iStent inject® and cataract surgery for mild-to-moderate primary open angle glaucoma in Japan: a cost-utility analysis.

AIM: To evaluate the cost-utility of iStent inject® with cataract surgery vs cataract surgery alone in patients with mild-to-moderate primary open angle glaucoma (POAG) in the Japanese setting from a public payer's perspective. METHODS: A Markov model was adapted to estimate the cost-utility of iStent inject® plus cataract surgery vs cataract surgery alone in one eye in patients with mild-to-moderate POAG over lifetime horizon from the perspective of Japanese public payer. Japanese sources were used for patients' characteristics, clinical data, utility, and costs whenever available. Non-Japanese data were validated by Japanese clinical experts. RESULTS: In the probabilistic base case analysis, iStent inject® with cataract surgery was found to be cost-effective compared with cataract surgery alone over a lifetime horizon when using the ¥5 000 000/quality-adjusted life year (QALY) willingness-to-pay threshold. The incremental cost-utility ratio (ICUR) was estimated to be ¥1 430 647/QALY gained and the incremental cost-utility ratio (ICER) was estimated to be ¥12 845 154/blind eye avoided. iStent inject® with cataract surgery vs cataract surgery alone was found to increase costs (¥1 025 785 vs ¥933 759, respectively) but was more effective in increasing QALYs (12.80 vs 12.74) and avoiding blinded eyes (0.133 vs 0.141). The differences in costs were mainly driven by costs of primary surgery (¥279 903 vs ¥121 349). In the scenario analysis from a societal perspective, which included caregiver burden, iStent inject® with cataract surgery was found to dominate cataract surgery alone. CONCLUSION: The iStent inject® with cataract surgery is a cost-effective strategy over cataract surgery alone from the public payer's perspective and cost-saving from the societal perspective in patients with mild-to-moderate POAG in Japan.

A cost-effectiveness analysis of iStent inject combined with phacoemulsification cataract surgery in patients with mild-to-moderate open-angle glaucoma in France.

OBJECTIVE: To investigate the cost-effectiveness of implementing iStent inject trabecular bypass stent (TBS) in conjunction with cataract surgery (Cat Sx) in patients with mild-to-moderate glaucoma from a societal perspective in France. The secondary objective was to explore the economic impact of iStent inject TBS in patients who comply to different degrees with their anti-glaucoma medications. METHODS: A previously published Markov model was adapted to estimate the cost-effectiveness of treatment with iStent inject TBS + Cat Sx versus Cat Sx alone over a lifetime time horizon in patients with mild-to-moderate open-angle glaucoma in France. Progression was modeled by health states reflecting increasing stages of vision loss. Disease progression was obtained from the two-year randomized clinical trial assessing safety and effectiveness of both interventions. French specific health-state utilities and costs were obtained through a targeted literature review. Model structure and inputs were validated by French ophthalmologists. Outcomes were expressed as incremental cost per quality-adjusted life-year (QALY) gained. The robustness of results was tested through sensitivity analyses. RESULTS: iStent inject TBS + Cat Sx reduced the number of medications needed and risk of blindness. Incremental cost and QALYs were €75 and 0.065 leading to an incremental cost-effectiveness ratio (ICER) of €1,154/QALY gained. ICER ranged from dominating for non-persistent patients to €31,127 patients fully persistent with their medication regime. Results from one-way sensitivity analysis had a maximum ICER of €29,000 when varying input parameters. iStent inject TBS + Cat Sx had an 86% chance of being cost-effective at a willingness-to-pay threshold of €30,000 per QALY gained. CONCLUSION: Results demonstrate that iStent inject TBS + Cat Sx is a cost-effective intervention for intraocular pressure reduction when compared to Cat Sx alone in France.

Quality of Life in Primary Open-Angle Glaucoma and Cataract: An Analysis of VFQ-25 and OSDI From the iStent inject® Pivotal Trial.

