Assessment of the E-value in the presence of bias amplification: a simulation study.

BACKGROUND: The E-value, a measure that has received recent attention in the comparative effectiveness literature, reports the minimum strength of association between an unmeasured confounder and the treatment and outcome that would explain away the estimated treatment effect. This study contributes to the literature on the applications and interpretations of E-values by examining how the E-value is impacted by data with varying levels of association of unobserved covariates with the treatment and outcome measure when covariate adjustment is applied. We calculate the E-value after using regression and propensity score methods (PSMs) to adjust for differences in observed covariates. Propensity score methods are a common observational research method used to balance observed covariates between treatment groups. In practice, researchers may assume propensity score methods that balance treatment groups across observed characteristics will extend to balance of unobserved characteristics. However, that assumption is not testable and has been shown to not hold in realistic data settings. We assess the E-value when covariate adjustment affects the imbalance in unobserved covariates. METHODS: Our study uses Monte Carlo simulations to evaluate the impact of unobserved confounders on the treatment effect estimates and to evaluate the performance of the E-Value sensitivity test with the application of regression and propensity score methods under varying levels of unobserved confounding. Specifically, we compare observed and unobserved confounder balance, odds ratios of treatment vs. control, and E-Value sensitivity test statistics from generalized linear model (GLM) regression models, inverse-probability weighted models, and propensity score matching models, over correlations of increasing strength between observed and unobserved confounders. RESULTS: We confirm previous findings that propensity score methods - matching or weighting - may increase the imbalance in unobserved confounders. The magnitude of the effect depends on the strength of correlation between the confounder, treatment, and outcomes. We find that E-values calculated after applying propensity score methods tend to be larger when unobserved confounders result in more biased treatment effect estimates. CONCLUSIONS: The E-Value may misrepresent the size of the unobserved effect needed to change the magnitude of the association between treatment and outcome when propensity score methods are used. Thus, caution is warranted when interpreting the E-Value in the context of propensity score methods.

The Cost-Effectiveness of an Advanced Hybrid Closed-Loop System Compared to Standard Management of Type 1 Diabetes in a Singapore Setting.

Background: Despite advances in technology, glycemic outcomes in people with type 1 diabetes (T1D) remain suboptimal. The MiniMed 780G (MM780G) advanced hybrid closed-loop (AHCL) system is the latest technology for T1D management with established safety and efficacy. This study explores the cost-effectiveness of MM780G AHCL compared against multiple daily injections (MDI) plus intermittently scanned continuous glucose monitor (isCGM). Methods: A cost-utility analysis was conducted, simulating lifetime outcomes for 1000 T1D individuals, with baseline hemoglobin A1c of 8.4%, using the IQVIA Core Diabetes Model (CDM) v9.5. A Singapore health care payer perspective was taken with 2023 costs applied. Treatment effects were taken from the ADAPT study and treatment-related events from a combination of sources. T1D complication costs were derived from local literature, and health state utilities and disutilities from published literature. Scenario analyses and probabilistic sensitivity analyses (PSAs) explored uncertainty. Cost-effectiveness was assessed based on willingness-to-pay (WTP) thresholds set to Singapore Dollars (SGD) 45,000 (United States Dollars [USD] 33,087) per quality-adjusted life year (QALY) and Singapore's gross domestic product (GDP) per capita of SGD 114,165 (USD 83,941) per QALY. Results: A switch from MDI plus isCGM to MM780G resulted in expected gains in life-years (+0.78) and QALYs (+1.45). Cost savings through reduction in T1D complications (SGD 25,465; USD 18,723) partially offset the higher treatment costs in the AHCL arm (+SGD 74,538; +USD 54,805), resulting in an estimated incremental cost-effectiveness ratio of SGD 33,797 (USD 24,850) per QALY gained. Findings were robust, with PSA outputs indicating 81% and 99% probabilities of cost-effectiveness at the stated WTP thresholds. Conclusion: MM780G is a cost-effective option for people with T1D managed in a Singapore setting.

