Clinical economics review: cost-effectiveness of treatment alternatives for gastro-oesophageal reflux disease

Aliment Pharmacol Ther 1996; 10: 865–873.

Clinical economics review : cost-effectiveness of treatment

alternatives for gastro-oesophageal reflux disease

S. SRIDHAR, J. HUANG, B. J. O’BRIEN* & R. H. HUNT

Division of Gastroenterology, Department of Medicine, McMaster University Medical Centre, Hamilton, Ontario, Canada;

and *Department of Clinical Epidemiology and Biostatistics, McMaster University, Centre for Evaluation of Medicines,

St Joseph’s Hospital, Hamilton, Ontario, Canada

Accepted for publication 24 June 1996

SUMMARY

Gastro-oesophageal reflux disease is a chronic

recurring disorder, which is widespread, especially in

Western societies. Faced with increasing health costs

and finite resources, an increasingly important part of

evaluating new treatments is economic appraisal. In

this paper, we review critically the published economic

INTRODUCTION

Gastro-oesophageal reflux disease (GERD) is a common

condition. The most frequent symptom of GERD is

heartburn, which occurs daily in up to 10% of the adult

population." Some studies indicate that up to 44% of

apparently healthy subjects experience heartburn at least

once per month."–& While patients with mild heartburn

may respond to antacids, the majority of GERD patients

will require antisecretory therapy. The use of anti-

secretory drugs is widespread in the management of

GERD, and acid suppression is now established as first-

line therapy. Currently the choice of first-line anti-

secretory therapy is between H#-receptor antagonists,

such as cimetidine, ranitidine, famotidine or nizatidine,

and proton pump inhibitors, such as omeprazole and

lansoprazole, and more recently pantoprazole.

Omeprazole has been found to be more effective than

Series Editors for Clinical Economics Reviews: K. Bodger, M. Daley &

R. V. Heatley.

Correspondence to : Prof. R. H. Hunt, Division of Gastroenterology, Depart-

ment of Medicine, McMaster University Medical Centre, Room 4W8, 1200

Main Street West, Hamilton, Ontario, Canada L8N 3Z5.

studies of the cost-effectiveness of treatments for gastro-

oesophageal reflux disease. Proton pump inhibitors are

considered the best choice for the management of

grades II–IV oesophagitis and are more cost-effective

than H#-receptor antagonists because of their fast

healing of oesophagitis, early relief of symptoms, and

prevention of recurrent oesophagitis and development

of complications.

cimetidine and ranitidine in terms of the proportion and

speed of healing, but more expensive than H#-receptor

antagonists based on drug acquisition costs.',(

Faced with the prospect of new medications such as

proton pump inhibitors that offer increased benefits at an

increased cost, many government payers for medicines

such as the National Formulary in Australia) and the

Provincial Formulary in Ontario, Canada* now require

evidence of cost-effectiveness (i.e. value for money) before

granting reimbursement status to new pharmaceutical

products under these programmes. Similar concerns

have been voiced in the United States, both in terms

of reimbursement for interventions under Federal

programmes such as Medicare and, more recently, in the

context of health-care reform and the growth of managed

care."! These pressures have given rise to a number of

studies comparing the costs and effects of alternative

treatments for the acute and chronic management of

GERD. The aim of this paper is to review the published

cost-effectiveness studies of GERD treatments and to

appraise their methodological strengths and weaknesses.

In pursuit of this objective, we begin with a brief overview

of the treatment alternatives and evidence on effec-

tiveness ; outline the principles of cost-effectiveness analy-

# 1996 Blackwell Science Ltd 865

866 S. SRIDHAR et al.

sis ; review published cost-effectiveness studies in GERD;

and conclude with an agenda for future research

targeting economic evaluation at treatment algorithms

rather than specific pharmaceuticals. A comprehensive

review of the literature was undertaken and studies with

clearly defined data were included. General practice

based studies were not included because of lack of

comparable quality.

TREATMENT OPTIONS

The two broad goals of GERD therapy are, first, to relieve

symptoms such as heartburn, epigastric or substernal

pain, and dysphagia. Symptom relief can be attempted or

augmented using either non-pharmacological methods

involving lifestyle modification or by the use of drugs.

