ORIGINAL PAPER
Available from: URL: http://www.jgld.ro/2014/4/7
DOI: http://dx.doi.org/10.15403/jgld.2014.1121.234.hrq
Health-related Quality of Life and Utilities in Gastric
Premalignant Conditions and Malignant Lesions: a Multicentre
Study in a High Prevalence Country
Miguel Areia1,2, Susana Alves2, Daniel Brito2, Ana Teresa Cadime2, Rita Carvalho2, Sandra Saraiva2, Sara Ferreira3, Joana
Moleiro3, António Dias Pereira3, João Carrasquinho4, Luís Lopes4, José Ramada4, Ricardo Marcos-Pinto1,5,6, Isabel Pedroto5,6,
Luís Contente7, Liliana Eliseu7, Ana Margarida Vieira7, Margarida Sampaio7, Helena Tavares Sousa7, Nuno Almeida8, Carlos
Gregório8, Francisco Portela8, Carlos Sofia8, Vânia Braga9, Elisabete Baginha10, Tiago Bana e Costa10, Cristina Chagas10,
Luís Lebre Mendes10, Pedro Magalhães-Costa10, Leopoldo Matos10, Francisco Rocha Gonçalves1,9, Mário Dinis-Ribeiro1,9
1) Center for Research in
Health Technologies and
Information Systems, Faculty
of Medicine, Porto University;
2) Gastroenterology Dept.,
Portuguese Oncology
Institute of Coimbra; 3)
Gastroenterology Dept.,
Portuguese Oncology Institute
of Lisbon; 4) Gastroenterology
Dept., Santa Luzia Hospital
- Viana do Castelo (Local
Health Unit of Alto Minho); 5)
Gastroenterology Dept., Santo
António General Hospital,
Hospital Centre of Porto; 6)
Institute of Biomedical Sciences
Abel Salazar,University of
Porto; 7) Gastroenterology
Dept., Hospital Unit of
Portimão (Hospital Center
of Western Algarve); 8)
Gastroenterology Dept.,
Coimbra University Hospital
Center; 9) Gastroenterology
Dept., Portuguese Oncology
Institute of Porto; 10)
Gastroenterology Dept.,
West Lisbon Hospital Centre,
Lisbon, Portugal
Address for correspondence:
Miguel Areia
Gastroenterology Department
Portuguese Oncology Institute
Coimbra, Portugal
miguel.areia75@gmail.com
Received: 25.07.2014
Accepted: 08.09.2014
ABSTRACT
Background & Aims: A recent review of economic studies relating to gastric cancer revealed that authors use
different tests to estimate utilities in patients with and without gastric cancer. Our aim was to determine the
utilities of gastric premalignant conditions and adenocarcinoma with a single standardized health measure
instrument.
Methods: Cross-sectional nationwide study of patients undergoing upper endoscopy (n=1,434) using the
EQ-5D-5L quality of life (QoL) questionnaire.
Results: According to EQ-5D-5L, utilities in individuals without gastric lesions were 0.78 (95% confidence
interval: 0.76-0.80), with gastric premalignant conditions 0.79 (0.77-0.81), previously treated for gastric cancer
0.77 (0.73-0.81) and with present cancer 0.68 (0.55-0.81). Self-reported QoL according to the visual analogue
scale (VAS) for the same groups were 0.67 (0.66-0.69), 0.67 (0.66-0.69), 0.62 (0.59-0.65) and 0.62 (0.54-0.70)
respectively. Utilities were consistently lower in women versus men (no lesions 0.71 vs. 0.78; premalignant
conditions 0.70 vs. 0.82; treated for cancer 0.72 vs. 0.78 and present cancer 0.66 vs. 0.70).
Conclusion: The health-related QoL utilities of patients with premalignant conditions are similar to those
without gastric diseases whereas patients with present cancer show decreased utilities. Moreover, women had
consistently lower utilities than men. These results confirm that the use of a single standardized instrument
such as the EQ-5D-5L for all stages of the gastric carcinogenesis cascade is feasible and that it captures
differences between conditions and gender dissimilarities, being relevant information for authors pretending
to conduct further cost-utility analysis.
Key words: gastrointestinal endoscopy − QoL − gastric cancer − intestinal metaplasia − atrophic gastritis.
Abbreviations: LYS: life-years saved; QALY: quality-adjusted life years; VAS: visual analogue scale; CI:
confidence interval.
INTRODUCTION
Gastric adenocarcinoma is
a health problem worldwide
due to its high incidence and
mortality rates, being the fourth
most common malignancy and
the second leading cause of
cancer death [1]. Its prognosis
is highly dependent on the stage
at diagnosis but usually presents
at an advanced stage requiring
demanding treatments and costs
and impairing quality of life (QoL), even for patients with a
good prognosis [2].
In health economics studies, the clinical strategies
adopted for a problem such as gastric cancer are compared by
simultaneously addressing their differences in terms of both
clinical benefits and the cost of achieving them [3]. Guidelines
recommend conducting cost-utility analysis where the use of
clinical benefits should be adjusted to patient preferences. Thus,
life-years saved (LYS) may be adjusted to utilities in terms of
QoL, quality adjusted life years (QALYs), meaning that 1 year
of life is multiplied by a utility factor between 1 and 0, providing
different values for each single year of life, resulting in an utility
value that will vary between 1 QALY (one year with perfect
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372
Areia et al
QoL) and 0 (death, by definition). These guidelines also suggest
that community preferences should be used instead of patient
preferences [4-6].
