Medical Decision Making

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A Review and Meta-analysis of Colorectal Cancer Utilities

Sandjar Djalalov, Linda Rabeneck, George Tomlinson, Karen E. Bremner, Robert Hilsden and Jeffrey S. Hoch
Med Decis Making 2014 34: 809 originally published online 5 June 2014
DOI: 10.1177/0272989X14536779

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A Review and Meta-analysis
of Colorectal Cancer Utilities
Sandjar Djalalov, PhD, Linda Rabeneck, MD, MPH, George Tomlinson, PhD,
Karen E. Bremner, BSc, Robert Hilsden, MD, PhD, Jeffrey S. Hoch, PhD
Objective. To perform a systematic review of utility
weights for colorectal cancer (CRC) health states reported
in the scientific literature and to determine the effects of
disease factors, patient characteristics, and utility meth-
ods on utility values. Methods. We identified 26 articles
written in English and published from January 1980 to
January 2013, providing 351 unique utilities for CRC
health states elicited from 6546 unique respondents. The
CRC utility data were analyzed using linear mixed-effects
models with CRC type, stage, time to or from initial care,
utility measurement instrument, and administration
method as independent variables. Results. In the base
case model, the estimated utility for a patient with stage
I to III CRC more than 1 year after surgery, rated using
a self-administered time tradeoff instrument, was 0.90.
Stage, time to or from initial care, and utility measurement
instrument were associated with statistically significant
Received 1 March 2012 from the Centre for Excellence in Economic
Analysis Research, Li Ka Shing Knowledge Institute, St. Michael’s
Hospital, Toronto, ON, Canada (SD, JSH); Institute of Health Policy,
Management and Evaluation and Department of Medicine, University
of Toronto, Toronto, ON, Canada (LR, GT, JSH); Pharmacoeconomics
Research Unit, Cancer Care Ontario, Toronto, ON, Canada (SD, LR,
JSH); Toronto General Hospital, Toronto, ON, Canada (KEB); Univer-
sity of Calgary, Calgary, AB, Canada (RH); Department of Medicine,
University Health Network/Mt. Sinai Hospital, Toronto, ON, Canada
(GT); and Canadian Centre for Applied Research in Cancer Control
(ARCC), Toronto, ON, Canada (SD, JSH). This research was sup-
ported by Canadian Institutes of Health Research (CIHR) grant
CST-85478 (‘‘CIHR Team in Population-Based Colorectal Cancer
Screening’’) and funding from ARCC. The Pharmacoeconomics
Research Unit is supported by Cancer Care Ontario and the Ontario
Ministry of Health and Long-Term Care. This research does not reflect
the views of the funders. ARCC is funded by a grant from the Canadian
Cancer Research Institute. Revision accepted for publication 29 April
2014.
Ó The Author(s) 2014
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DOI: 10.1177/0272989X14536779
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REVIEW
utility differences ranging from –0.19 to 0.02. Utilities for
patients with stage IV cancer were 0.19 lower (P \ 0.001)
than for those with stage I to III cancer. Utilities elicited
at more than 1 year after surgery were 0.05 higher than
those elicited at 3 months after surgery (P = 0.008). Esti-
mates of differences between utility measurement instru-
ments were sensitive to how repeated scores in the same
patient group were treated, and other findings were sensi-
tive to how the disease stage was modeled and method of
administration. Conclusions. Variations in reported utili-
ties are associated with factors such as cancer stage,
time to or from initial care, and utility measurement
instrument. More research is needed to study why appar-
ently similar patients report different quality of life. Key
words: colorectal cancer; quality of life; preferences; util-
ity assessment; meta-analysis. (Med Decis Making
2014;34:809–818)
C olorectal cancer (CRC) is one of the most com-
mon malignancies in the world and is the sec-
ond leading cause of cancer death in Western
countries, with incidence rates increasing for both
females and males.1 CRCs start in the cells that line
the inside of the colon or the rectum, and these cells
take several years to grow and transform into cancer.
If left untreated, the cancer cells can grow into the
muscle layers underneath and through the bowel
wall. If it is detected early, CRC is readily cured by
surgical resection. However, if it is detected late
and the tumor has already spread to other organs,
few patients survive longer than 5 years.2
Supplementary material for this article is available on the Medical
Decision Making Web site at http://mdm.sagepub.com/supplemental.