Two-year outcomes of leadless vs. transvenous single-chamber ventricular pacemaker in high-risk subgroups.

AIMS: This study compares clinical outcomes between leadless pacemakers (leadless-VVI) and transvenous ventricular pacemakers (transvenous ventricular permanent-VVI) in subgroups of patients at higher risk of pacemaker complications. METHODS AND RESULTS: This study is based on the Micra Coverage with Evidence Development (CED) study. Patients from the Micra CED study were considered in a high-risk subgroup if they had a diagnosis of chronic kidney disease Stages 4-5 (CKD45), end-stage renal disease, malignancy, diabetes, tricuspid valve disease (TVD), or chronic obstructive pulmonary disease (COPD) 12 months prior to pacemaker implant. A pre-specified set of complications and reinterventions were identified using diagnosis and procedure codes. Competing risks models were used to compare reinterventions and complications between leadless-VVI and transvenous-VVI patients within each subgroup; results were adjusted for multiple comparisons. A post hoc comparison of a composite outcome of reinterventions and device complications was conducted. Out of 27 991 patients, 9858 leadless-VVI and 12 157 transvenous-VVI patients have at least one high-risk comorbidity. Compared to transvenous-VVI patients, leadless-VVI patients in four subgroups [malignancy, HR 0.68 (0.48-0.95); diabetes, HR 0.69 (0.53-0.89); TVD, HR 0.60 (0.44-0.82); COPD, HR 0.73 (0.55-0.98)] had fewer complications, in three subgroups [diabetes, HR 0.58 (0.37-0.89); TVD, HR 0.46 (0.28-0.76); COPD, HR 0.51 (0.29-0.90)) had fewer reinterventions, and in four subgroups (malignancy, HR 0.52 (0.32-0.83); diabetes, HR 0.52 (0.35-0.77); TVD, HR 0.44 (0.28-0.70); COPD, HR 0.55 (0.34-0.89)] had lower rates of the combined outcome. CONCLUSION: In a real-world study, leadless pacemaker patients had lower 2-year complications and reinterventions rates compared with transvenous-VVI pacing in several high-risk subgroups. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT03039712.

Potential cost savings in the United States from a reduction in sensor-detected severe hypoglycemia among users of the InPen smart insulin pen system.

BACKGROUND: Severe hypoglycemia is a significant barrier to optimizing insulin therapy in both type 1 and type 2 diabetes and places a burden on the US health care system because of the high costs of hypoglycemia-related health care utilization. OBJECTIVE: To compare the frequency of sensor-detected severe hypoglycemic events (SHEs) among a population of continuous glucose monitoring (CGM) users on insulin therapy after initiation of the InPen smart insulin pen (SIP) system and to estimate the potential hypoglycemia-related medical cost savings across a population of SIP users. METHODS: SIP users of all ages with type 1 or type 2 diabetes were required to have at least 90 days of SIP use with a connected CGM device. The last 14 days of sensor glucose (SG) data within the 30-day period prior to the start of SIP use ("pre-SIP") and the last 14 days of SG data, along with the requirement of at least 1 bolus entry per day within the 61- to 90-day period after SIP start ("post-SIP"), were analyzed. Sensor-detected SHEs (defined as ≥10 minutes of consecutive SG readings at <54 mg/dL) were determined. Once factored, the expected medical intervention rates and associated costs were calculated. Intervention rates and costs were obtained from the literature. RESULTS: There were 1,681 SIP + CGM users from March 1, 2018, to April 30, 2021. The mean number of sensor-detected SHEs per week declined from 0.67 in the pre-SIP period to 0.58 in the post-SIP period (P = 0.008), which represented a 13% reduction. Assuming a range of 5%-25% of all sensor-detected SHEs resulted in a clinical event, the estimated cost reduction associated with reduced SHEs was $12-$59 and $110-$551 per SIP user per month and per year, respectively. For those aged at least 65 years, there were 166 SIP+CGM users and the reduction in the mean number of sensor-detected SHEs per week between the pre-SIP and post-SIP periods was 31%. CONCLUSIONS: Use of the SIP system with a connected CGM is associated with reduced sensor-detected severe hypoglycemia, which may result in significant cost savings. DISCLOSURES: Albert Chien, Glen Im, Kael Wherry, Janice MacLeod, and Robert A Vigersky are employees of Medtronic; Sneha Thanasekaran and Angela Gaetano were affiliated with Medtronic while doing this research. The submitted work did not involve study subject recruitment, enrollment, or participation in a trial and did not fall under human subject protection requirements (per the Department of Health and Human Services CFR Part 46) necessitating Internal Review Board approval or exemption.

