The health economics of Helicobacter pylori infection

Best Practice & Research Clinical Gastroenterology Vol. 21, No. 2, pp. 347e361, 2007 doi:10.1016/j.bpg.2006.11.004 available online at http://www.sciencedirect.com

10 The health economics of Helicobacter pylori infection Paul Moayyedi *

MD, PhD, FRCP

Professor of Gastroenterology Division of Gastroenterology, McMaster University Medical Centre, 1200 Main Street West, HSC room 4W8E, Hamilton, ON L8N 3Z5, Canada

Economic considerations are becoming increasingly important as health care becomes more expensive. Evidence for effectiveness is usually gained from randomised controlled trials (RCTs) but often there is insufficient evidence of the costs of alternative strategies in trials. Often, therefore, economic models are needed to extrapolate data from a variety of sources to give an indication of which strategy is cost effective. Helicobacter pylori (H. pylori) testing and treating in a wide variety of upper gastrointestinal diseases is a good example of the application of economic analyses to health care interventions. H. pylori eradication in peptic ulcer disease is very effective with systematic reviews giving a number needed to treat of around two compared to no therapy. RCTs have also suggested that treating H. pylori is also more effective and less expensive than continuous H2 receptor antagonist therapy and is therefore the dominant strategy in treating peptic ulcer disease. The impact of H. pylori eradication in infected patients with functional dyspepsia is less dramatic, with systematic reviews suggesting a number needed to treat of 14. Economic models suggest that in Europe H. pylori eradication is cost-effective compared to offering no treatment (e.g. in the UK we can be 95% certain this approach is cost effective if you are willing to pay $51/month free from dyspepsia). In the USA it is less certain that this is a cost-effective approach due to the higher cost of eradication therapy. H. pylori test and treat has been proposed as an alternative to early endoscopy in patients with uninvestigated dyspepsia. We have conducted an individual patient data meta-analysis of five RCTs that has addressed the cost effectiveness of this approach. Endoscopy was slightly more effective than H. pylori test and treat at relieving dyspepsia at one year but was not cost-effective as it cost $9000/dyspepsia cure at one year. Population H. pylori test and treat has been proposed as a strategy to prevent noncardia gastric cancer. RCTs have suggested this approach may be cost saving but more data are needed on whether H. pylori eradication will reduce gastric cancer mortality before this strategy can be recommended. Key words: Helicobacter pylori; cost-effectiveness; economic modelling; peptic ulcer disease; dyspepsia.

* Tel.: þ1 905 521 2100x76764; Fax: þ1 905 521 4958. E-mail address: [email protected]. 1521-6918/$ - see front matter ª 2006 Published by Elsevier Ltd.

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INTRODUCTION A century ago health care was relatively inexpensive1 but was also largely ineffective. Health technology has improved dramatically last 100 years with modern medicine able to effectively treat a vast array of diseases. These improvements have come at a price with health care now a significant proportion of the Gross Domestic Products of most developed countries.2 No society can afford to provide optimal timely health care to everyone that might benefit and rationing is an inevitable component of modern medicine. Health economics has emerged as an important discipline in medicine and aims to establish how scant resources are best utilised to improve health. Traditionally the clinical community has focused research efforts on establishing whether a new health care intervention is effective. Increasingly clinicians realise that this is insufficient and we must also establish that any health gain from a new intervention is good value for money. Helicobacter pylori (H. pylori) infection is an excellent example of a discovery that has led to improved treatment of a wide variety of upper gastrointestinal diseases. The question is whether the diagnosis and treatment of this infection is an efficient use of resources for health care budgets. This chapter will address this by giving an overview of the principles of health economic evaluation and then applying these to the diagnosis of and treatment of H. pylori in peptic ulcer disease, functional dyspepsia, undiagnosed dyspepsia and the general population. THE PRINCIPLES OF ECONOMIC EVALUATION OF HEALTH CARE INTERVENTIONS Types of health economic analysis The basic concept that underpins much of health economic evaluation is opportunity cost: the concept that if resources are used for a particular health care intervention then that money cannot be used for an alternative.3 As resources are scarce this inevitably means that some health care interventions will be funded at the expense of others. The purpose of health economic evaluation is to try and ensure that the resources invested in a given health intervention are appropriate. As opportunity cost is a key principle of health economics, evaluations always compare one intervention with an alternative even if that alternative is to do nothing. The differences in costs are compared with the difference in outcomes between the two interventions being studied. The overall evaluation of whether a strategy is an efficient use of resources compared to an alternative is given by the general formula: Cost intervention 1  cost intervention 2 Outcome intervention 1  outcome intervention 2 In the simplest form of analysis outcomes are assumed to be the same between the two strategies and the only thing that is measured is the difference in costs. This is termed a ‘cost analysis’ or ‘cost minimisation analysis’ and is the top half of the above equation. It is imperative that an economic analysis states which perspective is being taken in the analysis as an item may be a cost from one point of view but not another. For example, travel costs to receive a health care intervention would not be considered a cost from a health service perspective but would certainly be consider a cost by the patient. Similarly number of primary care visits for a specific medical condition