In a recent systematic review of the literature on economic
studies relating to gastric cancer our group found that authors
mostly used patient preferences instead of the recommended
community preferences and that utilities were obtained
by using several measurement instruments, including
questionnaires that were specifically created for comparing
gastric cancer treatments that should not be compared to
utilities in the general population. Also, models tend to
use utilities reported in other studies, usually conducted in
countries different from the population in the model, where
health valuations might have given different results [7]. Utilities
obtained in a population with a single questionnaire could
be very suitable for conducting cost-utility analysis on the
gastric cancer problem since they would provide comparative
utilities for all stages of the gastric cancer cascade from an
asymptomatic population to gastric cancer patients [8].
Thus, the aim of our study was to perform a cross-sectional
study to obtain utilities from a population that would include
patients without gastric lesions and also with all kinds of
upper gastrointestinal diseases, including patients with all
ranges of gastric premalignant conditions, patients submitted
to endoscopic treatments and patients with gastric cancer
submitted to all available treatments [9-11].
METHODS
This cross-sectional study was performed in 8 Portuguese
hospitals over 6 months, between 2012 and 2013, by delivering
a QoL related questionnaire to patients already scheduled for
routine upper gastrointestinal endoscopic examinations. The
questionnaire was the Portuguese version of the EQ-5D-5L and
the reference test for the diagnosis was the gastroenterology
diagnosis, including the histopathology result when applicable.
The planning, development and report of the study are
in accordance with the STROBE statement for reports on
observational studies [12, 13].
Portugal is considered to have a high-incidence of
gastric cancer according to the GLOBOCAN definition by
presenting an age-standardized incidence rate of 13.7 per
100,000 [14]. From all over the country, including north,
centre, south of Portugal and the two major cities of Lisbon
and Porto, 8 gastroenterology departments in 8 different
hospitals comprising 2 academic hospitals, 3 oncology
centers and 3 regional hospitals, were invited and agreed
to participate. Consecutive patients were included in each
hospital for 3 months and each patient scheduled for an upper
endoscopy procedure was invited to complete a questionnaire
before the examination to self-report their QoL on the day
of the examination.
The outcomes obtained were the self-reported answers
to the questionnaire, providing a measure of QoL on the
day of the upper endoscopy procedure, plus the diagnosis
provided by the attending gastroenterologist, which can be
based on the endoscopic diagnosis, pathology result or known
medical history, as applicable. To allow for generalization of
results, a selection of hospitals was made in order to obtain a
J Gastrointestin Liver Dis, December 2014 Vol. 23 No 4: 371-378
heterogeneous population in terms of both geographic location
and hospital setting.
The only inclusion criteria were the completion of an
already scheduled upper endoscopy along with a voluntary
signed informed consent specific to the study. Exclusion criteria
were emergency examinations, failure to provide informed
consent or any contraindication for upper endoscopy.
The study was approved by the Portuguese Data Protection
Authority (Authorization 4982/2012) after granting permission
for the compilation of multicenter national data, and also by
each hospital Ethics Committee. Confidentiality of all records
was ensured by removing the names of patients, doctors and
nurses from the reports before they were sent to the main
investigator.
Selection bias was minimized by asking all institutions for
a consecutive sample, having a very broad inclusion criteria
setting and carrying out the study in the whole country in
hospitals with very different population characteristics, for at
least 3 months in order to allow the inclusion of most types of
upper gastrointestinal diseases.
QoL questionnaire
The questionnaire used was the EQ-5D-5L developed
by the EuroQol Group, which is a standardized measure to
provide utilities for clinical and economic appraisal [15]. This
questionnaire was chosen because it can be applied to a wide
range of health conditions and treatments, provides a simple
descriptive profile and a single index value for each health
status, has been validated over many years in a number of
populations and settings, is the most recent version of the
EuroQol EQ-5D questionnaire and is available in several
translations, including an already validated and reliable
Portuguese version [16].
The EQ-5D-5L questionnaire comprises a descriptive
system and a visual analogue scale (VAS). The descriptive
system has 5 dimensions: mobility, self care, usual activities,
pain/discomfort and anxiety/depression, and each dimension
has 5 levels: no problems, slight problems, moderate problems,
severe problems, and extreme problems (the former EQ-5D
had only 3 choices per question, being called EQ-5D-3L).
Respondents are asked to indicate their health state by marking
the box against the most appropriate statement in each of the 5
dimensions. The digits for the 5 dimensions can be combined
in a 5-digit number describing the respondent’s health state.
Health states defined by the EQ-5D-5L descriptive system
were converted into a single index value to calculate utilities,
according to the recommendations of the EuroQol Group [17].
The similar EQ-5D-3L system was only recently validated
in the Portuguese population, by setting preferences for the
general population using the time trade-off technique and also
developing population norms [18, 19]. Because currently there
is no validated method to transform utilities from the EQ-5D3L to the EQ-5D-5L systems, we used the Spanish EQ-5D-5L
utilities. From the available options, the Spanish utilities are
the most similar, providing a Pearson’s correlation coefficient
of r=0.946 for both EQ-5D-3L population norms [18].
