Cost-utility analysis of a 'vonoprazan-first' strategy versus 'esomeprazole- or rabeprazole-first' strategy in GERD.

BACKGROUND: Gastroesophageal reflux disease (GERD) can be treated using a vonoprazan-first strategy (first-line treatment with vonoprazan), or esomeprazole-first/rabeprazole-first strategies (first-line treatment with proton-pump inhibitors [PPIs], esomeprazole/rabeprazole, followed by a switch to vonoprazan). This cost-utility analysis used long-term simulation modeling to evaluate the cost-effectiveness of a vonoprazan-first strategy compared with the esomeprazole-first and rabeprazole-first strategies. METHODS: A Markov simulation model was developed to evaluate the cost-effectiveness of vonoprazan-first, esomeprazole-first, and rabeprazole-first strategies, comprising healing and maintenance therapies, over 5 years (4-week cycles). Healing therapy began with the administration of a normal dose of drug per real-world practice. If patients were not healed endoscopically, either a longer duration of healing therapy was provided (vonoprazan), the dose was increased (rabeprazole), or patients were switched to vonoprazan (immediately for esomeprazole, and after dose-escalation for rabeprazole, respectively). Healed patients received maintenance (lower/same dose as healing therapy). Recurrence resulted in re-challenge with healing therapy. Transition probabilities were derived from the results of indirect comparisons (network meta-analysis) and costs calculated from the Japanese payer perspective. Outcomes were defined as quality-adjusted life years (QALYs), with utilities based on published values. RESULTS: Expected costs of the vonoprazan-, esomeprazole-, and rabeprazole-first strategies were ¥36,194, ¥76,719, and ¥41,105, respectively, over 5 years. QALY gains for vonoprazan-first strategy versus the esomeprazole- and rabeprazole-first strategies were 0.014 and 0.003, respectively. Both estimated incremental cost-effectiveness ratios were dominant and robust to two sensitivity analyses. CONCLUSIONS: Vonoprazan-first strategy increased QALYs and appeared to be cost-effective for GERD patients compared with the esomeprazole- or rabeprazole-first strategies.

Comparison the cost-efficacy of furazolidone-based versus clarithromycin-based quadruple therapy in initial treatment of Helicobacter pylori infection in a variable clarithromycin drug-resistant region, a single-center, prospective, randomized, open-label study.

Helicobacter pylori (Hp) drug resistant rate to clarithromycin (CLA) has increased to 20% to 50%, which cause concerns regarding its effectiveness in eradicating Hp, we aim to evaluate the cost-effectiveness of CLA-based versus furazolidone (FZD)-based quadruple therapy, and assess factors that affect anti-Hp efficacy.One hundred eighty-five patients were enrolled in this single-center, prospective, randomized, open-label study. In FZD group, 92 patients were treated with FZD plus esomeprazole, bismuth potassium citrate, and amoxicillin for 14 days. In CLA group, 93 patients were treated with the same regimen except FZD was replaced by CLA. Patients were tested 4 weeks post-treatment to confirm eradication.Of the 185 enrolled patients, 180 completed the study. On intention-to-treat analysis, Hp eradication rates in FZD and CLA groups were 90.22% and 86.02% (P = .378); in per-protocol analysis, their eradication rates were 93.26% and 87.91%, respectively (P = .220). Overall incidence of total side effects in FZD and CLA groups was 19.57% and 13.98%, and their severe side effects were 3.26% and 2.15%, respectively (P > .05). Cost-effectiveness ratios of FZD and CLA groups were 0.75 and 1.02, and incremental cost-effectiveness ratio of FZD group over CLA group was -3.62. Eradication failures were not associated with factors including gender, age, body mass index, smoking, alcohol consumption, educational level, and urban-rural distribution in this observation (P > .05).Despite increasing drug resistance to CLA, Hp eradication rates in FZD and CLA groups have no significant difference at present; as FZD-based quadruple therapy is more cost-effective, we recommend this regimen be a first-line choice for Hp eradication.