Healing oesophageal lesions should be followed by the

prevention of recurrence or complications of long-

standing oesophagitis such as peptic strictures and

epithelial metaplasia (Barrett’s oesophagus), and possibly

oesophageal cancer. In addressing both of these goals it

must be remembered that GERD is a chronic recurring

disease and management involves combining strategies

to heal the acute episode and subsequently to keep the

patient free from symptoms.

Non-pharmacological methods to resolve symptoms are

advocated in the first stage of managing symptomatic

GERD. Elevation of the head of the bed improves reflux

symptoms and enhances the effectiveness of drugs.""

However, because the majority of patients are daytime

refluxers, the efficacy of raising the head of the bed has

been questioned."#,"$ With regard to weight reduction,

there is no evidence to suggest that GERD is more

common in overweight individuals. However, patients

often note an increase in symptoms when they gain

weight and remission on weight loss. Reduction of

alcohol consumption and stopping smoking may also

help reflux-induced symptoms."%,"&

For many symptomatic patients, however, lifestyle

modification is either ineffective or compliance is poor.

For these patients and those with more troublesome or

severe disease, there are a variety of pharmaceutical

approaches.

Antacids

These provide symptomatic relief in a proportion of

patients with mild and infrequent reflux, and may

increase lower oesophageal sphincter tone."',"( Patients

with lesser grades of GERD may obtain symptomatic

benefit from antacids.

Prokinetic agents

Cisapride, the most promising prokinetic drug, acts by

enhancing the release of acetylcholine from the

myenteric plexus. Cisapride enhances oesophageal mo-

tility and increases lower oesophageal sphincter tone,

therefore reducing exposure of the oesophagus to gastric

acid reflux."),"* In comparative studies with H#-receptor

antagonists, cisapride is as effective as cimetidine and

ranitidine in improving symptoms and healing

oesophagitis of grade I–III.#! Studies also demonstrate

that cisapride plus an H#-receptor antagonist is better

than an H#-receptor antagonist or cisapride alone.#!,#"

Cisapride was useful in preventing recurrence of grade I

oesophagitis but not higher grades of the disease## and

long-term follow-up showed cisapride to be slightly

superior to placebo.#$

Over-the-counter H#-receptor antagonists

Patients, by experience or on the advice of others, may

attempt to obtain symptomatic benefit by using over-the-

counter (OTC) medications including low-dose H#-re-

ceptor antagonists. There has been a widely expressed

controversy over the OTC use of H#-receptor antagonists.

In one study in which 562 dyspeptic patients using

10 mg of ramotidine per day had grade II–IV oesophagitis

at baseline, the majority of oesophageal lesions healed

during the therapy.#% The OTC H#-receptor antagonists

can help patients who suffer from infrequent heartburn

and perhaps reduce visits to their doctors, thereby

potentially decreasing the financial burden on the health-

care system.

H#-receptor antagonists

H#-receptor antagonists inhibit gastric acid secretion by

competitive inhibition of H#-receptors on the parietal

cells. However, H#-receptor antagonists are less effective

against daytime food-stimulated acid secretion than

against basal acid secretion. It is known that healing of

oesophageal lesions requires greater acid suppression

and this is related to symptom relief and healing of

oesophagitis.#&,#' Cimetidine has been used for treatment

of reflux oesophagitis for nearly 18 years. It produces

# 1996 Blackwell Science Ltd, Aliment Pharmacol Ther 10, 865–873

867CLINICAL ECONOMICS REVIEW: COST-EFFECTIVENESS IN GERD

more rapid symptomatic relief than placebo, but is less

effective in improving endoscopic oesophagitis.#(

Ranitidine effectively improves the symptoms and endo-

scopic lesions within 6–12 weeks, depending upon the

endoscopic grading of the disease and duration of

therapy.#),#* The healing with nizatidine 300 mg varies

between 8–19% at 6 weeks for grades III and IV and

53–69% at 12 weeks for grade I disease.$!,$"

