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1.  Treating Helicobacter pylori infection in primary care patients with uninvestigated dyspepsia: the Canadian adult dyspepsia empiric treatment—Helicobacter pylori positive (CADET-Hp) randomised controlled trial 
BMJ : British Medical Journal  2002;324(7344):1012.
To determine whether a “test for Helicobacter pylori and treat” strategy improves symptoms in patients with uninvestigated dyspepsia in primary care.
Randomised placebo controlled trial.
36 family practices in Canada.
294 patients positive for H pylori (13C- urea breath test) with symptoms of dyspepsia of at least moderate severity in the preceding month.
Participants were randomised to twice daily treatment for 7 days with omeprazole 20 mg, metronidazole 500 mg, and clarithromycin 250 mg or omeprazole 20 mg, placebo metronidazole, and placebo clarithromycin. Patients were then managed by their family physicians according to their usual care.
Main outcome measures
Treatment success defined as no symptoms or minimal symptoms of dyspepsia at the end of one year. Societal healthcare costs collected prospectively for a secondary evaluation of actual mean costs.
In the intention to treat population (n=294), eradication treatment was significantly more effective than placebo in achieving treatment success (50% v 36%; P=0.02; absolute risk reduction=14%; number needed to treat=7, 95% confidence interval 4 to 63). Eradication treatment cured H pylori infection in 80% of evaluable patients. Treatment success at one year was greater in patients negative for H pylori than in those positive for H pylori (54% v 39%; P=0.02). Eradication treatment reduced mean annual cost by $C53 (−86 to 180) per patient.
A “test for H pylori with 13C-urea breath test and eradicate” strategy shows significant symptomatic benefit at 12 months in the management of primary care patients with uninvestigated dyspepsia.
What is already known on this topicDyspepsia is a common problem in primary health care, although controversy exists about its definitionStudies of H pylori eradication in patients with uninvestigated dyspepsia have shown reduced need for endoscopy and thus significant cost savings compared with a strategy of prompt endoscopyThe “test for H pylori and treat” strategy has been recommended for uninvestigated dyspepsia, but there have been no randomised controlled trials showing improvement in symptomsWhat this study addsWhen given eradication treatment in primary care, H pylori positive patients with uninvestigated dyspepsia show improvement in overall dyspepsia symptoms at 12 monthsThis supports the “test for H pylori and treat” strategy
PMCID: PMC102778  PMID: 11976244
2.  Economic Appraisal of Ontario's Universal Influenza Immunization Program: A Cost-Utility Analysis 
PLoS Medicine  2010;7(4):e1000256.
Beate Sander and colleagues assess the cost-effectiveness of the program that provides free seasonal influenza vaccines to the entire population of Ontario, Canada.
In July 2000, the province of Ontario, Canada, initiated a universal influenza immunization program (UIIP) to provide free seasonal influenza vaccines for the entire population. This is the first large-scale program of its kind worldwide. The objective of this study was to conduct an economic appraisal of Ontario's UIIP compared to a targeted influenza immunization program (TIIP).
Methods and Findings
A cost-utility analysis using Ontario health administrative data was performed. The study was informed by a companion ecological study comparing physician visits, emergency department visits, hospitalizations, and deaths between 1997 and 2004 in Ontario and nine other Canadian provinces offering targeted immunization programs. The relative change estimates from pre-2000 to post-2000 as observed in other provinces were applied to pre-UIIP Ontario event rates to calculate the expected number of events had Ontario continued to offer targeted immunization. Main outcome measures were quality-adjusted life years (QALYs), costs in 2006 Canadian dollars, and incremental cost-utility ratios (incremental cost per QALY gained). Program and other costs were drawn from Ontario sources. Utility weights were obtained from the literature. The incremental cost of the program per QALY gained was calculated from the health care payer perspective. Ontario's UIIP costs approximately twice as much as a targeted program but reduces influenza cases by 61% and mortality by 28%, saving an estimated 1,134 QALYs per season overall. Reducing influenza cases decreases health care services cost by 52%. Most cost savings can be attributed to hospitalizations avoided. The incremental cost-effectiveness ratio is Can$10,797/QALY gained. Results are most sensitive to immunization cost and number of deaths averted.
Universal immunization against seasonal influenza was estimated to be an economically attractive intervention.
Please see later in the article for the Editors' Summary
Editors' Summary
Annual outbreaks (epidemics) of influenza—a viral disease of the nose, throat, and airways—make millions of people ill and kill about 500,000 individuals every year. In doing so, they impose a considerable economic burden on society in terms of health care costs and lost productivity. Influenza epidemics occur because small but frequent changes in the viral proteins to which the immune system responds mean that an immune response produced one year by exposure to an influenza virus provides only partial protection against influenza the next year. Annual immunization with a vaccine that contains killed influenza viruses of the major circulating strains can boost this natural immunity and greatly reduce a person's chances of catching influenza. Consequently, many countries run seasonal influenza vaccine programs. These programs usually target people at high risk of complications from influenza and individuals likely to come into close contact with them, and people who provide essential community services. So, for example, in most Canadian provinces, targeted influenza immunization programs (TIIPs) offer free influenza vaccinations to people aged 65 years or older, to people with chronic medical conditions, and to health care workers.
Why Was This Study Done?
Some experts argue, however, that universal vaccination might provide populations with better protection from influenza. In 2000, the province of Ontario in Canada decided, therefore, to introduce a universal influenza immunization program (UIIP) to provide free influenza vaccination to everyone older than 6 months, the first large program of this kind in the world. A study published in 2008 showed that, following the introduction of the UIIP, vaccination rates in Ontario increased more than in other Canadian provinces. In addition, deaths from influenza and influenza-related use of health care facilities decreased more in Ontario than in provinces that continued to offer a TIIP. But is universal influenza vaccination good value for money? In this study, the researchers evaluate the cost-effectiveness of the Ontario UIIP by comparing the health outcomes and costs associated with its introduction with the health outcomes and costs associated with a hypothetical continuation of targeted influenza immunization.
What Did the Researchers Do and Find?
The researchers used data on TIIP and UIIP vaccine uptake, physician visits, emergency department visits, hospitalizations for influenza, and deaths from influenza between 1997 and 2004 in Ontario and in nine Canadian states offering TIIPs, and Ontario cost data, in their “cost-utility” analysis. This type of analysis estimates the additional cost required to generate a year of perfect health (a quality-adjusted life-year or QALY) through the introduction of an intervention. QALYs are calculated by multiplying the time spent in a certain health state by a measure of the quality of that health state. The researchers report that the cost of Ontario's UIIP was about twice as much as the cost of a TIIP for the province. However, the introduction of the UIIP reduced the number of influenza cases by nearly two-thirds and reduced deaths from influenza by more than a quarter compared with what would have been expected had the province continued to offer a TIIP, an overall saving of 1,134 QALYs. Furthermore, the reduction in influenza cases halved influenza-related health care costs, mainly because of reductions in hospitalization. Overall, this means that the additional cost to Ontario of saving one QALY through the introduction of the UIIP was Can$10,797, an “incremental cost-effectiveness ratio” of $10,797 per QALY gained.
What Do These Findings Mean?
In Canada, an intervention is considered cost-effective from the point of view of a health care purchaser if it costs less than Canadian $50,000 to gain one QALY. These findings indicate, therefore, that for Ontario the introduction of the UIIP is economically attractive. Indeed, the researchers calculate that even if the costs of the UIIP were to double, the additional cost of saving one QALY by introducing universal immunization would remain below $50,000. Other “sensitivity” analyses undertaken by the researchers also indicate that universal immunization is likely to be effective and cost-effective in Ontario if other key assumptions and/or data included in the calculations are varied within reasonable limits. Given these findings, the researchers suggest that a UIIP might be an appealing intervention in other Canadian provinces and in other high-income countries where influenza transmission and health-care costs are broadly similar to those in Ontario.
Additional Information
Please access these Web sites via the online version of this summary at
A PLoS Medicine Research Article by Kwong and colleagues describes how the introduction of universal influenza immunization in Ontario altered influenza-related health care use and deaths in the province
Wikipedia pages are available on QALYs and on cost-utility analysis (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
Bandolier, an independent online journal about evidence-based health-care, provides information about QALYs and their use in cost-utility analysis
The UK National Institute for Health and Clinical Excellence has a webpage on Measuring effectiveness and cost-effectiveness: the QALY
PMCID: PMC2850382  PMID: 20386727
3.  Efficacy and cost-effectiveness of the 13C-urea breath test as the primary diagnostic investigation for the detection of Helicobacter pylori infection compared to invasive and non-invasive diagnostic tests 
Helicobacter pylori (H. pylori) is one of the most common bacterial infections in humans. There is a risk factor for gastric or duodenal ulcers, gastric cancer and MALT (Mucosa Associated Lymphoid Tissue)-Lymphomas. There are several invasive and non-invasive methods available for the diagnosis of H. pylori. The 13C-urea breath test is a non-invasive method recommended for monitoring H. pylori eradication therapy. However, this test is not yet used for primary assessment of H. pylori in Germany.
What are the clinical and health economic benefits of the 13C-urea breath test in the primary assessment of H. pylori compared to other invasive and non-invasive methods?
A systematic literature search including a hand search was performed for studies investigating test criteria and cost-effectiveness of the 13C-urea breath test in comparison to other methods used in the primary assessment of H. pylori. Only studies that directly compared the 13C-urea breath test to other H. pylori-tests were included. For the medical part, biopsy-based tests were used as the gold standard.