OBJECTIVE: To assess quality of life (QOL) as measured by patient-reported outcomes (PRO) within the iStent inject® pivotal trial. DESIGN: Randomized controlled trial analysis of secondary outcomes. METHODS: The Vision Function Questionnaire (VFQ-25) and Ocular Surface Disease Index (OSDI) questionnaire were administered at baseline and at months 1, 6, 12, and 24. PRO responders were defined as patients reaching improvement based on minimally important differences. RESULTS: A total of 505 patients were randomized (386 iStent inject® [Glaukos], 119 surgery alone). The iStent inject® group exhibited a greater percentage of PRO responders across all follow-up visits over 24 months, averaging 58.0% vs 45.8%; P < .05 for VFQ-25 composite scores and 56.7% vs 48.9%; P < .05 for OSDI composite scores. Odds of being a responder in the iStent inject® group was 60% (P < .05) higher for the VFQ-25 and 32% (P > .05) higher for the ODSI. Driving (49.0% vs 28.8%; P < .05), ocular pain (59.3% vs 47.2%; P < .05), and general vision (71.8% vs 60.0%; P < .05) were the VFQ-25 subscales responsible for differences between treatment groups. At month 24, 76.5% of VFQ-25 responders and 62.5% of nonresponders were medication free regardless of treatment group (P < .05). CONCLUSIONS: Exploratory analysis suggests that by reducing medication dependence, implantation with the micro-scale iStent inject® device with cataract surgery may improve QOL vs cataract surgery alone over 24 months, with improvements influenced by ocular symptoms and vision-related activities.

Corneal cross-linking versus conventional management for keratoconus: a lifetime economic model.

AIMS: To assess the cost-effectiveness of corneal collagen cross-linking (CXL) versus no CXL for keratoconus in the United States (US). METHODS: A discrete-event microsimulation was developed to assess the cost-effectiveness of corneal cross-linking (CXL, Photrexa + KXL combination product) versus no CXL for patients with keratoconus. The lifetime model was conducted from a US payor perspective. The source for CXL efficacy and safety data was a 12-month randomized, open-label, sham-controlled, multi-center, pivotal trial comparing CXL versus no CXL. Other inputs were sourced from the literature. The primary outcome was the incremental cost per quality-adjusted life year gained. Costs (2019 USD) and effects were discounted 3% annually. The impacts of underlying uncertainty were evaluated by scenario, univariate, and probabilistic analyses. RESULTS: Starting at a mean baseline age of 31 years and considering a mixed population consisting of 80% slow-progressors and 20% fast-progressors, the CXL group was 25.9% less likely to undergo penetrating keratoplasty (PK) and spent 27.9 fewer years in advanced disease stages. CXL was dominant with lower total direct medical costs (-$8,677; $30,994 versus $39,671) and more QALYs (1.88; 21.80 versus 19.93) compared to no CXL. Considering the impact of reduced productivity loss in an exploratory scenario, CXL was associated with a lifetime cost-savings of $43,759 per patient. CXL was cost-effective within 2 years and cost-saving within 4.5 years. LIMITATIONS: Limitations include those that are common to similar pharmacoeconomic models that rely on disparate sources for inputs and extrapolation on short-term outcomes to a long-term analytical horizon. CONCLUSIONS: Keratoconus is a progressive and life-altering disease with substantial clinical, economic, and humanistic consequences. The economic value of cross-linking is maximized when applied earlier in the disease process and/or younger age, and extends to improved work productivity, out-of-pocket costs, and quality of life.

A Canadian Cost-Utility Analysis of 2 Trabecular Microbypass Stents at Time of Cataract Surgery in Patients with Mild to Moderate Open-Angle Glaucoma.