Address correspondence to Jeffrey S. Hoch, PhD, Pharmacoeconom-
ics Research Unit, Cancer Care Ontario, 620 University Avenue, Tor-
onto, ON M5G 2L7, Canada; e-mail: jeffrey.hoch@utoronto.ca.
809
 DJALALOV AND OTHERS
An economic evaluation is an important tool to
help prioritize the funding of treatments and inter-
ventions, allowing decision makers to distinguish
economically attractive health care investments
from those that do not represent good value for money
and make choices that maximize health gains per dol-
lar. An economic evaluation is particularly relevant
to cancer due to concerns about increasing expendi-
tures as the incidence of cancer increases and expen-
sive drugs are developed.
Most guidelines for economic evaluations recom-
mend expressing the results as an incremental cost-
effectiveness ratio (ICER). The ICER is the ratio of
the incremental difference in expected costs to the
incremental difference in expected outcomes of the
competing strategies.3–6 A cost-utility analysis is
a type of cost-effectiveness analysis in which the out-
come is expressed in quality-adjusted life-years
(QALYs). The QALY is a measure of length of life
weighted by a quality of life (QoL) utility weight. A
patient’s health states are assigned utility weights
ranging from a value of 1 for perfect health down to
a value of 0 for death.7 Thus, 10 years of life with
a utility weight of 0.80 equals 8.0 QALYs. The
QALY allows one to compare different health tech-
nology interventions across various conditions and
diseases, making it a potentially useful measure of
outcome for decision-making processes.
The 3 most widely used direct tools in cost-utility
analysis are the standard gamble (SG), time tradeoff
(TTO), and visual analog scale (VAS). The SG
includes both risk and choice related to specific out-
comes, and the TTO includes a choice in outcome but
no risk. The VAS includes neither risk nor choice, and
hence, it is not considered to be a true utility measure.8
Alternatively, utilities can be measured indirectly
using multiattribute health status classification sys-
tems with preference scores. The 2 most frequently
used systems in CRC QoL studies are the EuroQol 5
Dimensions (EQ5D) and Health Utilities Index 3
(HUI3). Responses to the 5 dimensions on the EQ5D
are converted to a utility score using country-specific
TTO weights derived from the general public.9 The
HUI3 covers 8 health-related dimensions: vision, hear-
ing, speech, ambulation, dexterity, emotion, cogni-
tion, and pain; each is assigned 1 of 5 or 6 levels to
indicate ability or disability.
To obtain reliable results and conclusions from
economic evaluations to inform policy makers, it is
important to have valid utility estimates. This is prob-
lematic because in the literature, utilities for CRC
health states vary widely. For instance, mean utilities
for stage IV metastatic CRC range from 0.2410 to
810  MEDICAL DECISION MAKING/AUGUST 2014
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0.84.11 Some of this variation might be due to differ-
ent methods of obtaining utilities as direct elicitation
methods can give different utilities from indirect
methods for the same patient population.12,13 Like-
wise, different direct methods can yield different util-
ity weights. Previous meta-analyses conducted for
prostate cancer14 and HIV/AIDS15 demonstrated
that the TTO generates higher utilities than does the
SG and that the SG in turn elicits higher utilities
than does the VAS, a rating scale method.
Another source of variability in utility estimates
for health states describing the same stage of CRC is
the elapsed time between the elicitation of the utility
and the period of initial care. Ramsey and others11
reported a utility weight of 0.72 for patients with
stage I CRC 13 to 24 months after diagnosis; the
same patients had a utility weight of 0.90 at 37 to 60
months after diagnosis. A QoL study conducted on
patients undergoing open colon resection reported
a utility of 0.63 two weeks after surgery16; after 12
weeks, the same patients reported a mean utility of
0.88. The reason for these increases is likely an
improvement in health status as a patient recovers
with time after the health intervention. A systematic
review17 of utilities for osteoporosis-related conditions
indicated the importance of considering the time since
the occurrence of a fracture during the elicitation of
utility weights. In addition, time is an important com-
ponent in decision models that involve transitions
between disease states with QoL that changes over
time. Results of economic evaluations of health inter-
ventions could be flawed if utilities are obtained with-
out consideration of ‘‘time to or from initial care.’’
