The promise of Immuno-oncology: implications for defining the value of cancer treatment.

The rapid development of immuno-oncology (I-O) therapies for multiple types of cancer has transformed the cancer treatment landscape and brightened the long-term outlook for many patients with advanced cancer. Responding to ongoing efforts to generate value assessments for novel therapies, multiple stakeholders have been considering the question of "What makes I-O transformative?" Evaluating the distinct features and attributes of these therapies, and better characterizing how patients experience them, will inform such assessments. This paper defines ways in which treatment with I-O is different from other therapies. It also proposes key aspects and attributes of I-O therapies that should be considered in any assessment of their value and seeks to address evidence gaps in existing value frameworks given the unique properties of patient outcomes with I-O therapy. The paper concludes with a "data needs catalogue" (DNC) predicated on the belief that multiple key, unique elements that are necessary to fully characterize the value of I-O therapies are not routinely or robustly measured in current clinical practice or reimbursement databases and are infrequently captured in existing research studies. A better characterization of the benefit of I-O treatment will allow a more thorough assessment of its benefits and provide a template for the design and prioritization of future clinical trials and a roadmap for healthcare insurers to optimize coverage for patients with cancers eligible for I-O therapy.

A cost-benefit analysis of smoking cessation prescription coverage from a US payer perspective.

INTRODUCTION: Smoking drives substantial direct health care spending, comprising 8.7% ($168 billion) of annual United States aggregated spending. Smoking cessation (SC) prescription use is an effective strategy to improve health outcomes, increase quit rates, and reduce economic burden. However, patient out-of-pocket costs may limit the use. Health care payers play a vital role in driving use through formulary decisions and copayment policies but must consider both the near-term financial investment as well as downstream effects of increased coverage on health care budgets. This study estimates the return on investment (ROI) of providing Affordable Care Act (ACA)-recommended prescription SC coverage. METHODS: A cost-benefit analysis (CBA) estimates the ROI of providing prescription SC coverage, based on pharmacy costs and savings from smoking-attributable medical expenditures among Medicare, Medicaid, and commercial plan enrollees over 10 years. The CBA incorporated national-level population demographics, smoking prevalence estimates, proportion of smokers attempting to quit, and the utilization of SC products. A five-state Markov chain model simulated patterns of quit attempts, relapse, and cessation assuming two quit attempts per year, no patient cost-sharing, and 25.4% utilization of prescription SC aids. Results include number of quitters, annual pharmacy and smoking-attributable medical costs, and ROI. RESULTS: After initial investment in SC treatment, smoking-attributable medical benefits accrue over time, generating a positive ROI by year 4 for commercial (11.3%) and Medicaid (78.4%) plans and by year 3 for Medicare (30.6%). Over 10 years, an average return of $1.18, $2.50, and $3.22 savings per dollar spent on SC prescriptions for commercial, Medicaid, and Medicare plans, respectively, may be realized. DISCUSSION: Given the proven efficacy of SC pharmacotherapy, near-term investments in supporting ACA-recommended SC coverage translate into a positive ROI. As smoking is a leading cause of morbidity and mortality, increased access to prescription SC medications may improve health outcomes and reduce smoking-attributable costs to payers over time.

Payer and Pharmaceutical Manufacturer Considerations for Outcomes-Based Agreements in the United States.

BACKGROUND: Considerable interest exists among health care payers and pharmaceutical manufacturers in designing outcomes-based agreements (OBAs) for medications for which evidence on real-world effectiveness is limited at product launch. OBJECTIVES: To build hypothetical OBA models in which both payer and manufacturer can benefit. METHODS: Models were developed for a hypothetical hypercholesterolemia OBA, in which the OBA was assumed to increase market access for a newly marketed medication. Fixed inputs were drug and outcome event costs from the literature over a 1-year OBA period. Model estimates were developed using a range of inputs for medication effectiveness, medical cost offsets, and the treated population size. Positive or negative feedback to the manufacturer was incorporated on the basis of expectations of drug performance through changes in the reimbursement level. Model simulations demonstrated that parameters had the greatest impact on payer cost and manufacturer reimbursement. RESULTS: Models suggested that changes in the size of the population treated and drug effectiveness had the largest influence on reimbursement and costs. Despite sharing risk for potential product underperformance, manufacturer reimbursement increased relative to having no OBA, if the OBA improved market access for the new product. Although reduction in medical costs did not fully offset the cost of the medication, the payer could still save on net costs per patient relative to having no OBA by tying reimbursement to drug effectiveness. CONCLUSIONS: Pharmaceutical manufacturers and health care payers have demonstrated interest in OBAs, and under a certain set of assumptions both may benefit.