Proton pump inhibitors

Omeprazole, lansoprazole and pantoprazole inhibit the

H+,K+-ATPase and block the final common pathway of

acid secretion by parietal cells. They are, therefore,

effective in inhibiting daytime, food-stimulated acid se-

cretion, in contrast to H#-receptor antagonists. Proton

pump inhibitors are superior to other drug classes in the

management of GERD. Omeprazole at 20 mg}day gave a

healing rate of 56 and 75% for grade I disease at 4 and 8

weeks, respectively. Healing for grade IV disease was

51% at 4 weeks and 71% at 8 weeks. With higher doses

(40 mg}day) the healing rate increased for the lower

grades of the disease to 74% at 4 weeks and 81% at 8

weeks.$#–$% Lansoprazole had a similar effect as ome-

prazole in healing different grades of GERD and may be

more effective in early relief of symptoms.#'

As should be clear from this very brief outline of GERD

therapy, there is a large and growing menu of choices for

managing this disease. In a world of unlimited resources,

choice of therapy might reasonably be driven by con-

ventional principles of efficacy and safety. In reality,

however, health-care payers (e.g. government) have

limited resources and want to allocate these in the most

efficient manner. In the management of GERD this is

manifested in concerns over the higher drug costs of

proton pump inhibitors such as omeprazole. For example,

based on Ontario prices, the data in Table 2 indicate that

a 1-year course of maintenance omeprazole (20 mg once

daily) is Can$860 compared to Can$301 for the same

duration of generic ranitidine (150 mg b.d.).

RATIONALE FOR ECONOMIC EVALUATION IN

GERD

Economic evaluation covers a number of specific

techniques such as cost-effectiveness analysis which can

be used to address the question of whether a programme,

project or intervention offers good value for money.

These methods have been used in health care since the

1960s, gaining much wider application in recent years

with a focus on both medical technology (Health Tech-

nology Assessment) and pharmaceuticals (Pharmaco-

economics). There exists a number of textbooks and

guidelines on how to conduct economic evaluation.$&

Economic appraisal is based on comparative inferences

requiring the outcomes and costs of a treatment to be

compared to some alternative ; it is not about comparing

costs of programmes in isolation from the programme

outcomes because such one-sided comparisons cannot

answer questions of value. GERD economic evaluation

studies have largely used the technique of cost-

effectiveness analysis, and therefore we will restrict our

comments to this technique. For cost-effectiveness analy-

sis, the analyst seeks to compare two or more treatments

over a relevant period in terms of both costs and patient

outcomes. The first point to note is that costs are not

restricted to drug acquisition costs at the initiation of

therapy. Table 1 shows the drug acquisition costs (in

Ontario, Canada) for a number of medications for GERD.

From this table it is evident that, for example, a 1-year

maintenance regimen with omeprazole is more costly

than that with ranitidine. However, the focus of econ-

omic appraisal is typically cost to the health-care system

and so for a chronic recurrent disease such as

oesophagitis it is necessary to factor in the ‘downstream’

costs averted due to the use of omeprazole in preference

to ranitidine. Such downstream costs may not be

pharmaceutical costs but those of further diagnostic tests

or physician visits. To quantify such downstream costs

the period over which treatments are compared must be

considered carefully. What is a meaningful measure of

patient benefit for a GERD cost-effectiveness study? Given

the therapeutic goals of treatment, it seems logical that a

preferred treatment is one that offers a greater period free

from symptoms and healed from oesophagitis. Such a

composite measure captures efficacy in terms of the speed

of healing of oesophagitis and reduced risk of recurrence.

A number of authors have, therefore, decided to use the

outcome measure of symptom-free days or healed days as

the measure of outcome. In principle this general

measure of ‘healthy time’ also permits broader com-

parisons with other disease areas where resources might

be allocated. What should one do with measured costs

and outcomes? The convention of cost-effectiveness

analysis proceeds in the following way. First, is Treat-

ment A dominant over Treatment B by having both a

lower overall cost with a higher overall effectiveness? If

this is true, then Treatment A is said to be dominant and



Table 1. Drug acquisition costs, excluding dispensing fees (Ontario, 1995)

Drug (dose)

Cost per

day

($)

Cost per

4 weeks

($)

Cost per

12 weeks

($)

Cost per

year

($)