Although a growing number of QoL studies18–29
have obtained utility estimates for CRC from clinical
trials, to our knowledge, there is no systematic review
of studies of utility measurements for CRC-related
health states that considers factors affecting utilities.
Meta-analyses of QoL estimates have been conducted
for HIV/AIDS,15 stroke,30 and prostate,14 breast,31
and lung32 cancers. The objective of this study was
to perform a systematic review of the literature on
utility weights for CRC health states and to determine
the association of disease characteristics, timing, and
methodological variables on utility weight estimates.
METHODS
Search Strategy for Utility Values
We conducted a literature search using Medline
and EMBASE databases for the period from January
 META-ANALYSIS OF COLORECTAL CANCER UTILITIES
1980 to January 2013. Key word searches covered
CRC, colorectal neoplasm, colon, rectum, QoL, health
utility, and QALY. These were combined with terms
for EQ5D, HUI3, SG, and TTO (Appendix 1; available
online at http://mdm.sagepub.com/supplemental).
The search terms for QoL and CRC were adapted
from a technology appraisal report for CRC, commis-
sioned by the National Institute for Health and Care
Excellence.33 We included articles if they focused
on CRC (which could include colon cancer, rectal
cancer, or CRC) and used a standard method of utility
assessment (direct or indirect). We excluded studies
that were 1) not published in English, 2) not full-
length articles (e.g., abstracts or correspondence), or
3) not original research (e.g., comments, editorials,
case studies, methodological articles, or reviews).
Some utilities were excluded because they were based
on patients whose utilities had already been included
previously or because they were not for CRC. All
abstracts were reviewed, and references of all selected
and some potential articles were checked to identify
any additional studies of interest. Each article identi-
fied through the literature review was assessed by 2
reviewers (SD, KEB). After the independent reviews,
the results were discussed, and either a consensus
was reached for each selected article or a third
reviewer (GT) was consulted to achieve a selection
consensus. See Appendix 1 for the search strategy
and Appendix 2 for a summary of the study selection.
From each publication, we extracted the following
information about the characteristics of the study: 1)
author, journal, and year of publication; 2) country,
mean age, and sex distribution of the study partici-
pants; 3) number of respondents; and 4) the following
characteristics of the utilities: a) CRC site, b) disease
stage, c) utility measurement instrument, d) adminis-
tration method (self-report or interviewer), e) time to
or from initial care, and f) source. Initial care included
chemotherapy, surgery, radiotherapy, and other
health interventions. Surgery included total mesorec-
tal excision, transanal endoscopic microsurgery, lapa-
roscopic colon resection, open colon resection, low
colorectal anastomosis, and colonic-anal J-pouch.
We categorized utilities for ‘‘time to or from initial
care’’ by the period of care during which they were
derived: before surgery, up to 3 months after surgery,
3 months to 1 year after surgery, more than 1 year after
surgery, and time not indicated. When the same utili-
ties were reported more than once, for example, in the
same article or in more than 1 article (the same author
could report it twice in different articles), duplicate
data (identified by comparing the characteristics and
number of patients) were excluded.
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Only the variables in our 6-item list above were
reported consistently enough in the source studies
to be extracted as predictors of utility. One conse-
quence of this was that several studies,34–39 varying
in other characteristics, published multiple utilities
that shared the same combination of the 6 extracted
characteristics. For example, Shiroiwa and others34
had 21 self-reported mean SG utilities for scenarios
describing stage IV CRC at the 1-year time point, dif-
fering by adverse events, treatment, and presence of
a stoma. In other publications, repeated utilities in
the same group of respondents were mainly for differ-
ent health states due to side effects on adjuvant treat-
ment,35,37 different treatment strategies,38,39 and
prospective measurement of utilities during the
long-term follow-up.36 Our statistical model (see
below) handles repeated data on the same subject
group, but we were still concerned that studies with
10 to 20 utilities for what we considered the ‘‘same’’
combination of characteristics would be overrepre-
sented in the analysis. Since we had no access to indi-
vidual patient data and did not wish to implement
more complex modeling, relying on assumptions of
correlations between repeated data, we assessed the
impact of using multiple utilities for the same patient
group by treating the data in 2 different ways. For the
‘‘main’’ model, we aggregated all repeated data from
a patient group with identical values of the 6 predic-
tors to a single mean and standard deviation (SD),
with a sample size set equal to the size of the group.