A Review of Empirical Analyses of Disinvestment Initiatives.

BACKGROUND: Disinvesting in low-value health care services provides opportunities for investment in higher value care and thus an increase in health care efficiency. OBJECTIVES: To identify international experience with disinvestment initiatives and to review empirical analyses of disinvestment initiatives. METHODS: We performed a literature search using the PubMed database to identify international experience with disinvestment initiatives. We also reviewed empirical analyses of disinvestment initiatives. RESULTS: We identified 26 unique disinvestment initiatives implemented across 11 countries. Nineteen addressed multiple intervention types, six addressed only drugs, and one addressed only devices. We reviewed 18 empirical analyses of disinvestment initiatives: 7 reported that the initiative was successful, 8 reported that the initiative was unsuccessful, and 3 reported that findings were mixed; that is, the study considered multiple services and reported a decrease in the use of some but not others. Thirty-seven low-value services were evaluated across the 18 empirical analyses, for 14 (38%) of which the disinvestment initiative led to a decline in use. Six of the seven studies that reported the disinvestment initiative to be successful included an attempt to promote the disinvestment initiative among participating clinicians. CONCLUSIONS: The success of disinvestment initiatives has been mixed, with fewer than half the identified empirical studies reporting that use of the low-value service was reduced. Our findings suggest that promotion of the disinvestment initiative among clinicians is a key component to the success of the disinvestment initiative.

Estimating Population Health Benefits Associated with Specialty and Traditional Drugs in the Year Following Product Approval.

OBJECTIVE: Compared to traditional drugs, specialty drugs tend to be indicated for lower prevalence diseases. Our objective was to compare the potential population health benefits associated with specialty and traditional drugs in the year following product approval. METHODS: First, we created a dataset of estimates of incremental quality-adjusted life-year (QALY) gains and incremental life-year (LY) gains for US FDA-approved drugs (1999-2011) compared to standard of care at the time of approval identified from a literature search. Second, we categorized each drug as specialty or traditional. Third, for each drug we identified estimates of US disease prevalence for each pertinent indication. Fourth, in order to conservatively estimate the potential population health gains associated with each new drug in the year following its approval we multiplied the health gain estimate by 10% of the identified prevalence. Fifth, we used Mann-Whitney U tests to compare the population health gains for specialty and traditional drugs. RESULTS: We identified QALY gain estimates for 101 drugs, including 56 specialty drugs, and LY gain estimates for 50 drugs, including 34 specialty drugs. The median estimated population QALY gain in the year following approval for specialty drugs was 4200 (IQR = 27,000) and for traditional drugs was 694 (IQR = 24,400) (p = 0.245). The median estimated population LY gain in the year following approval for specialty drugs was 7250 (IQR = 39,200) and for traditional drugs was 2500 (IQR = 58,200) (p = 0.752). CONCLUSIONS: Despite often being indicated for diseases of lower prevalence, we found a trend towards specialty drugs offering larger potential population health gains than traditional drugs, particularly when measured in terms of QALYs.

Financing a Cure for Diabetes in a Multipayer Environment.

BACKGROUND: Financing medical breakthroughs or cures is becoming increasingly challenging in the current fiscal environment. OBJECTIVES: In this paper, we develop the precise conditions needed for a financing mechanism, HealthCoin, to work between a private payer and Medicare, to incentivize the former to invest in breakthrough therapies or cures in the US. METHODS: We illustrate the valuation of such a currency for a cure of Type 2 diabetes. RESULTS: We show that without a HealthCoin, a private payer does not invest in the cure, a small fraction of the patients live up to age 65, Medicare pays for the full price of the cure at age 65 and incurs net loss in returns over the elderly ages, and the manufacturer only sells cures for those who reach age 65. In contrast, a HealthCoin is feasible in this market, incentivizing the private payer to invest in the cure during the non-elderly ages and leading to Pareto improvements for all three stakeholders. CONCLUSIONS: Discussions around the applicability of HealthCoin for breakthrough therapies on the horizon, such as gene therapies for blindness and hemophilia B, and the feasibility of instituting such payments through new legislations or demonstration projects could be of great value.

Survival among patients with advanced renal cell carcinoma in the pretargeted versus targeted therapy eras.

