Aliment Pharmacol Ther 2004; 19: 907–915.
doi: 10.1111/j.1365-2036.2004.01916.x
Costs and efficacy of three different esomeprazole treatment
strategies for long-term management of gastro-oesophageal
reflux symptoms in primary care
V. MEINECHE-SCHM IDT*, H . HAUSCHILD T JUHL , J. E. ØSTERG AARD*, A. LUCK OW*
& A. HVENEGA ARD 3,4 *General practice, Klampenborg, Lyngby and Herning, Denmark; Danish Institute for Health Services Research, Copenhagen,
Denmark
Accepted for publication 29 January 2004
SUMMARY
Background: A prospective, open, randomized multicentre study with parallel group design was conducted
in 155 general practice clinics, and included 1357
endoscopically uninvestigated patients with symptoms
suggestive of gastro-oesophageal reflux disease.
Aim: To assess the differences in direct medical costs
between a patient-controlled on-demand treatment strategy with esomeprazole, 20 mg daily, and general practitioner-controlled intermittent treatment strategies with
esomeprazole, 40 mg daily, for either 2 or 4 weeks.
Secondary objectives were to measure other costs, total
costs, patient satisfaction and time to first relapse.
Methods: The primary cost analysis was carried out as a
cost minimization analysis, comparing the direct medical costs in patients allocated to on-demand treatment
INTRODUCTION
Gastro-oesophageal reflux disease (GERD) is a common
disease, and the predominant symptom, heartburn,
affects 20–40% of adults.1, 2 Studies have demonstrated
that 35–50% of patients with reflux symptoms have
normal endoscopy.3 Furthermore, the health-related
2 Correspondence to: Dr V. Meineche-Schmidt, Christiansholmsvej 5, DK2930 Klampenborg, Denmark.
E-mail: [email protected]
Ó 2004 Blackwell Publishing Ltd
vs. those in patients allocated to either of the intermittent treatment strategies.
Results: The mean direct medical costs were 182, 221
and 195 euros for patient-controlled on-demand treatment and 2 weeks and 4 weeks of general practitioner-controlled intermittent treatment, respectively,
showing no statistically significant difference. The
comparable mean total costs were 211, 344 and
300 euros, i.e. significantly lower for patients treated
on-demand compared with either of the general
practitioner-controlled intermittent treatment strategies.
Conclusions: The mean total costs, but not the mean
direct medical costs, were higher in general practitioner-controlled intermittent treatment strategies with
esomeprazole compared with a patient-controlled ondemand treatment strategy.
quality of life is equally impaired in GERD patients with
or without oesophagitis.4
The lack of correlation with mucosal lesions makes
empirical treatment relevant. An evidence-based
appraisal of reflux disease management – the Genval
Workshop Report – identified proton pump inhibitors as
the most effective initial and long-term therapy in GERD
patients, and recommended that proton pump inhibitors
should be first-line therapy for the management of
GERD.5 Different maintenance therapies have been
suggested: daily low-dose proton pump inhibitor,
907
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V. MEINECHE-SCHMIDT et al.
on-demand use of proton pump inhibitor or intermittent
treatment courses.6
Qualitative research has suggested that there is
considerable scope for encouraging patients to
self-regulate with proton pump inhibitors, and that
many patients would be willing to do this if the strategy
was sanctioned by their general practitioner (GP). A
decrease in proton pump inhibitor prescriptions and
costs has been reported to be associated with patientcontrolled treatment strategies.7 The aim of the present
study was to provide quantitative evidence to test this
hypothesis.
Furthermore, the relapsing nature of GERD calls for an
economic evaluation of the long-term management
from a societal perspective, including both direct and
indirect costs.8, 9
MATERIALS AND METHODS
Study design
The study was carried out as a prospective, open,
randomized, multi-centre trial with a parallel group
design. Minimal interference during the study period
was secured in order to emulate the ‘real-life’ situation
as closely as possible within a randomized controlled
6 trial. Local ethics committees approved the trial and
written informed consent was obtained from all participating patients.