Industry Payments to Physicians and Prescriptions of Brand-Name Proton-Pump Inhibitors.

OBJECTIVE: To characterize the association between industry payments and prescriptions of 2 brand-name proton-pump inhibitors (PPIs). STUDY DESIGN: Cross-sectional retrospective. SETTING: Physicians nationwide. SUBJECTS AND METHODS: We identified all physicians receiving industry payments for Dexilant and Nexium 2014-2015 from the Open Payments database. We linked this to records of prescriptions for PPIs paid for by Medicare Part D these same years and compared the proportion of prescriptions written for Dexilant and Nexium in industry-compensated vs nonindustry compensated physicians. The number and dollar amount of payments were associated with the rate of drug prescriptions. RESULTS: We identified 254,452 physicians prescribing PPIs; 8586 and 2766 physicians received industry payments for Dexilant and Nexium, respectively. A total of 5052 of 7876 (64%) physicians compensated for Dexilant prescribed Dexilant vs 39,778 of 246,571 (16%) noncompensated physicians ( P < .001). For Nexium, 2525 of 2654 (95%) compensated physicians prescribed Nexium, compared to 123,913 of 252,067 (49%) noncompensated physicians. For both Dexilant and Nexium, there was a significant correlation between the number (ρ = 0.22, P < .001 and ρ = 0.12, P < .001) and dollar amount (ρ = 0.22, P < .001 and ρ = 0.13, P < .001) of payments and the percentage of prescriptions written for the compensated drug. Industry payments for Nexium remained associated with rate of prescription even after generic esomeprazole became available. CONCLUSION: Both the number and dollar amount of industry payments were associated with increased prescriptions for both Dexilant and Nexium. Although unable to show causality, this study suggests that industry payments may increase physician prescriptions of costly, brand-name drugs.

Using Drug Prescribing Patterns to Identify Stewards of Cost-Conscious Care.

PURPOSE: To characterize family physicians (FPs) who are stewards of care by consistently prescribing omeprazole over esomeprazole. METHODS: Cross-sectional analysis of physicians prescribing omeprazole or esomeprazole under Medicare Part D in 2014. RESULTS: There was a regional trend with 49% of Western FPs but only 6% of Southern FPs rarely prescribing esomeprazole. Physicians had increased odds of being a steward if they worked with a care coordinator (P < .001), at a patient-centered medical home (P < .001), or in a large practice (P < .001). CONCLUSIONS: If these findings are replicated across multiple drugs, future outreach could be conducted based on provider prescribing patterns.

Is the use of esomeprazole in gastroesophageal reflux disease a cost-effective option in Poland?

OBJECTIVES: To compare the cost-effectiveness of therapy of gastroesophageal reflux disease with esomeprazole and other proton pump inhibitors (PPIs) in Poland. MATERIALS & METHODS: Studies comparing esomeprazole with other PPIs in the treatment of erosive esophagitis, non-erosive reflux disease and gastroesophageal reflux disease maintenance therapy were systematically reviewed. 9 randomized clinical trials were selected, meta-analyses were conducted. Cost data derived from Polish Ministry of Health and Pharmacies in Wroclaw. RESULTS: In the treatment of erosive esophagitis esomeprazole was significantly more effective than other PPIs. Both for 4- and 8-week therapy respective incremental cost-effectiveness ratio values were acceptably low. Differences in effectiveness of non-erosive reflux disease therapy were not significant. The replacement of pantoprazole 20 mg with more effective esomeprazole 20 mg in the 6-month maintenance therapy was associated with a substantially high incremental cost-effectiveness ratio.

Assessing the chiral switch: approval and use of single-enantiomer drugs, 2001 to 2011.