Between December 2005 and October 2009, FDA approved six targeted therapies shown to significantly extend survival for advanced renal cell carcinoma (RCC) patients in clinical trials. This study aimed to examine changes in survival between the pretargeted and targeted therapy periods in advanced RCC patients in a real-world setting. Utilizing the 2000-2010 SEER Research files, a pre-post study design with a contemporaneous comparison group was employed to examine differences in survival outcomes for patients diagnosed with advanced RCC (study group) or advanced prostate cancer (comparison group, for whom no significant treatment innovations happened during this period) across the pretargeted therapy era (2000-2005) and the targeted therapy era (2006-2010). RCC patients diagnosed in the targeted therapy era (N = 6439) showed improved survival compared to those diagnosed in the pretargeted therapy era (N = 7231, hazard ratio (HR) for all-cause death: 0.86, P < 0.01), while the change between the pre-post periods was not significant for advanced prostate cancer patients (HR: 0.97, P = 0.08). Advanced RCC patients had significantly larger improvements in overall survival compared to advanced prostate cancer patients (z = 4.31; P < 0.01). More detailed year-to-year analysis revealed greater survival improvements for RCC in the later years of the posttargeted period. Similar results were seen for cause-specific survival. Subgroup analyses by nephrectomy status, age, and gender showed consistent findings. Patients diagnosed with advanced RCC during the targeted therapy era had better survival outcomes than those diagnosed during the pretargeted therapy era. Future studies should examine the real-world survival improvements directly associated with targeted therapies.

Optimizing the leveraging of real-world data to improve the development and use of medicines.

Health research, including health outcomes and comparative effectiveness research, is on the cusp of a golden era of access to digitized real-world data, catalyzed by the adoption of electronic health records and the integration of clinical and biological information with other data. This era promises more robust insights into what works in health care. Several barriers, however, will need to be addressed if the full potential of these new data are fully realized; these will involve both policy solutions and stakeholder cooperation. Although a number of these issues have been widely discussed, we focus on the one we believe is the most important-the facilitation of greater openness among public and private stakeholders to collaboration, connecting information and data sharing, with the goal of making robust and complete data accessible to all researchers. In this way, we can better understand the consequences of health care delivery, improve the effectiveness and efficiency of health care systems, and develop advancements in health technologies. Early real-world data initiatives illustrate both potential and the need for future progress, as well as the essential role of collaboration and data sharing. Health policies critical to progress will include those that promote open source data standards, expand access to the data, increase data capture and connectivity, and facilitate communication of findings.

Treatment dynamics of newly marketed drugs and implications for comparative effectiveness research.

OBJECTIVES: Clinicians and payers require rapid comparative effectiveness (CE) evidence generation to inform decisions for new drugs. We empirically assessed treatment dynamics of newly marked drugs and their implications for conducting CE research. METHODS: We used claims data to evaluate five drug-outcome pairs: 1) raloxifene (vs. alendronate) and fracture; 2) risedronate (vs. alendronate) and fracture; 3) simvastatin plus ezetimibe fixed-dose combination (simvastatin + ezetimibe) (vs. simvastatin alone) and cardiovascular events; 4) rofecoxib (vs. nonselective nonsteroidal anti-inflammatory drugs [ns-NSAIDs]) and myocardial infarction; and 5) rofecoxib (vs. ns-NSAIDS) and gastrointestinal bleed. We examined utilization dynamics in the early marketing period, including evolving utilization patterns, outcome risk among those treated with new versus established drugs, and prior treatment patterns that may indicate treatment resistance or intolerance. We addressed these challenges by replicating active CE monitoring with sequential matched cohort analysis. RESULTS: Patients initiating new drugs were more likely to have used other drugs for the same indication in the past, but the majority of patients in all new drug cohorts were treatment naive (82.0% overall). Patients initiating rofecoxib had higher predicted baseline risk of gastrointestinal bleed than did patients initiating ns-NSAIDs. Patients initiating risedronate and alendronate had similar predicted baseline risks of fracture, while those initiating raloxifene and simvastatin + ezetimibe had lower risks of outcomes of interest relative to their comparators. Prospective monitoring yielded results consistent with expectation for each example. CONCLUSIONS: Many challenges to assessing the CE of new drugs are borne out in empirical data. Attention to these challenges can yield valid CE results.

From concepts, theory, and evidence of heterogeneity of treatment effects to methodological approaches: a primer.