The VAS records the respondent’s self-rated health on a 20
cm vertical VAS, with endpoints labeled “the best health you
can imagine” and “the worst health you can imagine”.
Gastric cancer QoL
373
A correctly completed questionnaire was defined as a
questionnaire with each of the 5 multiple choice questions for
the descriptive system completed with a single cross and a clear
and readable number in the VAS.
of 0.05 and a power of 0.80, based on previous reports that for
normal patients the utility score was 0.90, for patients with
premalignant conditions 0.70 and for patients with gastric
cancer 0.50. We aimed at obtaining 100 patients for each of
these groups, to ensure that confidence intervals would not be
wider than ±0.10, in order to achieve statistically significant
differences between utilities [25].
Results are reported as means and 95% confidence interval
(CI) for continuous variables and percentages for proportions.
For comparative analysis the Student’s t-test was used for
continuous variables according to their normal distribution
and the Pearson chi-square test for dichotomous variables.
A two-sided p value <0.05 was considered to be statistically
significant. Results were analyzed in subgroups for confounding
factors such as age or gender but not for co-morbidities. No
data was missing from the retrieved questionnaires.
Endoscopic procedure
For each questionnaire the corresponding diagnosis was
obtained from the upper endoscopy result. Upper endoscopy
is considered the ideal procedure for the diagnosis of upper
gastrointestinal diseases due to its widespread availability,
improved accuracy for most diseases, relatively minor
invasiveness and possibility of performing diagnostic and/
or therapeutic procedures [20-24]. There were no specific
inclusion or exclusion criteria based on patient diagnosis,
endoscopists’ experience, type of endoscopic facility or scope.
Biopsies were done as deemed necessary, but not specifically
for participation in the study.
RESULTS
Sample size and statistical analysis
For the sample size calculation, an estimate of at least 44
patients per group would be needed for a level of significance
All subjects scheduled for an upper endoscopy were invited
and after exclusions for several factors such as refusing to
Table I. Main patient characteristics and utilities according to stages of the gastric carcinogenesis cascade
and most relevant upper gastrointestinal diseases
n (%)
Patients
EQ-5D-5L mean
(95% CI)
VAS mean
(95% CI)
1,434
Male gender
755 (52.6)
Age ≥ 50 years
1,063 (74.1)
Participating hospital: n (% global), (% gastric cancer)
Portuguese Oncology Institute of Coimbra
353 (24.6), (20.7)
Portuguese Oncology Institute of Lisbon
294 (20.5), (9.5)
Santa Luzia Hospital, Viana do Castelo
205 (14.3), (4.4)
Santo António General Hospital, Porto
168 (11.7), (1.8)
Hospital Unit of Portimão
142 (9.9), (4.9)
Coimbra’s University and Hospital Center
134 (9.3), (8.9)
Portuguese Oncology Institute of Porto
69 (4.8), (20.3)
West Lisbon Hospital Centre
69 (4.8), (2.9)
No gastric lesions
678 (47.3)
0.78 (0.76-0.80)
0.67 (0.66-0.69)
Gastric premalignant conditions
(gastritis, atrophy, intestinal metaplasia)
391 (27.3)
0.79 (0.77-0.81)
0.67(0.66-0.69)
Gastric adenocarcinoma
148 (10.3)
0.77 (0.73-0.81)
0.62 (0.59-0.65)
- Mucosectomy
17 (1.2)
0.78 (0.63-0.92)
0.62 (0.54-0.70)
- Surgery
69 (4.8)
0.77 (0.71-0.82)
0.62 (0.57-0.67)
Treated by:
- Chemo/Radiotherapy
38 (2.6)
0.83 (0.77-0.89)
0.63 (0.57-0.70)
24 (1.7)
0.68 (0.55-0.81)
0.62 (0.54-0.70)
155 (10.8)
0.77 (0.73-0.80)
0.66 (0.63-0.69)
Esophagitis
83 (5.8)
0.79 (0.74-0.74)
0.69 (0.65-0.73)
Peptic ulcer
36 (2.5)
0.78 (0.72-0.84)
0.62 (0.56-0.69)
Barrett’s esophagus
28 (1.9)
0.79 (0.67-0.90)
0.74 (0.66-0.80)
Present carcinoma
Other lesions*
Hiatal hernia
731
*Other lesions stand for all lesions in the esophagus, stomach or duodenum except for gastric premalignant
conditions or gastric adenocarcinoma. Only the most frequent reported are presented.
Legend: EQ-5D-5L: EuroQol EQ-5D-5L questionnaire; VAS scale: visual analogue scale of the EQ-5D-5L
questionnaire; CI: confidence interval.