30 medical studies are included. Compared to the immunoglobulin G (IgG) test, the sensitivity of the 13C-urea breath test is higher in twelve studies, lower in six studies and one study reports no differences. The specificity is higher in 13 studies, lower in three studies and two studies report no differences. Compared to the stool antigen test, the sensitivity of the 13C-urea breath test is higher in nine studies, lower in three studies and one study reports no difference. The specificity is higher in nine studies, lower in two studies and two studies report no differences. Compared to the urease test, the sensitivity of the 13C-urea breath test is higher in four studies, lower in three studies and four studies report no differences. The specificity is higher in five studies, lower in five studies and one study reports no difference. Compared to histology, the sensitivity of the 13C-urea breath test is higher in one study and lower in two studies. The specificity is higher in two studies and lower in one study. One study each compares the 13C-urea breath test to the 14C-urea breath test and the polymerase chain reaction (PCR) test, respectively, and reports no difference in sensitivity and specificity with the 14C-urea breath test, and lower sensitivity and higher specificity compared to PCR. The statistical significance of these differences is described for six of the 30 studies.
Nine health economic evaluations are included in the Health Technology Assessment (HTA) report. Among these studies, the test-and-treat strategy using the 13C-urea breath test is compared to test-and-treat using serology in six analyses and to test and treat using the stool antigen test in three analyses. Thereby, test-and-treat using the breath test is shown to be cost-effective over the serology based strategy in three models and is dominated by a test-and-treat strategy using the stool antigen test in one model. A cost-effectiveness comparison between the urea breath test approach and the empirical antisecretory therapy is carried out in four studies. Of these, two studies report that the strategy using the urea breath test is cost-effective over the empirical antisecretory therapy. In two studies, test-and-treat using the 13C-urea breath test is compared to the empirical eradication therapy and in five studies to endoscopy-based strategies. The breath test approach dominates endoscopy in two studies and is dominated by this strategy in one study.
All included medical and economic studies are limited to a greater or lesser extent. Additionally, the results of the studies are heterogeneous regarding medical and economic outcomes respectively. Thus, the majority of the medical studies do not report the statistical significance of the differences in sensitivity and specificity. In direct comparisons the 13C- urea breath test shows higher sensitivity and specificity than the IgG and stool antigen tests. In comparison to the urease test, results for sensitivity are inconsistent, and the specificity is slightly higher for the 13C-urea breath test. There are not enough results for comparisons between the 13C-urea breath test and the 14C-urea breath test, histology and PCR to describe tendencies.
The included economic studies suggest that the test-and-treat strategy using the 13C-urea breath test is cost-effective compared to test-and-treat using serology as well as empirical antisecretory therapies. Due to a lack of valid studies, it is not possible to assess the breath test approach in comparison to test-and-treat using the stool antigen test and the empirical eradication therapy respectively, regarding the cost-effectiveness. The results of economic analyses comparing test-and-treat using the breath test to endoscopy strategies are too heterogeneous to draw any conclusions. Overall, none of the included economic models is able to completely capture the complexity of managing patients with dyspeptic complaints.
Based on available medical and economic studies, there is no sufficient evidence to recommend test and-treat using 13C-urea breath testing for the detection of H. pylori infection as the standard procedure for the management of uninvestigated dyspepsia in the German health care system. In addition, it must be considered that the DVGS guidelines of the Deutsche Gesellschaft für Verdauungs- und Stoffwechselkrankheiten (DVGS) recommend endoscopy based methods for the management of patients with dyspeptic complaints.
PMCID: PMC3011289  PMID: 21289901
4.  Symptomatic gastro-oesophageal reflux disease: double blind controlled study of intermittent treatment with omeprazole or ranitidine 
BMJ : British Medical Journal  1999;318(7182):502-507.
To assess intermittent treatment over 12 months in patients with symptomatic gastro-oesophageal reflux disease.
Randomised, multicentre, double blind, controlled study. Patients with heartburn and normal endoscopy results or mild erosive changes received omeprazole 10 mg or 20 mg daily or ranitidine 150 mg twice daily for 2 weeks. Patients remaining symptomatic had omeprazole 10 mg or ranitidine dose doubled for another 2 weeks while omeprazole 20 mg was continued for 2 weeks. Patients who were symptomatic or mildly symptomatic were followed up for 12 months. Recurrences of moderate or severe heartburn during follow up were treated with the dose which was successful for initial symptom control.
Hospitals and primary care practices between 1994 and 1996.
677 patients with gastro-oesophageal reflux disease.
Main outcome measures
Total time off active treatment, time to failure of intermittent treatment, and outcomes ranked from best to worst.
704 patients were randomised, 677 were eligible for analyses; 318 reached the end of the study with intermittent treatment without recourse to maintenance antisecretory drugs. The median number of days off active treatment during follow up was 142 for the entire study (281 for the 526 patients who reached a treatment related end point). Thus, about half the patients did not require treatment for at least 6 months, and this was similar in all three treatment groups. According to outcome, 378 (72%) patients were in the best outcome ranks (no relapse or one (or more) relapse but in remission until 12 months); 630 (93%) had three or fewer relapses in the intermittent treatment phase. Omeprazole 20 mg provided faster relief of heartburn. The results were similar in patients with erosive and non-erosive disease.
Intermittent treatment is effective in managing symptoms of heartburn in half of patients with uncomplicated gastro-oesophageal reflux disease. It is simple and applicable in general practice, where most patients are seen.
Key messagesSymptomatic gastro-oesophageal disease can be managed successfully in half of patients with intermittent treatment with antisecretory drugsOmeprazole 20 mg once daily gives more rapid relief of symptoms than either omeprazole 10 mg once daily or ranitidine 150 mg twice daily. However, the choice of antisecretory drug has little effect on the overall outcomeRelapses are relatively infrequent and can be managed with short courses of repeat treatmentStarting intermittent treatment with omeprazole 20 mg once daily is more cost effective than a dose titration approach with omeprazole 10 mg once daily or ranitidine 150 mg twice dailyAn intermittent treatment strategy is simple and applicable in general practice, where most of these patients are seen
PMCID: PMC27748  PMID: 10024259
5.  The Stretta procedure versus proton pump inhibitors and laparoscopic Nissen fundoplication in the management of gastroesophageal reflux disease: A cost-effectiveness analysis 
The Stretta procedure is an endoscopic therapy for gastroesophageal reflux disease.
To evaluate the cost-effectiveness of the Stretta procedure and that of competing strategies in the long-term management of gastroesophageal reflux disease.
A Markov model was designed to estimate costs and health outcomes in Canadian patients with gastroesophageal reflux disease over five years, from a Ministry of Health perspective. Strategies included the use of daily proton pump inhibitors (PPIs), laparoscopic Nissen fundoplication (LNF) and the Stretta procedure. Probabilities and utilities were derived from the literature. Costs are expressed in 2006 Canadian dollars. Units of effectiveness were symptom-free months (SFMs) and quality-adjusted life years (QALYs), using a five-year time horizon.
In the analysis that used SFMs, the strategy using PPIs exhibited the lowest costs ($40 per SFM) and the greatest number of SFMs, thus dominating both the LNF and Stretta systems. But the cost-effectiveness analysis using QALYs as the measure of effectiveness showed that PPIs presented the lowest cost-effectiveness ratio, while both the LNF and Stretta strategies were associated with very high incremental costs (approximately $353,000 and $393,000, respectively) to achieve an additional QALY. However, the PPI strategy did not dominate the two other strategies, which were associated with better effectiveness.
If SFMs are used as the measure of effectiveness, PPIs dominate the Stretta and LNF strategies. However, if QALYs are used, the PPIs still present the lowest cost and LNF gives the best effectiveness. Regardless of the units of effectiveness or utility used in the present cost analysis, an approach of prescribing PPIs appears to be the preferred strategy.
PMCID: PMC2660813  PMID: 18560633
GERD; Proton pump inhibitors; Stretta procedure
6.  An evidence-based approach to the management of uninvestigated dyspepsia in the era of Helicobacter pylori 
OBJECTIVES: To provide Canadian primary care physicians with an evidence-based clinical management tool, including diagnostic and treatment recommendations, for patients who present with uninvestigated dyspepsia. RECOMMENDATIONS: The management tool has 5 key decision steps addressing the following: (1) evidence that symptoms originate in the upper gastrointestinal tract, (2) presence of alarm features, (3) use of nonsteroidal anti-inflammatory drugs (NSAIDs), (4) dominant reflux symptoms and (5) evidence of Helicobacter pylori infection. All patients over 50 years of age who present with new-onset dyspepsia and patients who present with alarm features should receive prompt investigation, preferably by endoscopy. The management options for patients with uninvestigated dyspepsia who use NSAIDs regularly are: (1) to stop NSAID therapy and assess symptomatic response, (2) to treat with NSAID prophylaxis if NSAID therapy cannot be stopped or (3) to refer for investigation. Gastroesophageal reflux disease can be diagnosed clinically if the patient's dominant symptoms are heartburn or acid regurgitation, or both; these patients should be treated with acid suppressive therapy. The remaining patients should be tested for H. pylori infection, and those with a positive result should be treated with H. pylori-eradication therapy. Those with a negative result should have their symptoms treated with optimal antisecretory therapy or a prokinetic agent. VALIDATION AND EVIDENCE: Evidence for resolution of the dyspepsia symptoms was the main outcome measure. Supporting evidence for the 5 steps in the management tool and the recommendations for treatment were graded according to the strength of the evidence and were endorsed by consensus of committee members. If no randomized controlled clinical trials were available, the recommendations were based on the best available evidence. LITERATURE REVIEW: Evidence was obtained from MEDLINE searches for pertinent articles published from 1966 to October 1999. The searches focused on dyspepsia, diagnosis and treatment. Additional articles were retrieved through a manual search of bibliographies and abstracts from international gastroenterology conferences.
PMCID: PMC1232536  PMID: 10870511
7.  The impact of incorporating Bayesian network meta-analysis in cost-effectiveness analysis - a case study of pharmacotherapies for moderate to severe COPD 
To evaluate the impact of using network meta-analysis (NMA) versus pair wise meta-analyses (PMA) for evidence synthesis on key outputs of cost-effectiveness analysis (CEA).