We calculated a weighted mean and SD that
accounted for variability between reported mean util-
ities as well as the average reported SD. Where the
same patient group was reported as being different
sizes, due to attrition over time, for example, the
mean of reported sample sizes was used. This
approach sometimes led to utilities for quite diver-
gent groups of health states being combined and
a concomitant increase in the SD of the group. In
our ‘‘supplementary’’ model, we kept all utilities sep-
arate. The variability between repeated utilities
under the same set of characteristics enters into one
of the variance components of the model (see below).
The published QoL studies reported cancer pro-
gression in either a numerical or Dukes staging sys-
tem or did not report stage at all. In the tumor-node-
metastasis (TNM) numerical system, stage I describes
the situation in which cancer has spread from the
inner lining into the middle layers of the colon or rec-
tum wall, stage II is when cancer has spread outside
the colon or rectum to nearby tissues, stage III is
when cancer has spread outside the colon or rectum
to nearby lymph nodes, and stage IV is when cancer
811
 DJALALOV AND OTHERS
has spread outside the colon or rectum to another part
of the body. We created an ‘‘undefined stages’’ cate-
gory to include those studies not reporting the cancer
stage or those providing a range of stages that did not
fit into our categories of I to III and IV (e.g., stage II–
IV). We also added utilities from the studies staged
using the Dukes classification system to the ‘‘unde-
fined stages’’ category as there were only a few of
them (9 utilities or 2.6% of total) and all of them pre-
sented mixed A, B, C, and D stages. Studies that we
added to the ‘‘undefined stages’’ lumped people
with metastatic and nonmetastatic disease together,
and therefore, it was not possible to reclassify them
using the TNM staging system and strata that we
defined in the study (stage I–III v. stage IV).
We grouped the different ways of measuring utili-
ties (SG, TTO, EQ5D, VAS, and HUI3). Given that the
EQ5D and HUI3 are both indirect measures and that
few (6%) utilities used the HUI3, we grouped the
EQ5D and HUI3 utilities into 1 category. The TTO
was treated as the reference category.
For method of administration, we used elicitation
by an interviewer as the reference category and self-
report by the respondent as the comparator. The
Mayo Clinic defines colon cancer as cancer in the
large intestine (colon) and rectal cancer as cancer in
the last several inches of the colon and refers to
them together as CRC.40,41 Accordingly, we consid-
ered 3 sites for CRC as reported in the reviewed
articles, using colorectal as the reference and rectal
and colon as the comparators. ‘‘CRC’’ is a combination
of the 2 more specific locations of ‘‘rectal’’ and
‘‘colon.’’ For time to or from initial care, the longest
time period was treated as the reference. In a second-
ary analysis of the data set comprising only directly
elicited utilities, we examined whether there was
a difference between the reference category of the
patient’s own health and descriptive scenarios.
Statistical Analysis
For both the main and supplemental data sets, we
tabulated the number of utilities and the simple arith-
metic mean utility for each level of the following var-
iables: disease site, stage, time to or from initial care,
instrument, method of administration, and source.
To estimate the independent contributions of disease
characteristics, timing, and methodological variables
on the reported utility estimates, we used a linear
mixed-effects (LME) model. In our model, the depen-
dent variable was the reported utility, and the inde-
pendent variables were CRC site, disease stage, time
to or from initial care, scaling method, and method
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of administration. This LME model allowed for 3 lev-
els of random variation:
1) The variance of the observed values around the true
mean utilities within a study: These are treated as
known and equal to the square of the standard errors
of each mean utility.
2) The variance between true mean utilities within
a study: This is also called residual error and repre-
sents the unexplained variation between true utili-
ties within a study after fitting a model with the
independent variables listed above.
3) The variance between studies: This is the study ran-
dom effect and represents the remaining variation
between the true study means after fitting a model
with the independent variables listed above.
An LME model accounts for the clustering of utility
values that come from the same study. This is impor-
tant because utilities that are derived from the same
subjects within the same study may be correlated.