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would be viewed as a cost from a health service perspective but not if only secondary care costs were being considered. Perspectives that are most often taken are societal and third party payer (such as a Ministry of Health or Health Insurance company) costs. A detailed cost analysis can involve a great deal of time and effort in ensuring all relevant costs are identified, measured accurately and valued appropriately. The valuation of costs is controversial. In the case of drug therapies this is taken at the current market value but in the case of medical time or procedures being performed it may not be appropriate to simply use what the hospital charges for its services. This is because hospitals often cross-subsidise and in the case of a local monopoly what a hospital charges may bare little relationship to the actual costs.4 The interpretation of a cost analysis is simple: whichever strategy is cheapest should be the option that is adopted. The problem with this type of analysis is that it is almost never an appropriate methodology to use as in health care you can rarely be sure that one intervention is going to have identical outcomes to an alternative.5 A good example where cost minimisation analysis was appropriate is the comparison of concentrators versus cylinders in providing home oxygen for patients with severe chronic obstructive pulmonary disease6 but I am not aware of any example in gastroenterology where this was the correct methodology to use. In almost all cases therefore it is important to assess outcomes as well as costs and this is considered in three other types of health economic evaluation: cost-effective, cost utility and cost benefit analyses. These three approaches differ in the way health outcome is valued. Cost-effectiveness analysis describes the cost per unit health improvement and avoids explicitly giving a value to the outcome. The units for example could be cost per life year saved or month free from dyspepsia. Each intervention would be assessed according to this outcome and the cost-effectiveness analysis would then inform a decision on the most efficient method of treating a given disorder (technical efficiency). This approach is intuitive but does not inform us as to whether treating that disease is a good use of resources in the first place (allocative efficiency). For example, assessing the cost per ulcer healed will allow us to compare different interventions that aim to heal ulcers but these units will have no meaning when assessing improvement in rheumatoid arthritis. As there are limited resources available to health care, often we need to make decisions about which health care program to invest in where the outcomes are very disparate. Cost utility and cost benefit analyses aim to do this. Cost utility analyses describe the cost of an intervention per outcome that encompasses length and quality of life. The usual approach is to evaluate the quality adjusted life years (QALY) gained with a value of one indicating perfect health and death is given a value of zero. There are several validated questionnaires that measure health related quality of life in terms of QALYs and all assess important aspects of health such as pain, social, physical and psychological function.7 QALYs are a generic measure that can be compared across all health care interventions and an expert working group has suggested that cost/QALY should be used as standard in economic evaluations.8 There are, however, concerns about measurement and interpretation of cost-utility analysis.9 The alternative is cost-benefit analysis which measures both costs and outcomes in monetary terms. This approach has the advantage that non-health outcomes such as waiting for treatment and the quality of the hospital environment can be measured. It is also the most explicit form of analysis but this is also a disadvantage as placing a monetary value on human life and suffering has stimulated vigorous ethical debate.10 Nevertheless, paying for medication to relieve modest degrees of suffering is something that most societies are accustomed to, so this form of analysis may be particularly useful in this setting.11 For example, most patients with dyspepsia have bought