OBJECTIVES: A "chiral switch" occurs in the pharmaceutical market when a drug made up of 2 enantiomer forms is replaced with a purified single-enantiomer version, often in the context of a patent expiration. We studied the prevalence of chiral switching in the United States over the past decade, including trends in use of, and expenditures on, these products in Medicaid. STUDY DESIGN: Retrospective analysis. METHODS: We used US Adopted Names prefixes (lev/levo/ar/es/dex/dextro) to identify all single-enantiomer drugs approved from 2001 to 2011. From publicly available US Food and Drug Administration (FDA) approval documents, we extracted the characteristics of the pivotal premarket trials for the single enantiomers. Specifically, we evaluated whether the single enantiomer was directly compared with the precursor racemic drug and whether there was evidence of superior efficacy. We used quarterly drug expenditure data from each state Medicaid program to chart trends in use of, and spending on, the single-enantiomer products and their racemic precursors during the study period. RESULTS: From 2001 to 2011, the FDA approved 9 single-enantiomer products: dexlansoprazole, levoleucovorin, levocetirizine, armodafinil, arformoterol, eszopiclone, escitalopram, dexmethylphenidate, and esomeprazole. Of those 9 drugs, 3 had at least 1 pre-approval randomized trial that included the racemic precursor as a direct comparator, but there was no evidence of superiority of the single enantiomer over the racemic at comparable doses. Between 2001 and 2011, US Medicaid programs spent approximately $6.3 billion on these 9 single-enantiomer drugs. CONCLUSIONS: Recently approved single-enantiomer drugs showed no evidence of superior efficacy over the older racemic precursors in the pivotal trials leading to their approval, and in a majority of cases, they were not directly compared.

Efficiency of naproxen/esomeprazole in association for osteoarthrosis treatment in Spain.

OBJECTIVE: To assess, from the perspective of the National Healthcare System, the efficiency of a fixed-dose combination of naproxen and esomeprazole (naproxen/esomeprazole) in the treatment of osteoarthritis (OA) compared to other NSAID, alone or in combination with a proton pump inhibitor (PPI). METHODS: A Markov model was used; it included different health states defined by gastrointestinal (GI) events: dyspepsia, symptomatic or complicated ulcer; or cardiovascular (CV) events: myocardial infarction, stroke or heart failure. The model is similar to the one used by NICE in its NSAID evaluation of OA published in 2008. The total costs (€, 2012), including drug and event-related costs, and the health outcomes expressed in quality-adjusted life years (QALY) were estimated in patients with increased GI risk, aged 65 or over, for a 1-year time horizon and a 6-month treatment with celecoxib (200mg/day), celecoxib+PPI, diclofenac (150mg/day)+PPI, etoricoxib (60mg/day), etoricoxib+PPI, ibuprofen (1,800mg/day)+PPI, naproxen (1,000mg/day)+PPI or naproxen/esomeprazole (naproxen 1,000mg/esomeprazole 40mg/day). The selected PPI was omeprazole (20mg/day). RESULTS: Naproxen/esomeprazole was a dominant strategy (more effective and less costly) compared to celecoxib, etoricoxib and diclofenac+PPI. Celecoxib+PPI and etoricoxib+PPI were more effective. Considering a cost-effectiveness threshold of €30,000 per additional QALY, naproxen/esomeprazole was cost-effective compared to ibuprofen+PPI and naproxen+PPI with incremental cost-effectiveness ratios (ICER) of €15,154 and €5,202 per additional QALY, respectively. CONCLUSIONS: A fixed-dose combination of naproxen and esomeprazole is a cost-effective, and even dominant, alternative compared to other options in OA patients with increased GI risk.

Potential costs of inappropriate use of proton pump inhibitors.

