Current standard values of health utility scores for evaluating cost-effectiveness in liver disease: A meta-analysis.

BACKGROUND: Health utility assessments have been developed for various conditions, including chronic liver disease. Health utility scores are required for socio-economic evaluations, which can aid the distribution of national budgets. However, the standard health utility assessment scores for specific health conditions are largely unknown. AIM: To summarize the health utility scores, including the EuroQOL 5-dimensions 5-levels (EQ-5D-5L), EuroQol-visual analogue scale, short from-36 (SF-36), RAND-36, and Health Utilities Index (HUI)-Mark2/Mark3 scores, for the normal population and chronic liver disease patients.
METHODS: A systematic literature search of PubMed and MEDLINE, including the Cochrane Library, was performed. Meta-analysis was performed using the RevMan software. Multiple means and standard deviations were combined using the StatsToDo online web program.
RESULTS: The EQ-5D-5L and SF-36 can be used for health utility evaluations during antiviral therapy for hepatitis C. HUI-Mark2/Mark3 indicated that the health utility scores of hepatitis B patients are roughly 30% better than those of hepatitis C patients.
CONCLUSION: The EQ-5D-5L is the most popular questionnaire for health utility assessments. Health assessments that allow free registration would be useful for evaluating health utility in patients with liver disease. ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.

Core Tip: This study summarized current knowledge about health utility assessments, including the EuroQOL 5-dimensions 5-levels (EQ-5D-5L), EuroQol-visual analogue scale, short from-36, RAND-36, and Health Utilities Index-Mark2/Mark3. The EQ-5D-5L is the most popular questionnaire for health utility assessments. Health utility assessments need to be used widely and routinely.

INTRODUCTION

The quality of health is an important factor when assessing medical management rather than simple survival periods[1,2]. Health utility is an important factor in medical assessments and socio-economic politics[3]. National health budgets have risen steadily in various countries, and governments need to deeply consider the need to maintain a socio-economic balance[4]. Therefore, health benefits should be compared with social costs to avoid national financial collapse.

It is difficult to quantify health quality at regular intervals[5]. We are developing wearable devices that can automatically obtain health data, including data regarding mental health. Some health utility assessments require the use of questionnaires, which are associated with low compliance and involve bothersome calculations[2,6,7]. Before launching our novel health utility assessment tool, we performed this meta-analysis in order to summarize the currently available health utility assessment tools. The most useful questionnaire for evaluating health status depending on liver disease status or sex is unclear. In addition, no universal health utility assessment values for specific liver diseases or the normal population have been reported. Therefore, we conducted a meta-analysis to estimate health utility assessment values for specific populations.

The EuroQOL 5-dimensions 5-levels (EQ-5D-5L) is the simplest instrument for evaluating health utility and has been widely translated into various languages with high reliability and validity[6,8-10]. It only involves five questions and five answering levels. The health utility scores produced by the EQ-5D-5L can be used to calculate quality-adjusted life year (QALY) values[8]. The Health Utilities Index Mark 2/Mark 3 is another instrument for evaluating health utility scores and can also be used to obtain QALY values[11]. However, the Health Utilities Index is complicated, as it involves 45 questions, which take a long time to answer. The short-form 36-item (SF-36) is also widely used to evaluate health quality, although it does not directly involve QALY evaluations[9,12,13].

There are two types of SF-36, and the copyrights to these tools belong to The RAND Corporation (Santa Monica, CA, United States)[14] and QualityMetric (Johnston, RI, United States), respectively[15]. However, most researchers do not actively consider which version they use[12]. Therefore, the exact method and results of such assessments are not always described in the literature (Table 1).

Table 1

Current health-related outcome for liver disease

Questionnaire	Total	Permission	Company/Organization
EQ-5D-5L	Five questions	Registration required	The EuroQol Research Foundation.
Health Utilities Index Mark 2 or 3	45 questions	Purchase required	Health Utilities Inc.
36-Item Short Form Survey	36 questions	Purchase required	QualityMetric
	36 questions	Free	The RAND Corporation

EQ-5D-5L: EuroQol 5-dimensions 5-levels.

In this meta-analysis, we describe the scores obtained with various health utility indexes (HUIs) in normal healthy populations or patients with different types of liver disease (Table 2)[16-32].