Racial/Ethnic Inequities in Use of Diabetes Technologies Among Medicare Advantage Beneficiaries With Type 1 Diabetes.

CONTEXT: Racial/ethnic inequities have been observed in diabetes care. OBJECTIVE: To measure changes in prevalence of continuous glucose monitoring (CGM) and insulin pump therapy among Medicare Advantage beneficiaries with type 1 diabetes by race/ethnicity and to determine the impact of socioeconomic factors on racial/ethnic inequities. DESIGN: The prevalence of CGM and pump use was assessed by race/ethnicity for Medicare Advantage beneficiaries annually from 2017 through 2020. Models predicting technology use by year, race/ethnicity, age, sex, endocrinology visits, and measures of socioeconomic status were fit. SETTING: Community. PATIENTS OR OTHER PARTICIPANTS: Beneficiaries with type 1 diabetes and 2 or more claims with a diabetes diagnosis in the coverage year. INTERVENTION(S): Insulin pump or CGM therapy. MAIN OUTCOME MEASURE(S): Use of diabetes technology by racial/ethnic group. RESULTS: Technology use increased from 2017 through 2020 in all racial/ethnic groups. The absolute difference in use between White and Black beneficiaries from 2017 to 2020 remained stable for insulin pumps (10.7% to 10.8%) and increased for CGM (2.6% to 11.1%). The differences in pump use from 2017 to 2020 narrowed between White and Hispanic beneficiaries (12.3% to 11.4%) and White and Asian beneficiaries (9.7% to 6.6%), whereas the opposite occurred for CGM use (3.0% to 15.5% for White vs Hispanic beneficiaries; 1.5% to 8.0% for White vs Asian beneficiaries). Racial/ethnic inequities persisted (P < .0001) after adjusting for other characteristics. CONCLUSIONS: Differences in diabetes technology use between racial/ethnic groups often persisted from 2017 through 2020 and could not be explained by demographics, socioeconomic status, or endocrinology visits.

Inequity in Adoption of Advanced Diabetes Technologies Among Medicare Fee-for-service Beneficiaries.

CONTEXT: Health inequity is often associated with race-ethnicity. OBJECTIVE: To determine the prevalence of insulin pump therapy and continuous glucose monitoring (CGM) among Medicare beneficiaries with type 1 diabetes (T1D) by race-ethnicity, and to compare diabetes-related technology users with nonusers. DESIGN: The prevalence of technology use (pump, CGM) was determined by race-ethnicity for enrollees in coverage years (CY) 2017-2019 in the Medicare fee-for-service database. Using CY2019 data, technology users were compared with nonusers by race-ethnicity, sex, average age, Medicare eligibility criteria, and visit to an endocrinologist. SETTING: Community. PATIENTS OR OTHER PARTICIPANTS: Beneficiaries with T1D and at least 1 inpatient or 2 outpatient claims in a CY. INTERVENTION(S): Pump or CGM therapy, visit to an endocrinologist. MAIN OUTCOME MEASURE(S): Diabetes-related technology use by race-ethnicity groups. RESULTS: Between 2017 and 2019, CGM and insulin pump use increased among all groups. Prevalence of insulin pump use was < 5% for Black and Other beneficiaries yet increased from 14% to 18% among White beneficiaries. In CY2019, 57% of White patients used a pump compared with 33.1% of Black and 30.3% of Other patients (P < 0.001). Black patients were more likely than White patients to be eligible because of disability/end-stage renal disease or to be Medicare/Medicaid eligible (both P < 0.001), whether using technology or not. Significant race-ethnicity differences (P < 0.001) existed between technology users and nonusers for all evaluated factors except visiting an endocrinologist. CONCLUSIONS: Significant race-ethnicity associated differences existed in T1D management. The gap in diabetic technology adoption between Black and White beneficiaries grew between 2017 and 2019.