We conducted Bayesian NMA of randomized clinical trials providing head-to-head and placebo comparisons of the effect of pharmacotherapies on the exacerbation rate in chronic obstructive pulmonary disease (COPD). Separately, the subset of placebo–comparison trials was used in a Bayesian PMA. The pooled rate ratios (RR) were used to populate a decision-analytic model of COPD treatment to predict 10-year outcomes.
Efficacy estimates from the NMA and PMA were similar, but the NMA provided estimates with higher precision. This resulted in similar incremental cost-effectiveness ratios (ICER). Probabilities of being cost-effective at willingness-to-pay thresholds (WTPs) between $25,000 and $100,000 per quality adjusted life year (QALY) varied considerably between the PMA- and NMA-based approaches. The largest difference in the probabilities of being cost-effective was observed at a WTP of approximately $40,000/QALY. At this threshold, with the PMA-based analysis, ICS, LAMA and placebo had a 43%, 30, and 18% probability of being the most cost-effective. By contrast, with the NMA based approach, ICS, LAMA, and placebo had a 56%, 19%, and 21% probability of being cost-effective. For larger WTP thresholds the probability of LAMA being the most cost-effective became higher than that of ICS. Under the PMA-based analyses the cross-over occurred at a WTP threshold between $60,000/QALY-$65,000/QALY, whereas under the NMA-based approach, the cross-over occurred between $85,000/QALY-$90,000/QALY.
Use of NMAs in CEAs is feasible and, as our case study showed, can decrease uncertainty around key cost-effectiveness measures compared with the use of PMAs. The approval process of health technologies in many jurisdictions requires estimates of comparative efficacy and cost-effectiveness. NMAs play an increasingly important role in providing estimates of comparative efficacy. Their use in the CEAs therefore results in methodological consistency and reduced uncertainty.
PMCID: PMC4007707  PMID: 24625208
Meta-analysis; Multiple treatment comparison; Bayesian analysis; Cost-effectiveness
8.  Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease (COPD) Using an Ontario Policy Model 
Executive Summary
In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions.
After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses.
The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at:
Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework
Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Pulmonary Rehabilitation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Long-Term Oxygen Therapy for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Chronic Respiratory Failure Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Hospital-at-Home Programs for Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Home Telehealth for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease Using an Ontario Policy Model
Experiences of Living and Dying With COPD: A Systematic Review and Synthesis of the Qualitative Empirical Literature
For more information on the qualitative review, please contact Mita Giacomini at:
For more information on the economic analysis, please visit the PATH website:
The Toronto Health Economics and Technology Assessment (THETA) collaborative has produced an associated report on patient preference for mechanical ventilation. For more information, please visit the THETA website:
Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation throughout the airways, parenchyma, and pulmonary vasculature. The inflammation causes repeated cycles of injury and repair in the airway wall— inflammatory cells release a variety of chemicals and lead to cellular damage. The inflammation process also contributes to the loss of elastic recoil pressure in the lung, thereby reducing the driving pressure for expiratory flow through narrowed and poorly supported airways, in which airflow resistance is significantly increased. Expiratory flow limitation is the pathophysiological hallmark of COPD.
Exacerbations of COPD contribute considerably to morbidity and mortality, and impose a burden on the health care system. They are a leading cause of emergency room visits and hospitalizations, particularly in the winter. In Canada, the reported average cost for treating a moderate exacerbation is $641; for a major exacerbation, the cost is $10,086.
The objective of this study was to evaluate the cost-effectiveness and budget impact of the following interventions in moderate to very severe COPD, investigated in the Medical Advisory Secretariat Chronic Obstructive Pulmonary Disease Mega-Analysis Series:
smoking cessation programs in moderate COPD in an outpatient setting:
– intensive counselling (IC) versus usual care (UC)
– nicotine replacement therapy (NRT) versus UC
– IC + NRT versus placebo
– bupropion versus placebo
multidisciplinary care (MDC) teams versus UC in moderate to severe COPD in an outpatient setting
pulmonary rehabilitation (PR) versus UC following acute exacerbations in moderate to severe COPD
long-term oxygen therapy (LTOT) versus UC in severe hypoxemia in COPD in an outpatient setting
– noninvasive positive pressure ventilation (NPPV) + usual medical care versus usual medical care in acute respiratory failure due to an acute exacerbation in severe COPD in an inpatient setting
– weaning with NPPV versus weaning with invasive mechanical ventilation in acute respiratory failure due to an acute exacerbation in very severe COPD in an inpatient setting
A cost-utility analysis was conducted using a Markov probabilistic model. The model consists of different health states based on the Global Initiative for Chronic Obstructive Lung Disease COPD severity classification. Patients were assigned different costs and utilities depending on their severity health state during each model cycle. In addition to moving between health states, patients were at risk of acute exacerbations of COPD in each model cycle. During each cycle, patients could have no acute exacerbation, a minor acute exacerbation, or a major exacerbation. For the purposes of the model, a major exacerbation was defined as one that required hospitalization. Patients were assigned different costs and utilities in each model cycle, depending on whether they experienced an exacerbation, and its severity.
Starting cohorts reflected the various patient populations from the trials analyzed. Incremental cost-effectiveness ratios (ICERs)—that is, costs per quality-adjusted life-year (QALY)—were estimated for each intervention using clinical parameters and summary estimates of relative risks of (re)hospitalization, as well as mortality and abstinence rates, from the COPD mega-analysis evidence-based analyses.
A budget impact analysis was also conducted to project incremental costs already being incurred or resources already in use in Ontario. Using provincial data, medical literature, and expert opinion, health system impacts were calculated for the strategies investigated.
All costs are reported in Canadian dollars.
All smoking cessation programs were dominant (i.e., less expensive and more effective overall). Assuming a base case cost of $1,041 and $1,527 per patient for MDC and PR, the ICER was calculated to be $14,123 per QALY and $17,938 per QALY, respectively. When the costs of MDC and PR were varied in a 1-way sensitivity analysis to reflect variation in resource utilization reported in the literature, the ICER increased to $55,322 per QALY and $56,270 per QALY, respectively. Assuming a base case cost of $2,261 per year per patient for LTOT as reported by data from the Ontario provincial program, the ICER was calculated to be $38,993 per QALY. Ventilation strategies were dominant (i.e., cheaper and more effective), as reflected by the clinical evidence of significant in-hospital days avoided in the study group.
Ontario currently pays for IC through physician billing (translating to a current burden of $8 million) and bupropion through the Ontario Drug Benefit program (translating to a current burden of almost $2 million). The burden of NRT was projected to be $10 million, with future expenditures of up to $1 million in Years 1 to 3 for incident cases.
Ontario currently pays for some chronic disease management programs. Based on the most recent Family Health Team data, the costs of MDC programs to manage COPD were estimated at $85 million in fiscal year 2010, with projected future expenditures of up to $51 million for incident cases, assuming the base case cost of the program. However, this estimate does not accurately reflect the current costs to the province because of lack of report by Family Health Teams, lack of capture of programs outside this model of care by any data set in the province, and because the resource utilization and frequency of visits/follow-up phone calls were based on the findings in the literature rather than the actual Family Health Team COPD management programs in place in Ontario. Therefore, MDC resources being utilized in the province are unknown and difficult to measure.
Data on COPD-related hospitalizations were pulled from Ontario administrative data sets and based on consultation with experts. Half of hospitalized patients will access PR resources at least once, and half of these will repeat the therapy, translating to a potential burden of $17 million to $32 million, depending on the cost of the program. These resources are currently being absorbed, but since utilization is not being captured by any data set in the province, it is difficult to quantify and estimate. Provincial programs may be under-resourced, and patients may not be accessing these services effectively.
Data from the LTOT provincial program (based on fiscal year 2006 information) suggested that the burden was $65 million, with potential expenditures of up to $0.2 million in Years 1 to 3 for incident cases.
From the clinical evidence on ventilation (i.e., reduction in length of stay in hospital), there were potential cost savings to the hospitals of $42 million and $12 million for NPPV and weaning with NPPV, respectively, if the study intervention were adopted. Future cost savings were projected to be up to $4 million and $1 million, respectively, for incident cases.
Currently, costs for most of these interventions are being absorbed by provider services, the Ontario Drug Benefit Program, the Assistive Devices Program, and the hospital global budget. The most cost-effective intervention for COPD will depend on decision-makers’ willingness to pay. Lack of provincial data sets capturing resource utilization for the various interventions poses a challenge for estimating current burden and future expenditures.
PMCID: PMC3384363  PMID: 23074422
9.  Cost-Effectiveness of Various Interventions for Newly Diagnosed Diabetic Macular Edema 
Ophthalmology  2013;120(9):1835-1842.
Anti-vascular endothelial growth factor therapies have revolutionized the treatment of clinically significant diabetic macular (CSDME); yet these agents are expensive, and whether they are cost-effective is unclear. The purpose of this study is to determine the most cost-effective treatment option for patients with newly diagnosed CSDME: focal laser photocoagulation alone (L), focal laser plus intravitreal ranibizumab (L+R), focal laser plus intravitreal bevacizumab (L+B), or focal laser plus intravitreal triamcinolone (L+T) injections.
Cost effectiveness analysis
Hypothetical cohort of 57 year old patients with newly-diagnosed CSDME.
Using a Markov model with a 25-year time horizon, we compared the incremental cost-effectiveness of treating patients with newly-diagnosed CSDME using L, L+R, L+B, or L+T. Data came from the DRCRnet randomized controlled trial, the Medicare Fee Schedule, and the medical literature.
Main Outcome Measures
Costs, quality-adjusted life years (QALYs), and incremental costs per QALY gained.