Table 2

List of previous studies and health utility assessments

Ref.	Subjects and countries	EQ-5D-5L	EQ-VAS	HUI-mark	SF-36	Type of SF-36	Others
Jenkinson et al[16]	Normal population from United Kingdom				O	RAND®
Ratcliffe et al[17]	Normal population/Liver transplantation patients from United Kingdom	Δ	Δ		O	Not described1
Chong et al[18]	Normal population from Canada	O	Δ	Δ	Δ1
Grieve et al[19]	Population from United Kingdom	O
Bondini et al[20]	Population from United States			O	Δ1		CLDQ
Dan et al[21]	Population from United States			O			SF-6D
Björnsson et al[22]	Population from Sweden	O			O	Not described1
Hsu et al[23]	Population from Vancouver				O	v2	HQLQv2
McDonald et al[24]	Population from United Kingdom	O
Scalone et al[25]	Population from United Kingdom	O	Δ
Vahidnia et al[26]	Population from United States	Δ	O
Kaishima et al[27]	Population from Japan	O
Blanco et al[28]	Population from Spain	Δ	O
Kesen et al[29]	HCV patients from Turkey				O	Not described1	HADS
Cortesi et al[30]	Population from Italy	O	O
Karimi Sari et al[31]	HCV patients from Iran				O	Not described1
Zanone et al[32]	HCV patients from Italy	O

Modified scale excluding from the analyses.

O: The eligible study including the analyses; Δ: The excluding outcomes due to different conditions; EQ-5D-5L: EuroQol 5-dimensions 5-levels; EQ-VAS: EuroQol-visual analogue scale; HUI-mark: Health utility index mark; SF-36: Short from-36; CLDQ: Chronic liver disease questionnaire; SF-6D: Short form 6-dimensions; HQLQv2: Hepatitis Quality of Life® survey version 2; HADS: Hospital anxiety and depression scale; HCV: Hepatitis C virus.

MATERIALS AND METHODS

Literature search

The PICOS scheme was used to set appropriate inclusion criteria. A systematic literature search of PubMed and MEDLINE, including the Cochrane Library, was performed independently by two authors (Ishunuki T and Ota S). The search was limited to human studies whose findings were reported in English. No restrictions were placed on the type of publication, the publication date, or publication status. The search strategy was based on different combinations of words for each database. For the PubMed database, the following combination was used: (("liver"[MeSH Terms] OR "liver"[All Fields] OR "livers"[All Fields] OR "liver s"[All Fields]) AND "qol"[All Fields]) AND (1990/1/1: 3000/12/12[pdat]). For the MEDLINE database, the following combination was used: [quality of life (QOL) and Liver].

Study selection

The two independent authors screened the titles and abstracts of the primary studies identified in the database search. Duplicate studies were excluded. The following inclusion criteria were employed for the meta-analysis: (1) Studies that compared QOL in patients who had liver disease; (2) Studies that compared QOL between male and female patients with liver disease; (3) Studies that reported at least one QOL outcome; and (4) If the same institute reported more than one study, only the most recent or the highest-level study was included.

Data extraction

The same two authors extracted the following primary data: (1) The questionnaires used for each QOL evaluation; (2) The first author, year of publication, and type of study; (3) The etiology of the disease and the number of times each intervention was performed; and (4) The timing of the evaluations.

Statistical analysis

Meta-analyses were performed using the RevMan software (version 5.3.; The Cochrane Collaboration). The mean differences (MD) between groups were calculated for continuous variables. The interquartile ranges of the data were transformed by dividing them by 1.35 to produce alternative standard deviation values. Multiple means and standard deviations were combined using the StatsToDo online web program (https://www.statstodo.com/index.php).

The chi-square test was used to evaluate heterogeneity, and the Cochran Q and I2 statistics were reported. The I2 value describes the percentage variation between studies in degrees of freedom. P values of <0.05 were considered significant.

RESULTS

EQ-5D-5L

The EQ-5D-5L has been widely investigated as a tool for evaluating general health in normal populations and patients with different stages of liver disease (Table 3)[17,18,22,25-27,30,32]. Health utility indices should be affected by age, sex, ethics, religion, and geography. However, the EQ-5D-5L produced similar utility indices for groups with different health statuses (Table 3), such as normal healthy individuals (0.8413 ± 0.1905) and hepatitis C virus (HCV)-infected patients with compensated or decompensated cirrhosis (0.8113 ± 0.2261 and 0.7903 ± 0.2182), HCV-infected patients exhibiting a sustained virologic response (SVR) (0.846 ± 0.1816), and patients with hepatocellular carcinoma 0.8127 ± 0.2084).

