Eur J Health Econ DOI 10.1007/s10198-017-0917-3
ORIGINAL PAPER
Cost analysis of colorectal cancer screening with CT colonography in Italy Paola Mantellini1 • Giuseppe Lippi2 • Lapo Sali3 • Grazia Grazzini1 • Silvia Delsanto4 • Beatrice Mallardi1 • Massimo Falchini3 • Guido Castiglione1 • Francesca Maria Carozzi1 • Mario Mascalchi3 • Stefano Milani3 • Leonardo Ventura1 Marco Zappa1
•
Received: 19 January 2017 / Accepted: 20 June 2017 Ó Springer-Verlag GmbH Germany 2017
Abstract Objective Unit costs of screening CT colonography (CTC) can be useful for cost-effectiveness analyses and for health care decision-making. We evaluated the unit costs of CTC as a primary screening test for colorectal cancer in the setting of a randomized trial in Italy. Methods Data were collected within the randomized SAVE trial. Subjects were invited to screening CTC by mail and requested to have a pre-examination consultation. CTCs were performed with 64- and 128-slice CT scanners after reduced or full bowel preparation. Activity-based costing was used to determine unit costs per-process, perparticipant to screening CTC, and per-subject with advanced neoplasia. Results Among 5242 subjects invited to undergo screening CTC, 1312 had pre-examination consultation and 1286 ultimately underwent CTC. Among 129 subjects with a positive CTC, 126 underwent assessment colonoscopy and 67 were ultimately diagnosed with advanced neoplasia (i.e., cancer or advanced adenoma). Cost per-participant of
Electronic supplementary material The online version of this article (doi:10.1007/s10198-017-0917-3) contains supplementary material, which is available to authorized users. & Paola Mantellini
[email protected] 1
Cancer Prevention and Research Institute – ISPO, Via Cosimo il Vecchio 2, 50139 Florence, Italy
2
Azienda USL Toscana Centro, P.za S. Maria Nuova 1, Florence, Italy
3
Department of Biomedical, Experimental and Clinical Sciences ‘‘Mario Serio’’, University of Florence, Viale Morgagni 50, Florence, Italy
4
im3D S.p.A., Via Livorno 60, Turin, Italy
the entire screening CTC pathway was €196.80. Average cost per-participant for the screening invitation process was €17.04 and €9.45 for the pre-examination consultation process. Average cost per-participant of the CTC execution and reading process was €146.08 and of the diagnostic assessment colonoscopy process was €24.23. Average cost per-subject with advanced neoplasia was €3777.30. Conclusions Cost of screening CTC was €196.80 perparticipant. Our data suggest that the more relevant cost of screening CTC, amenable of intervention, is related to CTC execution and reading process. Keywords CT colonography Colorectal cancer Mass screening Unit cost Cost-effectiveness Cost analysis JEL Classification I10
Introduction CT colonography (CTC) has proven to be effective for the diagnosis of colorectal cancer (CRC) and adenoma [1, 2] and is recommended for opportunistic screening of CRC [3], while its role as a primary population screening test is under evaluation [4]. CTC is a mini-invasive radiological examination for the colon consisting of a low-dose CT of the abdomen after colonic distension with air or carbon dioxide. Two- and three-dimensional reconstructions of CT data allow visualization of colonic walls. Unlike colonoscopy, CTC screening can be performed after a reduced bowel preparation, does not require sedation, and is usually well tolerated by subjects. A main limitation of CTC screening is represented by the lack of operative capabilities. When a polyp is detected by CTC, the patient has to undergo colonoscopy for confirmation and removal of the
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lesion. Several cost-effectiveness studies on CTC performed in screening and clinical settings and compared to no screening, to fecal blood testing, or to colonoscopy have been published and cost-effectiveness drivers were widely discussed [5–8]. In most of these studies, unit costs for CTC were computed taking into account the average reimbursement for abdominal and pelvic CT [9–11] and relevant cost differences were observed from one country to another [12–14]. In 11 US studies, costs of CTC ranged from 448 to 514 USD and in two European studies from €100 to €128, respectively [5]. In a UK study, the CTC cost was 128 GBP [5]. Such huge differences could be explained with the heterogeneity in comparators and parameter values used within all these studies. Moreover, some of the studies included only direct medical costs while others also considered indirect costs. Only a few studies evaluated extra-colonic findings. According to these observations, more extensive comparisons of screening CTC and fecal occult blood test, systematic evaluations of extra-colonic findings, and comprehensive sensitivity analyses were suggested in future studies. More recently, costs of CTC have been also evaluated in the randomized COlonoscopy or COlonography for Screening (COCOS) trial comparing population screening with CTC versus optical colonoscopy (OC) in the Netherlands [15, 16]. A randomized trial (SAVE study) [17] is ongoing in Italy to compare participation, diagnostic yield, and costs of four primary screening tests for CRC, namely CTC with reduced or full cathartic preparation, OC, and fecal immunochemical test (FIT) (three rounds). Participation and diagnostic yield at first screening round have already been published [18]. In this paper, we aimed to perform a cost analysis of the CTC screening pathway in the setting of a randomized trial (SAVE study).