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Areia et al
Table II. Utilities according to stages of the gastric carcinogenesis cascade in patients aged 50 or over, by gender
Age ≥ 50 years
Scale
p
EQ-5D-5L mean (95% CI)
Gender
Age ≥ 50 years
p
VAS mean (95% CI)
Male
Female
Male
Female
No gastric lesions
0.78
(0.76-0.81)
0.71
(0.67-0.75)
0.01
0.65
(0.63-0.68)
0.63
(0.60-0.66)
0.19
Gastric premalignant conditions
0.82
(0.79-0.85)
0.70
(0.66-0.74)
0.01
0.69
(0.66-0.73)
0.60
(0.57-0.63)
0.01
Gastric adenocarcinoma
0.78
(0.73-0.83)
0.72
(0.65-0.79)
0.15
0.62
(0.58-0.67)
0.59
(0.54-0.64)
0.33
Mucosectomy
0.77
(0.50-1.00)
0.70
(0.33-1.00)
0.69
0.61
(0.48-0.73)
0.52
(0.42-0.62)
0.25
Surgery
0.79
(0.72-0.87)
0.71
(0.62-0.80)
0.18
0.63
(0.55-0.70)
0.58
(0.51-0.66)
0.42
Chemo/Radiotherapy
0.85
(0.79-0.91)
0.76
(0.60-0.92)
0.19
0.64
(0.55-0.72)
0.60
(0.50-0.70)
0.59
0.70
(0.42-0.97)
0.66
(0.49-0.83)
0.79
0.66
(0.48-0.84)
0.60
(0.50-0.71)
0.52
Treated by:
Present carcinoma
Legend: EQ-5D-5L: EuroQol EQ-5D-5L questionnaire; VAS: visual analogue scale of the EQ-5D-5L questionnaire;
CI: confidence interval; *: Student’s t-test.
participate, endoscopy not performed, declined to complete
questionnaire or incomplete data, 1,434 questionnaires out
of 1,886 were completed correctly achieving a participation
rate of 76%. The characteristics of patients with incomplete
questionnaires were not possible to access because in most
cases the main data missing were the clinical issues such as
age, gender or diagnosis and not the fulfilling of the EQ-5D5L questionnaire.
The main patient characteristics and results for the most
relevant upper gastrointestinal diseases, including all stages
of the gastric carcinogenesis cascade, are reported in Table I.
Participants were 53% male with a mean age of 59 years. The
examination was considered normal in only 24% of cases, and
most relevant abnormalities detected were gastric premalignant
conditions such as gastritis, atrophy or intestinal metaplasia
and esophageal conditions such as hiatal hernia or esophagitis.
There were no relevant differences between participating
institutions in terms of patients’ diseases, except for there being
more cancer patients in the Oncology Centers, as expected
(13.7% vs. 4.7%, p=0.01).
In terms of the 5 dimensions of the EQ-5D-5L questionnaire,
75% to 93% of participants said they had no or only slight
problems in all five dimensions with better score for self-care
such as washing or dressing themselves and only 2.2% to
6.1% reported severe to extreme problems with worst score
for usual activities such as work, study, housework, family or
leisure. Anxiety was moderate to extreme in 21% of patients
without relevant differences among groups (no lesions 21%,
premalignant conditions 23%, gastric cancer 18%).
Although the numbers of included questionnaires vary
and are related to a diverse prevalence of these diseases in
the general population, VAS scores were consistently lower
than the EQ-5D-5L utilities, regardless of organ or severity of
disease, in all conditions analyzed.
Utilities for all stages of the gastric cancer cascade of
carcinogenesis, with subgroup analysis by gender and including
J Gastrointestin Liver Dis, December 2014 Vol. 23 No 4: 371-378
only patients aged 50 or over are summarized in Table II.
This subgroup analysis is justified by the fact that this is the
population (≥50 years) which is usually considered to be costeffective to offer endoscopic screening or surveillance strategies
[26]. No comparison between <50 and ≥50 years was made due
to the huge differences between groups in terms of available
questionnaires 371 vs. 1063 and gastric cancer cases 11 vs. 137.
Overall scores demonstrated that the two scales provided
similar results for patients without gastric lesions or with
gastric premalignant conditions with utilities lower for patients
who had present gastric cancer than for patients without gastric
lesions or those with premalignant conditions (0.68 versus
≥0.77, p=0.09).
When adjusting for gender and including only patients
aged 50 or above, the results consistently show that utilities
were lower for women than for men. This dissimilar scoring for
males and females achieves a statistically significant difference
in some normal or premalignant conditions in both scales.
DISCUSSION
This cross-sectional study of patients scheduled for an
upper endoscopy procedure provided utilities and selfreported QoL data for a nationwide population with a validated
questionnaire in a sample of patients embracing all stages of
the carcinogenic cascade for gastric adenocarcinoma. These
results, although specific to the studied population, might be
relevant to further cost-utility studies in gastric cancer as a
recent systematic review showed that utilities were relevant in
several studies for the final results of the economic analysis,
namely QoL in diseased patients and also after treatments for
cancer [7, 8].