Compared with L, the incremental cost-effectiveness of L+R and L+B were $89,903/QALY and $11,138/QALY, respectively. L+T was dominated by L. A probabilistic sensitivity analysis demonstrated, at a willingness-to-pay (WTP) of $50,000/QALY, that L was approximately 70% likely to be the preferred therapy over L+R and L+T. However, at a WTP of $100,000/QALY, more than 90% of the time, L+R therapy was the preferred therapy, compared with L and L+T. In the probabilistic sensitivity analysis, L+B was found to be the preferred therapy over L and L+T for any WTP value above $10,000/QALY. Sensitivity analyses revealed that the annual risk of cerebrovascular accident would have to be at least 1.5% higher with L+B than with L+R for L+R to be the preferred treatment. In another sensitivity analysis, if patients require < 8 injections per year over the remainder of the 25-year time horizon, L+B would cost less than $100,000/QALY, whereas L+R would be cost-effective at a WTP of $100,000/QALY if patients require fewer than 0.45 injections per year after year 2.
With bevacizumab and ranibizumab assumed to have equivalent effectiveness and similar safety profiles when used in the management of CSDME, bevacizumab therapy confers the greatest value among the different treatment options for CSDME.
PMCID: PMC3737388  PMID: 23642372
10.  Varying efficacy of Helicobacter pylori eradication regimens: cost effectiveness study using a decision analysis model 
BMJ : British Medical Journal  1998;316(7145):1648-1654.
Objective: To determine how small differences in the efficacy and cost of two antibiotic regimens to eradicate Helicobacter pylori can affect the overall cost effectiveness of H pylori eradication in duodenal ulcer disease.
Design: A decision analysis to examine the cost effectiveness of eight H pylori eradication strategies for duodenal ulcer disease with and without 13C-urea breath testing to confirm eradication.
Main outcome measures: Cumulative direct treatment costs per 100 patients with duodenal ulcer disease who were positive for H pylori.
Results: In model 1 the strategy of omeprazole, clarithromycin, and metronidazole alone was the most cost effective of the four strategies assessed. The addition of the 13C-urea breath test and a second course of omeprazole, clarithromycin, and metronidazole achieved the highest eradication rate (97%) but was the most expensive (£62.63 per patient). The cost of each additional effective eradication was £589.00 (incremental cost per case) when compared with the cost of treating once only with omeprazole, clarithromycin, and metronidazole; equivalent to the cost of a patient receiving ranitidine for duodenal ulcer relapse for more than 15 years. Eradication strategies of omeprazole, amoxycillin, and metronidazole were less cost effective than omeprazole, clarithromycin, and metronidazole alone. In model 2 the addition of the 13C-urea breath test after treatment, and maintenance treatment, increased the cost of all the strategies and reduced the cost advantage of omeprazole, clarithromycin, and metronidazole alone.
Conclusion: Small differences in efficacy can influence the comparative cost effectiveness of strategies for eradicating H pylori. Of the strategies tested the most cost effective (omeprazole, clarithromycin, and metronidazole alone) was neither the least expensive (omeprazole, amoxycillin, and metronidazole alone) nor the most effective (omeprazole, clarithromycin, and metronidazole with further treatment for patients found positive for H pylori on 13C-urea breath testing). Cost effectiveness should be an important part of choosing an eradication strategy for H pylori.
Key messages It is unlikely that randomised controlled trials to examine the effect of small differences in efficacy and cost between eradication regimens will ever be performed because of the large numbers of patients required Decision analysis models show that relatively small differences in efficacy and cost between several strategies for eradication of H pylori in patients with duodenal ulcer disease lead to large differences in their relative cost effectiveness The most cost effective strategy was neither the least expensive nor the most effective for eradication of H pylori For uncomplicated duodenal ulcer disease performing a 13C-urea breath test to identify patients failing eradication treatment is not cost effective if patients only receive acid suppression treatment for relapses that produce symptoms Performing a 13C-urea breath test to identify patients failing eradication treatment may only be cost effective in high risk patients
PMCID: PMC28565  PMID: 9603748
11.  MRI-Guided Focused Ultrasound Surgery for Uterine Fibroid Treatment: A Cost-Effectiveness Analysis 
To evaluate the cost-effectiveness of a treatment strategy for symptomatic uterine fibroids that employs Magnetic Resonance guided Focused Ultrasound (MRgFUS) as a first-line therapy relative to uterine artery embolization (UAE) or abdominal hysterectomy (HYST).
Materials and Methods
We developed a decision-analytic model to compare the cost-effectiveness of three treatment strategies: MRgFUS, UAE and HYST. Short and long-term utilities specific to each treatment were incorporated, allowing us to account for differences in quality of life across the strategies considered. Lifetime costs and quality-adjusted life-years (QALYs) were calculated for each strategy. An incremental cost-effectiveness analysis was performed, using a societal willingness-to-pay (WTP) threshold of $50,000 per QALY to designate a strategy as cost-effective. Sensitivity analysis was performed on all key model parameters.
In the base-case analysis, in which treatment for symptomatic fibroids started at age 40, UAE was the most effective and expensive strategy (22.81 QALYs, $22,164), followed by MRgFUS (22.80 QALYs, $19,796) and HYST (22.60 QALYs, $13,291). MRgFUS was cost-effective relative to HYST, with an associated incremental cost-effectiveness ratio (ICER) of $33,110/QALY. MRgFUS was also cost-effective relative to UAE – the ICER of UAE relative to MRgFUS ($270,057) far exceeded the WTP threshold of $50,000/QALY. In sensitivity analysis, results were robust to changes in most parameters, but were sensitive to changes in probabilities of recurrence and symptom relief following certain procedures, and quality of life associated with symptomatic fibroids.
MRgFUS is cost-effective relative to both UAE and hysterectomy for the treatment of women with symptomatic fibroids.
PMCID: PMC4321860  PMID: 25055272
12.  Cryptococcal Meningitis Treatment Strategies in Resource-Limited Settings: A Cost-Effectiveness Analysis 
PLoS Medicine  2012;9(9):e1001316.
David Boulware and colleagues assess the cost effectiveness of different treatment strategies in low- and middle-income countries for cryptococcal meningitis, one of the most common opportunistic infections of people with HIV.
Cryptococcal meningitis (CM) is the most common form of meningitis in Africa. World Health Organization guidelines recommend 14-d amphotericin-based induction therapy; however, this is impractical for many resource-limited settings due to cost and intensive monitoring needs. A cost-effectiveness analysis was performed to guide stakeholders with respect to optimal CM treatment within resource limitations.
Methods and Findings:
We conducted a decision analysis to estimate the incremental cost-effectiveness ratio (ICER) of six CM induction regimens: fluconazole (800–1,200 mg/d) monotherapy, fluconazole + flucytosine (5FC), short-course amphotericin (7-d) + fluconazole, 14-d of amphotericin alone, amphotericin + fluconazole, and amphotericin + 5FC. We computed actual 2012 healthcare costs in Uganda for medications, supplies, and personnel, and average laboratory costs for three African countries. A systematic review of cryptococcal treatment trials in resource-limited areas summarized 10-wk survival outcomes. We modeled one-year survival based on South African, Ugandan, and Thai CM outcome data, and survival beyond one-year on Ugandan and Thai data. Quality-adjusted life years (QALYs) were determined and used to calculate the cost-effectiveness ratio and ICER. The cost of hospital care ranged from $154 for fluconazole monotherapy to $467 for 14 d of amphotericin + 5FC. Based on 18 studies investigating outcomes for HIV-infected individuals with CM in resource-limited settings, the estimated mean one-year survival was lowest for fluconazole monotherapy, at 40%. The cost-effectiveness ratio ranged from $20 to $44 per QALY. Overall, amphotericin-based regimens had higher costs but better survival. Short-course amphotericin (1 mg/kg/d for 7 d) with fluconazole (1,200 mg/d for14 d) had the best one-year survival (66%) and the most favorable cost-effectiveness ratio, at $20.24/QALY, with an ICER of $15.11 per additional QALY over fluconazole monotherapy. The main limitation of this study is the pooled nature of a systematic review, with a paucity of outcome data with direct comparisons between regimens.
Short-course (7-d) amphotericin induction therapy coupled with high-dose (1,200 mg/d) fluconazole is “very cost effective” per World Health Organization criteria and may be a worthy investment for policy-makers seeking cost-effective clinical outcomes. More head-to-head clinical trials are needed on treatments for this neglected tropical disease.
Please see later in the article for the Editors' Summary.
Editors' Summary
Cryptococcal meningitis, a fungal infection of the membranes around the brain and spinal cord, affects about a million people every year (most of them living in sub-Saharan Africa and Southeast Asia) and kills about 640,000 people annually. People become infected with Cryptococcus neoformans, the fungus that causes cryptococcal meningitis and which is found in soil and dirt, by breathing it in. In healthy individuals, infection rarely causes disease. But in people living with AIDS, whose immune system has been damaged by HIV infection, and in people whose immune system is compromised for other reasons, the fungus can invade and damage many organs, including the brain. Cryptococcal meningitis, the symptoms of which include fever, stiff neck, headache, and vomiting, is diagnosed by looking for the fungus in fluid taken from the spinal cord in a procedure called a lumbar puncture. Cryptococcal meningitis is treated with antifungal drugs such as amphotericin, fluconazole, and flucytosine (induction therapy); recurrence of the infection is prevented by taking fluconazole daily for life or until the immune system recovers.
Why Was This Study Done?