Methods
Study design and invited population Data were collected within the SAVE trial whose protocol has been already described [17]. Briefly, 16,087 subjects, aged 55–64 years, living in the District of Florence, were randomly assigned and invited to one of four interventions for CRC screening: biennial FIT for three rounds; reduced preparation CTC; full preparation CTC and OC. All randomized subjects received an invitation letter by mail and an accompanying information leaflet with the description of the study. A reminder was sent to non-responders. In the CTC groups, non-responders to the reminder received an invitation to FIT. Subjects randomized to CTC and OC were asked to contact the screening service by phone or e-mail to have an appointment for a consultation. Whenever possible, assessment of exclusion criteria was attempted during phone calls. During the consultation, participants were informed about benefits and harms of the screening examination, the diet prescription, and the bowel preparation. If eligibility criteria were matched, the subjects signed an informed consent and were scheduled for the selected examination.
5,242 invited to CTC
417 excluded
4,825 eligible invitees
1,312 pre-CTC consultation attendees
Data source For costs estimation, several data sources were used (Appendix 1). Information concerning subject enrolment and CTC performances were stored in the SAVE trial database. Subjects’ enrolment started in February 2013 and ended in June 2014. Costs of labor per hour for nurses, radiographers, and radiologists were derived from the Tuscany region’s current rates. Costs of machineries and costs of imaging storage were obtained from corporate data and costs of materials were referred to commercial or corporate data. When needed, Italian VAT of 22% was applied. Costs for colonoscopy assessment were attributed according to Tuscany’s regional rates.
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1,286 CTC participants
126 CTC positive subjects compliant to OC
67 with advanced neoplasia Fig. 1 Flow chart of the SAVE trial (reduced and full preparation CTC groups pooled). CTC CT colonography, OC optical colonoscopy
Cost analysis of colorectal cancer screening with CT colonography in Italy
Subjects characteristics
Cost analysis methodology
Within the SAVE trial, 5242 subjects (Fig. 1) were invited to reduced (n = 2617) or full preparation (n = 2625) CTC screening. Among them, 214 met exclusion criteria and 203 had undelivered letters. Among the 4825 eligible invitees, 1312 were compliant to pre-CTC consultation and 1286 ultimately underwent CTC (678 in the reduced preparation group and 615 in the full preparation group). Seven subjects of 20 with an inadequate CTC repeated the examination. Hence, a total of 1293 CTC were performed. Sixty-five of 1286 subjects undergoing CTC were referred because of extracolonic findings; 126 of 129 subjects with a positive CTC underwent OC assessment. Overall, 161 lesions (advanced neoplasia, adenomas, hyperplastic polyps) were identified. Advanced neoplasia was diagnosed in 67 subjects.
We applied an activity-based costing method for the analysis. The costs of products were determined by the costs of the activities and the number of times activities were used (Fig. 2). Such a methodology was previously used for healthcare [20] and radiological studies [21, 22]. For cost estimation, we used the 2015 year of currency and the state of inflation index of -0.1% for 2015 and -0.1% for 2016. The cost evaluation of the entire program involved four steps.
CT colonography pathway The reduced preparation for CTC consisted of a 3-day lowfiber diet and 13.8 g of Macrogol (MOVICOL, Norgine, Milan, Italy) administered three times a day for 3 days before the examination, while the full preparation was a 3-day low-fiber diet and a 2-l solution of polyethylene glycol (MOVIPREP, Norgine, Milan, Italy) in split-dose the day before and the day of the examination. CTCs were performed in two different hospitals in the Florence District by trained personnel. Fecal tagging was obtained with 70 ml of iodinated oral contrast agent (GASTROGRAFIN, Bayer Schering PharmaAG, Berlin, Germany) administered 3 h before the procedure. Colonic distension was obtained by automatic carbon-dioxide insufflator (PROTOCOL2, Bracco—EZEM, Lake Success, NY, USA) after intravenous administration of 20 mg of scopolamine butylbromide (BUSCOPAN, Boehringer Ingelheim Italia, Milan, Italy), if not contraindicated. Low-dose (120 kVp, 50 effective mAs) CTCs were acquired with 64- and 128-slice CT scanners (Somatom Sensation 64 and Definition AS 128, Siemens, Erlangen, Germany). The acquired CTCs were transferred to a centralized reading center through the RIS/PACS metropolitan area network using decompressed Digital Imaging and Communications in Medicine (DICOM) standard format. In the reading center, CTCs were interpreted by an expert radiologist using a computer-aided diagnosis (CAD) system (CADCOLON, Im3D, Turin, Italy) as ‘‘first reader’’ [19]. According to the study protocol, subjects with a colonic mass or at least one polyp C6 mm were referred to assessment colonoscopy. Subjects with relevant extracolonic findings were invited to a consultation with the radiologist.