Cost-Effectiveness Analysis of Implantable Cardioverter Defibrillator Therapy for Primary Prevention Patients with Additional Risk Factors in Brazil

Abstract Background: Implantable cardiac defibrillators (ICDs) therapy for primary prevention (PP) of sudden cardiac arrest (SCA) is well-established but underutilized globally. The Improve SCA study has identified a cohort of patients called 1.5 primary prevention (1.5PP), based on PP patients with the presence of documented risk factors: non-sustained ventricular tachycardia, frequent premature ventricular contractions, left ventricular ejection fraction < 25%, and pre-syncope or syncope. Objective: This study evaluated the cost-effectiveness of ICD therapy compared to no ICD among 1.5PP patients in the Brazilian public healthcare system. Methods: Modified inputs to a published Markov model were applied to compare costs and outcomes of ICD therapy to no ICD therapy from the Brazilian payer's perspective. Mortality and utility estimates were obtained from the IMPROVE SCA trial. Additional effectiveness inputs were sourced from the literature. Cost inputs were obtained from the Brazilian Unified Health System and the Ministry of Health. Costs were discounted at 4.7%; quality-adjusted life years (QALYs) were discounted at 1.45%. This study applied a willingness-to-pay (WTP) value of three times Brazil's gross domestic product (GDP) in 2017, R$105,723 (Brazilian Real). Results: The total discounted lifetime costs for ICD therapy were R$100,920 compared to R$43,866 for no ICD therapy. Total discounted QALYs for ICD therapy and no ICD therapy were 9.85 and 7.15, respectively. The incremental cost effectiveness ratio was R$21,156 per QALY and less than the R$105,723 WTP threshold. Results from sensitivity analyses were consistent with base case results. Conclusions: ICD therapy compared to no ICD therapy is cost-effective in the 1.5PP population in Brazil. (Int J Cardiovasc Sci. 2021; [online].ahead print, PP.0-0)

Return to work after deceased donor kidney transplant under the kidney allocation system.

BACKGROUND: The Kidney Allocation System (KAS) includes a scoring system to match transplant candidate life expectancy with expected longevity of the donor kidney, and a backdating policy that gives waitlist time credit to patients waitlisted after starting dialysis treatment (post-dialysis). We estimated the effect of the KAS on employment among patient subgroups targeted by the policy. METHODS: We used a sample selection model to compare employment after transplant before and after KAS implementation among patients on the kidney-only transplant waitlist between December 4, 2011 and December 31, 2017. RESULTS: Post-dialysis transplant recipients aged 18-49 were significantly more likely to be employed 1-year post transplant in the post-KAS era compared to the pre-KAS era. Transplant recipients aged 35-64 with no dialysis treatment were significantly less likely to be employed 1 year after transplant in the post-KAS era compared to the pre-KAS era. CONCLUSIONS: This study provides the first assessment of employment after DDKT under the KAS and provides important information about both the methods used to measure employment after transplant and the outcome under the KAS. Changes in employment after DDKT among various patient subgroups have important implications for assessing long-term patient and societal effects of the KAS and organ allocation policy.

Contemporaneous Comparison of Outcomes Among Patients Implanted With a Leadless vs Transvenous Single-Chamber Ventricular Pacemaker.