The World Health Organization (WHO) recommends a 14-day regimen of intravenous (injected) amphotericin and oral flucytosine or fluconazole for induction therapy of cryptococcal meningitis. Unfortunately, this regimen is impractical in many resource-limited settings because of the cost of the drugs and hospital care and the need for intensive monitoring—amphotericin is extremely toxic. Consequently, high-dose fluconazole monotherapy is the usual treatment for cryptococcal meningitis in resource-limited countries, although this regimen is much less effective. Another regimen that has improved survival in trials is flucytosine with fluconazole for two weeks. However, flucytosine is very expensive and is not licensed in most sub-Saharan African countries. Stakeholders in developing countries badly need guidance, therefore, on which induction treatment for cryptococcal meningitis they should recommend to optimize outcomes in their particular countries. In this cost-effectiveness analysis (a study that compares the costs and health effects of different interventions), the researchers use costs in Uganda to estimate the survival, cost, and cost per benefit associated with various induction treatments for cryptococcal meningitis in HIV-infected patients.
What Did the Researchers Do and Find?
The researchers calculated the overall cost of six induction treatments using 2012 healthcare costs in Uganda for medications, supplies, and hospital care, and average laboratory costs for monitoring treatment from three African countries. They used data from published trials of cryptococcal meningitis treatment in resource-limited areas to estimate ten-week and one-year survival, life expectancy, and quality-adjusted life years (QALYs, the number of years of life added by an intervention, adjusted for the quality of life) for each intervention. Finally, they calculated the cost-effectiveness ratio (cost per QALY gained) and the incremental cost effectiveness ratio (ICER, the additional cost of a treatment strategy compared to fluconazole monotherapy divided by the incremental improvement in QALYs) for each intervention. The estimated costs per person for each induction treatment strategy ranged from US$154 for 14 days of fluconazole monotherapy to US$467 for 14 days of amphotericin plus flucytosine. Estimated average one-year survival was lowest for fluconazole (40%) and highest for short-course (seven days) amphotericin plus 14 days of fluconazole (66%), similar to other amphotericin-based treatments. Cost-effectiveness ratios ranged from US$20 per QALY for short-course amphotericin plus fluconazole to US$44 per QALY for 14 days of amphotericin plus flucytosine. Short-course amphotericin plus fluconazole had the lowest ICER (US$15.11 per additional QALY over fluconazole monotherapy).
What Do These Findings Mean?
These findings suggest that, among the treatments investigated, a seven-day course of amphotericin with high-dose fluconazole for at least two weeks is the most cost-effective induction treatment for cryptococcal meningitis in Uganda. Although this result should be generalizable to other African countries, it needs to be treated with caution because very few trials have actually looked at the clinical effectiveness of this particular regimen. While short short-course amphotericin appears to be substantially more effective than fluconazole monotherapy, large-scale trials comparing short-course amphotericin regimens with more traditional 14-day regimens in resource-limited countries must be undertaken before short-course amphotericin-based treatments are adopted. Notably, however, if these trials confirm that survival with short-course amphotericin with fluconazole is about 30% better than with fluconazole alone, the researchers calculate that moving to short-course amphotericin could save about 150,000 lives every year in sub-Saharan Africa at a cost of US$220 per life saved.
Additional Information
Please access these websites via the online version of this summary at
This study is further discussed in a PLOS Medicine Perspective by Andrew Farlow provides a clearinghouse for updated guidelines for cryptococcal diagnosis and treatment.
The US Centers for Disease Control and Prevention provides information on Cryptococcus neoformans and a training manual called the Cryptococcal Screening Program Training Manual for Healthcare Providers
NAM/aidsmap provides information about all aspects of infection with Cryptococcus neoformans, including a personal story about cryptococcal meningitis
AIDS InfoNet has a fact sheet on cryptococcal meningitis (in several languages)
The not-for-profit organization Project Inform, which provides information, inspiration, and advocacy for people with HIV/AIDS and hepatitis C (in English and Spanish), has a fact sheet on cryptococcal meningitis
The MedlinePlus encyclopedia has a page on cryptococcal meningitis (in English and Spanish)
PMCID: PMC3463510  PMID: 23055838
Archives of internal medicine  2011;171(3):218-225.
Aspirin reduces myocardial infarction but increases gastrointestinal bleeding. Proton pump inhibitors (PPIs) may reduce upper gastrointestinal bleed. We estimate the cost-utility of aspirin treatment with or without PPI for coronary heart disease (CHD) prevention among men at different risks for CHD and gastrointestinal bleed.
We updated a Markov model to compare costs and outcomes of low-dose aspirin+PPI (omeprazole 20-mg daily), low-dose aspirin alone, or no treatment for CHD prevention. We performed lifetime analyses in men with different risks for cardiovascular events and gastrointestinal bleed. Aspirin reduced nonfatal myocardial infarction by 30%, increased total stroke by 6%, and increased gastrointestinal bleed risk 2-fold. Adding PPI reduced upper gastrointestinal bleed by 80%. Annual aspirin cost was $13.99; generic PPI was $200.
In 45-year-old men with 10-year CHD risk of 10% and 0.8/1,000 annual gastrointestinal bleed risk, aspirin ($17,571 and 18.67 quality-adjusted life years [QALYs]) was more effective and less costly than no treatment ($18,483 and 18.44 QALYs). Compared with aspirin alone, aspirin+PPI ($21,037 and 18.68 QALYs) had an incremental cost/QALY of $447,077. Results were similar in 55- and 65-year-old men. The incremental cost/QALY of adding PPI was less than $50,000/QALY at annual gastrointestinal bleed probabilities greater than 4–6/1,000.
Aspirin for CHD prevention is less costly and more effective than no treatment in men over 45 with greater than 10-year, 10% CHD risks. Adding PPI is not cost-effective for men with average gastrointestinal bleed risk but may be cost-effective for selected men at increased risk for gastrointestinal bleed.
PMCID: PMC3137269  PMID: 21325111
14.  A New Approach to the Management of Uninvestigated Dyspepsia in Primary Care 
Medical Archives  2015;69(2):133-134.
The prevalence of dyspepsia in the general population worldwide is very high (20-40%). Upper abdominal complaints are one of the most common cause of patients’ visits to primary care settings. Making an accurate etiological diagnosis of dyspepsia is difficult, but is an important challenge and goal for every doctor in primary care practice. Clinical guidelines have standards for gastroesophageal reflux disease, management of Helicobacter infection and indications for the use of endoscopy (empiric treatment, prompt endoscopy, “test and treat”). In spite of the application of those standards, many patients experience no improvement in their symptoms or often the recurrence of disease.
This study presents a new approach to the diagnostic and therapeutic management of uninvestigated dyspepsia in primary care settings to provide long-term effective control of symptoms for family doctors.
Material and methods:
3000 unselected consecutive dyspeptic patients underwent abdominal ultrasound, and 1000 dyspeptic patients from the same group upper endoscopy.. In this approach diagnostic evaluation of dyspepsia includes: abdominal ultrasonography as a first line obligatory routine method and the exact estimation of nutritional condition.
Abdominal ultrasound, physical examination and BMI control have significant value in the diagnostic evaluation of dyspepsia. The therapeutic approach includes, besides general standards (acid suppressive drugs, eradication of H. pylori, prokinetic and antidepressant agents), life style modification and nutritional interventions as first-line treatments. In this approach the use of new drugs such as ursodeoxycholic acid (UDCA), pre and probiotics, and digestive enzymes supplements is recommended.
Throug the combination of different diagnostic procedures as first line methods, including abdominal ultrasound and nutritional condition (BMI), a family doctor can manage successfully uninvestigated dyspepsia at the primary care level.
PMCID: PMC4430015  PMID: 26005267
uninvestigated dyspepsia; abdominal ultrasound; obesity; BMI; life-style modifications; primary care
15.  Cost-effectiveness of systemic therapies for metastatic pancreatic cancer 
Current Oncology  2013;20(2):e90-e106.
Gemcitabine and capecitabine (gem-cap), gemcitabine and erlotinib (gem-e), and folfirinox (5-fluorouracil–leucovorin–irinotecan–oxaliplatin) are new treatment options for metastatic pancreatic cancer, but they are also more expensive and potentially more toxic than gemcitabine alone (gem). We conducted a cost-effectiveness analysis of these treatment options compared with gem.
A Markov model was constructed to examine costs and outcomes of gem-cap, gem-e, folfirinox, and gem in patients with metastatic pancreatic cancer from the perspective of a government health care plan. Ontario health economic and costing data (2010 Canadian dollars) were used. Efficacy data for the treatments were obtained from the published literature. Resource utilization data were derived from a chart review of consecutive metastatic patients treated for pancreatic cancer at Princess Margaret Hospital, Toronto, Ontario, 2008–2009, and supplemented with data from the literature. Utilities were obtained by surveying medical oncologists across Canada using the EQ-5D. Incremental cost-effectiveness ratios (icers) were calculated.
The icers for gem-cap, gem-e, and folfirinox compared with gem were, respectively, CA$84,299, CA$153,631, and CA$133,184 per quality-adjusted life year (qaly). The model was driven mostly by drug acquisition costs. Given a willingness-to-pay (wtp) threshold greater than CA$130,000/qaly, folfirinox was most cost-effective treatment. When the wtp threshold was less than CA$80,000/qaly, gem alone was most cost-effective. The gem-e option was dominated by the other treatments.
The most cost-effective treatment for metastatic pancreatic cancer depends on the societal wtp threshold. If the societal wtp threshold were to be relatively high or if drug costs were to be substantially reduced, folfirinox might be cost-effective.
PMCID: PMC3615875  PMID: 23559890
Pancreatic cancer; cost-effectiveness; chemotherapy
16.  Current Management Strategies in Acid-Related Disorders 
Acid-related disorders include not only reflux esophagitis and peptic ulcer, but also a subset of patients with endoscopy-negative dyspepsia. The management strategy differs between these diseases and therefore a precise diagnosis is important. The unaided clinical diagnosis is of limited value in patients with pain or discomfort in the upper abdomen, and endoscopy is therefore an important and cost-effective diagnostic tool.