One hundred and fifty-five general practice clinics took
part, and 1583 male and female patients aged
> 18 years with symptoms suggestive of GERD (heartburn as the predominant symptom with or without acid
regurgitation) for 3 days or more during the 7 days
prior to inclusion were enrolled.
Patients were not included in the study if any
significant ‘alarm symptoms’ (unintentional weight
loss, gastrointestinal bleeding, jaundice or any other
sign indicating serious or malignant disease) were
present, if they had a known history of complications
of GERD (Barrett’s oesophagus, oesophageal stricture,
ulcer or significant dysplastic changes in the oesophagus), if they had a history of oesophageal, gastric or
duodenal surgery (except for simple closure of an ulcer),
if they had symptoms that, in the opinion of the
investigator, were likely to be due to irritable bowel
syndrome, or if they fulfilled two or more of the
following criteria: (i) symptoms relieved by defecation;
(ii) symptoms associated with a change in the frequency
of stools; or (iii) symptoms associated with a change in
the form of stools. Additional exclusion criteria were:
pregnancy; Zollinger–Ellison syndrome; primary oesophageal motility disorders (achalasia, scleroderma or
primary oesophageal spasm); gastric or duodenal
ulcers within the last 3 months; malabsorption; malignancy or other concomitant disease with a poor
prognosis or which may interfere with the assessments
in the study; unstable diabetes mellitus; cerebrovascular disease; continuous concurrent therapy with diaze7 pam, phenytoin or warfarin; need for translator;
alcohol and/or drug abuse or any other condition
associated with poor compliance, including expected
non-co-operation, as judged by the investigator; previous participation in a study; or any contraindications
to esomeprazole.
The study consisted of a 4-week symptom control
phase followed by a 6-month management strategy
phase.
All patients received esomeprazole 40 mg once daily
for 4 weeks during the symptom control phase, and
those who were symptom free (defined as no more than
1 day with mild symptoms of GERD, i.e. heartburn with
or without acid regurgitation, during the previous
7 days) were randomized to 6 months of treatment
with one of the following regimens: esomeprazole,
20 mg daily, on demand, or intermittent treatment
courses with esomeprazole, 40 mg daily, for 2 weeks or
4 weeks. Randomization was performed for each centre
in equal proportions to the three treatment arms by a
computer-generated list of patient numbers and corresponding drug packs. All patients were allocated the
lowest number available.
The 4-week symptom control phase began at week
) 4 (visit 1) and the follow-up phase began at week 0
(visit 2); the study ended at week 26 (completion visit).
At visit 1, the patients’ medical and surgical history
was taken, a physical examination was performed,
symptoms were assessed and patients were given
esomeprazole 40 mg in the morning for 4 weeks. At
visit 2, patients’ symptoms and satisfaction with the
study treatment and health economic variables
(resource utilization) were assessed. Adverse events
were recorded.
After randomization, patients were instructed to
contact (visit) their GP if they experienced symptom
relapse. In such situations, the patients in the
on-demand arm and in the 4-week intermittent
arm were given a 4-week treatment course with
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ESOMEPRAZOLE MANAGEMENT OF GERD SYMPTOMS
esomeprazole, 40 mg daily, and the patients in the
2-week intermittent arm were given this treatment for
2 weeks. If symptom free at the end of this treatment
course, the patients continued the long-term treatment
to which they had originally been allocated. Several
relapses and treatment courses were possible during
the study period if the symptoms re-occurred after
successful treatment. Patients with persisting symptoms after a treatment course remained in the study,
but were treated at the discretion of the investigator.
Patients who left the study prematurely at any time
after randomization were followed with regard to
resource utilization (costs) for the remainder of the
6 months of follow-up.