The inverse of the variance in level 1 above is used
to weight the utility and represents the relative influ-
ence of that utility in model estimation. Sums of these
weights within a study were used to quantify the
influence of an entire study.
We present the LME regression results as a table of
coefficients with confidence intervals (CIs) and P val-
ues. The intercept obtained from this model is the
mean utility estimate for a patient with all predictor
variables equal to the reference category. In this
case, the reference refers to a patient diagnosed
with stage I to III CRC in continuous care, more than
1 year after surgery, and interviewed using the TTO.
The coefficient for a category represents the differ-
ence between the mean utility for that category and
the reference category, with everything else held con-
stant (e.g., stage IV is associated with a utility weight
0.17 lower than stages I–III). To illustrate the overall
congruency of the model with the observed utilities,
we plot the fitted values from the model against the
observed values, with the area of the plotting symbol
inversely proportional to the variance of the observed
mean utility. A larger circle represents a mean utility
value with a smaller variance, which is either a result
from a larger sample, from reduced person-to-person
variation, or from some combination of the two.
We used Wald statistic F tests to assess the overall
statistical significance of multicategory predictors.
For significant multicategory variables, we computed
multiple-comparison adjusted t tests and 95% CIs for
all pairwise comparisons of categories. The main
model was also run in a data set excluding the
EQ5D and HUI3 data utilities so that we could
 META-ANALYSIS OF COLORECTAL CANCER UTILITIES
examine the influence of the source of the utilities
(e.g., whether they were for a patient’s own health
or a scenario). In this model, we also examined
whether the source of utilities had a consistent effect
across methods of administration. All analyses above
were performed using R 3.0,42 and P values \0.05
were taken to indicate statistical significance.
The LME model estimates the mean utility as
a weighted sum of the predictor variables in which
the weights are the estimated fixed-effects regression
coefficients. This linear (identity) link connecting
mean utilities to the predictor variables and random
effects has 2 possible consequences for model mis-
specification. First, fitted values for utilities are not
restricted to lie in the range of 0 to 1, and secondly,
the effects of predictors are assumed to be additive
and constant at all underlying levels of utility. To
assess the robustness of our overall findings to these
2 issues, we refitted the model described above
with a logit link replacing the identity link. The
model was most easily specified and fitted using
a Bayesian approach in JAGS.43 Details of this model
are presented in Appendix 3.
RESULTS
Systematic Search
A broad search of the literature produced a total of
1464 studies. After screening the abstracts, we
selected 149 potentially relevant articles. The major-
ity of the articles focused on measuring QoL in gen-
eral and did not report utilities. Only 26 articles
reported utility values and met all of the other inclu-
sion criteria, and these were retained for the analysis.
The median number of utility values reported in each
article was 6 (interquartile range = 4–17). A total of
351 utility values were collected from 6546 respond-
ers; for the main model, these were aggregated to pro-
duce 157 utilities.
Study Characteristics
Just under a half (48%) of the 351 utilities were for
rectal cancer, about one third (37%) were for CRC
(colon and rectal cancers combined), and 15% were
for colon cancer (Table 1). Only 10% of the reported
utilities included radiotherapy and chemotherapy
in addition to surgery. Twenty-nine percent of the
utilities were for the advanced stage IV, 18% were
stages I to III, and 53% were ‘‘undefined stages.’’
Approximately 74% of the utilities were for the
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patients’ own health, and the remainder were from
descriptive scenarios of health states. The most fre-
quently used instrument was the TTO, used to derive
46% of the utilities. Patient populations were mainly
from Western Europe (9 studies) and North America
(5 studies). Three studies were from the United King-
dom and Australia, 2 were from Japan and South
Africa, and 1 was an international multicenter study.
Most of the participants were middle aged and older
(mean age = 62 years), with slightly more males (57%)
than females. A significant proportion of the utilities
(36%) were elicited more than 1 year after surgery,
and only 4.5% were from before surgery.