First step: process analysis In the screening CTC pathway, we detected four processes with the related action costs and drivers: (1) Invitation to screening CTC; (2) Pre-CTC consultation; (3) CTC execution and reading; (4) Assessment colonoscopy in subjects with a positive CTC. Second step: cost allocation For the determination of each action cost, we considered (1) labor costs; (2) costs for materials (specific, common and generic); (3) costs for technology (COT); (4) ‘‘extra costs’’ generated by out of corporate cost centers (i.e., histopathology examinations of biopsied samples). Labor costs Labor costs were calculated on the basis of: (a) payment received by staff for each specific action, (b) expertise, or (c) time-driven activity-based costing (tdABC) by measured times or transactional units of time. The transactional units of time were estimated by dividing the working timetable for the number of activities made in that time. Expertise meant the single expert opinion provided by a radiologist about time needed for extracolonic findings reporting and communicating.
Costs for materials Costs for materials were allocated to each activity considering: (a) commercial prices for specific materials, or (b) estimates (i.e., mean costs over ten activities), or (c) transactional units.
Costs of technology COT was fully allocated for dedicated equipment. For shared equipment, we used transactional drivers or
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PATHWAY Process A STEP 1 Process analysis
A1
A2
A3
B1
Process A A1
STEP 2 Cost allocaon
A2
B2
A3
B1
STEP 4 Product cost valorizaon
=
A1
+
B2
C2
A2
+ A3
€B
=
B1
+
B3
C1
C2
C3
€ Process C
B2
+
B3
€C
driver b
€B
=
C1
+
C2
+
C3
Process C
Process B driver a
C3
Process C
Process B
Process A €A
C1
€
Process A €A
B3
Process B
€ STEP 3 Process cost compung
Process C
Process B
€C
driver c
PRODUCT
Fig. 2 Steps involved in the activity-based costing method. Product cost valorization is a four-step process. The first step is process analysis. During this step, we look inside the whole product pathway, searching for processes involved. The second step is cost allocation. Costs are allocated not to the product, but directly to the activities inside the processes. The cost of each process is the cost of the activities needed for that process. The third step is process cost valorization, and the fourth is product cost valorization. The cost of
the final product is the cost of each process involved multiplied by the number of times it is used for. The number of times is expressed by ‘‘drivers’’ and each process has its own driver. For example, if 3.7519 invitations are needed to have one counseling participant, the invitation pathway cost for each consultation is 3.7519 times the invitation process cost. A1, A2, A3; B1, B2, B3; C1, C2, C3: activities
duration drivers, estimating times by transactional units of time. We did not use intensity drivers. To compute COT, we used ‘‘virtual depreciation’’ over a 5-year period plus annual maintenance costs. ‘‘Virtual’’ depreciation was calculated as follows: purchasing cost updated to 2015 divided by years of depreciation (5 years), intended for goods without any residual value at the end of the depreciation time.
Fourth step: product cost valorization
Extra costs
Costs estimation
Extra costs were allocated directly to the action by their commercial cost.
Costs of CTC screening pathway were computed as follows.
Third step: process cost computing The determination of process unit costs consisted of calculating the product between the cost of every consumed action and its driver. For example, to compute the mean pathway cost of each CTC, we used CTC as product unit (PU). If we have only one CTC out of 3.68 invitations, the invitation cost (for PU = CTC) will be 3.68 times the unit cost of the action of invitation.
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This step regarded the determination of product cost for each subject undergoing CTC. Costs of the whole pathway were calculated by summing PUs costs or by summing the total costs of each process incurring in the pathway and dividing them by the number of PUs (transactional method). Overhead costs were not considered.