BACKGROUND: Proton pump inhibitors (PPIs) are commonly overused in hospitalized patients. The objectives of this study were to determine the extent of their inappropriate initiation in patients with low risk for gastrointestinal hemorrhage, factors associated with their continuation on discharge and potential cost of this trend. METHODS: Retrospective examination of patients with low risk for gastrointestinal hemorrhage admitted to a tertiary-care teaching hospital over a 3-month period who received esomeprazole. The following information was collected: age, gender, PPI status (de novo or continued) and admitting diagnoses. Additional information collected from the de novo subgroup included indication for PPI, number of days on PPI and continuation of the drug on discharge. The cost of the medication was obtained from pharmacy records. RESULTS: Four hundred nine patients were admitted during the study period and 204 (49.9%) received PPI de novo. Among these, 155 patients (76%) had an inappropriate indication for PPI. Of these, 62 (40%) patients were continued on PPI on discharge. Older age was a significant predictor of continuation of PPI at discharge. The estimated cost of the inpatient and outpatient inappropriate use of PPI was $12,272 and $59,272, respectively. CONCLUSIONS: PPIs are overused in the majority of hospitalized patients with low risk for gastrointestinal bleeding and this practice gets perpetuated at discharge, especially in older patients. The cost of this phenomenon is alarming.

Patterns of proton pump inhibitor utilization in gastroesophageal reflux disease and the effect of restrictions on reimbursement: a nationwide prescription database study.

OBJECTIVE: To assess the drug utilization patterns for proton pump inhibitors (PPIs) prescriptions dispensed in periods with and without restrictions on reimbursement in a public healthcare system. MATERIAL AND METHODS: Data on all PPI prescriptions dispensed for gastroesophageal reflux disease (GERD) was retrieved from the Norwegian Prescription Database (NorPD) from 1 January 2004 to 31 January 2008. PPI utilization patterns were studied in new and current users of PPI in periods affected and not affected by a change in prescription policy. RESULTS: The policy change resulted in 39% of esomeprazole patients discontinuing PPI therapy during a 12-month period while 23% discontinued PPI therapy during a period not affected by the policy change. The shift frequency to a different PPI was low, 5% and 7% respectively, during periods not affected by policy change. Despite a required shift in most esomeprazole patients, 64% still continued on esomeprazole. Among the 36% who shifted from esomeprazole to a different PPI, 25% subsequently shifted back to esomeprazole. In new PPI users, the proportion of esomeprazole users declined from 57% before to 20% after the introduction of the policy change. CONCLUSIONS: Despite GERD being a chronic disease in most patients, there was a high degree of alteration seen in the utilization patterns of PPIs. A high proportion discontinued PPI therapy indicating mild symptoms or remission. The switching between different PPIs was low indicating good efficacy and tolerability in most patients. The policy change was more effective in new PPI users compared with the mandated shift in ongoing esomeprazole users.

Patented drug extension strategies on healthcare spending: a cost-evaluation analysis.

BACKGROUND: Drug manufacturers have developed "evergreening" strategies to compete with generic medication after patent termination. These include marketing of slightly modified follow-on drugs. We aimed to estimate the financial impact of these drugs on overall healthcare costs and also to examine the impact of listing these drugs in hospital restrictive drug formularies (RDFs) on the healthcare system as a whole ("spillover effect"). METHODS AND FINDINGS: We used hospital and community pharmacy invoice office data in the Swiss canton of Geneva to calculate utilisation of eight follow-on drugs in defined daily doses between 2000 and 2008. "Extra costs" were calculated for three different scenarios assuming replacement with the corresponding generic equivalent for prescriptions of (1) all brand (i.e., initially patented) drugs, (2) all follow-on drugs, or (3) brand and follow-on drugs. To examine the financial spillover effect we calculated a monthly follow-on drug market share in defined daily doses for medications prescribed by hospital physicians but dispensed in community pharmacies, in comparison to drugs prescribed by non-hospital physicians in the community. Estimated "extra costs" over the study period were €15.9 (95% CI 15.5; 16.2) million for scenario 1, €14.4 (95% CI 14.1; 14.7) million for scenario 2, and €30.3 (95% CI 29.8; 30.8) million for scenario 3. The impact of strictly switching all patients using proton-pump inhibitors to esomeprazole at admission resulted in a spillover "extra cost" of €330,300 (95% CI 276,100; 383,800), whereas strictly switching to generic cetirizine resulted in savings of €7,700 (95% CI 4,100; 11,100). Overall we estimated that the RDF resulted in "extra costs" of €503,600 (95% CI 444,500; 563,100). CONCLUSIONS: Evergreening strategies have been successful in maintaining market share in Geneva, offsetting competition by generics and cost containment policies. Hospitals may be contributing to increased overall healthcare costs by listing follow-on drugs in their RDF. Therefore, healthcare providers and policy makers should be aware of the impact of evergreening strategies.