LME Model for CRC Utilities
The results of the main model with n = 157 utilities
are shown in Table 2. The estimated utility for the ref-
erence case was 0.90 (95% CI = 0.80–0.99). Overall,
the effect of time to or from initial care was statisti-
cally significant (P = 0.021); utilities measured 3
months after surgery (–0.05; P = 0.008) were signifi-
cantly lower than utilities measured more than 1
year after surgery. Utilities for stage IV were 0.19
lower than for stages I to III (P \ 0.001). Utilities
from the SG were lower than those from the TTO (–
0.13; P = 0.022), and overall, there was significant var-
iability in mean utilities according to the measure-
ment instrument (P = 0.005) (Table 2). Figure 1
shows the 95% CIs for all pairwise comparisons
between categories for the variables of stage, cancer
site, and measurement instrument.
The results of the supplementary model with 351
utilities featured some differences when compared to
the main model (Table 2). The group of variables repre-
senting time to or from initial care was not statistically
significant. The measurement instrument was signifi-
cant in both models, but the findings for individual
instruments were inconsistent. The supplementary
model confirmed the main model results in which
the EQ5D/HUI3 is associated with higher utilities.
Exploratory analysis with only the directly elicited
utilities (i.e., without the EQ5D/HUI3) to examine the
effect of utility source (own health or scenarios)
showed that utilities for scenarios were 0.21 lower
than those for own health (95% CI = –0.31 to –0.10;
P = 0.001). The effects of time and stage were signifi-
cant and consistent in size with those in our main
model, but the differences between instruments
were smaller (results not shown).
Overall, the findings of the Bayesian logit-based
model were consistent with those of our linear mod-
els. The largest effects in the Bayesian model were
813
 DJALALOV AND OTHERS

Table 1 Study Characteristics

Main Model (Utilities: n = 157) Supplemental Model (Utilities: n = 351)

n (%) Mean n (%) Mean

CRC site
Colon 24 (15) 0.70 56 (16) 0.69
Rectal 76 (48) 0.80 112 (32) 0.79
Colorectal 57 (37) 0.73 183 (52) 0.67
Disease stage
Stage I–III 29 (18) 0.74 103 (29) 0.75
Stage IV 45 (29) 0.68 158 (45) 0.63
Undefined stagesa 83 (53) 0.80 90 (26) 0.80
Time to or from initial care
Before surgery 7 (4) 0.74 7 (2) 0.74
3 mo after surgery 37 (24) 0.77 87 (25) 0.77
1 y after surgery 47 (30) 0.73 149 (43) 0.63
.1 y after surgery 56 (36) 0.77 96 (27) 0.77
Not indicated 10 (6) 0.77 12 (3) 0.79
Utility measurement instrument
SG 11 (7) 0.56 39 (11) 0.51
TTO 72 (46) 0.79 166 (47) 0.72
EQ5D 33 (21) 0.76 66 (19) 0.75
HUI3 9 (6) 0.83 21 (6) 0.85
VAS 32 (20) 0.70 59 (17) 0.71
Administration
Interviewer 34 (22) 0.73 112 (32) 0.77
Self-report 123 (78) 0.76 239 (68) 0.68
Source
Own health 85 (74) 0.79 106 (40) 0.78
Scenario 30 (26) 0.63 158 (60) 0.63
Note: EQ5D = EuroQol 5 Dimensions; HUI3 = Health Utilities Index 3; SG = standard gamble; TTO = time tradeoff; VAS = visual analog scale.
a. Undefined stages include studies in which stages were not stated and combined Dukes stages.

seen for the variables and specific pairwise compari-
sons that were significant in the linear models. Nota-
bly, when we ran both the linear models and the logit
models using Bayesian methods, the fit of the logit
model was always better than the fit of the corre-
sponding linear model. However, interpretation of
the logit model is more difficult. For example, the
parameter for the SG versus the TTO is –0.64. To
understand how this affects mean utilities, consider
2 situations: 1) a situation with a mean TTO utility
of 0.5 and 2) a situation with a TTO utility of 0.8. In
case 1, the logit utility is log(0.5/0.5) = 0, and the pre-
dicted logit if the SG had been used is –0.64. The pre-
dicted mean utility is exp(–0.64)/(1 1 exp(–0.64)) =
0.35. In case 2, the logit utility is log(0.8/0.2) = 1.39,
and the predicted logit if the SG had been used is
0.75. The predicted mean utility is exp(0.75)/(1 1
exp(0.75)) = 0.67. Appendix 3 presents detailed
results from this model.