(1)
Invitation process To assess costs of the invitation process, we recorded the number of invitees, invitees matching exclusion criteria, invitation letters (i.e., first invitation, reminder to CTC and invitation to FIT in nonattending to reminder) and undelivered letters. For labor costs, we used total costs of dedicated employees. Mailing service was an outsourced activity and specific costs were taken into account.
Cost analysis of colorectal cancer screening with CT colonography in Italy
(2)
(3)
(4)
For this process, we did not consider materials and technology costs because they comprised only stationery and ordinary office furnishing. Mean costs for each CTC participant and for each invited subjects were computed. Pre-CTC consultation process To assess costs for pre-CTC consultation, we collected the number of subjects who attended consultation. For cost analysis, we used only direct labor costs of dedicated employees. For the consultation process, we had the following output costs: total cost of process, average cost for subject who underwent consultation and, downstream, average consultation cost for each CTC participant. CTC execution and reading process To evaluate the costs of CTC execution and reading, we collected the number of reduced and full bowel preparations, subjects undergoing CTC, repeated CTCs after an inadequate CTC and subjects with relevant extracolonic findings. For materials, we used actual costs for specific goods, or mean costs over ten CTC scans for generic and common goods. As specific goods we intend laxatives, insufflation tubes and iodinated oral contrast agent. For labor costs, we used tdABC (transactional drivers) for each worker (nurses, radiographers, and radiologists). We did not include CTC data transfer costs because we used the regional RIS/PACS. For imaging storage costs, we used the mean cost for our institution where digital archiving is outsourced. As CTC process output costs, we calculated the total SAVE project costs for CTC and the average cost for each subject undergoing CTC. For the action ‘‘manage an extracolonic finding’’, we used expertise timing. Assessment colonoscopy process To evaluate costs of assessment colonoscopy in subjects with positive CTC, we considered the number of positive CTCs, the performed assessment OCs and the subjects with ascertained colonic lesions. Regional reimbursement rates for colonoscopy and histopathology evaluation were used. Cost for every subject with advanced neoplasia was also computed.
Sensitivity analysis We performed a one-way and multi-way sensitivity analysis taking into account three parameters: (1) pre-CTC consultation time; (2) CTC execution time; (3) participation rate. Worst- and best-case scenarios were considered.
Results Numbers of managed cases, total costs for each phase of the process, cost for product unit (total cost of single phase divided by the number of managed cases), action drivers and cost for each subjects undergoing CTC are shown in Table 1. Detailed information about costs are available in Appendixes 1 and 2. Cost of the entire CTC screening pathway The cost of the entire screening pathway for each CTC participant was €196.80. Costs of invitation process The cost of this specific process was €17.04 for each screening CTC participant. Considering the 4825 subjects ultimately invited, the whole unit cost of invitation was €4.54 for each invitee. Costs of pre-CTC consultation process The cost of the consultation phase was €9.45 for each CTC participant. Being the total cost €12,156, the unit cost for each person compliant to consultation was €9.27 (12,156/1312). Costs of CTC execution and reading process Costs for the entire CTC execution and reading process were €145.29 per CTC performed and €146.08 for each subject attending CTC screening. The full bowel preparation cost was sensibly higher than that of the reduced one (€4.80 versus €1.98). Regarding CTC execution, the cost per CTC performed and for each participant to CTC screening was €119.40 (total cost: €153,555, number of CTCs 1293, action driver equal to 1.0000). CTC reading costs per-CTC executed and per-participant were the same (action driver equal to 1.0000) and the amount was €21.42. Cost for the management of extracolonic findings was €35.29 for every consultation and €1.78 (action driver equal to 0.0505) for every CTC participant. Costs of assessment colonoscopy process and cost for subject with advanced neoplasia The cost of the assessment colonoscopy process was evaluated considering the 126 subjects attending OC. The mean value for each OC performed was €247.30 (€31,160/126). Mean diagnostic assessment cost for each CTC participant was €24.23 (action driver equal to 0.0980). Cost for negative
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P. Mantellini et al. Table 1 Costs of screening CTC subdivided by process Process
Subjects
Total costs
Costs for product unit
Action drivers
Costs for each CTC unita
Invitation
4825
€21,907
€4.54
3.7519
€17.04
Recruiting subjects
5242
€6105
€1.16
4.0762
€4.75
Undelivered letters
203
€255
€1.26
0.1579
€0.20
Invitation
4825
€15,547
€3.22
3.7519
€12.09
Pre-CTC consultation
1312
€12,156
€9.27
1.0202
€9.45
CTC execution and reading
1293
€187,856
€145.29
1.0054
€146.08
Execution
1286
€153,555
€119.40
1.0000
€119.40
Reading
1293
€27,548
€21.42
1.0000
€21.42
Data storage
1293
€3474
€2.69
1.0054
€2.70
Data transfer
Re-examination Extracolonic findings Assessment colonoscopy Negative
Cost not included because of corporate RIS-PACS
7
€986
€140.83
0.0054
€0.77
65
€2294
€35.29
0.0505
€1.78
126 17
€31,160
€247.30
0.0980
€24.23
€2635
€155.00
n.a.
n.a.