350 P. Moayyedi

over the counter antacids so would be willing to state how much they would be willing to pay for other medications that might relieve their symptoms. Interpretation of economic analyses Each of these types of analysis can be useful in particular settings and given the emotive nature of health it is not surprising that there is no consensus as to the best method of valuing health outcomes. If a cost-effectiveness or cost-utility analysis is carried out there are four possible categories of results (Figure 1).12 If a new intervention is cheaper and more effective than the old treatment then it is clear the new treatment should be adopted (the new treatment is said to ‘dominate’ the old therapy). Similarly if a new intervention is more expensive and less effective then it is clear this should not be implemented (the new treatment is said to be ‘dominated’ by the old therapy). Usually, however, when a new health technology innovation is developed it results in better outcomes for patients but the manufacturing company will charge more than the traditional therapy. In this situation it will be unclear whether the new intervention is an efficient use of resources as this will depend on how much is willing to be paid for the health benefit (top right-hand corner of Figure 1). Rarely there is a new intervention which is less effective but less expensive than the old therapy and again it will be unclear whether the new intervention is an efficient use of resources (bottom lefthand corner of Figure 1).

New treatment more expensive

Willingness to pay per unit of treatment effect

New treatment dominated by existing treatment New treatment less effective

α

New treatment more effective

New treatment dominates existing treatment

New treatment less expensive

Figure 1. The cost-effectiveness plane. The angle (a) of the dotted line will vary according to the maximum willingness to pay for unit of effect. If the value falls below the dotted line then the new treatment should be adopted.

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Health economic modelling Data for health economic evaluation should be collected by randomised controlled trials (RCTs) that measure both costs and effects. However, in most cases, RCTs do not include data on resource use, and even when cost data is collected the primary outcome is almost always clinical rather than cost-effectiveness. Consequently, the sample size of studies may be insufficient to detect important differences in resource use when comparing alternative treatments. To overcome this problem health economic models have been developed.13 These can be regarded as decision trees that try to simulate the patient experience. The theoretical patient can instantaneously reach the end of the model with a given health outcome and this is a simple expected utility model. This type of model is suitable for looking at treatments over very short period of time. Often it is important to include time in the model (e.g. when looking at time to relapse after cancer treatment or looking at the number of life years saved) and this is usually modelled using a Markov process.14 In addition to considering time the model may or may not evaluate the uncertainty in each branch of the tree. A deterministic model will have branches that always have a fixed probability of a given outcome (e.g. H. pylori eradication rate is always 80%). Uncertainty in deterministic models can be explored by changing the values in a sensitivity analysis (e.g. the H. pylori eradication rate can be varied between 50% and 100%). If data are available to indicate the distribution of likely values for particular parameters, a stochastic model can be constructed, and uncertainty explored using Monte Carlo Simulation (e.g. each patient going through the model is assigned a different probability of having H. pylori eradicated with a mean of 80% and 95% confidence intervals of 70% to 90%). Results from this model can be displayed as a cost-effectiveness acceptability curve. This gives the probability of a new intervention being more cost-effective than the old therapy at a given willingness to pay for each unit of health outcome (Figure 2). This gives a brief overview of the different types of health economic evaluation. Let us see how these have been applied to the various diseases that have been associated with H. pylori. PEPTIC ULCER DISEASE The original maxim of peptic ulcer disease pathophysiology was no acid no ulcer15 which resulted in many patients taking long term acid suppressive therapy. The discovery that H. pylori infection is the main cause of uncomplicated peptic ulcer has resulted in a paradigm shift in the approach to the management of this disease. Both acid suppression and H. pylori eradication are effective at healing peptic ulcers but ulcers are very likely to relapse unless the organism is treated. A systematic review16,17 identified 27 randomised controlled trials that compared H. pylori eradication therapy with no treatment in 2509 patients after duodenal ulcer healing followed up for two months to five years. Relapse was much lower in the eradication therapy group (relative risk (RR) of relapse ¼ 0.2; 95% CI ¼ 0.15 to 0.26) with a number needed to treat (NNT) to prevent one ulcer relapse of two (95% CI ¼ 1.6 to 2.2). A similar effect was found in 11 RCTs in 1104 patients after gastric ulcer healing followed up for three months to five years. Relapse was again lower in the eradication group (RR ¼ 0.29; 95% CI ¼ 0.2 to 0.42) with a NNT ¼ 2.6 (95% CI ¼ 1.9 to 4.5). Whilst there is little doubt over the efficacy of H. pylori eradication therapy in peptic ulcer disease, it is still important to assess whether this is cost-effective. The strong clinical effect combined with the fact that only one course of relatively inexpensive