PURPOSE: To assess, from the Canadian public payer perspective, the cost-utility of implanting iStent Inject trabecular bypass stent (TBS) devices in conjunction with cataract surgery versus cataract surgery alone in patients with open-angle glaucoma (OAG) and visually significant cataract. DESIGN: Cost-utility analysis using efficacy and safety results of pivotal randomized clinical trial. PARTICIPANTS: Modeled cohort of patients with OAG (83.1% with mild disease, 16.9% with moderate disease) and visually significant cataract. METHODS: Open-angle glaucoma treatment costs and effects were projected over a 15-year time horizon using a Markov model with Hodapp-Parrish-Anderson glaucoma stages (mild, moderate, advanced, severe or blind) and death as health states. Patients in the mild or moderate OAG health states received implantation of iStent Inject during cataract surgery versus cataract surgery alone. On worsening of visual field defect and optic disc damage, patients could receive selective laser trabeculoplasty and trabeculectomy. We measured treatment effect as reduction in intraocular pressure (IOP) and mean medication use and estimated transition probabilities based on efficacy-adjusted visual field mean deviation decline per month. Healthcare resource utilization and utility scores were obtained from the literature. Cost inputs (2017 Canadian dollars [C$]) were derived using the Ontario Health Insurance Plan, expert opinion, medication claims datasets, and Ontario Drug Benefit Formulary medication consumption costs. We conducted deterministic and probabilistic sensitivity analyses to examine the impact of alternative model input values on results. MAIN OUTCOME MEASURES: Incremental cost per quality-adjusted life year (QALY) gained. RESULTS: Compared with cataract surgery alone, TBS plus cataract surgery showed a 99% probability of being more effective (+0.023 QALYs; 95% confidence interval [CI], 0.004 to 0.044) and a 73.7% probability of being cost-saving (net cost, -C$389.00; 95% CI, -C$1712.00 to C$850.70). In 95% of all simulations, TBS plus cataract surgery showed a cost per QALY of C$62 366 or less. Results were robust in additional sensitivity and scenario analyses. CONCLUSIONS: iStent Inject TBS implantation during cataract surgery seems to be cost effective for reducing IOP in patients with mild to moderate OAG versus cataract surgery alone.

Cost-effectiveness analysis of standalone trabecular micro-bypass stents in patients with mild-to-moderate open-angle glaucoma in Canada.

OBJECTIVES: To estimate the cost-utility of two trabecular micro-bypass stents (TBS) implantation vs standard of care (SOC) in patients with mild-to-moderate open-angle glaucoma (OAG) in the Canadian healthcare setting. METHODS: The deterioration in visual field (VF) defect over a 15-year time horizon was tracked using a Markov model with Hodapp-Parrish-Anderson stages of glaucoma (mild, moderate, advanced, severe/blind) and death as health states. Meta-analyses of randomized clinical trials were conducted to estimate the pooled reduction in intraocular pressure (IOP) and medication use due to TBS and SOC. The rate of decline in VF loss was adjusted by the extent of IOP reduction to estimate transition probabilities. Healthcare resource utilization, unit costs (2017 CAD), and progression-related utility scores were obtained by literature review, and medication costs with wastage were obtained from IMS Brogan PharmaStat. The impact of parameter and methodological uncertainty on costs and quality-adjusted life years (QALYs) was examined using probabilistic and 1-way sensitivity analyses. RESULTS: The meta-analysis showed an additional reduction of 1.13 medications/patient and an additional decrease in IOP of -1.10 mmHg at 36 months favoring TBS. TBS strongly dominated medication alone, due to higher improvement in quality-of-life (0.068 QALYs), fewer blind eyes (-0.0031), and a decrease in total healthcare costs of C$2,908.3 per patient over the time horizon (C$9,394.1 TBS vs C$12,302.4 medication alone). Sensitivity analyses showed that results were robust to the uncertainties in model inputs and assumptions. Time-to-dominance was 44 months (3.7 years). CONCLUSIONS: The TBS procedure was cost-effective over SOC in a 15-year time horizon, with quality-of-life gains.

Symptoms and Functional Limitations in the First Year Following a Myocardial Infarction: A Qualitative Study.