Importance: The safety and efficacy of leadless VVI pacemakers have been demonstrated in multiple clinical trials, but the comparative performance of the device in a large, real-world population has not been examined. Objective: To compare patient characteristics and complications among patients implanted with leadless VVI and transvenous VVI pacemakers. Design, Setting, Participants: The Longitudinal Coverage With Evidence Development Study on Micra Leadless Pacemakers (Micra CED) is a continuously enrolling observational cohort study evaluating complications, utilization, and outcomes of leadless VVI pacemakers in the US Medicare fee-for-service population. Patients implanted between March 9, 2017, and December 1, 2018, were identified and included. All Medicare patients implanted with leadless VVI and transvenous VVI pacemakers during the study period were enrolled. Patients with less than 12 months of continuous enrollment in Medicare prior to leadless VVI or transvenous VVI implant and with evidence of a prior cardiovascular implantable electronic device were excluded, leaving 5746 patients with leadless VVI pacemakers and 9662 patients with transvenous VVI pacemakers. Data were analyzed from May 2018 to April 2021. Exposures: Medicare patients implanted with leadless VVI pacemakers or transvenous VVI pacemakers. Main Outcomes and Measures: The main outcomes were acute (30-day) complications and 6-month complications. Results: Of 15 408 patients, 6701 (43.5%) were female, and the mean (SD) age was 81.0 (8.7) years. Compared with patients with transvenous VVI pacemakers, patients with leadless VVI pacemakers were more likely to have end-stage kidney disease (690 [12.0%] vs 226 [2.3%]; P < .001) and a higher mean (SD) Charlson Comorbidity Index score (5.1 [3.4] vs 4.6 [3.0]; P < .001). The unadjusted acute complication rate was higher in patients with leadless VVI pacemakers relative to transvenous VVI pacemakers (484 of 5746 [8.4%] vs 707 of 9662 [7.3%]; P = .02). However, there was no significant difference in overall acute complication rates following adjustment for patient characteristics (7.7% vs 7.4%; risk difference, 0.3; 95% CI, -0.6 to 1.3; P = .49). Pericardial effusion and/or perforation within 30 days was significantly higher among patients with leadless VVI pacemakers compared with patients with transvenous VVI pacemakers in both unadjusted and adjusted models (unadjusted, 47 of 5746 [0.8%] vs 38 of 9662 [0.4%]; P < .001; adjusted, 0.8% vs 0.4%; risk difference, 0.4; 95% CI, 0.1 to 0.7; P = .004). Patients implanted with leadless VVI pacemakers had a lower rate of 6-month complications compared with patients implanted with transvenous VVI pacemakers (unadjusted hazard ratio, 0.84; 95% CI, 0.68-1.03; P = .10; adjusted hazard ratio, 0.77; 95% CI, 0.62-0.96; P = .02). Conclusions and Relevance: In this study, despite significant differences in patient characteristics, patients in whom a leadless pacemaker was implanted were observed to have higher rates of pericardial effusion and/or perforation but lower rates of other device-related complications and requirements for device revision at 6 months. Understanding the benefits and risks associated with leadless VVI pacemakers compared with transvenous VVI pacemakers can help clinicians and patients make informed treatment decisions.

The improved survival rate and cost-effectiveness of a 7-day continuous subcutaneous insulin infusion set.

AIMS: The purpose of this article is to compare the insulin cost-savings of the Medtronic Extended Infusion Set (or EIS, a.k.a. Extended Wear Infusion Set) designed and labeled for up to 7-day use with rapid-acting insulins to the current standard of care, 2- to 3-day infusion sets. METHODS: There are three major improvements (reducing insulin waste, plastic waste, and adverse events) with the extended duration of infusion set wear. This analysis focuses on cost savings from reduced insulin wastage during set changes. Studies published on insulin infusion set survival and EIS clinical trial data (NCT04113694) were used to estimate device lifetime performance using a Markov chain Monte Carlo model, including the assessment of adverse effects and device failure. Total costs associated with infusion set change or failure were systematically found in published literature or estimated based on physical usage, and the direct impact on insulin costs was calculated. RESULTS: Based on the model and clinical data, EIS users can expect to change their infusion sets about 75 fewer times than standard set users each year. The costs related to unrecoverable insulin during an infusion set and reservoir change in the US were estimated to range from $19.79 to $22.48, resulting in approximately $1324 to $1677 in annual cost-savings for the typical user from minimizing insulin wastage. LIMITATIONS: The study only assessed devices used within a monitored setting, that is, clinical trials. In addition, the variability associated with healthcare standards and costs and individual treatment variability including insulin dosages, contribute to the uncertainties with the calculations. CONCLUSIONS: Our analysis demonstrates that by extending the duration of infusion set wear, there may be substantial cost savings by reducing insulin wastage.