352 P. Moayyedi 1.0

Proportion Cost-Effective Strategy X vs Y

C 0.9 0.8 0.7 0.6 0.5 0.4 0.3

A

0.2 0.1 0.0 0

B

Willingness to Pay ($) Figure 2. The cost effectiveness acceptability curve. As the amount a patient or third party payer is willing to pay increases, the probability that strategy X is more cost effective than Y increases. Point A is the probability that strategy X costs less than strategy Y (i.e. the analysis is only interested in the costs). Point B is the average incremental cost-effectiveness ratio. Point C is set in this example at an infinite willingness to pay and is the probability that strategy X is more effective than strategy Y (i.e. the analysis is only interested in effects and is equivalent to the one-sided p value).

eradication therapy is required suggests this is likely to be an efficient use of resources. Health economic modelling has also suggested this is a cost-effective approach17,18 compared with maintenance acid suppression or no treatment. Two randomised controlled trials reported that H. pylori eradication was significantly cheaper in duodenal ulcer patients than maintenance H2 receptor antagonist therapy with savings of over $500 in a US study19 and £40 in a UK study.20 This is therefore one of the rare examples in health economics where a new intervention is more effective and less expensive than the alternative and is said to be the dominant strategy. H. pylori eradication is the most cost-effective approach for healing peptic ulcers but it is possible that a third party payer would be better to use this money for other aspects of health care. This possibility would be addressed by cost-utility or cost benefit analyses but there is a paucity of these types of data for peptic ulcer disease.21 Nevertheless, peptic ulcer disease causes a significant reduction in quality of life22 and H. pylori eradication improves quality of life more effectively than maintenance acid suppression.23 FUNCTIONAL DYSPEPSIA The commonest cause of epigastric pain is functional dyspepsia with over 50% of endoscopies being unremarkable in patients referred to secondary care. The cause of this disorder is uncertain but it is likely to be multi-factorial with evidence of poor gastric accommodation, hypo-motility and hyperalgesia.24 The multi-factorial nature of NUD suggests that one therapy is unlikely to cure all patients and any intervention