Table 3

EuroQol 5-dimensions 5-levels

Ref.	Total	Mean	SD
Normal healthy individuals
Ratcliffe et al[17]	3386	0.85	0.03
Chong et al[18]	1518	0.821	0.011
Björnsson et al[22]	29353	0.819	0.217
Vahidnia et al[26]	1565	0.94	0.1
Cortesi et al[30]	6800	0.915	0.107
Total	42622	0.8413	0.1905
Compensated cirrhosis with hepatitis C
Chong et al[18]	24	0.74	0.085
Grieve et al[19]	40	0.55	0.34
Björnsson et al[22]	76	0.749	0.212
Scalone et al[25]	222	0.736	0.259
Kaishima et al[27]	20	0.824	0.106
Cortesi et al[30]	574	0.891	0.119
Zanone et al[32]	94	0.68	0.37
Total	1050	0.8113	0.2261
Decompensated cirrhosis with hepatitis C
Chong et al[18]	9	0.66	0.2
Grieve et al[19]	64	0.45	0.24
Björnsson et al[22]	53	0.565	0.266
Kaishima et al[27]	4	0.524	0.25
Cortesi et al[30]	523	0.859	0.14
Total	653	0.7903	0.2182
Sustained virologic response
Chong et al[18]	36	0.83	0.065
Grieve et al[19]	24	0.82	0.21
Björnsson et al[22]	52	0.792	0.209
Zanone et al[32]	91	0.89	0.18
Total	203	0.846	0.1816
Hepatocellular carcinoma
Chong et al[18]	15	0.65	0.21
Grieve et al[19]	64	0.45	0.24
Scalone et al[25]	85	0.777	0.241
Kaishima et al[27]	14	0.75	0.057
Cortesi et al[30]	545	0.867	0.146
Total	723	0.8127	0.2084

In general, the EQ-5D-5L produces significantly higher scores in males than in females (Figure 1A) (0.8267 ± 0.229 vs 0.7922 ± 0.239; P < 0.001). The mean total EuroQol-visual analogue scale score for the general population was found to be 79.796 ± 17.614 in two independent studies (Table 4)[26,30].

Figure 1

EuroQOL 5-dimensions 5-levels. A: Men vs women; B: Compensated liver cirrhosis vs sustained virologic response. EQ-5D-5L: EuroQol 5-dimensions 5-levels.

Table 4

EuroQol-visual analogue scale in normal healthy individuals

Ref.	Total	Mean	SD
Vahidnia et al[26]	1565	87.6	10.6
Cortesi et al[30]	6800	78	18.4
Total	8365	79.796	17.614

SF-36

The SF-36 consists of eight scales, including physical functioning (85.07 ± 15.40); role limitations due to physical health problems (RP)(82.50 ± 25.15); bodily pain (BP) (77.62 ± 17.55); general health perceptions (GH) (63.37 ± 14.16); vitality, energy, or fatigue (VT) (63.37 ± 14.16); social functioning (SF) (86.97 ± 15.13); role limitations due to emotional problems (RE) (83.94 ± 23.57); and general mental health (63.37 ± 14.16). Although the eligible healthy controls differed among countries and age groups, the health utility scores produced by each scale were similar (Table 5)[16,17,22,23].