Utilities measured by the EQ-5D-5L questionnaire showed
similar scores for patients without gastric lesions (0.78),
patients with premalignant conditions (0.82) and patients with
previously treated gastric cancer (0.77-0.79) but lower values
Gastric cancer QoL
375
Table III. Comparison of the current study with published cost-utility studies on gastric cancer and respective references used for utilities valuation
Present study
1. Values for the asymptomatic population
2. Normal is different from 1
3. Values for all gastric premalignant conditions (gastritis, atrophy, intestinal metaplasia and dysplasia)
4. Values for endoscopic treatment (mucosectomy)
5. Values for gastric cancer patients in 3 different stages of treatment (surgery, chemotherapy and/or radiotherapy and
best supportive care)
6. Different evaluations for men and women
Other studies
(1st author, year, country)
Intervention
Utilities references
Utility values from references
Comment on references used
Xie, 2008 [31]
Xie, 2008 [32]
Singapore
Screening (serology)
and treat H. pylori or
Screening (UBT) and
treat H. pylori
Wang Q, et al. 2003 [38]
H. pylori non-infected 1.00
(0.95-1.00)
H. pylori infected 0.90 (0.801.00)
Gastric cancer 0.38 (0.13-0.65)
Normal is 1
No values for population
No values for premalignant
gastric conditions
Just one value for gastric cancer
Xie, 2009 [33]
Canada
Screening (Stool Ag) or
Screening (serology) or
Screening (UBT†)
Delaney BC, et al. 2008 [39]
Ajani JA, et al. 2007 [40]
H. pylori uninfected 0.83
(0.80-0.86)
H. pylori infected 0.83 (0.800.86)
Gastric cancer 0.55 (0.47-0.63)
No values for population
No values for premalignant
gastric conditions
Same value for uninfected and
infected patients Just one value
for gastric cancer
Yeh, 2009 [37]
China
Screening (serology)
and treat H. pylori or
Universal treatment
Mathers CD, et al. 2000 [41]
Gold MR, et al. 1998 [25]
Normal gastric mucosa
0.56–0.94
Gastritis 0.56–0.94
Atrophy 0.56–0.94
Intestinal metaplasia 0.56–0.94
Dysplasia 0.56–0.94
Symptomatic gastric cancer
0.49 (0.17–0.79)
No values for population
Same value for all premalignant
lesions Just one value for gastric
cancer
Dan, 2006 [35]
Singapore
Endoscopy every 2
years
Glimelius B, et al. 1995 [42]
Blazeby JM, et al. 2004 [43]
Stages I and II (surgery) 0.65
Stage III (chemo radiotherapy)
0.4
Stage IV (palliative care) 0.5
No values for population
No values for premalignant
gastric conditions
Gupta, 2011 [30]
USA
Endoscopy + Barrett’s
surveillance or
Endoscopy
Inadomi JM, et al. 2003 [44]
Rubenstein JH, et al. 2007
[45]
Inadomi JM, et al. 2009 [46]
Cancer 0.5-0.75
Post-gastrectomy state 0.97
(0.8-1)
No values for population
No values for premalignant
gastric conditions
Value for cancer as a whole
Zhou, 2011 [34] China
Serum pepsinogens +
Endoscopy
World Health Organization
QoL (WHOQOL)- BREF
questionnaire [47]
Healthy residents 1.00
Gastric cancer patients 0.680.66
Normal is 1
No values for premalignant
gastric conditions
Just one value for gastric cancer
Dinis-Ribeiro, 2007 [29]
Portugal
Yearly magnification
chromoendoscopy +
Serum Pepsinogens
Kaptein AA, et al. 2005 [48]
Death 0
Chemotherapy 0.1–0.3
Surgery 0.4–0.8
Mucosectomy 0.8–0.95
No values for population
No values for premalignant
gastric conditions
Yeh, 2010 [36] USA
Endoscopic surveillance
every 1, 5 or 10 years
Hanmer J, et al. 2006 [49]
Gold MR, et al. 1998 [25]
Age-related quality weight
0.78-0.93
Gastric cancer 0.49 (0.17-0.79)
No values for population
No values for premalignant
gastric conditions
Just one value for gastric cancer
Legend: UBT: Urea Breath Test; Ag: Antigen.
for patients with present carcinoma (0.66) and for the same
clinical situations the EQ-5D-5L scores were always lower for
female than for male.
To the best of our knowledge this study is the first
providing utilities for all stages of the gastric cancer cascade
using a single health utilities measurement instrument. The
study provides very useful information for authors conducting
cost-utility analysis by incorporating utilities in their Markov
models [8].
Our main conclusion and contribution to the actual medical
practice is that the use of a single standardized instrument like
EQ-5D-5L for all stages of disease is feasible, that it captures
differences among stages (no lesions vs. premalignant
conditions vs. present cancer) and adjustments by gender are
relevant when incorporating utilities in economic models.
A second relevant conclusion is that the utilities varied
between different stages of disease in a much narrower set
of values (around 0.6 for cancer vs. 0.8 for no cancer) than
previously reported in other models (around 0.3 vs. 0.9 for
the same groups), raising the concern that utilities valuation
by using different questionnaires for different stages of disease,
as has been done in other models, might overvalue real
differences and overestimate the final economic conclusions
among strategies.
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376
Advantages of this study is that it includes patients on a
nationwide basis, from general and teaching hospitals, and
oncology centers, it covers more than 1400 reports, providing
more than 100 patients in each subgroup (no lesions vs.
premalignant lesions vs. gastric cancer) and utilities are
linked to a medical diagnosis confirmed by a doctor after
performing an endoscopy with biopsies when needed. In
addition, by including a range of upper gastrointestinal diseases
it means that utilities of the general population with the same
background are comparable.
To prevent selection bias as possible, a variety of hospitals
from all over the country were selected, participants were
consecutive and unselected, no change in routine practice was
necessary and the analysis of the results was blinded. Also,
anxiety caused by endoscopy that could influence the results
in terms of utilities was consistently similar among groups.