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is only going to achieve success in a proportion of patients. H. pylori infection causes a chronic inflammatory response in the gastric mucosa and it is plausible that this plays a role in functional dyspepsia.25 Most randomised controlled trials comparing H. pylori eradication therapy with placebo in functional dyspepsia have been negative and initial systematic reviews were contradictory.26,27 The discrepancies between these reviews have been explored28 and when all available data are included there is a small but highly statistically significant effect in favour of H. pylori eradication therapy. A Cochrane systematic review29 identified 17 RCTs evaluating 3566 functional dyspepsia and reported a significant effect in favour of H. pylori eradication (RR ¼ 0.90; 95% CI ¼ 0.86 to 0.94) with a NNT of 14 (95% CI ¼ 10 to 25). In contrast to the effect on peptic ulcer disease, the impact of H. pylori eradication on functional dyspepsia symptoms is small and whilst this is statistically significant the clinical significance of this finding is less certain. In this situation health economics is particularly important as the main consideration in deciding whether this modest benefit of H. pylori eradication in functional dyspepsia is worthwhile is determining the costeffectiveness of this strategy. There are no randomised trials assessing this, as the sample size would need to be very large to have sufficient power to show a benefit. We therefore have to rely on health economic models. The two strategies that H. pylori needs to be compared with are do nothing or acid suppressive therapy which has also been shown to have a small but statistically significant effect in reducing functional dyspepsia symptoms.30 Functional dyspepsia is a chronic relapsing and remitting disorder and therefore the modelling process should take this into account by evaluating symptoms over time. A Markov model is therefore the most appropriate technique to use and Monte Carlo simulation can also be performed to explore the effect of uncertainty in the costs and benefits of the strategies being compared. This approach was taken in a model comparing PPI therapy and H. pylori eradication therapy and found that the latter was more cost-effective.31 This was because acid suppression is effective but requires the patient to continue taking drugs long term whilst H. pylori is a one-week course of antibiotics that still reduces functional dyspepsia symptoms one year later.28 The other comparison that should be considered is whether it is worth treating functional dyspepsia at all and therefore a model should also be constructed comparing H. pylori eradication with no therapy. This has been reported for the UK26 and the model was updated using the same assumptions but evaluating the costs in a variety of European countries and the US. A Markov model (TreeAge DataPro version 4 - TreeAge Software Inc, Williamstown MA, USA) was constructed to compare H. pylori eradication with antacid (presumed to be an inexpensive placebo) in functional dyspepsia patients over a 12-month time frame. It was assumed that if patients continued to experience symptoms after therapy then they would visit their primary care physician on average three times in one year and would be given lifestyle advice. UK drug costs were obtained from the relevant National Formulary and primary care visits valued according to National guidelines. The relative risk of dyspepsia in patients treated with H. pylori eradication therapy was assumed to have a normal distribution with a mean and standard deviation derived from the pooled estimate from the Cochrane meta-analysis.29 A probabilistic sensitivity analysis was then conducted using Monte Carlo simulation of 5000 and results were expressed as a cost effectiveness acceptability curve (Figure 3). The model suggested that the H. pylori eradication strategy cost an extra $16 and patients obtained on average an extra 0.61 months free from dyspepsia giving a costeffectiveness ratio of $26/extra month free from dyspepsia. This is the average incremental cost effectiveness ratio and does not take into account the uncertainty in the data. Including the uncertainty in the data there is a 95% probability that H. pylori

354 P. Moayyedi

Probability cost effective

1.0 0.9 0.8 0.7 USA

0.6 0.5

UK

0.4

Italy

0.3

Germany

0.2

Spain

0.1 0.0 0

50

100

150

200

250

300

350

Willingness to Pay/month free from dyspepsia (€/$) Figure 3. Cost effectiveness acceptability curves for H. pylori eradication compared to antacid therapy for functional dyspepsia in different countries.

eradication will be a cost-effective in functional dyspepsia provided the patient is willing to pay $51/month free from dyspepsia (Figure 3). All European countries give similar results and the cost is much less than patients state they would be willing to pay to relieve dyspepsia symptoms32,33 so this is very likely to be cost-effective. In the US the incremental cost effectiveness ratio is higher due to the higher cost of eradication therapy with an average incremental cost effectiveness ratio is $150/month free from dyspepsia and the patient (or third party payer) needs to be willing to pay $300/month free from dyspepsia before we can be 95% certain that this strategy is cost-effective. This is more than patients state they would be willing to pay per month free from dyspepsia and it is not clear whether this is a cost-effective strategy in the US. These data emphasise that cost-effectiveness will vary in different countries even if the effect of treatment remains the same. UNDIAGNOSED DYSPEPSIA The previous sections assumed the dyspepsia patient had an endoscopy to define the diagnosis. Dyspepsia is a common problem with up to 40% of the population complaining of upper gastrointestinal symptoms34 and in primary care it is not possible to endoscope everyone. An estimated $1.1 billion is spent by the UK health service each year35 on dyspepsia and this figure is set to rise as demand for endoscopy is increasing.36 Every health care system therefore has to ration the availability of endoscopy in some way. The main driving force for endoscopy is the belief that early investigation will result in early gastric cancer being detected.37 Approximately one third of endoscopies are performed in patients <50 years old where gastric cancer is very rare.38 One obvious approach to this problem therefore, is to reduce the number of endoscopies performed in young patients. Guidelines from developed countries all advocate this strategy suggesting that uncomplicated dyspepsia patients under the age of 5039 or 55 years40e42 should not routinely have endoscopy. Opponents of this policy contend that endoscopy helps rationalise therapy and a randomised controlled trial showed early investigation was more cost-effective than empirical acid suppression with H2 receptor antagonists.43 This study was conducted before H. pylori test and treat had been proposed and a more sophisticated