Duodenal ulcer is caused by an interplay between gastric acid and Helicobacter pylori. The treatment is aimed at rapid symptom relief and healing and at the same time eradication of H. pylori. At present the best choice is the combination of a proton pump inhibitor and two effective antimicrobial drugs, e.g., clarithromycin and metronidazole. The proton pump inhibitor has dual effect in this combination it provides optimal symptom relief and healing, and it increases the anti-H. pylori-effect of the antimicrobial drugs. The risk of reinfection varies geographically; in Europe it is around 1 percent per year, and cure of the infection provides long-term, maybe life-long, cure of the ulcer disease. Some gastric ulcers are not H. pylori-related and the treatment strategy therefore includes a diagnostic test for this infection. If positive, treatment is similar to that in duodenal ulcer, while H. pylori-negative gastric ulcer patients are treated with antisecretory drugs alone.
Reflux esophagitis correlates with the degree of acid exposure to the esophagus, and intensive acid inhibition is the most effective non-surgical therapy. In most cases the disease is chronic and needs continuous long-term therapy to prevent relapse. A staged reduction in dosage of the acid inhibitory drug may be attempted when the esophagitis is healed and the patient has become symptom free, but full dose therapy is often needed.
Patients with endoscopy-negative dyspepsia are a heterogenous group and a more precise identification of the cause of the symptoms is a prerequisite for rational treatment. Empiric treatment can be tried in patients without alarm symptoms like bleeding or a palpable abdominal mass, and often an acid inhibitory drug is used. A more precise identification of those patients who have acid-related symptoms is possible using placebo controlled single-subject trials with an effective acid inhibitory drug, but in daily routine these drugs are simply given for a short period of time, and in case symptomatic relief is observed, the symptoms may be regarded as being acid-related and treated accordingly.
PMCID: PMC2589132
17.  The cost-effectiveness of celecoxib versus non-steroidal anti-inflammatory drugs plus proton-pump inhibitors in the treatment of osteoarthritis in Saudi Arabia 
Cyclooxygenase (COX)-2 inhibitors including celecoxib are as effective as non-selective non-steroidal anti-inflammatory drugs (ns-NSAIDs) in the treatment of osteoarthritis (OA) and have less gastrointestinal toxicity. Although they are associated with higher treatment costs, COX-2 inhibitors may simultaneously reduce costs associated with adverse events, hence, their overall economic benefit should be assessed.
To evaluate the incremental cost effectiveness ratio (ICER) of celecoxib versus ns-NSAIDs, with/without proton-pump inhibitor (PPI) co-therapy, for managing OA in Saudi Arabian subjects aged ≥65 years.
The National Institute for Health and Care Excellence health economic model from the UK, updated with relative risks of adverse events using CONDOR trial data, was adapted. Patients received celecoxib or ns-NSAIDs, with/without omeprazole. The effectiveness measure was quality-adjusted life years (QALYs) gained per patient. The analysis was conducted from the patient’s perspective. Frequencies of resource use for adverse events were based on data collected in July 2012 from seven private hospitals in Jeddah, Saudi Arabia. Probabilistic sensitivity analysis was performed to construct cost-effectiveness acceptability curves (CEACs).
Over a 6-month treatment duration, QALYs gained per patient were higher with celecoxib (0.37) and celecoxib plus PPI (0.40) versus comparators. Ibuprofen plus PPI showed the lowest expected cost per patient (US$ 1,314.50 versus US$ 1,422.80 with celecoxib plus PPI and US$ 1,543.50 with celecoxib). Celecoxib plus PPI was the most cost-effective option with an ICER of US$ 1,805.00, followed by celecoxib (ICER, US$ 7,633.33) versus ibuprofen plus PPI. Over 2- and 5-year treatment durations, celecoxib plus PPI, and celecoxib, showed higher QALYs gained/patient and lower ICERs versus comparators. These ICERs are <1 gross domestic product/capita in Saudi Arabia in 2013 (US$ 25,961).
CEACs over 6 months’ treatment showed a significantly higher likelihood that celecoxib plus PPI and celecoxib alone would be more cost effective versus comparators once the willingness to pay is over US$ 2,000.00.
After considering new adverse event risks, celecoxib with/without PPI co-therapy was deemed very cost effective for medium- and long-term use in Saudi Arabian OA patients aged ≥65 years.
PMCID: PMC4467807  PMID: 26061682
Celecoxib; Non-steroidal anti-inflammatory drugs; Saudi Arabia; Cost effectiveness; Osteoarthritis
18.  What Is Heartburn Worth? 
T o determine the best treatment strategy for the management of patients presenting with symptoms consistent with uncomplicated heartburn.
We performed a cost-utility analysis of 4 alternatives: empirical proton pump inhibitor, empirical histamine2-receptor antagonist, and diagnostic strategies consisting of either esophagogastroduodenoscopy (EGD) or an upper gastrointestinal series before treatment. The time horizon of the model was 1 year. The base case analysis assumed a cohort of otherwise healthy 45-year-old individuals in a primary care practice.
Empirical treatment with a proton pump inhibitor was projected to provide the greatest quality-adjusted survival for the cohort. Empirical treatment with a histamine2receptor antagonist was projected to be the least costly of the alternatives. The marginal cost-effectiveness of using a proton pump inhibitor over a histamine2-receptor antagonist was approximately $10,400 per quality-adjusted life year (QALY) gained in the base case analysis and was less than $50,000 per QALY as long as the utility for heartburn was less than 0.95. Both diagnostic strategies were dominated by proton pump inhibitor alternative.
Empirical treatment seems to be the optimal initial management strategy for patients with heartburn, but the choice between a proton pump inhibitor or histamine2-receptor antagonist depends on the impact of heartburn on quality of life.
PMCID: PMC1495356  PMID: 10718898
cost-utility analysis; heartburn; proton pump inhibitor; histamine2-receptor antagonist; quality of life
19.  Defining the Value of Future Research to Identify the Preferred Treatment of Meniscal Tear in the Presence of Knee Osteoarthritis 
PLoS ONE  2015;10(6):e0130256.
Arthroscopic partial meniscectomy (APM) is extensively used to relieve pain in patients with symptomatic meniscal tear (MT) and knee osteoarthritis (OA). Recent studies have failed to show the superiority of APM compared to other treatments. We aim to examine whether existing evidence is sufficient to reject use of APM as a cost-effective treatment for MT+OA.
We built a patient-level microsimulation using Monte Carlo methods and evaluated three strategies: Physical therapy (‘PT’) alone; PT followed by APM if subjects continued to experience pain (‘Delayed APM’); and ‘Immediate APM’. Our subject population was US adults with symptomatic MT and knee OA over a 10 year time horizon. We assessed treatment outcomes using societal costs, quality-adjusted life years (QALYs), and calculated incremental cost-effectiveness ratios (ICERs), incorporating productivity costs as a sensitivity analysis. We also conducted a value-of-information analysis using probabilistic sensitivity analyses.
Calculated ICERs were estimated to be $12,900/QALY for Delayed APM as compared to PT and $103,200/QALY for Immediate APM as compared to Delayed APM. In sensitivity analyses, inclusion of time costs made Delayed APM cost-saving as compared to PT. Improving efficacy of Delayed APM led to higher incremental costs and lower incremental effectiveness of Immediate APM in comparison to Delayed APM. Probabilistic sensitivity analyses indicated that PT had 3.0% probability of being cost-effective at a willingness-to-pay (WTP) threshold of $50,000/QALY. Delayed APM was cost effective 57.7% of the time at WTP = $50,000/QALY and 50.2% at WTP = $100,000/QALY. The probability of Immediate APM being cost-effective did not exceed 50% unless WTP exceeded $103,000/QALY.
We conclude that current cost-effectiveness evidence does not support unqualified rejection of either Immediate or Delayed APM for the treatment of MT+OA. The amount to which society would be willing to pay for additional information on treatment outcomes greatly exceeds the cost of conducting another randomized controlled trial on APM.
PMCID: PMC4472814  PMID: 26086246
20.  Cost-Effectiveness of Treating Multidrug-Resistant Tuberculosis 
PLoS Medicine  2006;3(7):e241.
Despite the existence of effective drug treatments, tuberculosis (TB) causes 2 million deaths annually worldwide. Effective treatment is complicated by multidrug-resistant TB (MDR TB) strains that respond only to second-line drugs. We projected the health benefits and cost-effectiveness of using drug susceptibility testing and second-line drugs in a lower-middle-income setting with high levels of MDR TB.
Methods and Findings
We developed a dynamic state-transition model of TB. In a base case analysis, the model was calibrated to approximate the TB epidemic in Peru, a setting with a smear-positive TB incidence of 120 per 100,000 and 4.5% MDR TB among prevalent cases. Secondary analyses considered other settings. The following strategies were evaluated: first-line drugs administered under directly observed therapy (DOTS), locally standardized second-line drugs for previously treated cases (STR1), locally standardized second-line drugs for previously treated cases with test-confirmed MDR TB (STR2), comprehensive drug susceptibility testing and individualized treatment for previously treated cases (ITR1), and comprehensive drug susceptibility testing and individualized treatment for all cases (ITR2). Outcomes were costs per TB death averted and costs per quality-adjusted life year (QALY) gained. We found that strategies incorporating the use of second-line drug regimens following first-line treatment failure were highly cost-effective compared to strategies using first-line drugs only. In our base case, standardized second-line treatment for confirmed MDR TB cases (STR2) had an incremental cost-effectiveness ratio of $720 per QALY ($8,700 per averted death) compared to DOTS. Individualized second-line drug treatment for MDR TB following first-line failure (ITR1) provided more benefit at an incremental cost of $990 per QALY ($12,000 per averted death) compared to STR2. A more aggressive version of the individualized treatment strategy (ITR2), in which both new and previously treated cases are tested for MDR TB, had an incremental cost-effectiveness ratio of $11,000 per QALY ($160,000 per averted death) compared to ITR1. The STR2 and ITR1 strategies remained cost-effective under a wide range of alternative assumptions about treatment costs, effectiveness, MDR TB prevalence, and transmission.
