Quality of life and costs of patients prior to colorectal surgery

ABSTRACT

Objective: To assess the quality of life and societal costs of patients prior to colorectal surgery in the Netherlands.

Methods: This study is embedded in a previous randomized controlled trial (SANICS II). The quality of life was measured using EQ-5D-5L questionnaires. The iMTA medical consumption questionnaire (iMCQ) and the iMTA productivity costs questionnaire (iPCQ) were used to identify and measure healthcare and productivity costs. Subgroup analyses were performed based on age and gender.

Results: A total of 178 patients were included in the cost analysis and a total of 161 patients in the quality of life analysis. The three-month mean societal cost per patient amounted to €3,211 of which €1,459 was due to productivity losses. The mean utility was 0.88 per patient. Gender was an important predictor in quality of life with men scoring significantly higher than women (0.92 versus 0.82) at p < 0.0001.

Conclusion: Colorectal cancer represents a high economic burden in the Netherlands. Further research with repeated cost and quality of life measurements would be needed to explore the change over time and the effects of surgery.

KEYWORDS:

• Colorectal cancer
• costs
• quality of life
• Netherlands

1. Introduction

Colorectal cancer (CRC) is the third most common cancer (10% of the total) in men and second in women (9.2% of the total) worldwide [1]. The incidence of CRC is higher in Netherlands when compared to other countries in Western Europe [2]. Nearly 15,427 new cases of CRC were reported in 2016 and the incidence has been steadily increasing at a rate of 13%-18% per year (1990–2016) [3]. Prevalence of CRC is further expected to rise as a result of national CRC screening and ageing Dutch population [4,5].

Survival rates have increased in patients with CRC due to improvements in (neo) adjuvant treatment and surgical approaches [6,7]. However, this is also accompanied with side effects including physical discomfort and difficulties in terms of life satisfaction [8], depression [9] and psychological distress [10] which may ultimately lower the quality of life. Additionally, CRC imposes a significant economic burden for the patient and society [11,12].

The economic burden of CRC is determined by many different factors and to better focus on what items may be important, the burden of disease (BoD) studies assessing the quality of life and financial aspects of a particular disease over a defined period of time are essential [13]. Cost elements in BoD studies include healthcare costs, patient and family costs and productivity losses among patients and caregivers.

There is limited information about cost and quality of life on CRC [11,12,14] with very few or no studies from the Netherlands, especially the burden of CRC prior to surgery is largely unknown. To our knowledge, this is the first study to estimate the costs prior to colorectal surgery in the Netherlands. The aim of this study is, therefore, to estimate the societal costs and the quality of life of CRC patients prior to surgery. This study will further provide important results for future health economic analyses of new interventions in patients with CRC and increases the understanding of the CRC-related costs per patient in the interval between diagnosis and treatment.

2. Methods

2.1. Study design

In this study, we estimated the costs in monetary terms and quality of life in utilities. Although other approaches are also well established, a bottom-up, prevalence-based approach from a societal perspective was used since this approach is considered as the most appropriate for assessing the cost of illness [15]. This study is embedded in the SANICS II trial which is a multicenter randomized controlled trial, the details of which are described elsewhere [16,17]. In brief, the SANICS II study investigates the clinical effectiveness and cost-effectiveness of perioperative nutrition compared with standard care (nil by mouth) in patients undergoing colorectal surgery. In this study, we report costs and quality of life prior to colorectal surgery. Both the treatment arms were pooled for the purpose of this study.

2.2. Population and setting

Five hospitals (three hospitals from the Netherlands and two hospitals from Denmark) participated in the original trial. For this study, patients in Dutch hospitals only were included. Patients who are above 18 years of age and undergoing elective segmental colorectal resection with anastomosis were eligible for inclusion. Patients with previous gastric or esophageal resection, peritoneal carcinomatosis, preexistent or creation of an ileostomy, steroid use, and use of medication that disrupts the acetylcholine metabolism were excluded. Furthermore, patients with the benign colorectal disease were excluded for this study. The medical ethics committee of Catharina Hospital (Eindhoven, the Netherlands) granted the approval for the original study. Written informed consent was obtained from all the included participants.

