The comparative effectiveness and cost-effectiveness of ranibizumab for neovascular macular degeneration revisited.

BACKGROUND: To compare a near decade of follow-up, newer control cohort data, use of both the societal and third party insurer cost perspectives, and integration of unilateral/bilateral therapy on the comparative effectiveness and cost-effectiveness of intravitreal ranibizumab therapy for neovascular, age-related macular degeneration (AMD). METHODS: Value-Based Medicine®, 12-year, combined-eye model, cost-utility analysis employing MARINA and HORIZON clinical trial data. Preference-based comparative effectiveness outcomes were quantified in (1) QALY (quality-adjusted life-year) gain, and (2) percent improvement in quality-of-life, while cost-effectiveness outcomes were quantified in (3) the cost-utility ratio (CUR) and financial return-on-investment (ROI) to society. RESULTS: Using MARINA and HORIZON trial data and a meta-analysis control cohort after 24 months, ranibizumab therapy conferred a combined-eye patient value (quality-of-life) gain of 16.3%, versus 10.4% found in 2006. The two-year direct ophthalmic medical cost for ranibizumab therapy was $46,450, a 33.8% real dollar decrease from 2006. The societal cost perspective CUR was -$242,920/QALY, indicating a $282,517 financial return-on-investment (ROI), or 12.3%/year to society for direct ophthalmic medical costs expended. The 3rd party insurer CUR ranged from $21,199/QALY utilizing all direct, medical costs, to $69,591/QALY using direct ophthalmic medical costs. CONCLUSIONS: Ranibizumab therapy for neovascular AMD in 2015, considering treatment of both eyes, conferred greater patient value gain (comparative effectiveness) and improved cost-effectiveness than in 2006, as well as a large monetary return-on-investment to the Gross Domestic Product and nation's wealth. The model herein integrates important novel features for neovascular age-related macular degeneration, vitreoretinal cost effectiveness analyses, including: (1) treatment of both eyes, (2) a long-term, untreated control cohort, and (3) the use of societal costs.

The Burden of Retinal Venous Occlusion: An Assessment of Fellow Eyes in 1000 Cases.

OBJECTIVE: To assess retinal vein occlusion (RVO) clinical features to create a simulation model quantifying the preference-based, patient value gain (benefit) and cost-utility (cost-effectiveness) of RVO therapy. DESIGN: Retrospective analysis data integrated with patient utilities and an ocular cost-utility model for RVO. PARTICIPANTS: One thousand consecutive Wills Eye Hospital Retina Service RVO patients seen from January 2010 through April 2011. METHODS: Value-Based Medicine analysis assessing the demographic features and vision in affected eyes and fellow eyes of RVO patients. MAIN OUTCOME MEASURES: Presenting vision, final vision, conversion incidence of fellow eyes to RVO, and patient value gain in quality-adjusted life-years (QALYs). RESULTS: Among 1000 patients, 332 (33.2%) presented with central retinal vein occlusion (CRVO), 53 (5.3%) with hemiretinal vein occlusion (HRVO), and 615 (61.5%) with branch retinal vein occlusion (BRVO). Mean follow-up for the entire RVO cohort was 3 years. One hundred and one patients (10.1%) had bilateral baseline RVO and, among the 826 unilateral cases seen more than once, 37 (4.5%) developed a fellow-eye RVO, a unilateral-to-bilateral conversion rate of 1.5%/year. Among the 101 baseline bilateral cases, 66% (66/101) had the same RVO variant bilaterally (CRVO/CRVO, HRVO/HRVO, or BRVO/BRVO). Mean CRVO baseline vision was 20/63-2 and final vision was 20/63-1 (P = 0.16). Thirty percent of patients had less than or equal to baseline fellow-eye vision. Within combined HRVO/BRVO cohorts, mean baseline vision was 20/50-2 and final vision was 20/50+1 (P = 0.0004). Thirty percent of patients also had less than or equal to baseline fellow-eye vision. The proportion of RVO patients with fellow-eye vision less than or equal to the RVO primary-eye baseline vision increased to 44% by year 16. CONCLUSIONS: Thirty percent of all RVO patients had less than or equal to baseline vision in the fellow eye. Among unilateral RVO cases, 1.5%/year developed fellow-eye RVO. These findings have implications for cost-utility analysis, because bilateral vision loss yields greater QALY loss and an increased financial burden compared with unilateral loss. Referent to total therapeutic QALY gain (100%), if a treated RVO was always considered the better-seeing eye, the actual clinical scenario demonstrates that the average CRVO patient gains 38% as much value and the average HRVO/BRVO patient gains 37% as much.

SOCIETAL COSTS ASSOCIATED WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION IN THE UNITED STATES.