Treatment of MDR TB using second-line drugs is highly cost-effective in Peru. In other settings, the attractiveness of strategies using second-line drugs will depend on TB incidence, MDR burden, and the available budget, but simulation results suggest that individualized regimens would be cost-effective in a wide range of situations.
Editors' Summary
Tuberculosis (TB) remains one of the most entrenched diseases on the planet—an estimated one in three people worldwide are infected with Mycobacterium tuberculosis, which causes the disease. Although effective drugs exist, a major reason for the failure to stem the spread of TB lies in the rise of drug-resistant strains of the bacterium. Some strains are resistant to several drugs; patients with this sort of infection are said to have multidrug-resistant (MDR) TB. The development of drug-resistant strains is fostered when health-care workers do not follow treatment guidelines or fail to ensure that patients take the whole treatment course. The World Health Organization recommends an approach to TB control called “DOTS,” which has been adopted by many countries. (See the link below for an explanation of what DOTS involves.) The antibiotics that are used in DOTS are described as “first-line” treatment drugs. They are highly effective against non-resistant TB but much less so against MDR TB. There are other, more expensive, “second-line” antibiotics that perform better against MDR TB.
  Why Was This Study Done?
Despite the worrying rise in MDR TB cases, the much higher cost of using second-line drugs is prompting some policy-makers to question the merits of introducing them in poor countries with limited resources. However, with MDR TB accounting for nearly a third of TB cases in some countries, first-line therapies seem unlikely to be sufficient in the long term. Second-line strategies, or “DOTS-Plus” strategies, are either standardized for a particular region or are chosen for individual patients on the basis of drug susceptibility tests. The researchers wanted to investigate whether standardized or individualized second-line regimens could save lives and be cost-effective in poor countries.
  What Did the Researchers Do and Find?
The researchers used a method called modeling. They took information already available about TB in Peru, where for every 100,000 people there are 120 new TB infections every year, and 4.5% of existing cases are MDR TB. The researchers then calculated what might happen over the next 30 years, comparing the likely effects of five alternative strategies. In four, new cases were given first-line drugs for 6 months. Those who were not cured were then treated in different ways. In DOTS, they were retreated with a second course of the same drugs; in STR1 they were given an 18-month standardized course of second-line and first-line drugs; in STR2, only confirmed MDR TB patients were given an 18-month standardized course of second-line and first-line drugs; and in ITR1, confirmed MDR TB patients were given a personalized regimen of second-line drugs. The fifth strategy, ITR2, tested all patients for drug susceptibility at the outset of treatment, and those with MDR TB were given an individualized course; those not cured were tested again and given another individualized course.
  Compared with DOTS, both the STR1 and STR2 strategies averted 4.8 deaths per 100,000 population, at a cost of $8,700 per averted death—with STR2 being a better value for money since it treated only confirmed MDR TB cases with the more expensive, second-line drugs. Of the individualized treatments, ITR1 averted an extra 0.9 deaths at a cost of $12,000 per averted death; ITR2 averted a further 1.2 deaths but at a much higher $160,000 per saved life.
  What Do These Findings Mean?
Despite the slightly higher cost of ITR1, the extra number of lives it would save compared with STR2 makes it a good approach for treatment in Peru. However, cost-effectiveness varies with other factors. If the difference in cost between the two strategies became higher than $9,500 per patient, STR would be preferable. And, if MDR TB were present in 10% of all TB cases, ITR2—with comprehensive drug susceptibility testing for all TB patients—would be best.
  The findings are of interest not just in Peru but in other developing countries where MDR TB is a growing problem. The researchers maintain that, in areas where DOTS has not yet been fully implemented, it would be more efficient to expand DOTS than to introduce DOTS-Plus. But they add that it would be beneficial to expand DOTS as well as implement DOTS-Plus. Individualized treatment after drug susceptibility testing is likely to be cost-effective even in the poorest of countries, which should give impetus to governments and organizations in those countries where MDR TB is a growing concern to modify their approach to treatment.
  Additional Information.
Please access these Web sites via the online version of this summary at
• Basic information about tuberculosis can be found on the Web site of the US National Institute of Allergy and Infectious Diseases
• The Web site of the World Health Organization's Stop TB department outlines both the DOTS and DOTS-Plus strategies
•  TB Alert, a UK-based charity that promotes TB awareness worldwide, has information on TB in several European, African, and Asian languages
Resch and colleagues found that treatment of MDR TB using second-line drugs is highly cost-effective in Peru.
PMCID: PMC1483913  PMID: 16796403
21.  Screening and Rapid Molecular Diagnosis of Tuberculosis in Prisons in Russia and Eastern Europe: A Cost-Effectiveness Analysis 
PLoS Medicine  2012;9(11):e1001348.
Daniel Winetsky and colleagues investigate eight strategies for screening and diagnosis of tuberculosis within prisons of the former Soviet Union.
Prisons of the former Soviet Union (FSU) have high rates of multidrug-resistant tuberculosis (MDR-TB) and are thought to drive general population tuberculosis (TB) epidemics. Effective prison case detection, though employing more expensive technologies, may reduce long-term treatment costs and slow MDR-TB transmission.
Methods and Findings
We developed a dynamic transmission model of TB and drug resistance matched to the epidemiology and costs in FSU prisons. We evaluated eight strategies for TB screening and diagnosis involving, alone or in combination, self-referral, symptom screening, mass miniature radiography (MMR), and sputum PCR with probes for rifampin resistance (Xpert MTB/RIF). Over a 10-y horizon, we projected costs, quality-adjusted life years (QALYs), and TB and MDR-TB prevalence. Using sputum PCR as an annual primary screening tool among the general prison population most effectively reduced overall TB prevalence (from 2.78% to 2.31%) and MDR-TB prevalence (from 0.74% to 0.63%), and cost US$543/QALY for additional QALYs gained compared to MMR screening with sputum PCR reserved for rapid detection of MDR-TB. Adding sputum PCR to the currently used strategy of annual MMR screening was cost-saving over 10 y compared to MMR screening alone, but produced only a modest reduction in MDR-TB prevalence (from 0.74% to 0.69%) and had minimal effect on overall TB prevalence (from 2.78% to 2.74%). Strategies based on symptom screening alone were less effective and more expensive than MMR-based strategies. Study limitations included scarce primary TB time-series data in FSU prisons and uncertainties regarding screening test characteristics.
In prisons of the FSU, annual screening of the general inmate population with sputum PCR most effectively reduces TB and MDR-TB prevalence, doing so cost-effectively. If this approach is not feasible, the current strategy of annual MMR is both more effective and less expensive than strategies using self-referral or symptom screening alone, and the addition of sputum PCR for rapid MDR-TB detection may be cost-saving over time.
Please see later in the article for the Editors' Summary
Editors' Summary
Tuberculosis (TB)—a contagious bacterial disease—is a major public health problem, particularly in low- and middle-income countries. In 2010, about nine million people developed TB, and about 1.5 million people died from the disease. Mycobacterium tuberculosis, the bacterium that causes TB, is spread in airborne droplets when people with active disease cough or sneeze. The characteristic symptoms of TB include fever, a persistent cough, and night sweats. Diagnostic tests include sputum smear microscopy (examination of mucus from the lungs for M. tuberculosis bacilli), mycobacterial culture (growth of M. tuberculosis from sputum), and chest X-rays. TB can also be diagnosed by looking for fragments of the M. tuberculosis genetic blueprint in sputum samples (sputum PCR). Importantly, sputum PCR can detect the genetic changes that make M. tuberculosis resistant to rifampicin, a constituent of the cocktail of antibiotics that is used to cure TB. Rifampicin resistance is an indicator of multidrug-resistant TB (MDR-TB), the emergence of which is thwarting ongoing global efforts to control TB.
Why Was This Study Done?
Prisons present unique challenges for TB control. Overcrowding, poor ventilation, and inadequate medical care increase the spread of TB among prisoners, who often come from disadvantaged populations where the prevalence of TB (the proportion of the population with TB) is already high. Prisons also act as reservoirs for TB, recycling the disease back into the civilian population. The prisons of the former Soviet Union, for example, which have extremely high rates of MDR-TB, are thought to drive TB epidemics in the general population. Because effective identification of active TB among prison inmates has the potential to improve TB control outside prisons, the World Health Organization recommends active TB case finding among prisoners using self-referral, screening with symptom questionnaires, or screening with chest X-rays or mass miniature radiography (MMR). But which of these strategies will reduce the prevalence of TB in prisons most effectively, and which is most cost-effective? Here, the researchers evaluate the relative effectiveness and cost-effectiveness of alternative strategies for screening and diagnosis of TB in prisons by modeling TB and MDR-TB epidemics in prisons of the former Soviet Union.
What Did the Researchers Do and Find?
The researchers used a dynamic transmission model of TB that simulates the movement of individuals in prisons in the former Soviet Union through different stages of TB infection to estimate the costs, quality-adjusted life years (QALYs; a measure of disease burden that includes both the quantity and quality of life) saved, and TB and MDR-TB prevalence for eight TB screening/diagnostic strategies over a ten-year period. Compared to annual MMR alone (the current strategy), annual screening with sputum PCR produced the greatest reduction in the prevalence of TB and of MDR-TB among the prison population. Adding sputum PCR for detection of MDR-TB to annual MMR screening did not affect the overall TB prevalence but slightly reduced the MDR-TB prevalence and saved nearly US$2,000 over ten years per model prison of 1,000 inmates, compared to MMR screening alone. Annual sputum PCR was the most cost-effective strategy, costing US$543/QALY for additional QALYs gained compared to MMR screening plus sputum PCR for MDR-TB detection. Other strategies tested, including symptom screening alone or combined with sputum PCR, were either more expensive and less effective or less cost-effective than these two options.