Table 5

Short from-36: Healthy controls

Ref.	Total	Mean	SD
Physical function
Björnsson et al[22]	339	87	19
Jenkinson et al[16] M 60	681	80	22.1
Jenkinson et al[16] W 60	684	74.8	23.5
Ratcliffe et al[17]	8883	85.4	2.55
Hsu et al[23]	9367	85.8	20
Total	19954	85.07	15.40
Role physical
Björnsson et al[22]	339	82	32
Jenkinson et al[16] M 60	717	78.8	36.1
Jenkinson et al[16] W 60	757	76.8	36.9
Ratcliffe et al[17]	9151	83.7	4.4
Hsu et al[23]	9367	82.1	33.2
Total	20331	82.50	25.15
Body pain
Björnsson et al[22]	339	72	27
Jenkinson et al[16] M 60	724	78.8	23.6
Jenkinson et al[16] W 60	779	75	25.1
Ratcliffe et al[17]	9214	80	3.05
Hsu et al[23]	9367	75.6	23
Total	20423	77.62	17.55
General health
Björnsson et al[22]	339	68	24
Jenkinson et al[16] M 60	707	62.9	20.3
Jenkinson et al[16] W 60	763	59	21.4
Ratcliffe et al[17]	9089	61.1	2.75
Hsu et al[23]	9367	65.8	18
Total	20265	63.37	14.16
Vitality, energy, fatigue
Björnsson et al[22]	339	68	24
Jenkinson et al[16] M 60	707	62.9	20.3
Jenkinson et al[16] W 60	763	59	21.4
Ratcliffe et al[17]	9089	61.1	2.75
Hsu et al[23]	9367	65.8	18
Total	20265	63.37	14.16
Social function
Björnsson et al[22]	339	88	21
Jenkinson et al[16] M 60	729	86.9	22.6
Jenkinson et al[16] W 60	783	85.9	22.6
Ratcliffe et al[17]	9219	87.8	2.8
Hsu et al[23]	9367	86.2	19.8
Total	20437	86.97	15.13
Role emotional
Björnsson et al[22]	339	86	29
Jenkinson et al[16] M 60	714	85.8	29.5
Jenkinson et al[16] W 60	756	83.3	32.5
Ratcliffe et al[17]	9159	83.7	4.4
Hsu et al[23]	9367	84	31.7
Total	20335	83.94	23.57
Mental health, emotional, well-being
Björnsson et al[22]	339	50	10
Jenkinson et al[16] M 60	697	78	17.5
Jenkinson et al[16] W 60	742	74.4	18.5
Ratcliffe et al[17]	9014	74.6	2.35
Hsu et al[23]	9367	77.5	15.3
Total	20159	75.64	12.23

Compensated liver cirrhosis vs sustained virologic response

Patients with hepatitis C had achieved an SVR exhibited significantly better health utility scores for each SF-36 scale (Figure 2)[22,29,31] and the EQ-5D-5L (Figure 1B)[18,19,22,32] than those with compensated liver cirrhosis (Table 6)[18,19,22,29,31,32]. In particular, significant differences in the scores for RP (61.5 ± 31.6 vs 73.3 ± 27.3), GH (64.8 ± 20.9 vs 74.8 ± 18.5), VT (70.5 ± 24.0 vs 78.1 ± 18.4), RE (56.8 ± 32.0 vs 68.1 ± 27.3), and the EQ-5D-5L (0.6863 ± 0.3065 vs 0.846 ± 0.1816) were seen between these groups. These results indicate that health utility indices improve by 10%-20% after patients with hepatitis C achieve an SVR.

Figure 2

Short from-36: Compensated liver cirrhosis A: Physical function; B: Role physical; C: Body pain; D: General health; E: Vitality; F: Social function; G: Role emotional; H: Mental health.

Table 6

Compensated liver cirrhosis vs sustained virologic response

Questionnare	Compensated LC	SVR	P value	% improvement
SF-36: Physical function	79.3 ± 19.3	83.9 ± 17.8	0.07	105.8
SF-36: Role physical	61.5 ± 31.6	73.3 ± 27.3	0.004	119.2
SF-36: Body pain	80.8 ± 23.1	85.4 ± 21.3	0.09	105.7
SF-36: General health	64.8 ± 20.9	74.8 ± 18.5	< 0.001	115.4
SF-36: Vitality	70.5 ± 24.0	78.1 ± 18.4	0.002	110.8
SF-36: Social function	77.0 ± 19.0	83.3 ± 15.6	0.05	108.2
SF-36: Role emotional	56.8 ± 32.0	68.1 ± 27.3	< 0.001	119.9
SF-36: Mental health	77.2 ± 16.8	81.3 ± 15.2	0.12	105.3
EQ-5D-5L	0.6863 ± 0.3065	0.846 ± 0.1816	< 0.001	123.3

LC: Liver cirrhosis; SVR: Sustained virologic response; SF-36: Short from-36; EQ-5D-5L: EuroQol 5-dimensions 5-levels.