PURPOSE: The purpose of this study was to use a cross-sectional prevalence-based health care economic survey to ascertain the annual, incremental, societal ophthalmic costs associated with neovascular age-related macular degeneration. METHODS: Consecutive patients (n = 200) with neovascular age-related macular degeneration were studied. A Control Cohort included patients with good (20/20-20/25) vision, while Study Cohort vision levels included Subcohort 1: 20/30 to 20/50, Subcohort 2: 20/60 to 20/100, Subcohort 3: 20/200 to 20/400, and Subcohort 4: 20/800 to no light perception. An interviewer-administered, standardized, written survey assessed 1) direct ophthalmic medical, 2) direct nonophthalmic medical, 3) direct nonmedical, and 4) indirect medical costs accrued due solely to neovascular age-related macular degeneration. RESULTS: The mean annual societal cost for the Control Cohort was $6,116 and for the Study Cohort averaged $39,910 (P < 0.001). Study Subcohort 1 costs averaged $20,339, while Subcohort 4 costs averaged $82,984. Direct ophthalmic medical costs comprised 17.9% of Study Cohort societal ophthalmic costs, versus 74.1% of Control Cohort societal ophthalmic costs (P < 0.001) and 10.4% of 20/800 to no light perception subcohort costs. Direct nonmedical costs, primarily caregiver, comprised 67.1% of Study Cohort societal ophthalmic costs, versus 21.3% ($1,302/$6,116) of Control Cohort costs (P < 0.001) and 74.1% of 20/800 to no light perception subcohort costs. CONCLUSION: Total societal ophthalmic costs associated with neovascular age-related macular degeneration dramatically increase as vision in the better-seeing eye decreases.

Longitudinal Commercial Claims-Based Cost Analysis of Diabetic Retinopathy Screening Patterns.

BACKGROUND: Diabetic retinopathy is one of the most common complications of diabetes. The screening of patients with diabetes to detect retinopathy is recommended by several professional guidelines but is an underutilized service. OBJECTIVE: To analyze the relationship between the frequency of retinopathy screening and the cost of care in adult patients with diabetes. METHODS: Truven Health MarketScan commercial databases (2000-2013) were used to identify the diabetic population aged 18 to 64 years for the performance of a 2001-2013 annual trend analysis of patients with type 1 and type 2 diabetes and a 10-year longitudinal analysis of patients with newly diagnosed type 2 diabetes. In the trend analysis, the prevalence of diabetes, screening rate, and allowed cost per member per month (PMPM) were calculated. In the longitudinal analysis, data from 4 index years (2001-2004) of patients newly diagnosed with type 2 diabetes were combined, and the costs were adjusted to be comparable to the 2004 index year cohort, using the annual diabetes population cost trends calculated in the trend analysis. The longitudinal population was segmented into the number of years of diabetic retinopathy screening (ie, 0, 1-4, 5-7, and 8-10), and the relationship between the years of screening and the PMPM allowed costs was analyzed. The difference in mean incremental cost between years 1 and 10 in each of the 4 cohorts was compared after adjusting for explanatory variables. RESULTS: In the trend analysis, between 2001 and 2013, the prevalence of diabetes increased from 3.93% to 5.08%, retinal screening increased from 26.27% to 29.58%, and the average total unadjusted allowed cost of care for each patient with diabetes increased from $822 to $1395 PMPM. In the longitudinal analysis, the difference between the screening cohorts' mean incremental cost increase was $185 between the 0- and 1-4-year cohorts (P <.003) and $202 between the 0- and 5-7-year cohorts (P <.023). The cost differences between the other cohorts, including $217 between the 0- and 8-10-year cohorts (P <.066), were not statistically significant. CONCLUSIONS: Based on our analysis, the annual retinopathy screening rate for patients with diabetes has remained low since 2001, and has been well below the guideline-recommended screening levels. For patients with type 2 diabetes, the mean increase in healthcare expenditures over a 10-year period after diagnosis is not statistically different among those with various retinopathy screening rates, although the increase in healthcare spending is lower for patients with diabetes who were not screened for retinopathy compared with patients who did get screened.

The Cost-Effectiveness of Ranibizumab for the Treatment of Diabetic Macular Edema.