The efficacy, safety and cost-effectiveness of hydrotalcite versus esomeprazole in on-demand therapy of NERD: A multicenter, randomized, open-label study in China.

OBJECTIVE: The aim of the study was to investigate whether hydrotalcite was comparable to esomeprazole, a proton pump inhibitor, in on-demand therapy for non-erosive reflux disease (NERD). METHODS: This was a multicenter, randomized, open-label clinical trial with initial and on-demand therapy. Patients who had complete symptom relief in the initial therapy were randomized to either hydrotalcite or esomeprazole in the on-demand therapy. The percentage of patients who quit on-demand therapy in the two groups and the cost-effectiveness of the treatment were evaluated as primary end points. The rate of symptom relief and the improvement of symptom score for initial therapy and the weekly average symptom score and weekly average number of days on treatment for on-demand therapy were evaluated as secondary end points. RESULTS: In total, 398 patients were recruited in the initial therapy group, among whom 253 were included in on-demand therapy, with 127 patients in the hydrotalcite group and the remaining 126 in the esomeprazole group. 14 (11.0%) patients in the hydrotalcite group and six (4.8%) in the esomeprazole group quit the on-demand therapy due to unsatisfactory symptom control (P = 0.065). Cost-effectiveness calculated as the ratio of the cost of hydrotalcite to that of esomeprazole (per person/day) was 35.3% in the on-demand therapy. Similar number of patients achieved symptom relief in both groups. CONCLUSION: Hydrotalcite is a good option of on-demand therapy for NERD patients due to its cost-effectiveness and speed of action.

Esomeprazole and aspirin fixed combination for the prevention of cardiovascular events.

Low dose aspirin therapy plays a fundamental role in both the primary and secondary prevention of cardiovascular events. Although the evidence using low dose aspirin for secondary prevention is well-established, the decision to use aspirin for primary prevention is based on an evaluation of the patient's risk of cardiovascular events compared to their risk of adverse events, such as bleeding. In addition to the risk of bleeding associated with long term aspirin administration, upper gastrointestinal side effects, such as dyspepsia often lead to discontinuation of therapy, which places patients at an increased risk for cardiovascular events. One option to mitigate adverse events and increase adherence is the addition of esomeprazole to the medication regimen. This review article provides an evaluation of the literature on the concomitant use of aspirin and esomeprazole available through February 2013. The efficacy, safety, tolerability, cost effectiveness, and patient quality of life of this regimen is discussed. A summary of the pharmacokinetic and pharmacodynamic interactions between aspirin and esomeprazole, as well as other commonly used cardiovascular medications are also reviewed. The addition of esomeprazole to low dose aspirin therapy in patients at high risk of developing gastric ulcers for the prevention of cardiovascular disease, significantly reduced their risk of ulcer development. Pharmacokinetic and pharmacodynamic studies suggested that esomeprazole did not affect the pharmacokinetic parameters or the antiplatelet effects of aspirin. Therefore, for those patients who are at a high risk of developing a gastrointestinal ulcer, the benefit of adding esomeprazole likely outweighs the risks of longer term proton pump inhibitor use, and the combination can be recommended. Administering the two agents separately may also be more economical. On the other hand, for those patients at lower risk of developing a gastrointestinal ulcer, both the additional risk and cost make the inclusion of a proton pump inhibitor unwarranted.

