18
|
38.18
|
38.18
|
38.18
|
1.00
|
Viewpoint workplace license
|
10.03
|
10.03
|
10.03
|
10.03
|
10.03
|
1.00
|
Facility fee
|
214.82
|
216.97
|
219.14
|
221.33
|
223.54
|
1.01
|
Facility services
|
198.85
|
200.84
|
202.85
|
204.88
|
206.93
|
1.01
|
Energy supply
|
15.78
|
16.09
|
16.42
|
16.75
|
17.08
|
1.02
|
Water supply
|
11.66
|
11.78
|
11.89
|
12.01
|
12.13
|
1.01
|
Personnel costs
|
Administration
|
|
|
|
|
|
|
out-patient clinic
|
19.65
|
19.38
|
18.97
|
18.43
|
18.31
|
1.02
|
endoscopy ward
|
12.88
|
12.74
|
12.35
|
12.04
|
11.99
|
1.02
|
Diagnostic procedure
|
|
|
|
|
|
|
medical staff
|
668.90
|
660.48
|
644.15
|
626.82
|
623.94
|
1.02
|
assistant staff
|
487.58
|
481.48
|
469.54
|
456.92
|
454.82
|
1.02
|
Total costs
|
2,145.08
|
2,118.76
|
2,093.26
|
2,066.05
|
2,065.26
|
|
Annual full cost pricing was based on a total median exam time of 12.4 minutes as identified for liver sonography a capacity utilization of 75%. The full costs were calculated on the basis of patients, who did not require sonography HCC screening according to a low PAGE-B risk score of ≤ 9 points. Factor, inflation rate.
|
Nationwide cost reduction by PAGE-B adapted HCC screening was derived from population-based source data (additional Table 2), reporting cHB prevalence rates of 0.3% up to 0.7% in Germany [15–18]. Treatment criteria according to management guidelines were considered, as only patients under second-generation NA therapy are eligible for PAGE-B scoring [3]. Due to the limited population-based data on cHB and liver fibrosis in Germany, only a relevant HBV viral load (> 2000 IU/ml) in 14.7% and an elevated ALT activity in 43.8–59.4% were considered among HBsAg-positive patients [16, 19]. These data resulted in an estimated number of 15,493 (6.4%) up to 49,026 (8.7%) HBsAg-positive patients with antiviral therapy indication in Germany [16, 19]. Corresponding annual NA therapy costs for a total of 7,475,132 treatment days resulted in coherent patient numbers (n = 20,480) in Germany [20]. Eventually the proportion of a low risk PAGE-B score (≤ 9 points) was derived from two trials and from our cHB population, resulting in 24.7% [8], 38.6% [9] and 44.1% (Table 1), respectively. This range eventually results in a total number of 3,827–21,620 NA treated cHB patients with low HCC risk in Germany.
The estimated population-based costs reduction for HCC screening in Germany was 185,830–1,049,815 € per year, based on the full costs for liver sonography and the loss of GDP (Table 6). Extrapolation for a 5-year period, which covers an average of 4.63 postponed sonographies per patient, resulted in a cost reduction (incl. GDP) of 861,934 up to 4,869,346 € for the German population.
Table 6
Screening costs for hepatitis B patients (PAGE-B ≤ 9 pts.) in Germany
Sonography costs (Euro)
|
Nmin
|
Nmax
|
Costs/Exam
|
Costmin
|
Costmax
|
|
3,827
|
21,620
|
22.8
|
87,257
|
492,936
|
Opportunistic wage costs (Euro)
|
Nmin
|
Nmax
|
Costs/Exam
|
Costmin
|
Costmax
|
Male patients (28.7%)
|
1,098
|
6,205
|
---
|
---
|
---
|
Female patients (71.3%)
|
2,729
|
15,415
|
---
|
---
|
---
|
Employed male patients (-4.1%)
|
1,053
|
5,951
|
17.5
|
18,433
|
104,134
|
Employed female patients (-3.3%)
|
2,639
|
14,906
|
15.6
|
41,162
|
232,539
|
Total wage costs
|
---
|
---
|
---
|
59,595
|
336,674
|
Sonography costs incl. wage loss
|
---
|
---
|
---
|
146,851
|
829,610
|
Opportunistic GDP loss (Euro)
|
Nmin
|
Nmax
|
Costs/Exam
|
Costmin
|
Costmax
|
Employed male patients (-4.1%)
|
1,053
|
5,951
|
26.7
|
28,124
|
158,879
|
Employed female patients (-3.3%)
|
2,639
|
14,906
|
26.7
|
70,451
|
398,000
|
Total GDP loss
|
|
|
|
98,574
|
556,879
|
Sonography costs incl. GDP loss
|
---
|
---
|
---
|
185,830
|
1,049,815
|
Full cost pricing for liver sonography was based on the median total exam time (12.4 minutes). Opportunistic costs for diagnostic sonography was based on the median turnaround time (45 minutes). The total costs were calculated on basis of the estimated cHB prevalence in Germany with antiviral treatment indication (n = 15,493 − 49,026), which was adjusted by the rate of patients (24.7%-44.1%) with a PAGE-B score ≤ 9 points. Wage costs and gross domestic productivity (GDP) were also adjusted by the unemployment rates of 4.1% for men and 3.3% for women. Pts., points.
|