The patients were instructed to enter data into a diary
each month regarding contacts with other health care
providers, hospitalizations, purchased over-the-counter
medication and absence from work. The patients
received new diaries every second month. After
26 weeks (6 months), the patients visited the general
practice clinic for a completion visit (visit 3), where
health care economic variables and satisfaction with the
treatment were assessed. In the follow-up phase,
unscheduled health care contacts were guided by the
patient’s need for a change in therapy or for medical
consultation. If unscheduled visits occurred, the same
variables were assessed.
8 The study design is given in Figure 1.
Figure 1. Study design. GERD, gastro-oesophageal reflux disease.
Ó 2004 Blackwell Publishing Ltd, Aliment Pharmacol Ther 19, 907–915
909
Study objectives
The primary objective of this study was to assess the
difference in direct medical costs between three treatment strategies with esomeprazole: (i) patient-controlled
on-demand treatment with esomeprazole, 20 mg daily;
(ii) GP-controlled intermittent 2-week courses with
esomeprazole, 40 mg daily, in case of symptom relapse;
(iii) GP-controlled intermittent 4-week courses with
esomeprazole, 40 mg daily, in case of symptom relapse.
The assessment was made by comparing on-demand
treatment with intermittent treatment for 2 weeks and
4 weeks.
Secondary objectives were to measure and compare
other costs (transportation costs and indirect costs) and
total costs (the sum of direct medical costs and other
costs) during the 6-month follow-up period. Other
secondary objectives were to measure patient satisfaction with the different treatment strategies and to assess
the time to first relapse.
Data collection
Data on resource utilization were collected in the case
report forms filled in by the GP during the study period
and were limited to GERD disease.
Direct medical costs included study medication, other
prescribed or over-the-counter medication, unsched-
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V. MEINECHE-SCHMIDT et al.
uled health care contacts, tests, procedures and
hospitalizations. Direct non-medical costs included
transportation costs, and indirect costs included costs
due to time spent travelling to and attending health
care visits (leisure time and/or working hours) and
absence from work because of GERD (‘sick days’). All
costs in the period after randomization were included
in the calculations; however, costs due to visit 3 were
excluded if the visit was performed only to fulfil the
study protocol.
Data on medication use, contacts with health care
providers and information about absence from work
were collected using a combination of patient diaries
and interview carried out by the GPs. Data on
hospitalizations (diagnosis and procedure codes) were
obtained from discharge letters. GERD symptoms (heartburn, acid regurgitation) were assessed at each visit as
none, mild, moderate or severe, and the frequency of
heartburn was assessed as the number of days with
episodes during the last week. Patient satisfaction with
treatment was assessed at visits 2 and 3 (or at the
discontinuation visit if the patient was withdrawn from
the study). The patient was handed a sheet of paper and
asked to tick the answer that best described the degree
of satisfaction: completely satisfied, very satisfied, quite
satisfied, satisfied, dissatisfied, very dissatisfied or completely dissatisfied.
The time to first relapse was defined as the number of
days from visit 2 until the first GERD-related consultation at the GP’s surgery.
Statistical methods
The sample size was set in order to achieve a test power
of 80% if the true difference in direct medical costs
between two treatment regimens was 27 euros [Danish
kroner (DKK) 200]. The sample size calculation was
based on a Monte Carlo simulation with 30 000
patients for each treatment strategy providing estimates
of standard deviations of direct medical costs.
Standard parametric testing methods were not applicable for the comparison of direct medical costs, other
costs (non-medical direct costs and indirect costs) and
total costs because the data were incompatible with
Gaussian models. Bootstrapping was conducted using
1000 replications of the mean difference between the
two groups. P values were estimated on the basis of
the distributions of bootstrapped mean differences and
2.5 and 97.5 percentiles were calculated. The Kolmog-
orov–Smirnov test was used to test for normality. All
statistical tests were two-sided with a 5% level of
significance. Intention-to-treat was applied as the
primary analysis.
The time to first relapse was compared using survival
analysis and the log-rank test. Fisher’s exact test was
used to analyse patient satisfaction.