The effectiveness and value of novel treatments for cystic fibrosis.

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, California Health Care Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, America's Health Insurance Plans, Anthem, Allergan, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Boehringer-Ingelheim, Cambia Health Services, CVS, Editas, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, HealthFirst, Health Partners, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Pfizer, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, and United Healthcare. Seidner, Rind, and Pearson are employed by ICER. Tice reports contracts to his institution, University of California, San Francisco, from ICER during the conduct of this study. Wherry has nothing to disclose.

Comparison of cost-effectiveness of implantable cardioverter defibrillator therapy in patients for primary prevention in Latin America: an analysis using the Improve SCA study.

OBJECTIVE: The mortality benefit of implantable cardioverter defibrillators (ICDs) for primary prevention (PP) of sudden cardiac arrest (SCA) has been well-established, but ICD therapy remains globally underutilized. The results of the Improve SCA study showed a 49% relative risk reduction in all-cause mortality among ICD patients with 1.5 primary prevention (1.5PP) characteristics (patients with one or more risk factors, p < 0.0001). We evaluated the cost-effectiveness of ICD compared to no ICD therapy among patients with 1.5PP characteristics in three Latin American countries and analyzed the factors involved in cost-effectiveness. METHODS: We used a published Markov model that compares costs and outcomes of ICD to no ICD therapy from local payers' perspective and included country-specific and disease-specific inputs from the Improve SCA study and current literature. We used WHO-recommended willingness-to-pay (WTP) thresholds to assess cost-effectiveness and compared model outcomes between countries. RESULTS: Incremental costs per QALY (quality-adjusted life year) saved by ICD compared to no ICD therapy are Colombian Pesos COP$46,729,026 in Colombia, Mexican Pesos MXN$246,016 in Mexico, and Uruguayan Pesos UYU$1,213,614 in Uruguay in the base case scenario; all three figures are between 1-3-times GDP per capita for each country. One-way and probabilistic sensitivity analyses confirm the base case scenario results. Non-cardiac accumulated deaths are lower in Mexico, resulting in a comparatively increased cost-effective ICD therapy. LIMITATIONS: The Improve SCA study was not randomized, so clinical results could be biased; however, measures were taken to reduce this bias. Costs and benefits were modelled beyond the timeline of direct observation in the Improve SCA study. CONCLUSIONS: ICD therapy is cost-effective in Mexico and Uruguay and potentially cost-effective in Colombia for a 1.5PP population. Variability in ICER estimates by country can be explained by differences in non-cardiac deaths and cost inputs.

Implantable cardioverter defibrillator therapy is cost effective for primary prevention patients in Taiwan: An analysis from the Improve SCA trial.

OBJECTIVE: Implantable cardiac defibrillators (ICDs) for primary prevention (PP) of sudden cardiac arrest (SCA) are well-established but underutilized globally. The Improve SCA study has identified a cohort of patients called 1.5 primary prevention (1.5PP) based on PP patients with the presence of certain risk factors. We evaluated the cost-effectiveness of ICD therapy compared to no ICD among the PP population and the subset of 1.5PP patients in Taiwan. METHODS: A Markov model was run over a lifetime time horizon from the Taiwan payer perspective. Mortality and utility estimates were obtained from the literature (PP) and the IMPROVE SCA trial (1.5PP). Cost inputs were obtained from the Taiwan National Health Insurance Administration (NHIA), Ministry of Health and Welfare. We used a willingness-to-pay (WTP) threshold of NT$2,100,000, as established through standard WTP research methods and in alignment with World Health Organization recommendations. RESULTS: The total discounted costs for ICD therapy and no ICD therapy were NT$1,664,259 and NT$646,396 respectively for PP, while they were NT$2,410,603 and NT$905,881 respectively for 1.5PP. Total discounted QALYs for ICD therapy and no ICD therapy were 6.48 and 4.98 respectively for PP, while they were 10.78 and 7.71 respectively for 1.5PP. The incremental cost effectiveness ratio was NT$708,711 for PP and NT$441,153 for 1.5PP, therefore ICD therapy should be considered cost effective for PP and highly cost effective for 1.5PP. CONCLUSIONS: ICD therapy compared to no ICD therapy is cost-effective in the whole PP population and highly cost-effective in the subset 1.5PP population in Taiwan.