Antacid

Gaviscon (20 mL q.d.s.) 0±4 11 34 146

Sucralfate

Sulcrate (1 g q.d.s.) 1±8 52 156 682

Cisapride

Prepulsid (10 mg q.d.s.) 1±1 59 176 765

H#-receptor antagonist

Ranitidine (150 mg b.d.) 0±8 23 69 301

Zantac (150 mg b.d.) 2±2 61 184 800

Proton pump inhibitor

Omeprazole}Losec (20 mg once daily) 2±3 66 199 865

Source : Pharmacy of McMaster University Medical Centre 1995.

there is a strong case for adopting this treatment. In

many circumstances, however, we observe non-domi-

nance in that Treatment A would be more costly but

more effective than Treatment B. In this situation it is

conventional to calculate what is known as an in-

cremental cost-effectiveness ratio, which is the ratio of

the difference in cost (Treatment A minus Treatment B)

to the difference in effect. This ratio tells us the added cost

of achieving 1 more unit of outcome by using Treatment

A in preference to Treatment B. The interpretation of this

ratio is then a value judgement about whether we are

willing to pay the additional cost for the additional

outcome, given that we could use the resources in other

ways.

GERD COST-EFFECTIVENESS STUDIES

In Table 2 we summarize six cost-effectiveness studies of

alternative treatments for reflux oesophagitis identified

from the literature.$'–%" A literature search identified

three additional studies by Bate, Hillman and Stal-

hammer, but, on closer inspection, all three of these

studies reported data that had been published previously

and were, therefore, not included in our review.%#–%% The

studies originate from the UK, the US and Sweden, and

mainly compare omeprazole with an H#-receptor anta-

gonist over periods from one acute episode to 12 months.

The studies vary with respect to the cost data collected

from drug costs only to all direct health care costs and

indirct costs (i.e. production loss due to work absence).

Effect data are typically combinations of healing and

relapse information to yield symptom-free months or

healed weeks. We review each of these studies briefly.

Bate, 1991

This study is based on two clinical trials conducted by

Bate that compared both omeprazole and ranitidine and

omeprazole and cimetidine in terms of endoscopic healing

of oesophagitis and symptom relief.$' The period for the

economic analysis is one acute episode of oesophagitis.

The data from this study indicate that for a cohort of 100

patients, 69 would be healed at 8 weeks on omeprazole

vs. 38 on ranitidine at a cost of £5199 for omeprazole vs.

£4723 for ranitidine. This is, therefore, a case where the

omeprazole therapy is non-dominant because it offers

higher outcome but at a higher cost. Rather than

calculating the ‘ incremental ’ cost-effectiveness ratio, the

author calculates average cost-effectiveness ratios for

each treatment group separately. That is, he divides the

treatment costs for omeprazole by the effectiveness for

omeprazole and compares this ratio to the treatment cost

divided by the proportion healed for ranitidine, and

argues that the cost per healed patient is greater with

ranitidine compared with omeprazole and, therefore,

that omeprazole is more ‘cost-effective ’ than ranitidine.

As has been demonstrated elsewhere in relation to

management of acid-related diseases, the calculation of

such average ratios is highly suspect because it invokes a

third point of reference of no therapy where patients are

assumed to incur zero cost and achieve zero outcome.%&

In this circumstance, it is far more meaningful for

decision-makers to have an assessment of the additional

cost required to achieve the additional units of effect.

The main limitations of the Bate study are : first, it

considers only drug costs and not health-care costs more

widely ; and, second, the very short period of one acute



Table

2.Cost

-effec

tiven

ess

studie

sofalter

native

trea

tmen

tsfo

rre

flux

disea

se

Auth

or

Yea

rCountr

yCom

pariso

nCost

sEffec

tsPer

iod

Analy

sis

Bate

*$'

1991

UK

OM

P20

mg

once

daily

vs.

RA

NDru

gco

sts

(a)

%hea

led

One

episode

Aver

age

cost

-

150

mg

b.d

.(b

)%

sym

pto

mfree

effec

tiven

ess

OM

P20

mg

once

daily

vs.

CIM

(c)

%w

ith

(a)and

(b)

400

mg

q.d

.s.

Bate

&Ric

hard

son$(

1992

UK

OM

P20

mg

once

daily

vs.