Figure 2 shows that the LME model fits reasonably
well except for overestimation of the lowest utilities.
None of the predicted utilities was outside the range
of 0 to 1. The squared correlation (akin to R2) between
the fitted values and the observed utilities was 0.80.
DISCUSSION
Our literature search found no previously con-
ducted systematic reviews or meta-analyses on CRC
utilities. To fill this need, we conducted this study
to compute pooled utility estimates from published
studies of CRC health state utilities. Our study esti-
mated a utility of 0.90 for a patient diagnosed with
stage I to III CRC, more than 1 year after surgery,
and interviewed using the TTO. We found that the
effect of time to or from initial care (mainly surgery)
on QoL was statistically significant. For instance,
a sharp decline was evident immediately after sur-
gery with gradual improvement as time passed,
which is in agreement with the assumption that
‘‘time to or from initial care’’ matters. Our results

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 Table 2 Linear Mixed-Effects Model for Utilities

Main Model (Utilities: n = 157) Supplemental Model (Utilities: n = 351)

Coefficient P Value Coefficient P Value
Estimate P Value 95% CI (Entire Variable) Estimate P Value 95% CI (Entire Variable)

Intercept 0.90 \0.001 0.80 to 0.99 \0.001 0.85 \0.001 0.76 to 0.95
Site
Colorectal Reference
Colon 0.04 0.411 –0.05 to 0.12 0.290 0.03 0.549 –0.07 to 0.13 0.534
Rectal –0.04 0.380 –0.11 to 0.04 –0.03 0.504 –0.12 to 0.06
Time to or from initial care
.1 y after surgery Reference
Before surgery –0.07 0.059 –0.15 to 0.01 0.021 –0.07 0.137 –0.15 to 0.02 0.134
3 mo after surgery –0.05 0.008 –0.09 to –0.01 –0.05 0.020 –0.09 to –0.01
1 y after surgery –0.01 0.509 –0.05 to 0.03 –0.02 0.295 –0.06 to 0.02
Not indicated –0.09 0.038 –0.18 to –0.01 –0.08 0.157 –0.19 to 0.03
Stage
Stage I–III Reference
Stage IV –0.19 \0.001 –0.25 to –0.14 \0.001 –0.20 \0.001 –0.24 to –0.15 \0.001
Mixed stages –0.06 0.202 –0.15 to 0.03 –0.06 0.233 –0.17 to 0.04
Instrument
TTO Reference
EQ5D/HUI3 0.02 0.451 –0.04 to 0.09 0.005 0.10 0.005 0.03 to 0.16 0.043
SG –0.13 0.022 –0.23 to –0.02 –0.01 0.694 –0.06 to 0.04

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VAS –0.03 0.230 –0.09 to 0.02 0.05 0.063 –0.01 to 0.10
Method of administration
Interviewer Reference
Self-report –0.03 0.537 –0.128 to 0.069 0.537 –0.05 0.373 –0.16 to 0.06
Note: EQ5D = EuroQol 5 Dimensions; HUI3 = Health Utilities Index 3; SG = standard gamble; TTO = time tradeoff; VAS = visual analog scale.

815
 DJALALOV AND OTHERS
Figure 1 Pairwise comparisons of stage, type of cancer, and utility
measurement instrument.
also showed that the before surgery and 3 months
after surgery ‘‘time’’ points were significant predic-
tors of utilities. This indicates the importance of strat-
ifying patients according to the time to or from initial
care when eliciting utilities to use in economic eval-
uations since time appears to be a surrogate marker of
the health state. This is important for Markov models
with longer cycle lengths or shorter time horizons
because they might miss this distinction. We found
that patients with CRC rate their own health signifi-
cantly higher than nonpatients rate scenarios of the
same health state. This trend may be explained by
patients’ adaptation to their health states. This find-
ing is in line with those of other meta-analyses con-
ducted for prostate cancer14,15 and HIV/AIDS. We
also found that self-administered utility elicitation
yields different utilities from interviewer-administered
elicitation, in particular when estimating scenar-
ios.44,45 We found no difference in QoL between
816  MEDICAL DECISION MAKING/AUGUST 2014
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Figure 2 The observed versus fitted utility values for the linear
mixed-effects base model. The diagonal line indicates equal
observed and fitted values. The areas of the plotted circles repre-
sent the study sample size. The squared correlation value is 0.80.
patients with colorectal, colon, and rectal cancers.