[The communication with patients about analogue substitution is complex]. / Kommunikation med patienter om analog medicinsubstitution er kompleks.

Information about "effect" was considered more important than "price" on analogue substitution by a group of patients using the original medicine, esomeprazol, and having mixed experiences with generics. The word "cheap" implied negative associations to the expected effect and was associated with perception of more side effects. Patients adapted individually to substitution, e.g. by self-payment and -dosing.Furthermore they expressed themselves in methaphors, which was a figure lacking in written information to them. This qualitative study supports the need for, as well as more knowledge on, patient-oriented information and -dialogue on analogue substitution of medicines.

Esomeprazole formulary exclusion: impact on total health care services use and costs.

Esomeprazole was excluded from the United Healthcare formulary for all commercial health plan members January 1, 2007. A retrospective analysis of the Ingenix LabRx database (September 1, 2005, through June 30, 2007) evaluated the effect of this exclusion on health care utilization and costs in a real-world setting. Total medical care services, including pharmacy claims, were examined for 6 months before and after the esomeprazole exclusion. Patients aged ≥ 18 years were included if they had continuous health plan enrollment (September 1, 2005, through June 30, 2007), ≥ 1 esomeprazole prescription during the index period (March 1 through August 31, 2006), and ≥ 2 esomeprazole prescriptions (with no switch to another proton pump inhibitor [PPI]) during the baseline period (sliding 6-month window from September 1 through August 31, 2006). During the 6-month post-exclusion period (January 1 through June 30, 2007), 19.5% of patients remained on esomeprazole, 43% switched to another PPI, and 37.5% had no prescription PPI claims. Compared with the previous 6 months, post-exclusion was associated with increased health care utilization, including a 4.2% increase in number of inpatient visits, and a 2.7% increase in other services (eg, laboratory testing, ambulatory procedures). Esomeprazole prescriptions decreased by 76.5%, whereas overall pharmacy claims for all drug classes (including gastrointestinal drugs) increased by 5.2%. Six-month prescription drug costs decreased by $177/patient (95% confidence interval [CI], $160-$194/patient), whereas costs for total medical services increased by $450/patient (95% CI, $259-$640/patient), resulting in a net increase of $273/patient (95% CI, $137-$408/patient). Total and gastrointestinal-related medical services costs were significantly higher for those switching to another PPI versus those continuing esomeprazole. Inpatient utilization contributed most (44.5%) to increased costs of nongastrointestinal comorbidities. This study provides real-world evidence that formulary exclusions can lead to unintended increases in overall health care utilization and costs that exceed anticipated pharmacy budget savings.

Randomised clinical trial: the burden of illness of uninvestigated dyspepsia before and after treatment with esomeprazole--results from the STARS II study.

BACKGROUND: Patients with dyspepsia often experience troublesome symptoms. AIM: To assess the burden of uninvestigated dyspepsia (symptoms, health-related quality of life [HRQL] and work productivity) before and after 8 weeks' esomeprazole treatment. METHODS: Patients (n=1250) with uninvestigated dyspepsia (no endoscopy within 6 months and ≤ 2 endoscopies within 10 years) underwent a 1-week esomeprazole acid-suppression test before randomisation to 7 weeks' esomeprazole or placebo. The Reflux Disease Questionnaire (RDQ), Quality of Life in Reflux and Dyspepsia (QOLRAD) and Work Productivity and Activity Impairment (WPAI) questionnaires were completed at baseline (1-week off-treatment) and 8 weeks. WPAI results were further analysed among patients who responded to the acid-suppression test. RESULTS: The highest baseline symptom score was for the RDQ dyspepsia domain, and the highest disease burden was for QOLRAD vitality and food/drink problems. After 8 weeks, significant improvements vs. placebo were observed for all RDQ and QOLRAD domains. The sub-population of acid-suppression test responders, but not the total WPAI population, had a significant work productivity improvement vs. placebo. CONCLUSIONS: Uninvestigated dyspepsia is associated with high symptom load and impacts on HRQL and work productivity. Esomeprazole improves HRQL among such patients, and improves work productivity among 1-week acid-suppression trial responders. ClinicalTrials.gov identifier: NCT00251992.