Implicit in the growing interest in patient-centered outcomes research is a growing need for better evidence regarding how responses to a given intervention or treatment may vary across patients, referred to as heterogeneity of treatment effect (HTE). A variety of methods are available for exploring HTE, each associated with unique strengths and limitations. This paper reviews a selected set of methodological approaches to understanding HTE, focusing largely but not exclusively on their uses with randomized trial data. It is oriented for the "intermediate" outcomes researcher, who may already be familiar with some methods, but would value a systematic overview of both more and less familiar methods with attention to when and why they may be used. Drawing from the biomedical, statistical, epidemiological and econometrics literature, we describe the steps involved in choosing an HTE approach, focusing on whether the intent of the analysis is for exploratory, initial testing, or confirmatory testing purposes. We also map HTE methodological approaches to data considerations as well as the strengths and limitations of each approach. Methods reviewed include formal subgroup analysis, meta-analysis and meta-regression, various types of predictive risk modeling including classification and regression tree analysis, series of n-of-1 trials, latent growth and growth mixture models, quantile regression, and selected non-parametric methods. In addition to an overview of each HTE method, examples and references are provided for further reading.By guiding the selection of the methods and analysis, this review is meant to better enable outcomes researchers to understand and explore aspects of HTE in the context of patient-centered outcomes research.

Impact of patient sample on costs of events in pharmacoeconomic models.

Pharmacoeconomic guidelines have focused on improving the measurement of effectiveness, but have largely ignored the assessment of cost inputs. We explored differences in adverse event cost estimates derived from three different sources in a case study of selective COX2 NSAIDs. We found substantial differences in costs of adverse events across data sources. We also determined that treatment costs associated with adverse events differed substantially based upon inclusion/exclusion criteria. Health services researchers should be deliberate in the choice of adverse event treatment costs that are used in decision analytic models. Future guidelines should seek to delineate best practices for cost calculations.

Economic analysis of triptan therapy for acute migraine: a Medicaid perspective.

STUDY OBJECTIVE: To compare triptan therapies for migraine in terms of the cost to treat 100 migraine attacks and the cost per successfully treated patient (cost/success), by analyzing utilization and reimbursement data from state Medicaid programs. DESIGN: Pharmacoeconomic analysis. DATA SOURCE: Clinical efficacy data were obtained from a previously published meta-analysis for 11 triptan-dose combinations: almotriptan 12.5 mg; eletriptan 20 and 40 mg; naratriptan 2.5 mg; rizatriptan 5 and 10 mg; sumatriptan 25, 50, and 100 mg; and zolmitriptan 2.5 and 5 mg. Triptan reimbursement data were obtained from the Medicaid Drug Rebate Program of seven geographically dispersed states (Florida, Georgia, Illinois, North Carolina, Ohio, Wisconsin, and West Virginia). MEASUREMENTS AND MAIN RESULTS: Efficacy measures were derived based on data from the published meta-analysis that evaluated headache pain status at 2 and 24 hours after triptan dosing. Reimbursement data for the triptans were applied to a previously developed model of migraine treatment outcomes to calculate the cost to treat 100 migraine attacks and the cost/success. Sensitivity analysis around dosing assumptions was conducted to assess robustness of estimates. Across the seven states, the two treatments associated with the lowest cost to treat 100 migraine attacks were eletriptan 20 mg (range $1549-$1658) and eletriptan 40 mg ($1578-$1661). Naratriptan 2.5 mg (range $1734-$2018), sumatriptan 25 mg ($1853-1954), and zolmitriptan 5 mg ($1854-$1960) were associated with the highest cost to treat 100 migraine attacks. Eletriptan 40 mg was associated with the lowest cost/success (range $57.03-$60.05); naratriptan 2.5 mg ($99.39-$115.65), sumatriptan 25 mg ($107.11-$112.93), and rizatriptan 5 mg ($99.41-$111.25) were associated with the highest cost/success values. Changes in dosing assumptions did not significantly change the rank ordering of triptans across either economic end point. CONCLUSIONS: Eletriptan 20- and 40-mg doses were shown to be associated with the lowest cost to treat 100 migraine attacks and the lowest cost/success in both the baseline and sensitivity analyses. These findings are consistent with results of similar economic analyses that compared multiple triptan therapies.

An economic evaluation of triptan products for migraine.