2.3. Data collection

Cost and quality of life were collected by means of questionnaires for the period between August 2014 and February 2017, at a single time point (baseline). The baseline questionnaires were handed out to the patients on the first day of their admission.

2.4. Cost perspective

The study followed the Dutch guidelines for health economic evaluations, which promotes cost calculation from a societal perspective meaning that all the health care costs and patient and family costs of CRC were accounted for [18].

Cost estimation was followed in 3 steps namely: 1. Identification, 2. measurement and 3. Valuation.

Step I: Identification of costs:

Costs included were those related to preoperative CRC care and were categorized as 1. Health care cost (i.e. hospitalizations, medical procedures, medications etc.), 2. Patient and family costs (i.e. Travel and time costs) and 3.Costs in other sectors (i.e. productivity costs). As there are no registrations available for time and travel costs, they were excluded.

Step II: Measurement of costs

Self-reported questionnaires for health-care consumption and productivity losses were used in this study. The iMTA Medical consumption questionnaire (MCQ) was used to measure the health-care utilization and the iMTA productivity cost questionnaire (PCQ) was used to measure the costs due to productivity losses in two domains related to 1) paid work due to absenteeism and presenteeism, and 2) unpaid work [19]. Both the questionnaires are commonly used in the Netherlands to assess healthcare and productivity losses. These questionnaires are generic and the items are not related to any specific disorder. The recall period for the MCQ is 3 months and for the PCQ is 4 weeks. The PCQ costs per patient were extrapolated to 3 months.

Step III: Valuation of costs

The costs were expressed and analyzed in Euros and were indexed for the year 2017. The updated Dutch Manual for Cost Analysis in Health Care Research was used for the valuation of the health-care costs [18]. The identified health services consumed by the patient were multiplied with their corresponding unit prices. Total costs were estimated by summing the individual services. All medication costs were derived from the website with the official listing of drugs with prices: www.medicijnenkosten.nl. Medication costs were based on the price per dosage of the drug in the Netherlands. In case of uncertainty regarding a medication, the lowest cost price was used. Medications without a specific name were omitted (for example, when a patient mentions antibiotics or ‘medicine for stomach protection’). Productivity losses were valued using the friction cost method which takes into account production losses confined to the period needed to replace the sick employee (85 days) [20]. Friction costs were applied to patients below the retirement age.

2.5. Quality of life perspective

Quality of life was assessed using the Dutch five level, five-dimensional EuroQoL (EQ-5D-5L) questionnaire consisting of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension was scored on a five-point scale which represented ‘no problems’, ‘slight problems’, ‘moderate problems’, ‘severe problems’ and ‘extreme problems’. The 5 dimensions can be summed into a health state. Utility values can be calculated for these health states, using preferences elicited from a general population, the so-called Dutch algorithm [21].

2.6. Statistical methods

All statistical analyses were performed using IBM SPSS Statistic V.24. For Windows (IBM corp., Armond, NY, USA). Since the cost data are typically highly skewed, non-parametric bootstrapping (with 5000 replications) was used to estimate the 95% confidence intervals around the mean difference in all the cost categories. Subgroup analyses were performed according to the gender (male and female) and median age (older age group is >67 years; younger age group is <67 years). Age and gender are two potentially important demographic characteristics and were available in our study. Estimates such as means, medians, standard deviation and confidence intervals were reported. Mann-Whitney U test was used to compare the cost means.

3. Results

3.1. Demographic characteristics

A total of 184 patients participated in the RCT of which 178 patients completed the cost questionnaires and 161 patients completed the EQ-5D-5L questionnaires. This is a complete case analysis and therefore we did not have any missing data in this study. More than half of them were men (n = 104; 64.59%) and the mean age of the patients was 67.55 years (SD 9.55). The number of patients in the younger age group was slightly higher than in the older age group (83 versus 78).