HUI Mark-2/Mark-3

Hepatitis B and C are the main causes of viral-associated chronic liver disease (Figure 3)[20,21]. The health utility scores of hepatitis B patients were significantly better than those of hepatitis C patients (0.6312 ± 0.2867 vs 0.8186 ± 0.1886); i.e., there was a roughly 30% difference between the scores of these patients.

Figure 3

Health Utilities Index-Mark2 or 3: Hepatitis C HUI: Health Utilities Index.

DISCUSSION

Which HUI should be used for normal populations or patients with chronic liver disease?

In this meta-analysis, we summarized the findings of previous studies examining health utility evaluations in patients with chronic liver disease. Various questionnaires have been used to evaluate health utility in different populations/at different times. The EQ-5D-5L is the most popular of the questionnaires used to examine health utility scores internationally[17].

One of the concerns regarding the application of health utility scores is their sensitivity[33]. For example, the health utility scores produced by the EQ-5D-5L for patients with compensated cirrhosis and decompensated cirrhosis did not differ significantly (Table 3). On the other hand, the health utility scores for hepatitis C patients with compensated liver cirrhosis and those who achieved an SVR differed significantly according to both the SF-36 and EQ-5D-5L (Table 6). This indicated that both questionnaires are suitable for evaluating health utility in hepatitis C patients after viral elimination. Although the health utility scores derived from the EQ-5D-5L were calculated from 5 questions, the score range of the EQ-5D-5L (123.3%) was greater than that of the SF-36 (105.8%-119.2%). Therefore, the EQ-5D-5L could be suitable for evaluating health utility scores in this specific disease state. On the other hand, EQ-5D-5L-derived health utility scores are based on only five personal factors, mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Therefore, their sensitivity and any ceiling effects should be validated in each language and ethnic group.

It is well known that the prevailing subtype of viral hepatitis differs depending on the geographic region[34]. Hepatitis B is the prevailing subtype in East Asia[13], whereas hepatitis C is the most common in Western countries[35]. Both types of hepatitis can be controlled by nucleic acid analogs[36]. In this meta-analysis, the HUI scores of hepatitis C patients were roughly 30% lower than those of hepatitis B patients. The differences between hepatitis B and hepatitis C need to be investigated using the EQ-5D-5L and SF-36 in future.

The second concern regarding the use of questionnaires for health assessments relates to the number of questions in each questionnaire. The EQ-5D-5L consists of only five questions[8], whereas the other tools consist of 36[14-16] or 45[11] questions. The number of questions affects study compliance, especially in the elderly[37]. If possible, the number of questions should be minimized.

The last concern is about gaining permission to use such questionnaires for health utility assessments. It takes great effort to develop a questionnaire. However, health utility assessments need to be repeated continuously. In certain human health emergencies, the use of some vaccines has been allowed without patent royalties having to be paid[38]. Commercial companies that own the rights to health assessments should reconsider their policies regarding their use.

CONCLUSION

Health assessments that allow free registration would be useful for evaluating health utility in patients with liver disease. Alternatively, a portable QOL tracker could be used to perform QOL evaluations of any patient-reported outcome, and we are currently developing such a tracker.

ARTICLE HIGHLIGHTS

Research background

The most useful questionnaire for evaluating health status depending on liver disease status or sex is unclear.

Research motivation

No universal health utility assessment values for specific liver diseases or the normal population have been reported.

Research objectives

The objective of this study was to conduct a meta-analysis to estimate health utility assessment values for specific populations in the liver disease.

Research methods

A systematic literature search was performed using PubMed and MEDLINE, including the Cochrane Library.

Research results

The short from-36 and EuroQOL 5-dimensions 5-levels (EQ-5D-5L) can be used for health utility evaluations during antiviral therapy for hepatitis C.

Research conclusions

The EQ-5D-5L is the most popular questionnaire for health utility assessments. Health assessments that allow free registration would be useful for evaluating health utility in patients with liver disease.

Research perspectives

Alternatively, a portable quality of life (QOL) tracker could be used to perform QOL evaluations of any patient-reported outcome in future.

ACKNOWLEDGEMENTS

We thank Sandy Tan and Miyako Nara for their valuable discussions and help in preparing this manuscript.