Cost-Effectiveness of Ivacaftor Therapy for Treatment of Cystic Fibrosis Patients With the G551D Gating Mutation.

OBJECTIVES: Cystic fibrosis (CF) is a rare genetic disease with no cure. Until recently, treatment has targeted symptoms of the disease and not the disease-causing genetic defect. Ivacaftor is included in a new class of breakthrough drugs targeting the genetic defects of CF. We sought to estimate the long-term cost-effectiveness of ivacaftor from a US payer perspective. METHODS: We developed an individual-level microsimulation model that followed a cohort of heterogeneous US CF patients over a lifetime. The primary outcome of interest was quality-adjusted life years (QALYs). We also compared unadjusted life years, count of acute pulmonary exacerbations, and count of lung transplants over a lifetime between patients treated with ivacaftor plus best supportive care and patients treated with best supportive care alone. We conducted one-way and probabilistic sensitivity analyses to test the impact of various model inputs and uncertainties. RESULTS: We found a substantial increase in QALYs, life years, and treatment costs over a lifetime for patients treated with ivacaftor plus best supportive care versus best supportive care alone. Discounted results for ivacaftor were 22.92 QALYs and $8 797 840 in total lifetime costs compared to 16.12 QALYs and $2 336 366 lifetime costs for best supportive care alone. The incremental cost-effectiveness ratios (ICERs) were $950 217 per QALY. Results from the probabilistic sensitivity analysis indicated a 0% chance that ivacaftor was cost-effective at a willingness-to-pay (WTP) threshold of $500 000 per QALY. CONCLUSIONS: Treatment with ivacaftor plus best supportive care versus best supportive care alone is not cost-effective at or near commonly accepted WTP thresholds.

Using Medicare Claims to Identify Acute Clinical Events Following Implantation of Leadless Pacemakers.

BACKGROUND: There is heightened interest in how real-world data (RWD) can be used to supplement or replace traditional mechanisms for collecting clinical information. A critical component in evaluating utility of RWD is assessing the validity and reliability of event measurement. Only two studies have validated Medicare claims with physician-adjudicated data collected in a clinical study and none in the pacemaker patient population. This study compares events identified in physician-adjudicated clinical registry data collected in the Micra Post-Approval Registry (PAR) with events identified via Medicare administrative claims in the Micra Coverage with Evidence (CED) Study. METHODS: Patients who were dually enrolled in the Micra CED and the Micra PAR between March 9, 2017 and December 1, 2017 were included in the validation analysis. All patients intended to be implanted with a Micra device were eligible for participation in the Micra PAR. All Medicare fee-for-service beneficiaries implanted with a Micra device who met the 12-month continuous enrollment criteria were included in the Micra CED. We compared the count of acute (30-day) complications identified in the Medicare claims and the physician-adjudicated PAR data to assess agreement between data sources. RESULTS: There were 230 patients dually enrolled in the Micra CED and Micra PAR studies during the study period. Overall, there were 17 acute events reported in either the Micra CED or the Micra PAR, with 95% agreement in the identification of events and absence of events between studies. Study disagreement between events reported in either study varied: arteriovenous fistula (50%), pulmonary embolism (67%), hemorrhage/hematoma (75%), and deep vein thrombosis (100%). Among physician-adjudicated events, there was no disagreement between the Micra CED and Micra PAR studies in any event type. CONCLUSION: Findings from this study demonstrate high agreement in event identification between Medicare claims data and registries for patients implanted with Micra leadless pacemakers.