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empirical strategy would be to offer a non-invasive test for H. pylori and those that are positive given eradication therapy. Patients not infected with H. pylori would be offered acid suppression with proton pump inhibitors as would positive patients that remained symptomatic after eradication therapy.44 An H. pylori test and treat strategy has been shown to reduce endoscopy workload that persists for at least five years.45 Furthermore, in contrast to peptic ulcer disease and functional dyspepsia there are a number of RCTs that have evaluated the cost-effectiveness of H. pylori test and treat compared to endoscopy. It is therefore possible to use primary data to establish the most costeffective strategy for managing dyspepsia rather than relying on health economic models. A systematic review identified five cost-effective RCTs46e50 comparing endoscopy with H. pylori test and treat involving almost 2000 participants. Pooling the data should allow a precise estimate of the costs and the benefits of these competing approaches but this raises another problem with economic analysis. Studies were performed in the UK, Holland and Denmark and different unit costs were applied to each item of resource use. Furthermore, traditional methods of meta-analysis to pool cost-effectiveness cannot be used as it is incorrect to pool costs and effects separately. This is because costs and effects are correlated at the individual patient level.51 For example, a patient who is cured of symptoms is likely to consume fewer health service dyspepsia resources. An individual patient data systematic review52 was therefore conducted that prospectively obtained costs and outcomes from the five RCTs at an individual patient level. The same costs could be applied to the resources used in each of the trials and an analysis could be performed that would take into account the fact that costs and outcomes are correlated. This analysis showed that endoscopy was more effective than H. pylori test and treat in curing dyspepsia at one year but that this effect was small (relative risk of remaining dyspeptic in endoscopy arm ¼ 0.95; 95% CI ¼ 0.92 to 0.99).52 Endoscopy was also more expensive, with H. pylori test and treat costing $389 (95% CI ¼ $275 to $502) less per patient using US costs.52 It is estimated that on average endoscopy was costing $9,000 per cure of dyspepsia at one year compared to an H. pylori test and treat strategy. Taking into account the uncertainty in the data a third party payer would need to be willing to pay approximately $180,000 per cure of dyspepsia at one year to be 95% certain that a prompt endoscopy strategy is cost-effective. This is too expensive for any society to afford and suggests the slightly less effective but much cheaper H. pylori test and treat strategy should be employed. This has been a recommended strategy by all major recent dyspepsia guidelines.39e42,53 There is still the question of whether H. pylori test and treat is more cost-effective than empirical acid suppression with proton pump inhibitors. There have been five RCTs50,54e57 that have compared these strategies but some have not included costs and the papers are too heterogeneous to pool. The most comprehensive study was a cluster randomised Danish trial57 that compared primary care centres allocated to empirical PPI therapy, H. pylori test and treat, or empirical PPI therapy followed by H. pylori test and treat if symptoms did not resolve. Seven hundred and twentytwo dyspepsia patients were included in the study and there was no difference in dyspepsia scores, patient satisfaction or quality of life between the three groups. Endoscopy utilisation was statistically significantly higher in the empirical PPI arm and health service dyspepsia costs were lower in the H. pylori test and treat arms although this did not reach statistical significance.57 Dyspepsia improvement was most marked in H. pylori positive patients receiving eradication therapy. This is consistent with three randomised controlled trials58e60 that have compared H. pylori eradication with placebo antibiotics (all received acid suppression) in infected dyspepsia subjects in