When comparing our study results to the study by Gold
et al used for the sample size calculation, utilities values in
other diseases returned similar results to ours: for esophageal
problems 0.70 vs. 0.69 and for peptic ulcer 0.66 vs. 0.62. Also,
in a study performed in our country using the same EQ-5D
questionnaire in gastrointestinal patients (n=125), utilities for
gastric cancer (n=5) ranged between 50 and 70, including our
result of 0.62 [27].
The finding of different utilities between male and female
is in accordance with a similar study in Portugal and also in
other countries, confirming that this consistent result should
be incorporated in cost-utility models [19, 28].
The relevance of the present study to the already available
literature comes from the existence of several problems within
the methodology of cost-utility studies published. We think
these problems might have been overcome with the present
study (see Table III) [25, 29-49]. Xie et al, Dan et al, Gupta
et al, Zhou et al, Dinis-Ribeiro et al did not use values for the
asymptomatic population; Xie et al and Zhou et al used 1 as
the value for the normal population; only Yeh et al had values
for premalignant gastric conditions; only Dinis-Ribeiro et al
had values for the post mucosectomy stage; only Dan et al and
Dinis-Ribeiro et al presented more than a single value for all
gastric cancer patients, irrespective of the type of treatment
performed and only two authors used a single reference to
obtain the utilities for their models: the study by Wang Q et al
that is in Chinese and not available to most clinicians, and the
study by Dinis-Ribeiro et al that used a systematic review of
studies embracing several different questionnaires on patients
with diagnosed or treated gastric cancer. Finally, not a single
model evaluated differently the male and female utilities.
We think that it is very important to use a single validated
instrument for all stages of disease so that utilities among
different stages are not overestimated by the use of different
and not comparable questionnaires. Also, as suggested by the
guidelines, utilities valuation should come from community
preferences as ours did and not only from diseased patients
[4].
The results of our study have implications on the
interpretation of previous models on endoscopic surveillance
of gastric premalignant conditions because the wider utilities’
values used by others could result from using different
questionnaires for different clinical situations, thereby
J Gastrointestin Liver Dis, December 2014 Vol. 23 No 4: 371-378
Areia et al
overestimating differences in utilities and the final model
outcome between strategies.
This study has some limitations that need to be addressed:
in one hospital the questionnaires were completed after
performing upper endoscopy while in all the others this was
done before the examination and, although it is expected
that answers to items such as mobility, self-care, usual
activities and pain or discomfort are not influenced by the
examination, the item on anxiety might be influenced by
whether the questionnaire was completed before or after the
endoscopy. Also, in the absence of standard health values for
the Portuguese population for the validated questionnaire
used (EQ-5D-5L) we used values for the Spanish population.
Although the populations are different and their valuation
of QoL will be dissimilar, the closest possible proximity and
geographic location should provide some degree of similarity.
CONCLUSIONS
Our results confirm the applicability of using a single
standardized instrument such as EQ-5D-5L for all stages of
disease as it captures differences in utilities among stages and
gender and wider differences among stages reported in previous
models might result from the use of different instruments and
overestimate real dissimilarities. These conclusions may be
relevant to further cost-utility analysis in gastric cancer and
should be incorporated by authors in their models.
Conflicts of interest: No conflicts to declare for all authors.
Authors’ contribution: M.A., F. R.G. and M.D-R. planned and
conducted the study, interpreted data and drafted the manuscript.
All the authors included patients, provided a critical revision of the
manuscript and approved the final manuscript version.
Acknowledgements: The authors would like to thank Jean Burrows
and Ana Cláudia Jorge for the linguistic revision of the manuscript
and many nurses and administrative staff for their participation,
namely: Conceição Craveiro, Cristina França, Ana Cristina Ferreira,
Marina Pedrosa, Filipe Santos, Sara Baptista, Mónica Moreira, Anabela
Oliveira, Paula Paixão, Cidália Soares, Rui Caturrinho, Anabela
Parente, Florbela Pinto, Sandra Aires, Celeste Peixoto, Paulo Sousa,
Joaquim Correia, Patrícia Nicolau, Cláudia Cavaco, Eunice Sequeira,
Suzana Carreira, Eulália Cunha, Sara Antunes, Teresa José, Suzel
Grade, Alexandra Luís.
REFERENCES
1 Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates
of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer
2010;127:2893-2917.
2 Hundahl SA, Phillips JL, Menck HR. The National Cancer Data Base
Report on poor survival of U.S. gastric carcinoma patients treated
with gastrectomy: Fifth Edition American Joint Committee on Cancer
staging, proximal disease, and the „different disease” hypothesis. Cancer
2000;88:921-932.
3 Dinis-Ribeiro M, Lopes C, da Costa-Pereira A, et al. A follow up model
for patients with atrophic chronic gastritis and intestinal metaplasia. J
Clin Pathol 2004;57:177-182.
Gastric cancer QoL
4 Russell LB, Gold MR, Siegel JE, Daniels N, Weinstein MC. The role
of cost-effectiveness analysis in health and medicine. Panel on CostEffectiveness in Health and Medicine. JAMA 1996;276:1172-1177.
5 Siegel JE, Weinstein MC, Russell LB, Gold MR. Recommendations for
reporting cost-effectiveness analyses. Panel on Cost-Effectiveness in
Health and Medicine. JAMA 1996;276:1339-1341.