Cost analysis
The primary cost analysis was a cost minimization
analysis, comparing the total direct medical costs
assessed for patients allocated to the on-demand
maintenance strategy with those for patients allocated
to the intermittent treatment strategy for 2 weeks, on
the one hand, and with those for patients allocated to
the intermittent treatment strategy for 4 weeks, on the
other, over a 6-month follow-up period. The choice of a
cost minimization analysis was based on the hypothesis
that the differences in clinical outcomes between the
treatment strategies would not be significant.
The perspective for the assessment of costs in this study
was societal, i.e. unit costs were assigned to the
resources irrespective of who bore the cost. Therefore,
unit costs should ideally reflect the real (or opportunity)
costs rather than tariffs. However, real costs were not
available and therefore different tariffs were used as the
best available approximation. The cost of a contact or
visit to a health care provider and the costs of tests or
procedures in primary care were based on 2001 tariffs
from the Danish National Security Scheme.10 The costs
of tests and procedures carried out in the hospital sector
(out-patient clinics) were based on 2001 tariffs from the
Ministry of Health.11
The costs of hospitalizations were derived from Diagnosis Related Groups (DRG) scales, which means that
the costs were calculated per admission, depending on
the reason for admission and the main discharge
diagnosis. Nord-DRG version 1.7 was used to group
the patients, and Danish 2001 tariffs were applied.11 In
the economic analysis, only GERD-related admissions
were assessed. All discharge letters from hospital
contacts were reviewed by one of the authors (VM-S)
and an external expert gastroenterologist in order to
assess whether an admission was GERD related. The
reviewers were unaware of the allocation of the patients
to the study arms.
For patients allocated to the on-demand treatment
arm, the cost of study medication was based on actual
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ESOMEPRAZOLE MANAGEMENT OF GERD SYMPTOMS
use and on the cheapest commercially available packages. For patients allocated to the intermittent treatment arms, the cost of a course was based on the cost of
medication for a whole course, i.e. it was assumed that
the patient took esomeprazole each day for 2 or
4 weeks, whether or not the number of days on
medication exceeded the study period.
The cost of other prescribed medication was also based
on actual use and on the cheapest available packages.
The cost of over-the-counter medication was based on
the amount bought during the study period. Over-thecounter medication bought before the study period was
not included, although some of it may have been used
during the study period. Over-the-counter medication
bought at the end of the study period was included,
although some of it was probably used after the study
period. It was assumed that the randomization and the
relatively large sample size counterbalanced these
uncertainties.
With regard to other costs, the cost calculations were
based on the mode of transportation and distance
covered. Unit costs were derived from railway schedules
for public transport, national taxi fares per kilometre
and tables of allowances per kilometre for private car, as
published by the national taxation offices. The cost of
workdays lost due to GERD was calculated as lost
wages, based on average national wages [Danmarks
Statistik (Statistics Denmark)].
All costs were initially calculated in DKK. The
exchange rate to euros was 1 euro ¼ 7.44 DKK (the
average for 2001 from the National Bank of
Denmark).
RESULTS
A total of 1583 patients were enrolled in the 4-week
symptom control phase and 1396 patients were randomized into the following management study (107 did
not meet the randomization criteria, 46 experienced
adverse events, 15 were lost to follow-up and 19 were
excluded for other reasons). A total of 39 patients
were excluded during the management period for not
meeting the inclusion or exclusion criteria, leaving
1357 patients for the intention-to-treat analysis.
Baseline data were well balanced between the study
arms (Table 1). The mean age of the included patients
was 53 years and equal numbers of men and women
were included. Most of the patients reported moderate
symptoms in the week prior to inclusion.
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911
Costs
The mean direct medical costs were 182, 221 and
195 euros in the on-demand treatment group, intermittent 2-week treatment group and intermittent
4-week treatment group, respectively (Table 2). The
difference in mean direct medical cost between the
on-demand and 2-week intermittent treatment groups
was ) 39 euros [95% confidence interval (CI), ) 107 to
13; P ¼ 0.19], between the on-demand and 4-week
intermittent treatment groups was ) 12 euros (95% CI,
) 44 to 20; P ¼ 0.44) and between the 2-week and
4-week intermittent treatment groups was 26 euros
(95% CI, ) 31 to 100; P ¼ 0.48).