3.2. Costs

The mean societal cost per patient amounted to € 3,211 over a period of 3 months of which 45.4% (€1,459) was due to productivity losses. (Table 1). Total healthcare sector costs represented 54.5% (€1,752) of the total societal costs of which hospitalizations at 23.9% (€420), visits to the outpatient clinic at 21.9% (€385) and treatment procedures at 20.8% (€365) were the main contributors (Table 1).

Table 1. Total resource use and costs (Euros) and Utilities.

	Users			Resource use per patient		Cost per patient(€)
	Unit	N	Percent	Mean	SD	Mean	SD	Median	95%CI
Health Care Costs
General Practioner	Contact	121	67.97	1.62	2.25	53	80	33	[43, 66]
Medications	Various	122	68.53	-	-	107	269	9	[71, 149]
Outpatient clinic	Contact	151	84.83	4.8	4.51	385	345	320	[335, 436]
Allied health professionals	Contact	43	24.15	1.51	3.75	44	132	0	[27, 65]
Homecare	hour	18	10.11	4.26	19.05	149	779	0	[54, 277]
Hospital stay	Nightstay	36	20.22	0.93	3.01	420	1,336	0	[247, 633]
Emergency room visits	Contact	20	11.23	0.16	0.48	43	124	0	[26, 61]
Ambulance	Trip	7	3.93	0.06	0.37	41	231	0	[13, 79]
Diagnostics	Test	43	24.15	0.43	0.88	140	321	0	[96, 189]
Treatment	Procedure	25	14.05	0.12	0.33	365	1,209	0	[208, 556]
Total Healthcare costs		178	100			1,752	2,583	854	[1,403, 2,147]
Productivity costs
Paid homecare	hour	30	16.21	33.21	110.63	1290	4,010	0	[743, 1,888]
Inability to do Unpaid labour	hour	24	0.1297	12.44	46.28	168	730	0	[77,285]
Total Productivity Costs		46	0.2486			1,459	4,096	0	[894, 2,088]
Societal Costs						3,211	5,008	1164	[2,534, 3,936]
Utilities						0.88	0.15	0.90

*SD, standard deviation; CI, confidence interval (2.5th percentile, 97.5thpercentile).

Patients stayed on an average 0.9 days in a hospital and had 1.5 consults with allied health professionals (e.g. physiotherapist, social worker). Patients were unable to perform paid labor for 33.2 hours (4.15days) and unpaid labor for 12.4 hours (1.55 days). Nearly 67.9% of patients used general practitioner services and 84.8% had outpatient visits. Seven patients (3.9%) used ambulance service and 20 patients (11.2%) had emergency visits to the hospital. Forty three patients (24.1%) had a diagnostic test and 25 patients (14%) had a treatment procedure performed in the three months prior to CRC surgery.

The younger age group showed societal costs at €4,449 compared to the older age group at €1,946 (p = 0.073). The mean general practitioner costs were significantly higher for the older age group (64 versus 43 at p = 0.014). Paid care and total productivity costs were also significantly higher for younger age group (2,548 versus 3 at p < 0.0001; and 2,752 versus 135 at p < 0.0001 respectively). The mean societal costs for men were €3,465 and that for women €2,759 with no statistical significance. Mean general practitioner care costs were significantly higher in women when compared to men (€74 versus €42) at p = 0.003. Mean home care costs were significantly higher for women (€263 versus €85) at p = 0.016 (Table 2)

Table 2. Costs(expressed in euros) and utilities of colorectal cancer patients according to gender and age.