OBJECTIVE: A composite outcome measure in migraine treatment assessment is useful to clinical decision-makers and payers as it can provide a more accurate reflection of effectiveness and allows for more complete modeling of economic value. The objective of this study was to compare the total triptan cost to treat 100 migraine patient attacks and the cost per successfully treated patient (CPSTP) for six marketed triptans using a composite measure of effectiveness, the "successfully treated" migraine (defined as requiring only one triptan dose to treat one migraine attack during a 24-h period). METHODS: This analysis was conducted from the perspective of the payer. Clinical data were abstracted from a rigorous, published meta-analysis. Two-hour response and pain-free response were used in conjunction with the recurrence rate reported in the meta-analysis to calculate the number of doses used by treatment successes and failures. The average wholesale price per dose was then used to calculate total triptan cost. RESULTS: Of the nine oral triptan doses compared, eletriptan 40 mg was associated with both the lowest total triptan cost for treating 100 migraine attacks ($1560) and with the lowest CPSTP ($56.39). CONCLUSIONS: The relative CPSTP rankings for migraine therapies are dependent on the definition of treatment success and relative pricing. The results of this study support the use of eletriptan for the treatment of acute migraine based on the model assumptions. This study can be used to assist in formulary considerations and offers a model that can be adapted by health-care decision-makers.

Treatment of overactive bladder: a model comparing extended-release formulations of tolterodine and oxybutynin.

OBJECTIVE: The objective of this study was to compare 1-year total healthcare costs for patients with overactive bladder (OAB) initiating treatment with extended-release formulations of tolterodine and oxybutynin: tolterodine tartrate extended-release capsules (tolterodine ER) versus extended-release oxybutynin chloride (oxybutynin ER). METHODS: A model was developed from the payer perspective using data from the PharMetrics Patient-Centric database. Monthly discontinuation rates were derived from a cohort of newly treated patients with OAB (tolterodine ER, n = 15 394 or oxybutynin ER, n = 7934). All were assumed to be receiving therapy for at least 1 month. Medical management costs were based on reimbursement for all services for a matched cohort of patients taking tolterodine ER and oxybutynin ER. Medical management costs for those discontinuing therapy were based on patients receiving OAB care without pharmacotherapy (n = 29 992). Drug costs were from AnalySource (December 2004). RESULTS: After the 11-month follow-up period, 21% of patients taking tolterodine ER and 15% of patients taking oxybutynin ER remained on original therapy. One-year average total costs per patient for those started on tolterodine ER were dollar 8876 and dollar 9080 for oxybutynin ER, a difference of dollar 204 per year. Sensitivity analyses indicated results were robust to changes in drug cost and probability of discontinuation. When discontinuation rates were held equal, cost differences continued to favor tolterodine ER (21%, dollar 272/yr; 15%, dollar 233/yr). CONCLUSION: Those taking tolterodine ER had lower monthly drug and medical management costs. This resulted in a total average annual cost savings of dollar 204 per patient for those started on tolterodine ER. At the end of 1 year, patients with OAB were more likely to remain on original drug treatment taking tolterodine ER versus oxybutynin ER.

Triptans for migraine therapy: a comparison based on number needed to treat and doses needed to treat.

OBJECTIVE: Managed care and other decision makers need sound comparative information to support the formulary selection process and reimbursement decisions for the treatment of migraine. The objective of this study was to compare currently marketed triptan therapies using number-needed-to-treat (NNT) and doses-needed-to-treat (DNT) measures. DNT was further used to derive triptan treatment cost to achieve 100 successfully treated patients such that the cost-effectiveness of each treatment regime could be compared from the payer perspective. METHODS: Using published meta-analysis data to categorize patients as treatment success or failure, an NNT and a DNT were derived for each triptan. Treatment success was defined as achieving a 2-hour pain response, sustained through 24 hours postdose. Costs were derived by multiplying DNT by the average wholesale price (AWP) minus 15% for each triptan. RESULTS: Eletriptan 40 mg had the lowest NNT, with 361 patients needing to be treated in order to have 100 patients achieve clinical benefit; rizatriptan 5 mg had the highest NNT (597 patients). Eletriptan 40 mg required 388 doses to successfully treat 100 patients.the lowest number of doses of the triptans considered; rizatriptan 5 mg required the highest number (662 doses). Eletriptan 40 mg had the lowest total triptan cost of USD 5,630 to successfully treat 100 patients. The highest total triptan cost of treatment was USD 11,136 for naratriptan 2.5 mg. CONCLUSIONS: Eletriptan 40 mg provides the best value in terms of the lowest DNT, assuming an approximately equal AWP discount for each triptan. Eletriptan 40 mg also was found to have the lowest total triptan cost to successfully treat 100 patients. Future research should further explore the utility of DNT in managed care decision making.

Economic burden of uncomplicated urinary tract infections: direct, indirect and intangible costs.