When the total costs were compared, the respective
figures were 211, 344 and 300 euros (Table 2) The
difference in mean total cost between the on-demand
and 2-week intermittent treatment groups was
) 132 euros (95% CI, ) 224 to ) 55; P < 0.001),
between the on-demand and 4-week intermittent
treatment groups was ) 91 euros (95% CI, ) 162 to
) 30; P ¼ 0.002) and between the 2-week and 4-week
intermittent treatment groups was 43 euros (95% CI,
) 44 to 135; P ¼ 0.48).
As shown in Figure 2, the costs for study medication
contributed the most to the direct medical costs in all
treatment strategies.
Clinical outcomes
After the 4-week symptom control phase, 92% of the
included patients were symptom free. Overall, 79% and
78% of the patients in the 2-week and 4-week
intermittent treatment arms experienced one or more
symptomatic relapses leading to GP contact during
6 months, and half of the relapses occurred within
2 weeks after randomization. The average numbers of
relapses (s.d.) were 0.13 (0.49) in the on-demand arm,
2.82 (2.83) in the 2-week intermittent treatment arm
and 2.08 (1.75) in the 4-week intermittent treatment
arm.
In contrast, only 8% of patients in the on-demand arm
needed to consult their GP during the 6 months of
observation (data not shown).
Most patients were satisfied with their management
at the end of the study (96%, 96% and 97% in the
on-demand arm, 2-week intermittent treatment arm
and 4-week intermittent treatment arm, respectively,
with no significant differences between the arms). In
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V. MEINECHE-SCHMIDT et al.
Variable
Mean age (s.d.) (years)
Females (%)
Heartburn last week (%)
Mild
Moderate
Severe
Epigastric pain last week (%)
None
Mild
Moderate
Severe
Regurgitation last week (%)
None
Mild
Moderate
Severe
Employment (%)
Paid
Sick pens.
Retired
Unemployed
Student
Housekeeper
Transportation (%)
Public
Private car
Taxi
Bicycle
Walking
Other
Total time (including transport)
for visit [mean hours and (s.d.)]
Cost
Direct medical costs
Physician contacts
Tests and procedures
Study medication
GERD medication, prescribed
GERD medication, OTC
Hospitalization
Total direct medical costs
Direct non-medical costs
Transportation costs
Indirect costs
Costs for travel and visit time
Costs for workdays lost
Total costs
On-demand
treatment
(n ¼ 453)
Intermittent
course (2 weeks)
(n ¼ 449)
Intermittent
course (4 weeks)
(n ¼ 455)
52 (15)
47
53 (14)
50
53 (15)
54
10
68
22
10
68
22
10
68
22
21
23
45
11
22
24
44
10
17
24
46
13
14
26
47
12
14
27
46
13
16
25
45
14
53
8
30
4
2
3
54
10
26
5
2
2
53
10
30
4
1
3
12
68
1
10
9
0
9
65
1
8
16
1
13
65
2
7
13
0
1.1 (0.4)
1.1 (0.3)
1.2 (0.4)
On-demand
treatment
(n ¼ 453)
Intermittent
course (2 weeks)
(n ¼ 449)
Intermittent
course (4 weeks)
(n ¼ 455)
10.2
5.7
143.7
6.5
0.9
14.7
181.7
52.2
8.1
87.4
20.6
2.6
49.9
220.6
38.4
9.0
120.0
10.5
1.5
15.5
194.9
(38.4)
(37.6)
(78.9)
(29.8)
(4.0)
(162.4)
(230.6)
(58.6)
(38.2)
(88.2)
(72.0)
(7.7)
(625.9)
(678.8)
Table 1. Baseline characteristics
Table 2. Direct medical costs, direct nonmedical costs and indirect costs per patient
in euros excluding VAT. Mean values and
(s.d.); intention-to-treat analysis
(42.7)
(59.0)
(101.3)
(36.7)
(4.6)
(166.1)
(266.1)
1.7 (7.1)
12.2 (28.8)
10.1 (20.0)
6.9 (22.8)
21.0 (171.1)
211.4 (348.1)
49.9 (58.7)
61.2 (337.9)
344.0 (824.7)
36.3 (37.8)
59.0 (490.6)
300.4 (574.3)
GERD, gastro-oesophageal reflux disease; OTC, over-the-counter.