	Male		Female			Age below 67		Age above 67
	Mean	SD	Mean	SD	P value	Mean	SD	Mean	SD	P value
Healthcare costs
General practitioner	42	65	74	97	0.003	43	76	64	82	0.014
Medication	95	215	128	345	0.639	101	212	113	318	0.214
Outpatient clinic	380	349	394	341	0.745	379	357	390	334	0.562
Allied health professionals	41	138	50	122	0.672	39	121	49	143	0.386
Homecare	85	650	263	963	0.016	106	759	193	801	0.044
Hospital stay	466	1551	339	830	0.766	290	797	553	1716	0.142
Emergency room visits	34	111	60	144	0.125	34	96	52	147	0.582
Ambulance	48	272	28	130	0.946	47	279	34	170	0.977
Diagnostics	112	231	190	434	0.635	172	383	108	239	0.261
Treatment	481	1,407	160	698	0.794	480	1,254	248	1,156	0.870
Total Healthcare costs	1,787	2,784	1,690	2,201	0.513	1,696	2,309	1,810	2,849	0.411
Productivity costs
Paid Homecare	1,506	4,458	904	3,050	0.664	2,548	5,361	3	29	<0.001
Inability due to unpaid labor	171	843	164	472	0.262	203	661	132	797	0.185
Total Productivity Costs	1,678	4,546	1,068	3,132	0.780	2,752	5,414	135	797	<0.001
Societal costs	3,465	5,487	2,759	4,016	0.432	4,449	6,184	1,946	2,950	0.073
Utilities	0.92	0.12	0.82	0.16	<0.001	0.90	0.14	0.86	0.15	0.860

3.3. Utilities

The mean utility was 0.88 (SD: 0.15) per patient prior to intervention and surgery. Men had a significantly higher utility when compared to the women (0.92 versus 0.82) at p < 0.0001. The utilities for the younger and older age groups were not different between the groups (0.90 versus 0.86 p = 0.86). With regards to pain/discomfort, 24.2% of the total patients experienced slight problems. The frequency of five dimensions as measured using EQ-5D-5L questionnaires is reported in Table 3.

Table 3. Frequency of reported problems by dimension.

EQ-5D Dimension
Mobility	No problems	129 (80.1%)
	Slight problems	12 (7.5%)
	Moderate problems	18 (11.2%)
	Severe problems	1 (0.6%)
	Unable to	1 (0.6%)
	Total	161
Self-Care	No problems	155 (96.3%)
	Slight problems	3 (1.9%)
	Moderate problems	2 (1.2%)
	Severe problems	0
	Unable to	1 (0.6%)
	Total	161
Usual Activity	No problems	122 (75.8%)
	Slight problems	23 (14.3%)
	Moderate problems	11 (6.8%)
	Severe problems	2 (1.2%)
	Unable to	3 (1.9%)
	Total	161
Pain/Discomfort	No pain	101 (62.7%)
	Slight pain	39 (24.2%)
	Moderate pain	18 (11.2%)
	Severe pain	3 (1.9%)
	Unable to	0
	Total	161
Anxiety/Depression	No anxiety	128 (79.5%)
	Slight slight anxiety	26 (16.1%)
	Moderate anxiety	4 (2.5%)
	Severe anxiety	2 (1.2%)
	Unable to	1 (0.6%)
	Total	161

4. Discussion

CRC represents a high economic burden in the Netherlands. In 2011, in the Netherlands, costs of CRC were about 488 millon euros, that is 0.5% of the total healthcare costs and nearly 87% of these total costs were attributed to hospital costs [22]. In this study, the mean societal cost per CRC patient was estimated at €3,211 in the 3 months prior to surgery. The productivity losses represent a major part of these costs at 45.4% of total costs.

In the UK, Hall et al estimated costs of cancer care with the health-care perspective that showed mean 15-month cumulative health-care costs for CRC at £12,643 (approximately €15,945) per patient and concluded that <65 age group incurred greater costs than the >65 years age group which is in line with our study [23]. The study also demonstrated that the majority of the costs occurred within the first 6 months from diagnosis suggesting high costs during the primary treatment phase. Extracting the costs for the 3-month period from this study (15,945/15*3) results in €3,189, very similar to the 3-month societal costs in our study. An Asian study estimated direct medical costs at 24.81%, direct non-medical care costs at 38.04% and indirect costs at 37.14% of the total cost [24]. In this study, direct medical costs (healthcare costs) comprised of 54.5% and indirect costs (productivity costs) accounted for 45.4% of the total costs.