Our findings provide evidence supporting the
important effect of stage on QoL. We found that util-
ities for patients with stage IV cancer (usually with
metastasis) were 0.19 lower than for patients with
stage I to III cancer (Table 2). These results confirm
that QoL impairment due to stage is clinically signif-
icant and recognizably different.
We used a different approach to the grouping of
utility elicitation methods than previous utility
meta-analyses.15 We grouped 2 indirect methods
(EQ5D and HUI3) since use of the HUI3 was rare,
and we used the direct TTO method as the reference
category. The methods of the VAS and SG were kept
as separate categories, given how frequently they
were employed in our data. The indirect methods
yielded differences that were not statistically signifi-
cant from the direct TTO method in the main model.
The SG ratings were the lowest in both main and
supplementary models. This result is inconsistent
with the findings of meta-analyses of utilities for
HIV/AIDS, prostate cancer, and other studies. The
majority of utilities in our study were derived from
patients with CRC who rated their own health, and
patients usually rate their own health higher than
patients without CRC would rate descriptions of sim-
ilar health states, as noted above.
Our model offers a tool to adjust utilities for con-
textual influences. For instance, if 2 QoL studies in
similar patient populations were measured at
 META-ANALYSIS OF COLORECTAL CANCER UTILITIES
different times, for example, 3 months after surgery
and more than 1 year after surgery, our regression
results indicate that the utility estimates obtained at
3 months would be 0.05 lower than those more than
1 year after surgery. Consequently, an ICER based on
utilities at 3 months could be 50% lower than an
ICER based on utilities more than 1 year after surgery.1
There are limitations in our analysis. We did not
categorize the health states by symptom type and
severity due to the lack of symptom information in
the publications. However, we used cancer stage in
our analysis to reflect disease severity. We assume that
time matters because it reflects transition between
health states. Published utilities were presented in 2
staging systems: numerical and Dukes. We used an
undefined stages variable to represent combined numer-
ical and Dukes stages; studies in which stages were not
indicated were also included with this indicator vari-
able. The effect of the undefined stages variable was
not statistically significant. We combined the EQ5D
and HUI3 as indirect measures because very few utilities
were obtained using the HUI3. We did not include
demographic variables such as sex, race, education, or
socioeconomic status of the respondents in our model
as these data were inaccessible from the reported results
that we used for our analysis. Our supplemental model
results are influenced by two studies, van den Brink and
others23 and Shiroiwa and others,34 that together pro-
vided 28% of all observed utilities and represented
patients with rectal cancer and CRC at mixed and
advanced stages who rated their own health and scenar-
ios using the EQ5D and SG, respectively.
There are a number of areas in which further
research is required. More standardization in the
reporting of study results is required in terms of com-
mon terminologies for stage, time periods, times of
care, and patient groups. Given our results, future
meta-analyses and systematic reviews on utilities
should take method of administration and sources of
utilities into account. More research is needed to study
why ‘‘similar’’ patients appear to report different QoL
utility weights. The prevalence of CRC is increasing as
life expectancy increases and treatment outcomes
improve. However, surveillance and terminal care
health state data are quite limited. Further QoL
research to derive robust utility estimates for use in
economic evaluations is needed.
CONCLUSIONS
With limited resources to treat cancer, the second
leading cause of mortality in the world, careful
REVIEW
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consideration of the costs and effectiveness of new
treatment options is required; QoL, measured with
utility weights, is an important consideration in the
effectiveness and cost-effectiveness of treatments.
The present study provides estimates for the effects
of patient and disease characteristics on CRC utili-
ties. Variations in utility are also associated with fac-
tors such as method of administration and utility
instrument. Our research suggests that cost-effective-
ness analyses could possibly reach different conclu-
sions based on utilities derived from different
studies. Our pooled utility estimates based on a com-
prehensive review of the published literature can be
used by analysts to assess the impact of systematic
differences on utility values.
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