Positive (with polypectomy)
109
€22,890
€210.00
n.a.
n.a.
Pathology (lesions detected)
161
€5635
€35.00
n.a.
n.a.
0.0000
€0.00
Complications
0
Total cost
€0 €253,079
€196.80
The four processes of CTC screening pathway and their values are indicated in bold CTC CT colonography, n.a. not applicable a
Product unit 9 action driver
colonoscopy was €155.00 (in 17 subjects), whereas cost for colonoscopy with polypectomy was €210.00 (in 109 subjects). Cost for each histopathology examination was €35.00 (161 lesions detected). Costs of bowel preparation were not included. Among the 126 subjects undergoing an assessment colonoscopy, 67 had a diagnosis of advanced neoplasia with a unit cost of €3777.30 (€253,079.00/67). Sensitivity analysis Results of the sensitivity analysis are shown in Table 2. In the worst scenario that took into account a pre-CTC consultation time of 38 min, a CTC execution time of 25 min and a participation rate of 15%, cost of CTC per-participant increased from €196.02 to €232.32. Considering the best scenario, in which pre-CTC consultation and CTC execution times were 10 and 15 min, respectively, and the participation rate was 40%, cost of CTC per-participant decreased from €196.02 to €175.33.
Discussion Costs analysis of the SAVE trial may offer useful information on the general structure of the CTC screening cost in Italy. In our setting, the average cost per subject
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undergoing the screening CTC pathway was €196.80. The analysis of the four organizational processes indicated that the CTC execution and reading phase accounted for 74.2% of the entire pathway cost. In particular, COT, cost of labor, and materials accounted for 36.6, 31.4 and 28.9%, respectively. Cost for radiologist consultation for extracolonic findings within the CTC execution and reading process was €1.78 for each CTC participant. CRC screening has proved to be cost-effective compared to no screening, but no single strategy is consistently dominant over the others [12]. Several cost-effectiveness studies were published comparing the role of CTC to OC as screening test [14, 23, 24]. Overall, the results were much influenced by the relative unit costs of CTC and OC. However, most of the studies were based on clinical reimbursement rates of abdominal or pelvic CT [9, 11, 14, 22] and, to our knowledge, only one study addressed a process-oriented CTC costs analysis in a population-based screening trial in the Netherlands (COCOS) [15]. Taking into account that caution must be exercised in generalizing the COCOS results to other countries because of differences in healthcare system, reimbursement rates and in costs of equipment and personnel, the unit cost of screening CTC in the COCOS study (€169.40) was quite lower than those reported in previous cost-effectiveness analyses ($488 and $514) [9, 11].
4825
No
bc
Longer counseling
d
Lower participation
Higher participation
B
C
bc
Worst-case costs with lower participation
Best-case costs with higher participation
3 9 C/40%
a
11.35
30.27
17.04 5.16
19.77
9.45
2.06
2.97
2.52
40.81%
15.30%
27.19%
5.06 (-4.21)
19.38 (?10.11)
19.38 (?10.11)
5.06 (-4.21)
bc
bc
1.0202
1312
9.27
PRE-CTC consultation process
Some costs do not fit exactly because costs of extracolonic findings were not computed here
bc base case, n.a. not applicable
Base case with observed participation
39C Best case with higher participation Costs per participant
2 9 B/15%
4.54
Worst case with lower participation
29B
1 9 A/26.65%
4.54
Base case with observed participation
4.54
100%
100%
100%
bc
19A
Costs per invitee
As observed in trial
A
Participation pattern
Worst case (b ? d)
Best case (a ? c)
2
3
Multi-way sensitivity analysis
bc
Shorter counseling
c
bc bc
15-min scan
15-min scan
a
b
3.7519
4.54
Invitation process
Process
€/base case
Action driver One-way sensitivity analysis
1
Table 2 Results of the sensitivity analysis
134.59
158.05
145.30
53.84
23.71
38.72
40.00%
15.00%
26.65%
134.59
158.05 (?12.69)
bc
bc
158.05 (?12.69)
134.59 (-10.64)
1.0054
1293
145.29
CTC
a
24.23
24.23
24.23
6.46
6.46
6.46
2.61%
2.61%
2.61%
bc
bc
bc
bc
bc
bc
0.0980
126
247.30
Assessment colonoscopy
n.a.
n.a.
n.a.
n.a.
n.a.
n.a.
n.a.
n.a.
n.a.