BACKGROUND AND OBJECTIVES: This qualitative interview study was designed to highlight the symptoms and functional limitations experienced by patients in the year following a myocardial infarction (MI). This information can support the use or development of patient-reported outcome (PRO) instruments in the post-MI population. METHODS: Individual face-to-face interviews were conducted with 38 participants who had experienced an MI (with or without ST segment elevation) within the past month to <6 months (n = 17), or 6 months to ≤12 months (n = 21). Using content and thematic analysis, patient reports of symptoms and functional limitations were coded and then grouped into categories. The specific content and frequency of the symptom and functional limitation reports were summarized. RESULTS: Nearly half of all symptom expressions were related to fatigue. Within this fatigue category, patients reported experiencing general tiredness, as well as a loss of physical energy, mental energy, and/or motivation. Chest pain and discomfort, sleep disruption, and shortness of breath were also frequently reported. Additionally, patients reported emotional effects, including worry and depression, as well as a negative impact on relationships and social activities. CONCLUSIONS: Patients reported a wide variety of symptoms and functional limitations after an MI. Fatigue was the most commonly reported symptom and included several specific dimensions related to tiredness. Consideration of these concepts associated with the patient's experience following an MI may yield novel endpoints for use in clinical trials and better therapies.

Assessing an early modern Fenland population: Whittlesey (Cambridgeshire).

Improvement writers argued that drainage would bring prosperity and population growth to fenland communities; locals counter-argued that their communities were already thriving. The detailed surviving records from early modern Whittlesey, in the Isle of Ely, are analysed here to test the accuracy of these opposing claims. Using the returns of the 1523 Lay Subsidy, the 1563 ecclesiastical census, the Lady Day 1674 Hearth Tax records and the 1676 Compton Census, together with bishops' transcripts and probate inventories, this article finds that although the population did indeed increase after drainage, the pre-drainage population was also increasing. The Michaelmas 1664 Hearth Tax records are analysed to uncover something of the character of the inhabitants and the 1674 Lady Day returns are then used to test the relative wealth of the community compared with that of sub-regions throughout England identified by Tom Arkell. Finally, there is a discussion of Whittlesey's housing stock.

Initial combination therapy reduces the risk of cardiovascular events in hypertensive patients: a matched cohort study.

This study evaluated the effects of initial versus delayed treatment with a drug combination on blood pressure (BP) control and the risk of cardiovascular (CV) events in hypertensive patients. Clinical trials suggest that the time to BP control is an important determinant of long-term outcomes, but real-world evidence is scarce. Using electronic medical charts (2005-2009), we retrospectively analyzed 1762 adult patients with BP elevation initiating combination therapy matched 1:1 with similar patients initiating monotherapy and later switched to combination therapy. Incidence rate ratios of CV events (myocardial infarction, stroke/transient ischemic attack, or hospitalization for heart failure) or all-cause death and Kaplan-Meier analyses of time to BP control were compared between cohorts. Hazard ratios indicating the effects of initial treatment on CV events and BP control were estimated using time-varying Cox proportional hazard models. Initial combination therapy was associated with a significant reduction in the risk of CV events or death (incidence rate ratio, 0.66 [95% confidence interval, 0.52-0.84]; P=0.0008). After 6 months of therapy, 40.3% and 32.6% of patients with initial versus delayed combination treatment reached BP control, respectively. Achieving target BP was associated with a statistically significant risk reduction of 23% for CV events or death (hazard ratio, 0.77 [95% confidence interval, 0.61-0.96]; P=0.0223); the residual effect of initial combination therapy did not reach statistical significance (hazard ratio, 0.84 [95% confidence interval, 0.68-1.03]; P=0.0935). Initial combination therapy was associated with a significant risk reduction of cardiovascular events. More rapid achievement of target BP was found to be the main contributor to the estimated risk reduction.

Cost-effectiveness analysis of valsartan versus losartan and the effect of switching.