6 Weinstein MC, Siegel JE, Gold MR, Kamlet MS, Russell LB.
Recommendations of the Panel on Cost-effectiveness in Health and
Medicine. JAMA 1996;276:1253-1258.
7 Areia M, Carvalho R, Cadime AT, Rocha Goncalves F, Dinis-Ribeiro
M. Screening for gastric cancer and surveillance of premalignant
lesions: a systematic review of cost-effectiveness studies. Helicobacter
2013;18:325-337.
8 Areia M, Dinis-Ribeiro M, Rocha Goncalves F. Cost-utility analysis
of endoscopic surveillance of patients with gastric premalignant
conditions. Helicobacter 2014 Aug 28.
9 Dinis-Ribeiro M, Areia M, de Vries AC, et al. Management of
precancerous conditions and lesions in the stomach (MAPS): guideline
from the European Society of Gastrointestinal Endoscopy (ESGE),
European Helicobacter Study Group (EHSG), European Society
of Pathology (ESP), and the Sociedade Portuguesa de Endoscopia
Digestiva (SPED). Endoscopy 2012;44:74-94.
10 Dinis-Ribeiro M, Pimentel-Nunes P, Afonso M, Costa N, Lopes C,
Moreira-Dias L. A European case series of endoscopic submucosal
dissection for gastric superficial lesions. Gastrointest Endosc
2009;69:350-355.
11 Ribeiro-Mourao F, Pimentel-Nunes P, Dinis-Ribeiro M. Endoscopic
submucosal dissection for gastric lesions: results of an European inquiry.
Endoscopy 2010;42:814-819.
12 Vandenbroucke JP, von Elm E, Altman DG, et al. Strengthening the
Reporting of Observational Studies in Epidemiology (STROBE):
explanation and elaboration. Ann Intern Med 2007;147:W163-W194.
13 von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC,
Vandenbroucke JP. The Strengthening the Reporting of Observational
Studies in Epidemiology (STROBE) statement: guidelines for reporting
observational studies. Ann Intern Med 2007;147:573-577.
14 Ferlay J, Soerjomataram I, Ervik M, et al. Cancer Incidence and Mortality
Worldwide: IARC CancerBase No. 11 [Internet]. GLOBOCAN 2012
v10. Lyon, France: International Agency for Research on Cancer, 2013.
Available from: http://globocan.iarc.fr.
15 EuroQol Group. EuroQol-a new facility for the measurement of healthrelated quality of life. Health Policy 1990;16:199-208.
16 Ferreira PL, Ferreira LN, Pereira LN. Contribution for the validation
of the Portuguese version of EQ-5D. Acta Med Port 2013;26:664-675.
17 Herdman M, Gudex C, Lloyd A, et al. Development and preliminary
testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life
Res 2011;20:1727-1736.
18 Ferreira LN, Ferreira PL, Pereira LN, Oppe M. The valuation of the
EQ-5D in Portugal. Qual Life Res 2014;23:413-423.
19 Ferreira LN, Ferreira PL, Pereira LN, Oppe M. EQ-5D Portuguese
population norms. Qual Life Res2014;23:425-430.
20 Hirota WK, Zuckerman MJ, Adler DG, et al; Standards of Practice
Committee, American Society for Gastrointestinal Endoscopy. ASGE
guideline: the role of endoscopy in the surveillance of premalignant
conditions of the upper GI tract. Gastrointest Endosc 2006;63:570580.
21 Areia M, Amaro P, Dinis-Ribeiro M, et al. External validation of a
classification for methylene blue magnification chromoendoscopy in
premalignant gastric lesions. Gastrointest Endosc 2008;67:1011-1018.
377
22 Areia M, Amaro P, Dinis-Ribeiro M, et al. Estimation of the extent of
gastric intestinal metaplasia by methylene blue chromoendoscopy. Eur
J Gastroenterol Hepatol 2008;20:939-940.
23 Dinis-Ribeiro M, da Costa-Pereira A, Lopes C, et al. Magnification
chromoendoscopy for the diagnosis of gastric intestinal metaplasia and
dysplasia. Gastrointest Endosc 2003;57:498-504.
24 Areia M, Dinis-Ribeiro M, Portuguese Society of Digestive Endoscopy.
One day of upper gastrointestinal endoscopy in a southern European
country. GE J Port Gastrenterol 2014;21:97-101.
25 Gold MR, Franks P, McCoy KI, Fryback DG. Toward consistency in
cost-utility analyses: using national measures to create conditionspecific values. Med Care 1998;36:778-792.
26 Areia M, Pimentel-Nunes P, Marcos-Pinto R, Dinis-Ribeiro M. Gastric
cancer: an opportunity for prevention. Acta Med Port 2013;26:627-629.
27 Ravasco P, Monteiro-Grillo I, Camilo ME. Does nutrition influence
quality of life in cancer patients undergoing radiotherapy? Radiother
Oncol 2003;67:213-220.
28 Konig HH, Bernert S, Angermeyer MC, et al. Comparison of population
health status in six european countries: results of a representative survey
using the EQ-5D questionnaire. Med Care 2009;47:255-261.