157.66
195.44
182.68
168.36
185.33
161.87
n.a.
1160
172.57
Only negative CTC
Overall
n.a.
n.a.
n.a.
n.a.
n.a.
n.a.
n.a.
n.a.
n.a.
404.96
442.74
429.98
415.66
432.63
409.17
n.a.
126
419.87
Only positive CTC
175.33
232.32
196.02
n.a.
n.a.
n.a.
n.a.
n.a.
n.a.
181.89
219.67
206.91
192.59
209.56
186.10
n.a.
1286
196.80
Total CTC with positivea
Cost analysis of colorectal cancer screening with CT colonography in Italy
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The similarity of the SAVE and COCOS studies for setting and methodology enables us to speculate on the main reasons for differences in costs between the two studies and propose feasible modifications aimed to reduce CTC screening costs. Overall, our CTC screening pathway was €35.34 more expensive than that of the COCOS trial. In particular, costs of depreciation of CT scanners, insufflators, and workstations were higher in the Italian study than in the Dutch one. Furthermore, in the SAVE trial, COT was calculated taking into account the effective cost of the equipment employed and depreciation costs were calculated in 5 years according to the Italian public administration accounting rules. After normalization of depreciation for COT and assuming a full workload for insufflators and workstation (6000 scans per year), the major differences between the two trials remain the higher cost of labor in the Netherlands and the extra-cost of the attending radiologist during the examination in Italy (Supplementary Table). Based on our results, the following cost-containment strategies can be forwarded. For instance, reducing COT and skipping pre-CTC consultation could positively influence the entire screening pathway costs. In particular, COT may be reduced by trying to contain operating costs of CT scanners, for example changing the contracts of purchase or using long-term renting. The best-case scenario considered in the sensitivity analysis, in which a decrease in time needed for pre-CTC consultation and CTC execution is foreseen, only offers a modest saving in the CTC process cost (€4). A greater reduction could be obtained by replacing the pre-CTC consultation with the routinely invitation modalities of FIT organized CRC screening, in which invited subjects receive a personal invitation by mail and collect the FIT kit in a pharmacy or health district. Similarly, subjects invited to CTC screening could collect bowel preparation. These combined strategies could reduce costs of the CTC screening pathway by about 25% (from €196.80 to €145.89). Finally, according to the participation rate observed in the SAVE trial, the adoption of reduced bowel preparation can positively influence not only participation [18] but also reduce costs to €144.40. We recognize some limitations of our study. First, CTC pathway costs were evaluated within the frame of a randomized screening study. They could be different from those effectively observed within a population-based screening program. For example, in the SAVE trial, a dedicated radiologist attended the CTC execution. In a clinical setting, this cost may be reduced if the attending radiologist is involved in reporting CTC or talking with patients during CTC execution. Second, we could not
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compute costs of follow-up of extracolonic findings, since no further diagnostic work-up or surveillance for such findings were included in the SAVE trial protocol. In previous studies, the average costs per participant for the follow-up of extracolonic findings were estimated to be around 28–34 USD [25, 26]. Third, CTC screening costs were not compared with FIT because the third round of biennial FIT in SAVE trial is still underway [17]. Fourth, overhead costs were not included in our analysis, as in Italy a national standardized disposition to evaluate overhead costs is not available. Finally, according to study design, our analysis was limited to the evaluation of medical costs. However, we are aware that the estimation of non-medical costs (e.g., time lost for participants) can be a relevant issue for future cost-effectiveness evaluations aimed at comparing CTC screening and FIT. Our data suggest that the more relevant cost of screening CTC in an Italian trial is related to CTC execution and reading process. General cost-containment strategies to be entertained include skipping pre-CTC consultation with direct collection of bowel preparation by the participants, adoption of a reduced cathartic preparation, containment of operating costs of CT scanners, and attainment of full workload for insufflators and reading workstation. Present data could support new cost-effectiveness evaluations for tailoring the best strategies aimed at the introduction of new diagnostic technologies in organized oncologic screening. Funding The SAVE study was funded by a grant from the Tuscany Region, Italy (POR CREO FESR 2007–2013 LINEA D’INTERVENTO 1.1.c, SAVE project, number 2009DUA000000000089835900120000000002). The funding source had no role in study design, in the collection, analysis and interpretation of data, in the writing of the report, and in the decision to submit the article for publication. Compliance with ethical standards Conflict of interest SD is an employee of im3D. All other authors have no conflicts of interest. Informed consent All participants gave their written informed consent. Research involving human participants The study was conducted according to the Declaration of Helsinki and approved by the Ethical Committee of the Local Health Unit of Florence (Number 432/2010).