RA

N

150

mg

b.d

.(incl

udes

switch

es

over

tim

e)

Dru

gco

sts

Hea

ling,re

lapse

One

yea

rCost

com

pariso

n

Hillm

an

etal

.†$)

1992

US

Sta

ge

1th

erapy

vs.

OM

P(2

0m

g

once

daily)vs.

RA

N(1

0m

gb.d

.)

Direc

thea

lth-c

are

cost

s

Sym

pto

m-fre

em

onth

s7

month

sDom

inance

and

aver

age

cost

-effec

tiven

ess

Jonss

on

&Sta

lham

mer

‡$*

1993

Sw

eden

Main

tenance

OM

P(2

0m

g

once

daily)vs.

main

tenance

RA

N(1

50

mg

b.d

.)vs.

inte

rmitte

ntOM

Pvs.

inte

rmit-

tentRA

N

Direc

tand

indirec

t

cost

s

Hea

lthy

days

12

month

sDom

inance

Lin

dber

g%!

1994

Sw

eden

OM

P(2

0m

gonce

daily)vs.

RA

N

(150

mg

b.d

.)

Direc

tand

indirec

t

cost

s

Hea

led

wee

ks

12

wee

ks

Aver

age

cost

-

effec

tiven

ess

Blo

om

%"

1995

US

Sta

ge

1th

erapy

vs.

OM

P(2

0m

g

once

daily)vs.

RA

N

(150

mg

b.d

.)vs.

RA

N

(150

mg

q.d

.s.)

Direc

thea

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are

cost

s

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pto

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onth

s7

month

sDom

inance

and

aver

age

cost

-effec

tiven

ess

Abbre

via

tions:OM

P,om

epra

zole

;RA

N,ra

nitid

ine;CIM

,ci

met

idin

e;FA

M,fa

motidin

e.

*Sam

edata

publish

edagain

as

Bate

,1994.%#

†Sam

edata

publish

edagain

as

Hillm

an,1994.%$

‡Sam

edata

,in

part

,publish

edagain

as

Sta

lham

mer

,1993.%%



episode does not allow for the inclusion of the costs and

adverse effects associated with recurrence of oesophagitis

beyond the first event.

Bate & Richardson, 1992

This is an extension of the earlier study by Bate and an

attempt to compare initial treatment of oesophagitis with

omeprazole vs. ranitidine beyond the first acute event to

a period of 1 year, thereby including information on

recurrence.$( One of the difficulties in adopting this

extended period for the analysis is that the authors must

make a series of assumptions about treatment algorithms

over time. That is, they make a number of assumptions

about what therapy would be assigned to patients who

are not healed after 4 weeks of treatment, or not healed

after 8 weeks, and so on. However, the treatment

algorithms do not allow for any switch from the original

drug assignment ; that is, patients originally assigned to

ranitidine are assumed to complete the year on ranitidine

and simply increase dosage if they are unresponsive to

therapy. The study only compares drug costs between

two groups and concludes that over a 1-year period the

treatment of 100 patients would cost £41515 for

ranitidine vs. £31417 for omeprazole.

The main concerns with this study centre around the

validity of the treatment algorithms proposed to extend

the period to 1 year. No formal process (e.g. Delphi panel)

was used to determine the most appropriate management

strategies for these treatment algorithms and the reader

is told that they are based on ‘clinical experience’ of the

primary author. Rather than conducting the analysis

exclusively in terms of a comparison of two drugs over

1 year (i.e. the patient is ‘ locked into’ ranitidine therapy

at increasing doses throughout the year), it may have

been useful to also consider treatment algorithms that

involve switches between drugs. For example, a treat-

ment algorithm might be considered where the patient is

initially assigned to ranitidine (150 mg b.d.) for 4–8

weeks but, if not healed at this time, switched to

omeprazole. Similarly, one might be interested in healing

the acute episode with a proton pump inhibitor and

switching to continuous maintenance therapy with an

H#-receptor antagonist. In the primary care setting, H

#-

receptor antagonists are still prescribed because of their

efficacy in relieving symptoms and healing milder grades

of oesophagitis. Long-term treatment with H#-receptor

antagonists should be tailored to the individual patient as

it is difficult to predict who is going to relapse. However,

higher grades of disease are known to relapse. The logic

of this approach is that we should be less interested in

economic comparison of drugs per se and more interested

in the cost-effectiveness of the overall clinical manage-

ment strategies and the ways in which these drugs could

be used optimally in those strategies.