Cost reduction associated with restriction policy on dispensing intravenous esomeprazole in Lebanon.

OBJECTIVES: To assess the impact of the pharmacist on cost through simple implementation of restriction policy on IV drug usage during pharmacy dispensing procedure. SETTING: In-patient floors of a Hospital. METHODS: All medication orders for IV esomeprazole, received at the pharmacy during a 24-month period, were reviewed for appropriate IV route of administration. Two separate time intervals, pre- and post- implementation of restriction dispensing policy, were used to determine cost impact of pharmacy intervention. MAIN OUTCOME MEASURE: The cost difference between pre- and post-restriction periods. RESULTS: During the pre-restriction period, the majority of esomeprazole IV vials were dispensed to patients able to tolerate oral medications and who were admitted to non-intensive care units. The average monthly consumption of IV esomeprazole was 1,439 vials in the pre-restriction period as compared to 346 vials in the post-restriction period. Therefore, the associated cost was reduced by an average of $21,233 per month. CONCLUSION: Even though the clinical role of pharmacy practice in Middle Eastern countries is limited, this study highlighted the impact of the pharmacist on cost through the implementation of restriction policy during dispensing procedure, leading to a cost reduction by four folds.

The gain in quality-adjusted life months by switching to esomeprazole in those with continued reflux symptoms in primary care: EncomPASS--a cluster-randomized trial.

OBJECTIVES: Proton pump inhibitors (PPIs) are effective in gastroesophageal reflux disease (GERD), but their cost effectiveness is unknown. This is usually determined by cost/quality-adjusted life year (QALY) gained, but whether PPI therapy improves QALYs has not been assessed in a randomized trial. The PPI acid suppression symptom (PASS) test is a five-item questionnaire that identifies patients with persistent acid-related symptoms. We evaluated whether a PASS test-based management strategy of changing GERD therapy to esomeprazole in those with continued symptoms on another PPI or H(2) receptor antagonist therapy would be cost effective. We expressed the data in terms of cost per quality-adjusted life months (QALM), as this was a 4-week trial. METHODS: This is a multicenter, cluster-randomized, open-label study in primary care physician centers across Canada. Primary care physician centers were randomized to intervention or control arms. Patients on acid-suppressing medication were identified from primary care records and asked to complete the PASS test. PASS test failures at baseline assessment continued current therapy in control practices or switched to esomeprazole 20 or 40 mg daily (the dose was at the clinician's discretion) for 4 weeks in intervention practices. A planned secondary end point was QALM gain, measured using the validated Euroqol (EQ-5D) completed at baseline and 4 weeks. Medication use was also assessed by questionnaire. Canadian unit generic costs were applied to all GERD drugs, except to esomeprazole and lansoprazole, wherein proprietary costs were used (all costs in Canadian $). Data were analyzed using bootstrap sampling. RESULTS: A total of 1,564 patients were recruited from 134 intervention sites and 92 control sites. Data were evaluable for 808 intervention and 445 control patients. The mean (±standard deviation) QALM at 4 weeks in the intervention group was 0.885±0.164 compared with 0.814±0.179 in the control group, resulting in a mean 0.071 (95% CI=0.091-0.051) QALM gain (P<0.0001). Esomeprazole was cost effective for PASS test failures, with a mean cost of $763 (95% CI=456-1,414) per QALM gain. CONCLUSIONS: Esomeprazole was associated with a statistically significant gain in QALMs and was cost effective in primary care patients with persistent acid-related symptoms identified by the PASS test.