PURPOSE: To assess the incremental, comparative effectiveness (patient value gain) and cost effectiveness (financial value gain) associated with 0.3-mg intravitreal ranibizumab injection therapy versus sham therapy for diabetic macular edema (DME). DESIGN: Value-Based Medicine (Center for Value-Based Medicine, Flourtown, PA) 14-year, cost-utility analysis using patient preferences and 2012 United States real dollars. PARTICIPANTS: Published data from the identical Ranibizumab Injection in Subjects with Clinically Significant Macular Edema with Center Involvement Secondary to Diabetes Mellitus (RISE and RIDE) clinical trials. METHODS: An incremental cost-utility analysis was performed using societal and third-party insurer cost perspectives. Costs and outcomes were discounted with net present value analysis at 3% per annum. MAIN OUTCOME MEASURES: The incremental comparative effectiveness was measured in: (1) quality-adjusted life year (QALY) gain and (2) percent patient value (quality-of-life) gain. Cost effectiveness was quantified with the cost-utility ratio (CUR) measured as $/QALY. RESULTS: The 14-year, incremental patient value gain conferred by intravitreal ranibizumab therapy for diabetic maculopathy was 0.9981 QALY, equating to an 11.6% improvement in quality of life. The direct, ophthalmic medical cost for ranibizumab therapy in 1 eye was $30 116, whereas for 2 eyes it was $56 336. The direct, nonophthalmic, medical costs saved from decreased depression, injury, skilled nursing facility admissions, nursing home admissions, and other vision-associated costs totaled $51 758, resulting in an overall direct medical cost of $4578. The net mean societal cost for bilateral ranibizumab therapy was -$30 807. Of this total, decreased caregiver costs accrued a $31 406 savings against the direct medical costs, whereas decreased wage losses accrued a $3978 savings. The third-party insurer CUR for bilateral ranibizumab therapy was $4587/QALY. The societal cost perspective for bilateral therapy was -$30 807/QALY, indicating that ranibizumab therapy dominated sham therapy because it conferred both a positive QALY gain of 0.9981 and a financial value gain (positive financial return on investment) of $30 807 referent to the direct ophthalmic medical costs expended. CONCLUSIONS: Intravitreal ranibizumab therapy for the treatment of DME confers considerable patient (human) value gain. It also accrues financial value to patients, public and private insurers, and society.

United States comparative costs and absenteeism of diabetic ophthalmic conditions.

OBJECTIVE: This retrospective cohort study examined the impact of diabetic macular edema (DME), diabetic retinopathy (DR), or diabetes on annual health benefit costs and absenteeism in US employees. METHODS: Claims data from 2001 to 2012 was extracted from the Human Capital Management Services Group Research Reference Database on annual direct/indirect health benefit costs and absences for employees aged ≥ 18 years. Employees with DME, DR, or diabetes were identified by International Classification of Diseases, Ninth Revision, Clinical Modification codes. Employees were divided into two groups, drivers or nondrivers, and examined in separate analyses. For drivers and nondrivers, the DME, DR, and diabetes cohorts were compared with their respective control groups (without diabetes). Two-part regression models controlled for demographics and job-related characteristics. RESULTS: A total of 39,702 driver and 426,549 nondriver employees were identified as having ≥ 1 year's continuous health plan enrollment. Direct medical costs for drivers with DME, DR, or diabetes were $6470, $8021, and $5102, respectively (>2.8 times higher and statistically significant compared with driver controls). Nondrivers with DME and DR incurred significantly higher sick leave and short-term disability costs compared with the nondrivers with diabetes and nondriver controls. In drivers with DME, the majority of days of absence were for short- and long-term disability (12.41 and 11.43 days, respectively). In drivers with DR, the majority of days of absence were for short-term disability (10.70 days). In nondrivers with DME and nondrivers with DR, the majority of days of absence were for sick leave (5.74 and 4.93 days, respectively) and short-term disability (5.08 and 4.93 days, respectively). CONCLUSION: DME and DR are associated with substantial direct medical cost and absenteeism in this real-world sample of medically insured employees. This research highlights the negative impact of DME and DR on annual costs and absenteeism and may assist employers in assessing the impact of these conditions on employees.

Retrospective analysis of first-line anti-vascular endothelial growth factor treatment patterns in wet age-related macular degeneration.