In another Finnish study by Niilo Farkkila, which estimates the costs CRC at different states of the disease, primary treatment (0–6 months after diagnosis) and advanced treatment states had the highest reported costs [25]. The cost for the 6-month interval between diagnosis and treatment (primary treatment period) was €22,200 which included direct health care costs, informal care costs and productivity losses. Productivity losses caused by CRC was substantial at €5,098 at the primary treatment state [25]. The overall costs vary depending on the number of years spent with CRC and degree of severity. It is therefore difficult to directly compare our study with this study and other previous studies due to various reasons. First, our study assessed the costs of patients for the period of 3 months and did not include the operative and postoperative costs which are considered to be the main cost drivers. Previous studies estimated total costs annually or longer than 12 months including surgery. Second, variations in valuation methodology such as using the human capital approach in previous studies and friction cost method in this study could affect the total costs. Higher productivity costs were estimated in Farkilla that used the human capital approach.

In our study, the quality of life scores was relatively high (0.88) and higher than the previous studies [14,26]. Comparison to utility values in other studies should however be interpreted with caution as different tariffs for EQ-5D-5L have been used. To our knowledge, no study is available with utility value of the general Dutch population. Further comparison with the general Dutch population would be worthwhile. A study by Farkkila estimating the health-related quality of life in CRC showed a utility value of 0.760 in the primary treatment group (0–6 months after diagnosis) [14]. Similarly, another study evaluating nationwide health utility showed a score of 0.67 in the acute period (<1 year) after a colon cancer diagnosis [26]. The high utility scores in our study could potentially be explained by the fact that our estimation was conducted just before surgery and that patients have a current better quality of life because of the surgery surveyance. Measurement of quality of life scores could also be biased or confounded due to the setting (hospital) or feelings of anxiety/excitement prior to surgery. The significant higher utility scores by men in our study could be explained by the fact that women usually self-report worse health than men [27,28]. It is however difficult to assess if the differences in utility values are clinically meaningful which is beyond the scope of this study and further research would be required to investigate this.

This study has several limitations. First, costs and quality were estimated only at one time point. Baseline questionnaires were filled out on median preoperative day 1 (range preoperative day 8 to postoperative day 11). The recall period for the iMCQ and iPCQ were 3 months and 4 weeks respectively and iPCQ was extrapolated to 3 months. Second, we used a self-reported questionnaire which is known to cause recall bias. Third, we did not estimate transportation fees and out of pocket expenses which may have led to an underestimation of the total costs. Lastly, we recruited the patients from the clinical trial which may limit the generalizability of the results. Limited use of exclusion criteria was used in an attempt to increase the generalizability of results.

Considering the fact that the median duration from the time of diagnosis to initiation of treatment for CRC in the Netherlands is 21 median days [29]. This paper provides an understanding of the initial costs of patients with CRC. The study reveals the importance of healthcare costs and productivity losses received by cancer patients. Earlier detection and improved treatments will hopefully lead to improved survival and reduced additional costs.

In conclusion, this study reveals that CRC costs impose substantial economic costs in the Netherlands. This study provides important information for future economic analyses and comparison of new interventions in patients with CRC.We recommend further research with larger sample and repeated cost and quality of life measurements to explore the change over time and the effects of surgery.

5. Expert opinion

The economic burden of colorectal cancer is high. Important economic elements include healthcare costs and productivity losses among patients and caregivers. To date there is however, a scarcity of economic data and a large heterogeneity across studies is observed limiting comparisons. We recommend standardization of reporting and costing methods and development of data collection resources that improve the comparability of studies over time. In addition, to tackle colorectal cancer efficiently, we recommend to conduct cost-effectiveness analyses. Data from this article could serve as reference.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Authors contribution statement

MH, SE and ML conceived the study; MP, MH, SE participated in its design; MP, BS and EP contributed to data collection. MP performed the analysis and drafted the manuscript. MH, BS, SE and ML helped drafting the manuscript. All authors reviewed and approved the final manuscript.

Additional information

Funding

This paper was not funded.