Appendix 1 See Table 3.
Cost analysis of colorectal cancer screening with CT colonography in Italy Table 3 Inputs used for cost calculations for case-based analysis and process costs Variables
Base case
Source
Invitees
5242
SAVE trial
Invitees with undelivered letters
203
SAVE trial
Invitees matching exclusion criteria
214
SAVE trial
Eligible invitees
4825
SAVE trial
Subjects attending consultation
1312
SAVE trial
27.19%
(1312/4825)
CTC participants Subjects with repeated CTC Extracolonic findings
1286
SAVE trial
26.65%
(1286/4825)
7
SAVE trial
0.54%
(7/1286)
65 5.05%
SAVE trial (65/1286)
Total number of CTC
1293
(7 ? 1286)
Subjects with positive CTC
129
SAVE trial
10.03%
(129/1286)
Compliance to assessment colonoscopy Subjects with advanced neoplasia
126
SAVE trial
9.80%
(126/1286)
67
SAVE trial SAVE trial
‘‘Invitation’’ process Labor costs for organization
€6.10
15 h/months for 17 months. Gross cost per hour €23.94
Unit cost for organization
€1.16
(€6105/5242)
Costs for mailing (outsourced activity) First letter
€6317
5028 letters, €1.256 each
Remainder
€4633
3688 letters, €1.256 each
Invitation to FIT for non-responders
€4597
3539 letters, €1.299 each (different contents)
€255
203 letters, €1.256 each
Undelivered letters Total cost of invitation Unit cost for invitation
€15,802 €3.28
(€15,816/4825)
Total process cost
€21,907
(€6105 ? €15,825)
Unit process cost
€4.54
(€21,921/4825)
Labor cost for consultation
€12.15
401 h in 17 months. Gross cost per hour €30.33
Unit process cost for consultation
€9.27
SAVE trial
‘‘Pre-CTC consultation’’ process
(€12,156/1312) SAVE trial
‘‘CTC execution and reading’’ process €68,695
(€53.13 9 1293)
Virtual annual depreciation
€152,880
As described in text
Annual maintenance
€60,000
Corporate data
VAT
€46,834
Italian VAT 22%
Total number of CT scans in year 2013
6901
Corporate hospital data
COT CT equipment ‘‘Sensation 64’’ for each scan
€37.64
[(€152,880 ? €60,000 ? €46,834)/6901]
Cost of technology (COT) CT scanner: Siemens Somaton Sensation 64
CT scanner: Siemens Somaton Definition AS 128 Virtual annual depreciation
€203,000
As described in text
Annual maintenance
€75,000
Corporate data
VAT
€61,160
Italian VAT 22%
Total number of CT scans in year 2013
10,199
Corporate hospital data
COT CT equipment ‘‘Definition 128’’ for each scan Mean COT for shared CT scanners for each CTC
€33.25
[(€203,000 ? €75,000 ? €61,160)/10,199]
€35.02
Weighted mean between €37.64 and €33.25
123
P. Mantellini et al. Table 3 continued Variables
Base case
Source
Virtual annual depreciation
€2800
As described in text
Annual maintenance
None
Corporate data
VAT
€616
Italian VAT 22%
Colon insufflation equipment (two insufflators)
Mean number of CTC for year
913
[(1286 ? 7)/17 9 12]
€3.74
[(2800 ? 616)/913]
Virtual annual depreciation Annual maintenance
€6746 €4000
As described in text Corporate data
VAT
€2364
Italian VAT 22%
Mean number of CTC for year
913
[(1286 ? 7)/17 9 12]
Mean COT for workstation
€14.36
[(€6746 ? €4000 ? €2364)/913]
Total COT for SAVE trial
€68,695
(€53.23 9 1293)
COT for each CTC
€53.13
(€35.02 ? €3.74 ? €14.36)
Mean COT for shared insufflation equipment CTC reading workstation with CAD
Imaging storage Total
€3474
(€2.69 9 1293)
Unit cost for each CTC
€2.69
Corporate hospital data
€29.78
(€3.32 ? €0.15 ? €4.23 ? €18.30 ? €3.78)
Materials (VAT 22% included) Specific materials for each case Laxatives for full preparation
€4.80
Commercial cost, VAT included
Full preparations
615
48%
Laxatives for reduced preparation
€1.98
Commercial cost, VAT included
Reduced preparations Mean cost of full and reduced preparations
678
52%
Drinking water (1 l)
€0.15
Commercial cost, VAT included
Gastrografin
€4.23
Corporate cost, VAT included
Insufflation tube
€18.30
Corporate cost, VAT included
CO2 (mean 4 l/case)
€3.78
Corporate cost €0.946/l, VAT included
Common and generic materialsa
€12.28
Mean over 10 CT scan
€3.32
Cost of materials for each CTC
€42.06
(€29.78 ? €12.28)
Total cost of materials for SAVE trial
€54,385
(€42.06 9 1293)
Cost of labor €24.86
Based on current rates for nurses
Cost for hour, radiographer
€27.47
Based on current rates for technicians
Cost for hour, radiologist
€70.57
Based on current rates for radiologist
CTC execution (including starting, set-up and unset)
€38.58
(€8.63 ? €9.53 ? €20.41)
Cost for hour, nurse
Mean surface occupation time for 1 CTC scan (min.)