INTRODUCTION: This study compared the number of, and expenditures on, first-line intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections between patients who were treated with aflibercept or ranibizumab for wet age-related macular degeneration (AMD). METHODS: This was a retrospective cohort study based on U.S. administrative claims data. Selected patients had initiated first-line intravitreal anti-VEGF treatment with ranibizumab or aflibercept (index date) between November 18, 2011 and April 30, 2013, were aged ≥ 18 years on the index date, had 12 months of continuous insurance enrollment prior to the index date (baseline period), were diagnosed with wet AMD during the baseline period or on the index date, and had at least 6 or 12 months of follow-up enrollment after the index date without switching to a different anti-VEGF agent (follow-up periods). Outcomes measured within the 6 and 12 month follow-up periods included the number of, and healthcare expenditures on, intravitreal anti-VEGF injections. Multivariable regressions compared the outcomes between aflibercept and ranibizumab. RESULTS: The 6 months analyses included 319 aflibercept patients and 1,054 ranibizumab patients (12 month analyses: 57 and 374, respectively). Over the first 6 months after the index date, neither the number of injections (aflibercept mean = 3.8 ± 1.6; ranibizumab mean = 3.9 ± 1.9) nor the expenditures on injections (aflibercept mean = $7,468 ± $4,211; ranibizumab mean = $7,816 ± $4,834) differed significantly between aflibercept patients and ranibizumab patients (in multivariable regression treating ranibizumab as reference: incidence rate ratio = 0.97, 95% confidence interval [CI] 0.91-1.03, P = 0.277; cost ratio = 0.96, 95% CI 0.89-1.04, P = 0.338). Differences were also insignificant in the 12 month analyses. The overall mean days between injections differed by only 1.8 (95% CI 1.3-2.3) days between the aflibercept patients and ranibizumab patients (42.4 and 40.6, respectively). CONCLUSION: Aflibercept and ranibizumab were used at a similar frequency resulting in similar intravitreal anti-VEGF injection healthcare expenditures among wet AMD patients initiating first-line intravitreal anti-VEGF treatment.

Risk of infections in rheumatoid arthritis patients switching from anti-TNF agents to rituximab, abatacept, or another anti-TNF agent, a retrospective administrative claims analysis.

OBJECTIVE: This study compared the incidence and hazard of ICD-9-CM-coded infections and severe infections in rheumatoid arthritis (RA) patients treated with subsequent-line (SL) BIOs (BIO) after switching from first-line (FL) anti-TNF therapy (anti-TNF). METHODS: Retrospective analysis of a large U.S. claims database. RA patients initiating an FL anti-TNF between 1/1/2004 and 3/31/2010 were identified and followed forward in time to capture all SL BIO episodes through 3/31/2010. SL BIO episodes were classified into: abatacept, adalimumab, etanercept, infliximab, or rituximab. Multivariate mixed-effects survival models compared the hazard of infections and severe infections across the SL BIO episodes with adjustment for demographic and clinical confounders. RESULTS: In total, 4332 SL BIO episodes were identified: mean age 55 years; 80% female. In adjusted analyses: when compared to rituximab, the hazard of all infections was significantly higher for adalimumab (hazard ratio [HR] = 1.31, 95% confidence interval [CI] = 1.09-1.55), etanercept (HR = 1.44, 95% CI = 1.20-1.72), and infliximab (HR = 1.30, 95% CI = 1.07-1.57), and insignificantly different for abatacept (HR = 1.18, 95% CI = 0.98-1.41); when compared to rituximab, the hazard of severe infection was significantly higher for infliximab (HR = 1.62, 95% CI = 1.03-2.55), and insignificantly different for abatacept (HR = 1.21, 95% CI = 0.78-1.88), adalimumab (HR = 1.10, 95% CI = 0.72-1.68), and etanercept (HR = 1.27, 95% CI = 0.83-1.95). CONCLUSIONS: In RA patients treated with SL BIO, a 30-44% higher hazard of all infection was observed in anti-TNFs versus rituximab with a 62% higher hazard of severe infection observed in infliximab versus rituximab. This study used a non-randomized, observational design and is therefore subject to confounding from unmeasured factors that influence both treatment choice and infection risk.

How to aggregate health? Separability and the effect of framing.

BACKGROUND: Unweighted summation or quality-adjusted life year (QALY) utilitarianism is the most common way to aggregate health benefits in a cost-effectiveness analysis. A key qualitative principle underlying QALY utilitarianism is separability: those individuals unaffected by a policy choice should not influence the policy choice. Separability also underlies several of the alternatives for QALY utilitarianism that have been proposed. OBJECTIVES: To test separability and to test whether the support for separability is affected by the framing of the choice questions. METHODS: In 2 experiments, 345 student subjects (162 in the first experiment, and 183 in the second experiment) were asked to select 1 of 2 possible treatments, with each treatment resulting in a different distribution of health across individuals. The only aspect that varied across choice questions was the state of the patients whose health was unaffected by the act of choosing a policy. In each experiment, we used 2 frames. In the implicit frame, it was implied but not plainly expressed what outcomes the treatments had in common. In the explicit frame, common outcomes of the 2 treatments were directly stated. The 2 experiments differed in the way the explicit frame was presented (verbal v. numerical). RESULTS: The support for separability was significantly greater in the explicit frame. The proportion of violations in the implicit frame was 44% in Experiment 1 and 31% in Experiment 2, while in the explicit frame, the proportion of violations was 28% in Experiment 1 and 8% in Experiment 2. CONCLUSIONS: Framing affected the support for separability, raising issues as to whether it is possible to achieve a canonical representation of social choices.