A better understanding of how antimicrobial therapies affect the total cost of lower uncomplicated urinary tract infection, including direct (e.g., doctor visits), indirect (e.g., productivity) and intangible (e.g., pain) costs would facilitate selection of an optimal therapeutic approach. The results of this literature review indicate that the there is a considerable societal burden from uncomplicated urinary tract infection, with approximately USD 1 billion in indirect and over USD 600 million in direct costs in 1995. However, no single identified study incorporated all three cost components, there are gaps in the knowledge concerning the current extent of these costs, and there are no comparative assessments based on total cost. Research is needed to provide current insights on the burden of uncomplicated urinary tract infection in terms of direct, indirect and intangible costs.

Economic and patient-reported outcomes of oral triptans in the treatment of migraine.

Migraine places a tremendous burden on patients, employers, the healthcare system and society. Triptans often effectively reduce pain and suffering caused by migraine and return patients to their typical routine. Seven triptans are marketed in the USA, and prescribers and payers need information to compare their effectiveness and value. However, studies that compare the treatment and economic impact between the seven triptans are limited. Meta-analyses are a useful source of information to make comparisons between the triptans and provide essential information for clinical and formulary decision makers. Future research should assess and expand upon the use of composite outcome measures that capture the desired response to treatment, consider the placebo effect in migraine, and make comparisons among the available triptans.

Economic evaluation of enoxaparin as prophylaxis against venous thromboembolism in seriously ill medical patients: a US perspective.

OBJECTIVE: To determine the cost and cost effectiveness of adding venous thromboembolism (VTE) prophylaxis with enoxaparin, a low-molecular-weight heparin, to standard care for acutely ill, hospitalized medical patients. METHODS: A pharmacoeconomic model was developed to simulate the 6- to 14-day course of enoxaparin prophylaxis evaluated in the MEDENOX trial in a US healthcare setting. Clinical results as reported for the trial were applied to resource use and treatment costs in a US healthcare environment. The model projects hospital length of stay and cost for an acute medical admission from a third-party payer perspective, as well as costs for the course of enoxaparin. RESULTS: VTE prophylaxis with enoxaparin would account for 1.2% to 2.4% of the cost of a hospital admission, with an additional $23 +/- $28 to $99 +/- $122 to complete the course of prophylaxis out of hospital. Incremental cost effectiveness of VTE prophylaxis relative to no prophylaxis ranges from $1249 to $3088 per VTE avoided. Venous thromboembolism prophylaxis appears to be a break-even intervention, with the cost recouped through avoided treatment, if the rate of treated VTE without prophylaxis is at least 3-4%. DISCUSSION AND CONCLUSIONS: The MEDENOX trial demonstrated that prophylaxis with enoxaparin substantially decreases the risk of VTE among acutely ill, hospitalized medical patients. Economic analysis indicates that this protection represents a small increase in current treatment costs. Prophylaxis is cost effective in terms of incremental cost per VTE avoided. Furthermore, there is a reasonable likelihood that the cost of prophylaxis will be offset by avoided future VTE treatment.

Cost effectiveness of treatment of Parkinson's disease with entacapone in the United States.

OBJECTIVE: To determine the cost effectiveness of adjunctive therapy with entacapone versus standard treatment (levodopa) without entacapone for patients in the US with Parkinson's disease (PD) who experience 'off-time' (re-emergence of the symptoms of PD) while receiving levodopa. STUDY DESIGN: A Markov model was used to estimate 5-year costs and effectiveness of standard treatment with and without entacapone. METHODS: Probabilities, unit costs, resource utilisation data and utilities were obtained from published literature, clinical trial reports, a national database, and clinical experts. PD disability was measured using the daily proportion of off-time and Hoehn and Yahr scale scores. The analysis measured costs from a societal and third-party payer perspective, and effectiveness as gains in quality-adjusted life-years (QALYs) and years without progression to >25% off-time. RESULTS: From a societal perspective, entacapone therapy resulted in an incremental cost of US dollars 9327 per QALY gained compared with standard treatment. Treatment with entacapone also provided an additional 7.6 months with < or =25% off-time/day compared with standard treatment. Sensitivity analyses indicated that the model is sensitive to changes in rates of improvement/deterioration of off-time, and to the number of doses per day of levodopa with adjunctive entacapone. CONCLUSIONS: The addition of entacapone to standard treatment for patients receiving levodopa who experience off-time provides additional QALYs and gain in time with minimal fluctuations. Results of this modelling exercise suggest that therapy with entacapone may be cost effective when compared with standard treatment for PD.