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ESOMEPRAZOLE MANAGEMENT OF GERD SYMPTOMS
Figure 2. Direct medical costs in euros. GERD, gastro-oesophageal
reflux disease; OTC, over-the-counter.
the on-demand treatment arm, 80% of the patients
were ‘very satisfied’, compared with 74% in the
2-week intermittent treatment arm and 84% in the
4-week intermittent treatment arm; thus, significantly
more patients in the 4-week than in the 2-week
intermittent treatment arm were ‘very satisfied’ (data
not shown).
DISCUSSION
Proton pump inhibitors have been shown to be effective
in the treatment of GERD and a ‘step down’ approach
has been suggested as the preferred treatment for
symptomatic patients.5 However, patients with GERD
suffer from chronic relapsing disease and, accordingly,
long-term management strategies are important, both
economically as well as clinically.
9 Wahlqvist et al. compared three strategies for the
treatment of patients with endoscopy-negative GERD:
on-demand treatment, intermittent courses and continuous treatment following first relapse.12 The study
used a simple Markov model to compare the cost
effectiveness, and demonstrated considerably lower
direct medical costs for on-demand treatment compared
with any of the other treatments. However, the study
was not comparable with the present investigation:
esomeprazole, 20 mg, on demand was compared with
omeprazole, 20 mg daily, for 4 weeks (intermittent
courses) and omeprazole, 20 mg daily, as continuous
treatment, and the patients were referred for endoscopy.
Patients with diseases of a relapsing nature have the
opportunity to adapt their treatment individually. It has
been shown that, in spite of the way in which proton
pump inhibitors are prescribed, most patients ‘design’
Ó 2004 Blackwell Publishing Ltd, Aliment Pharmacol Ther 19, 907–915
913
their own treatment over time,13 which probably
reflects the fact that they do not want to use ‘expensive’
drugs once symptoms have been controlled.
The relapsing nature of the disease raises the question
as to what extent the GP should monitor the condition
over time. On the one hand, the prescription of
intermittent treatment courses will allow the GP to
interview patients about the development of sinister
symptoms and refer them for endoscopy if needed. On
the other hand, patients may wonder why they have to
consult their GP for the same problems over and over
again, and why they are prescribed medication for
several weeks, when they know by experience that their
symptoms can be controlled within days.
This study was designed to emulate ‘real-life’ treatment as closely as possible within a clinical trial.
However, several deviations from ‘real life’ in this study
must be admitted: (i) patients were allocated to different
treatments with esomeprazole and comparison with
other treatments (lifestyle, H2-blockers, antacids) was
not addressed; (ii) patients did not have to pay for the
study medication, which may have resulted in a greater
use of medication than in a ‘real-life’ situation; (iii) the
study protocol mandated contacts and visits that may
not have occurred in ‘real life’, as patients on long-term
treatment for GERD might obtain prescriptions by
telephone; (iv) the study protocol mandated continuous
medication for 2 or 4 weeks, whereas patients in ‘real
life’ tend to stop medication along the way, depending
on symptom control.13
With respect to the study protocol, a number of efforts
were made to address these obstacles. The GP was asked
to state whether a contact was due to the study
protocol, or would have occurred in ‘real life’, and only
costs for ‘real-life’ events were calculated. To reflect
possible cost-conscious patient self-medication, two
treatment arms for intermittent treatments were included: 4 weeks (recommended) and 2 weeks (often
enough to control symptoms).