20.83
908 CT scans in 44 rounds, 7 h and 12 min/round
Mean radiologist labor time (min.)
17.35
908 CT scans in 44 rounds, 6 h/round
Nurse’s cost Radiographer’s cost
€8.63 €9.54
(cost for hour/60 9 €20.83 min) (cost for hour/60 9 €20.83 min)
Radiologist’s cost
€20.41
(cost for hour/60 9 €17.35 min)
CTC reading (except extracolonic findings)
€7.06
(cost for hour/60 9 min)
Time for reading a CTC with CAD (min.)
6.00
Adjusted mean workstation clock report
Extra time for extracolonic findings (min.)
30.00
Expertise
Cost of labor for each CTC (except extracolonic findings)
€45.64
(€38.58 ? €7.06)
Extra charge for each extracolonic finding
€35.29
(€70.57/60 9 30)
Mean extra charge to manage extracolonic findings
€1.77
(€35.29 9 65/1293)
Total cost of labor for SAVE trial
€61,302
(€45.64 9 1293 ? €35.29 9 65)
123
Cost analysis of colorectal cancer screening with CT colonography in Italy Table 3 continued Variables
Base case
Source
Total process cost
€187,856
COT, imaging storage, cost of materials, cost of labor
Optical colonoscopy without findings
17
SAVE trial Tuscany regional rate
‘‘Assessment colonoscopy’’ process Optical colonoscopy without findings, cost for each
€155.00
Optical colonoscopy with findings
109
SAVE trial
Optical colonoscopy with findings, cost for each
€210.00
Tuscany regional rate
Pathology, number of lesions
161
SAVE trial
Pathology, cost for each lesion Total
€35.00 €31,160
Tuscany regional rate (€17 9 155 ? €104 9 210 ? €161 9 35)
Average cost for each optical colonoscopy
€247.30
(€31,160/126)
CTC CT colonography, FIT fecal immunochemical test, VAT value added tax a
Including: Scopolamine Butylbromide 20 mg; disposable materials: injection needles, faucets, syringes, gloves, covers and clothing. Some values are rounded up or down to nearest Euro value
Appendix 2 See Table 4. Table 4 Inputs used for cost calculations for case-based analysis and processes costs
Process
Data
Source
Case number
4825
Appendix 1
Total cost
€21,907
Appendix 1
Cost-for-case (unit process cost)
€4.54
Appendix 1
Driver over CTC responders
3.75
(4825 invites/1286 responders)
Case number
1312
Appendix 1
Total cost
€12,156
Appendix 1
Cost-for-case (unit process cost)
€9.27
Appendix 1
Driver over CTC responders
1.0202
(1312 counseling/1286 responders)
Case number
1293
Appendix 1
Total cost
€187,856
Appendix 1
Cost-for-case (unit process cost)a
€145.29
Appendix 1
Driver over CTC responders
1.01
(1293 CTC scan/1286 responders)
Case number
126
Appendix 1
Total cost
€31,160
Appendix 1
Cost-for-case (unit process cost)
€247.30
Appendix 1
Driver over CTC responders
0.0980
(126 colonoscopy/1286 responders)
‘‘Invitation’’ process
Case number ‘‘Pre-CTC consultation’’ process
Case number ‘‘CTC execution and reading’’ process
Case number ‘‘Assessment colonoscopy’’ process
CTC CT colonography a
This cost does not fit with the same in Appendix 1 because of re-examined subjects
123
P. Mantellini et al.
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