29 Dinis-Ribeiro M, da Costa-Pereira A, Lopes C, Moreira-Dias L. Feasibility
and cost-effectiveness of using magnification chromoendoscopy and
pepsinogen serum levels for the follow-up of patients with atrophic
chronic gastritis and intestinal metaplasia. J Gastroenterol Hepatol
2007;22:1594-1604.
30 Gupta N, Bansal A, Wani SB, Gaddam S, Rastogi A, Sharma P.
Endoscopy for upper GI cancer screening in the general population: a
cost-utility analysis. Gastrointest Endosc 2011;74:610-624.
31 Xie F, Luo N, Blackhouse G, Goeree R, Lee HP. Cost-effectiveness
analysis of Helicobacter pylori screening in prevention of gastric cancer
in Chinese. Int J Technol Assess Health Care 2008;24:87-95.
32 Xie F, Luo N, Lee HP. Cost effectiveness analysis of population-based
serology screening and (13)C-Urea breath test for Helicobacter pylori
to prevent gastric cancer: a markov model. World J Gastroenterol
2008;14:3021-3027.
33 Xie F, O‘Reilly D, Ferrusi IL, et al. Illustrating economic evaluation
of diagnostic technologies: comparing helicobacter pylori screening
strategies in prevention of gastric cancer in Canada. J Am Coll Radiol
2009;6:317-323.
34 Zhou L, Guan P, Sun LP, He QC, Yuan Y, Zhou BS. Health economic
assessment for screening of gastric cancer in a high risk population in
northeastern China. Chin J Cancer Res 2011;23:21-24.
35 Dan YY, So JB, Yeoh KG. Endoscopic screening for gastric cancer. Clin
Gastroenterol Hepatol 2006;4:709-716.
36 Yeh JM, Hur C, Kuntz KM, Ezzati M, Goldie SJ. Cost-effectiveness
of treatment and endoscopic surveillance of precancerous lesions to
prevent gastric cancer. Cancer 2010;116:2941-2953.
37 Yeh JM, Kuntz KM, Ezzati M, Goldie SJ. Exploring the cost-effectiveness
of Helicobacter pylori screening to prevent gastric cancer in China in
anticipation of clinical trial results. Int J Cancer 2009;124:157-166.
38 Wang Q, Jin PH, Lin GW, Xu SR, Chen J. Cost-effectiveness of
Helicobacter pylori screening to prevent gastric cancer: Markov decision
analysis. Zhonghua Liu Xing Bing Xue Za Zhi 2003;24:135-139.
39 Delaney BC, Qume M, Moayyedi P, et al. Helicobacter pylori test and
treat versus proton pump inhibitor in initial management of dyspepsia
in primary care: multicentre randomised controlled trial (MRC-CUBE
trial). BMJ 2008;336:651-654.
40 Ajani JA, Moiseyenko VM, Tjulandin S, et al. Quality of life with
docetaxel plus cisplatin and fluorouracil compared with cisplatin
J Gastrointestin Liver Dis, December 2014 Vol. 23 No 4: 371-378
378
and fluorouracil from a phase III trial for advanced gastric or
gastroesophageal adenocarcinoma: the V-325 Study Group. J Clin Oncol
2007;25:3210-3216.
41 Mathers CD, Murray CJ, Lopez AD, et al. Estimates of healthy life
expectancy for 191 countries in the year 2000: methods and results.
Global Programme on Evidence for Health Policy Discussion Paper
No 38. Geneva: World Health Organization, 2001. http://www.who.
int/healthinfo/paper38.pdf
42 Glimelius B, Hoffman K, Graf W, et al. Cost-effectiveness of palliative
chemotherapy in advanced gastrointestinal cancer. Ann Oncol
1995;6:267-274.
43 Blazeby JM, Conroy T, Bottomley A, et al. Clinical and psychometric
validation of a questionnaire module, the EORTC QLQ-STO 22,
to assess quality of life in patients with gastric cancer. Eur J Cancer
2004;40:2260-2268.
44 Inadomi JM, Sampliner R, Lagergren J, Lieberman D, Fendrick AM,
Vakil N. Screening and surveillance for Barrett esophagus in high-
J Gastrointestin Liver Dis, December 2014 Vol. 23 No 4: 371-378
Areia et al
45
46
47
48
49
risk groups: a cost-utility analysis. Ann Intern Med 2003;138:176186.
Rubenstein JH, Inadomi JM, Brill JV, Eisen GM. Cost utility of screening
for Barrett‘s esophagus with esophageal capsule endoscopy versus
conventional upper endoscopy. Clin Gastroenterol Hepatol 2007;5:312318.
Inadomi JM, Somsouk M, Madanick RD, Thomas JP, Shaheen NJ.
A cost-utility analysis of ablative therapy for Barrett‘s esophagus.
Gastroenterology 2009;136:2101-2114 e1-6.
WHO. World Health Organization Quality of Life (WHOQOL- BREF).
World Health Organization, 2004.
Kaptein AA, Morita S, Sakamoto J. Quality of life in gastric cancer.
World J Gastroenterol 2005;11:3189-3196.
Hanmer J, Lawrence WF, Anderson JP, Kaplan RM, Fryback DG. Report
of nationally representative values for the noninstitutionalized US adult
population for 7 health-related quality-of-life scores. Med Decis Making
2006;26:391-400.