Hillman et al., 1992

This study compared three strategies : stage 1 therapy

involving lifestyle modification, as described above, vs.

omeprazole, vs. ranitidine.$) The duration of this analysis

was 7 months and the authors collected information on

direct health-care costs and computed an effect in terms

of symptom-free months using both healing and re-

currence data. The authors conclude that omeprazole is

dominant over both ranitidine and stage 1 therapy,

yielding a higher number of symptom-free months and

lower costs over a 7-month period. In assessing treatment

algorithms and management of recurrent oesophagitis,

this study used an expert physician panel to derive

consensus views.

One of the concerns about this study is that the results

appear to be most sensitive (according to the sensitivity

analysis) to the costs of complications during follow-up,

such as surgery. For example, the study assumes that

during the follow-up of patients with persistent

oesophagitis, approximately half of those whose con-

dition is unresponsive would undergo surgery (fundo-

plication) at a cost of US$26393. The problem is that,

similar to the Bate & Richardson study, this study

assumes that patients will not be switched from ranitidine

to omeprazole if they are unresponsive to therapy on the

former. This study design was probably dictated by the

lack of FDA approval for the long-term use of omeprazole

in the United States. It is, therefore, unrealistic in most

health-care systems and means that a higher proportion

of patients assigned to ranitidine in the model will end up

with the high cost of surgery, which drives up the total

treatment costs for the ranitidine group relative to the

omeprazole group. Again, it might be more useful to

evaluate hybrid algorithms where omeprazole is con-

sidered as either first- or second-line therapy.

Bloom, 1995

This is a re-working of the original Hillman paper (see

above), but includes a new comparison of ranitidine

150 mg q.d.s. which was approved for the treatment of



oesophagitis in the United States subsequent to the

Hillman study.%$ This study reaches similar conclusions

to the Hillman study, in that omeprazole is dominant over

both ranitidine regimens and also stage 1 therapy. Since

this study invokes the same assumptions as the Hillman

study, the same concerns arise regarding treatment

failure and use of surgery in the ranitidine groups.

Although published in 1995, this study also uses the

original 1989 prices used in the Hillman analysis. To the

extent that the prescribing of generic H#-receptor

antagonists is becoming more widespread in several

health-care systems, for example as a result of the growth

of managed care in the United States, this may be a more

relevant comparator where generics exist and would

reduce the costs of treatment with ranitidine.

Jonsson & Stalhammer, 1993

This study compares four different strategies for man-

agement of oesophagitis : maintenance omeprazole,

maintenance ranitidine, intermittent omeprazole and

intermittent ranitidine.$* The authors present in-

formation on direct and indirect costs, and quantify

effects in terms of healthy days based on recurrence and

healing probabilities. The study is a cost-effectiveness

model over a period of 12 months which utilizes the

statistical approach known as a Markov model which

permits for transition between different states of health

(e.g. healed or not healed) over time. The authors

conclude that omeprazole is both more effective and less

costly than ranitidine for both treatment strategies for

intermittent or maintenance treatment. These data

indicate that maintenance omeprazole is more costly but

more effective than intermittent omeprazole. This study

does not suffer from many of the weaknesses of the other

studies already discussed. For example, the authors do

permit switching between drug regimens: if patients

have failed to respond to ranitidine, they are switched to

omeprazole over the period of 12-month follow-up.

Therefore, the basis of the comparison is one of treatment

strategies rather than drug use alone.

Lindberg, 1994

This Swedish study compared initial treatment with

either ranitidine or omeprazole over a 12-week period,

where direct health-care costs and indirect costs were

compared to outcomes in terms of weeks without

oesophagitis.%! The author concludes that initial therapy

with omeprazole is dominant over ranitidine yielding a

greater number of healed weeks (6±75 vs. 3±71) in the

12-week period at a lower cost.