What Do These Findings Mean?
These findings suggest that, in prisons in the former Soviet Union, annual screening with sputum PCR will most effectively reduce TB and MDR-TB prevalence and will be cost-effective. That is, the cost per QALY saved of this strategy is less than the per-capita gross domestic product of any of the former Soviet Union countries. The paucity of primary data on some facets of TB epidemiology in prisons in the former Soviet Union and the assumptions built into the mathematical model limit the accuracy of these findings. Moreover, because most of the benefits of sputum PCR screening come from treating the MDR-TB cases that are detected using this screening approach, these findings cannot be generalized to prison settings without a functioning MDR-TB treatment program or with a very low MDR-TB prevalence. Despite these and other limitations, these findings provide valuable information about the screening strategies that are most likely to interrupt the TB cycle in prisons, thereby saving resources and averting preventable deaths both inside and outside prisons.
Additional Information
Please access these websites via the online version of this summary at
The World Health Organization provides information (in several languages) on all aspects of tuberculosis, including general information on tuberculosis diagnostics and on tuberculosis in prisons; a report published in the Bulletin of the World Health Organization in 2006 describes tough measures taken in Russian prisons to slow the spread of TB
The Stop TB Partnership is working towards tuberculosis elimination; patient stories about tuberculosis are available (in English and Spanish)
The US Centers for Disease Control and Prevention has information about tuberculosis, about its diagnosis, and about tuberculosis in prisons (some information in English and Spanish)
A PLOS Medicine Research Article by Iacapo Baussano et al. describes a systematic review of tuberculosis incidence in prisons; a linked editorial entitled The Health Crisis of Tuberculosis in Prisons Extends beyond the Prison Walls is also available
The Tuberculosis Survival Project, which aims to raise awareness of tuberculosis and provide support for people with tuberculosis, provides personal stories about treatment for tuberculosis; the Tuberculosis Vaccine Initiative also provides personal stories about dealing with tuberculosis
MedlinePlus has links to further information about tuberculosis (in English and Spanish)
PMCID: PMC3507963  PMID: 23209384
22.  Efficacy of omeprazole, famotidine, mosapride and teprenone in patients with upper gastrointestinal symptoms: an omeprazole-controlled randomized study (J-FOCUS) 
BMC Gastroenterology  2012;12:42.
In Japan, treatment guidelines are lacking for patients with upper gastrointestinal symptoms. We aimed to compare the efficacy of different drugs for the treatment of uninvestigated upper gastrointestinal symptoms.
This was a randomized, open-label, parallel-group multicenter study. Helicobacter pylori-negative, endoscopically uninvestigated patients ≥ 20 years of age with upper gastrointestinal symptoms of at least moderate severity (Global Overall Symptom score [GOS] ≥ 4 on a 7-point Likert scale) were randomized to treatment with omeprazole (10 mg once daily), famotidine (10 mg twice daily), mosapride (5 mg three times daily) or teprenone (50 mg three times daily). The primary endpoint was sufficient relief of upper gastrointestinal symptoms after 4 weeks of treatment (GOS ≤ 2). UMIN clinical trial registration number: UMIN000005399.
Of 471 randomized patients, 454 were included in the full analysis set. After 4 weeks of treatment, sufficient symptom relief was achieved by 66.9% of patients in the omeprazole group, compared with 41.0%, 36.3% and 32.3% in the famotidine, mosapride and teprenone groups, respectively (all, p < 0.001 vs omeprazole). There were no treatment-related adverse events.
The favorable efficacy and safety profiles of omeprazole in relieving uninvestigated upper gastrointestinal symptoms support its use as first-line treatment in this patient group in Japan. Patients who show no improvement in symptoms despite PPI use, and those with alarm symptoms (such as vomiting, GI bleeding or acute weight loss) should receive further investigation, including prompt referral for endoscopy.
Trial registration
PMCID: PMC3419613  PMID: 22548767
Omeprazole; Famotidine; Mosapride; Teprenone; Uninvestigated upper gastrointestinal symptoms
23.  A randomised controlled trial of four management strategies for dyspepsia: relationships between symptom subgroups and strategy outcome. 
BACKGROUND: The first step in the management of uncomplicated dyspepsia in primary care often consists of prescribing empirical therapy, but in certain cases prompt endoscopy might be preferred. Any decision is usually based on the patient's symptoms and the presumed underlying pathology that causes these symptoms. AIM: To assess the relationship between symptom subgroups and the effect of management strategies on primary care patients with dyspepsia. DESIGN OF STUDY: Randomised controlled trial. SETTING: All patients presenting successively with a new episode of dyspepsia between January 1995 and November 1997. METHOD: The results of four management strategies in dyspeptic primary care patients were compared and the value of subgrouping within this trial was estimated. Patients were allocated to one of either (a) empirical treatment in which therapy was based on the presented symptoms, or empirical treatment with (b) omeprazole or (c) cisapride regardless of the presented symptoms, or (d) prompt endoscopy followed by the appropriate treatment. Patients were retrospectively classified into the subgroups for each strategy using baseline data. The yield of each strategy was measured by counting the number of strategy failures in the first year. RESULTS: Of the 349 included patients, 326 were analysed. No statistically significant difference could be demonstrated between the strategies or between the symptom subgroups. However, patients in the reflux-like subgroup showed a trend towards a better outcome in all empirical strategies. Ulcer-like dyspepsia seemed to benefit from omeprazole. The non-specific subgroup seemed to benefit from cisapride but also had the highest proportion of strategy failure. Prompt endoscopy did not appear especially useful in any subgroup. CONCLUSION: Although this study has relatively low power, we conclude that the use of symptom subgroups seems to be a sensible approach when choosing empirical therapy in dyspepsia. Patients with reflux-like symptoms seem to have the best prognosis in the first year in every strategy.
PMCID: PMC1314070  PMID: 11510389
24.  Photodynamic therapy for Barrett’s esophagus with high-grade dysplasia: A cost-effectiveness analysis 
To assess the cost-effectiveness of photodynamic therapy (PDT) and esophagectomy (ESO) relative to surveillance (SURV) for patients with Barrett’s esophagus (BE) and high-grade dysplasia (HGD).
A Markov decision tree was constructed to estimate costs and health outcomes of PDT, ESO and SURV in a hypothetical cohort of male patients, 50 years of age, with BE and HGD. Outcomes included unadjusted life-years (LYs) and quality-adjusted LYs (QALYs). Direct medical costs (2003 CDN$) were measured from the perspective of a provincial ministry of health. The time horizon for the model was five years (cycle length three months), and costs and outcomes were discounted at 3%. Model parameters were assigned unique distributions, and a probabilistic analysis with 10,000 Monte Carlo simulations was performed.
SURV was the least costly strategy, followed by PDT and ESO, but SURV was also the least effective. In terms of LYs, the incremental cost-effectiveness ratios were $814/LY for PDT versus SURV and $3,397/LY for ESO versus PDT. PDT dominated ESO for QALYs in the base-case. The incremental cost-effectiveness ratio of PDT versus SURV was $879/QALY. In probabilistic analysis, PDT was most likely to be cost-effective at willingness-to-pay (WTP) values between $100/LY and $3,500/LY, and ESO was most likely to be cost-effective for WTP values over $3500/LY. For quality-adjusted survival, PDT was most likely to be cost-effective for all WTP thresholds above $1,000/QALY. The likelihood that PDT was the most cost-effective strategy reached 0.99 at a WTP ceiling of $25,000/QALY.
In male patients with BE and HGD, PDT and ESO are cost-effective alternatives to SURV.
PMCID: PMC2657694  PMID: 17431509
Barrett’s esophagus; High-grade dysplasia; Photodynamic therapy
25.  Cost Effectiveness of Mirabegron Compared with Tolterodine Extended Release for the Treatment of Adults with Overactive Bladder in the United Kingdom 
Overactive bladder (OAB) is highly prevalent and is associated with considerable morbidity and reduced health-related quality of life. β3-adrenergic receptor (β3-AR) stimulation is a novel alternative to antimuscarinic therapy for OAB.
The objective of this analysis was to assess the cost effectiveness of the β3-AR agonist mirabegron relative to tolterodine extended release (ER) in patients with OAB from a UK National Health Service (NHS) perspective.
A Markov model was developed to simulate the management, course of disease, and effect of complications in OAB patients over a period of 5 years. Transition probabilities for symptom severity levels and probabilities of adverse events were estimated from the results of the randomised, double-blind SCORPIO trial in 1,987 patients with OAB. Other model inputs were derived from the literature and on assumptions based on clinical experience.
Total 5-year costs per patient were £1,645.62 for mirabegron 50 mg/day and £1,607.75 for tolterodine ER 4 mg/day. Mirabegron was associated with a gain of 0.009 quality-adjusted life-years (QALYs) with an additional cost of £37.88. The resulting incremental cost-effectiveness ratio (ICER) was £4,386/QALY gained. In deterministic sensitivity analyses in the general OAB population and several subgroups, ICERs remained below the generally accepted willingness-to-pay (WTP) threshold of £20,000/QALY gained. The probability of mirabegron 50 mg being cost effective relative to tolterodine ER 4 mg was 89.4 % at the same WTP threshold.
Mirabegron 50 mg/day is likely to be cost effective compared with tolterodine ER 4 mg/day for adult patients with OAB from a UK NHS perspective.
Electronic supplementary material
The online version of this article (doi:10.1007/s40261-014-0240-z) contains supplementary material, which is available to authorized users.
PMCID: PMC4300413  PMID: 25491433

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