Patient diaries were used to enter the day-to-day use of
medication, purchased medicine, prescribed or over-thecounter, and absence from work. Under-reporting may
flaw patient diaries. To minimize the recall time,
patients were asked to enter data into the diary every
month and received new diaries every second month
during the study. Although this approach ‘disturbed’
the patient and was a deviation from ‘real life’, it was
chosen as the best compromise between securing
complete data and staying close to ‘real life’.
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V. MEINECHE-SCHMIDT et al.
Based on standard micro-economic theory, it must be
expected that the provision of free study medication
may have influenced the consumption of medicine, and
thus the direct medical costs. This could have biased the
cost estimates upwards. The effect would probably be
most pronounced in the on-demand arm, in which the
patients decided their own consumption level, and
consequently the real cost advantage of on-demand
treatment may be larger than that observed in this
study.
Costs for hospitalizations were included in the study,
based on the hypothesis that the treatment quality in
primary health care may influence the need for
treatment in the secondary sector. In this study, two
patients (both allocated to the 2-week intermittent
treatment arm) were subjected to reflux surgery during
the study period. These costs were included in the study.
As this can be disputed, we re-calculated the study
results without costs for hospitalizations: in this case,
the total cost for on-demand treatment was
196.6 euros, for 2-week intermittent treatment was
294.0 euros and for 4-week intermittent treatment
was 284.9 euros, leaving the overall conclusion of the
study unchanged.
Patient satisfaction was high in all study arms,
indicating that self-administration vs. having to see
the GP was not a significant issue from the patients’
perspective over a period of 6 months.
The present study focused on health care costs, and no
significant differences were detected in direct medical
costs or patient satisfaction between the treatment
arms. However, from a societal perspective, the different
management strategies led to different expenditures:
there was a significantly lower total cost for the
on-demand treatment strategy compared with the
intermittent treatment courses.
Furthermore, from an economical point of view, a
treatment strategy does not need to be cost saving to be
considered to be cost effective. If a treatment strategy is
considered to be more effective in terms of clinical
outcome (i.e. time to first relapse and patient satisfaction), and is neither less expensive nor more expensive,
it may be argued that the treatment strategy is cost
effective.
It must be emphasized that the study reflected medical
practice, resource utilization, prices and structures in
the Danish health care system. Therefore, our results
may not be directly applicable to other health care
systems.
From a clinical point of view, on-demand treatment
means less contact between GPs and patients and
possibly less monitoring. The lower total costs for
on-demand treatment must be balanced against a
possible higher risk for the development of complications of GERD (stricture or malignancy).
In the literature, conflicting long-term consequences of
proton pump inhibitor treatment of GERD have been
reported from secondary care: increased development of
lesions,14 persisting endoscopic findings15 and reduced
risk of stricture formation.16 GERD has been identified
as a risk factor for the development of oesophageal
adenocarcinomas,17 and gastrin has been shown to
induce proliferation in Barrett’s lesions.18 These findings
need to be better understood before long-term
on-demand proton pump inhibitor treatment is recommended for wide use. The natural history of GERD
during long-term on-demand therapy with proton
pump inhibitors in uninvestigated patients from primary care is not known. Adopting the on-demand
strategy in these patients should be accompanied by
advice to seek medical care if symptoms deteriorate.
CONCLUSION
In the present study, which compared the direct medical
costs for patient-controlled on-demand treatment with
those of GP-controlled intermittent treatment (for 2 or
4 weeks) with esomeprazole, it was not possible to
demonstrate any statistically significant difference in the
direct medical costs between the three groups over a
period of 6 months. However, the inclusion of other
costs (transportation costs and indirect costs) made
patient-controlled on-demand treatment a cost saving
treatment strategy compared with both of the
GP-controlled intermittent treatments.
No cost difference could be detected between the
2-week and 4-week intermittent treatment courses, but
patient satisfaction was lower when 2-week courses
were applied.
ACKNOWLEDGEMENT
This study was supported by AstraZeneca, Denmark.
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