This study has some of the strengths and weaknesses of

the other published studies. On the negative side, the

duration of the study is short at only 12 weeks. On the

positive side, this study does permit switching between

drugs. For example, those with unhealed oesophagitis at

8 weeks in either treatment group are assumed to receive

omeprazole 40 mg once daily for 4 weeks.

DISCUSSION

Today, in every clinical specialty, physicians are facing

the challenge of providing the best care they can for their

patients within financial constraints of health-care

payers. In gastroenterology with the recent introduction

of more effective yet expensive alternative treatment for

oesophagitis, such as the proton pump inhibitors, there is

increasing concern as to whether such a new alternative

therapy can offer value for money. Therefore, economic

evaluation has been increasingly used in recent years by

many countries to scrutinize the cost-effectiveness of any

new therapeutic modalities.

Since oesophagitis is a chronic recurrent disease,

treatments are expensive, especially with the advent of

proton pump inhibitors which achieve greater benefit at

greater cost. Most of the studies we have reviewed

compared the clinical and economic impact of proton

pump inhibitors and H#-receptor antagonists on the

management of oesophagitis, and concluded that treat-

ment with proton-pump inhibitors such as omeprazole is

a preferred initial therapy for patients with persistent,

symptomatic oesophagitis in whom phase 1 therapy fails.

Omeprazole was associated with 17 and 22% lower cost

than treatment with ranitidine and phase 1 regimens,

and 80% lower cost for major complications.$) A number

of studies found omeprazole to be a dominant therapy for

patients with oesophagitis with better outcomes at a

lower cost. Omeprazole leads to faster healing and

symptom relief in patients with oesophagitis and could be

considered the most effective choice of treatment.',( It is

also evident from the economic studies that treatment

with omeprazole is more cost-effective than ranitidine.

However, two recent reviews have indicated that the

newer proton pump inhibitor, lansoprazole (30 mg}day),

had similar effects on healing oesophagitis as omeprazole,

was even better to achieve earlier and faster relief of

symptoms,#',%' and has been considered more cost-



effective than treatment with omeprazole

(20 mg}day).%(,%) However, it is important to bear in

mind that the current economic studies are mostly based

on short-term clinical trials. It is not suitable to assign the

results from short-term studies to a chronic recurrent,

usually life-long, disease such as oesophagitis. Thus,

studies on the long-term economic impact on the

management of oesophagitis are urgently needed.

The economic studies reviewed in this paper mainly

focused on the direct medical costs, while direct non-

medical costs (those paid by patients) were largely

ignored. These costs may account for an increasing

proportion of the total cost particularly with the advent

of OTC H#-receptor antagonists where patients may elect

to purchase such products as part of their strategy for

managing this disease. Furthermore, there are a number

of issues concerning the extent to which the results of

any economic analysis could be simply applied from one

country to another, since health-care systems and

pharmaceutical markets often are very different between

countries. For example, in our recent publication re-

garding cost-effectiveness of Helicobacter pylori

eradication in duodenal ulcers, we found that 84% of

ranitidine prescriptions dispensed are generics rather

than for the proprietary Zantac, however generic

ranitidine is not yet available in some countries such as

the United States.%* Another difference between studies is

the chosen outcome measures. Some studies use symp-

tom relief as an end-point of the trials, while others adopt

endoscopic healing of oesophagitis. Clearly these are not

the same scale and do not reassuringly reflect studies of

the same grade of disease. Future economic studies of

oesophagitis should include both direct and indirect

medical costs and non-medical costs. In the management

of patients with gastro-oesophageal reflux disease and

oesophagitis, physicians should be aware of the recurring

nature of the disease and that switching from H#-

receptor antagonist to a proton pump inhibitor would be

logical and cost-effective if treatment with H#-receptor

antagonists fails, since proton pump inhibitors have

demonstrated a therapeutic gain across all grades of

oesophagitis.

ACKNOWLEDGEMENTS

Dr B. J. O’Brien was funded by an MRC}PMAC Health

Research Foundation Career Award. The authors thank

Rita Chan of the Department of Pharmacy, McMaster

University Medical Centre, for providing information on

drug costs in Ontario, and Barbara McGlinchey for typing

the manuscript.

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Clinical economics review: cost-effectiveness of treatment alternatives for gastro-oesophageal reflux disease