OBJECTIVES: Losartan will shortly become generic, and this may encourage switching to the generic drug. However, valsartan was shown in a meta-analysis to be statistically superior in lowering blood pressure (BP) to losartan. This paper examines the costs of treatment with these two drugs and the potential consequences of switching established valsartan patients to generic losartan. METHODS: A US payer cost-effectiveness model was developed incorporating the risk of cardiovascular disease (CVD) events related to systolic blood pressure (SBP) control comparing valsartan to continual losartan and switching from valsartan to generic losartan. The model, based upon a meta-analysis by Nixon et al. and Framingham equations, included first CVD event costs calculated from US administrative data sets and utility values from published sources. The modeled outcomes were number of CVD events, costs and incremental cost per quality-adjusted life-year (QALY) and life-year (LY). RESULTS: Fewer patients had fatal and non-fatal CVD events with valsartan therapy compared with continual losartan and with patients switched from valsartan to generic losartan. The base-case model results indicated that continued treatment with valsartan had an incremental cost-effectiveness ratio of $27,268 and $25,460 per life year gained, and $32,313 and $30,170 per QALY gained, relative to continual losartan and switching treatments, respectively. Sensitivity analyses found that patient discontinuation post-switching was a sensitive parameter. Including efficacy offsets with lowered adherence or discontinuation resulted in more favorable ratios for valsartan compared to switching therapy. LIMITATIONS: The model does not evaluate post-primary CVD events and considers change in SBP from baseline level as the sole predictor of CVD risk. CONCLUSIONS: Valsartan appears to be cost-effective compared to switching to generic losartan and switching to the generic drug does not support a cost offset argument over the longer term. Physicians should continue to consider the needs of individual patient and not cost offsets.

Effect of persistent use of antihypertensives on blood pressure goal attainment.

OBJECTIVE: Discontinuation rates with antihypertensive drugs in real life are high. The present study investigates the relationship between persistence with antihypertensive drugs (AHT) and blood pressure (BP) goal attainment in daily clinical practice. METHODS: In the PHARMO Record Linkage System, which includes drug dispensing and hospital records for > 2 million inhabitants in the Netherlands, new users of AHT > or = 18 years were identified for the period 1999-2004. Patients with elevated blood pressure (systolic BP > or = 140 and/or diastolic BP > or = 90 mmHg) within 6 months prior to onset of AHT treatment and a BP measurement within 6-12 months of treatment onset were included in the study cohort. Persistent AHT use was determined by summing the number of days of continuous treatment (gap between dispensings < 30 days) from start of treatment onwards. Patients with a BP below 140/90 mmHg at the first BP measurement within 6-12 months of treatment onset were defined as having attained goal. RESULTS: The study included 1271 patients with a mean systolic BP of 174 +/- 22 mmHg and a mean diastolic BP of 100 +/- 12 mmHg. Persistent AHT use was associated with a 40% increased chance of BP goal attainment (RR(adj) = 1.41; 95% CI: 1.08-1.85) after adjustment for gender, age, systolic blood pressure at start, and time to the BP measurement. CONCLUSION: Persistent use of AHT leads to increased blood pressure goal attainment in daily clinical practice.

The effect of discontinuation of antihypertensives on the risk of acute myocardial infarction and stroke.

OBJECTIVE: Adherence to antihypertensive drug treatment is suboptimal. The present study investigates the effect of early treatment discontinuation with antihypertensive drugs on the risk of acute myocardial infarction (AMI) or stroke in daily clinical practice. METHODS: In the PHARMO Record Linkage System, which includes all records of drug dispensings and hospitalisations for > or = 2 million subjects in the Netherlands, new users of antihypertensive (AHT) drugs > or = 18 years of age were studied during the period 1 January 1993 - 1 October 2002 to determine the risk of AMI or stroke related to persistence with AHT. Patients were initially followed for 2 years to determine persistence with AHT, and then for a further 2 years or until the first hospital admission for AMI or stroke, death, or end of the study period. Patients using AHT for secondary prevention of cardiovascular disease were excluded from the study cohort. RESULTS: The study cohort included 77 193 AHT users. The percentage of non-persistent patients was 55% at 2 years, with the lowest non-persistence rates for angiotensin-receptor blockers (ARBs) and ACE-inhibitors (40%) and the highest rates for beta-blockers, calcium-channel blockers (CCBs) and diuretics (54-61%). Non-persistent AHT use was associated with a 15% increased risk of AMI (RR 1.15; 95% CI 1.00-1.33) and a 28% increased risk of stroke (RR 1.28; 95% CI 1.15-1.45). CONCLUSIONS: The results of this study show that in daily clinical practice early discontinuation of antihypertensive drug treatment in primary prevention increases the risk of subsequent AMI or stroke.