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primary care. H. pylori eradication was superior to placebo (RR ¼ 0.82, 95% CI ¼ 0.73 to 0.91) with a number needed to treat of nine (95% CI ¼ 6 to 20).61 The health service dyspepsia costs from these trials were lower in the H. pylori test and treat arm62 but this did not reach statistical significance in any of the studies. As yet an individual patient data meta-analysis has not been performed on these data. Overall these data suggest that H. pylori test and treat is more cost-effective than empirical PPI therapy in infected dyspepsia patients. As the prevalence of H. pylori in the population falls, infection will become a rare event and in these circumstances it is likely that empirical acid suppression will become the most appropriate management plan.63 GASTRIC CANCER Gastric cancer is the second most common cancer killer world wide.64 H. pylori has been implicated as the main cause of distal gastric cancer65 as it causes a chronic active gastritis that leads to pre-malignant changes of intestinal metaplasia, gastric atrophy and dysplasia.66 There is emerging randomised controlled trial evidence that H. pylori eradication may arrest or reverse these changes in the gastric mucosa.67e69 The question is whether a population H. pylori test and treat strategy will reduce mortality from gastric cancer.70 There have been randomised controlled trials that have addressed this issue68,69,71 but none has been sufficiently powered to demonstrate a significant effect of H. pylori eradication in preventing distal gastric cancer. Two randomised controlled trials have evaluated the cost savings that might accrue from such a program and both suggest that population H. pylori test and treat results in health service dyspepsia cost savings.72,73 Indeed on trial suggested the program may become cost saving after ten years74 although this study did not discount costs (i.e. did not account for the money spent up front is worth ‘more’ than money saved in the future). We are therefore in the unusual situation of having more information about the economic outcomes of population H. pylori test and treat than the efficacy of the strategy. This poses a problem for economic analyses as it is not possible to definitively model whether H. pylori eradication is a cost-effective strategy in preventing distal gastric cancer. If a strategy is completely ineffective, it does not matter how cheap it is to deliver as it will not be cost effective. Economics models are still useful, however, as they can evaluate whether it is worth investing in a trial in the first place by asking the question ‘if H. pylori test and treat prevents distal gastric cancer then will it be cost-effective?’ There have been a number of health economic models using a variety of assumptions and techniques.72,75e81 All models suggest that H. pylori test and treat is cost-effective under most reasonable assumptions and this provides a clear mandate for trials. In contrast to the other examples however it does not provide a clear answer as to whether we should adopt this strategy at the moment as there is insufficient information. CONCLUSIONS Health economics has become increasingly sophisticated in helping clinicians make decisions on the most cost-effective interventions to provide for their patients. The cost-effectiveness plane is particularly helpful and the role of H. pylori eradication is a good example of this. H. pylori test and treat is cost-effective in a number of clinical settings but the rationale behind this decision varies and this strategy occupies three out of the four quadrants on the cost-effectiveness plane (Figure 4). H. pylori

The health economics of Helicobacter pylori infection 357 New treatment more expensive

Willingness to pay per unit of treatment effect

New treatment more effective

New treatment less effective

New treatment less expensive

Figure 4. Where H. pylori test and treat in a variety of clinical scenarios falls on the cost-effectiveness plane. Points falling below and to the right of the dotted line suggest H. pylori test and treat is cost-effective. Red dot, H. pylori test and treat compared to endoscopy in undiagnosed dyspepsia; blue dot, H. pylori eradication compared to maintenance acid suppression peptic ulcer disease; green dot, H. pylori eradication compared to no treatment in functional dyspepsia.

eradication is preferable to long term acid suppression as it is cheaper and more effective (bottom right hand corner of the cost-effectiveness plane) (Figure 4). H. pylori eradication is also cost-effective in infected functional dyspepsia patients as it is more expensive but more effective than antacid therapy and the cost/per month free from dyspepsia is acceptable in most countries (top right-hand corner of the graph) (Figure 4). H. pylori test and treat is also more cost-effective than endoscopy in undiagnosed dyspepsia as although it is slightly less effective, it is much cheaper (bottom left-hand corner of the cost-effectiveness plane) (Figure 4). Health economic analysis has also developed methods of expressing uncertainty in the data so we can ensure these decisions are robust. We can be confident that H. pylori test and treat is a cost-effective strategy for peptic ulcer disease, functional dyspepsia and undiagnosed dyspepsia as sufficient data exist. This is in contrast to population H. pylori test and treat to prevent distal gastric cancer, where there is insufficient information and all health economics can tell us is that more data is needed. REFERENCES 1. Boonen A, Severens JL & van der Linden S. A tale of two cities: hospitalization costs in 1897 and 1997. Int J Tech Assess Health Care 2004; 20: 236e241.

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