A Choice-Based Conjoint Analysis of the Psychiatrist Decision-Making Process Used in Determining When to Discharge Adults With Major Depressive Disorder Hospitalized for Active Suicidal Ideation With Intent.

ABSTRACT: To ascertain the relative importance of attributes considered when deciding to discharge patients hospitalized with major depressive disorder (MDD) and active suicidal ideation with intent, a choice-based conjoint analysis was conducted via online survey among US-based psychiatrists actively managing such patients. Potential attributes and attribute levels were identified. Attribute importance in decision to discharge and the discharge time frame were assessed. One hundred psychiatrists completed the survey. The relative importance of attributes were current MDD severity (relative importance weight [out of 100] 24.8 [95% confidence interval, 23.3-26.3]), clinician assessment of current suicidal ideation (20.8 [18.5-23.0]), previous history of suicide attempts (16.7 [15.9-17.6]), psychosocial support at discharge (13.0 [11.7-14.4]), postdischarge outpatient follow-up (9.8 [8.8-10.8]), current length of hospital stay (9.2 [8.1-10.3]), and suicidal ideation at admission (5.7 [4.8-6.6]). Thus, current clinical symptoms were considered the most important attributes by psychiatrists when discharging patients initially hospitalized with MDD and active suicidal ideation with intent.

Association of diabetes-related kidney disease with cardiovascular and non-cardiovascular outcomes: a retrospective cohort study.

BACKGROUND: Diabetes-related kidney disease is associated with end-stage renal disease and mortality, but opportunities remain to quantify its association with cardiovascular and non-cardiovascular morbidity outcomes. METHODS: We used the Truven Health MarketScan Commercial Claims and Encounters Database, 2010-2014, which includes specific health services records for employees and their dependents from a selection of large employers, health plans, and government and public organizations. We used administrative claims data to quantify the association between diabetes-related kidney disease and end-stage renal disease, myocardial infarction, congestive heart failure, stroke, and infections. Cox proportional hazard regression models were used to estimate adjusted hazard ratios of developing complications. RESULTS: Among 2.2 million patients with diabetes, 7.1% had diabetes-related kidney disease: 13.5%, stage 1-2; 33.8%, stage 3; 13.2% stages 4-5; 39.5%, unknown stage. In multivariable Cox proportional hazard models adjusted for demographic characteristics, baseline comorbid conditions, and total hospital days during the baseline period, hazard ratios for each outcome increased with greater diabetes-related kidney disease severity (stage 1-2 vs. stage 4-5) compared with no diabetes-related kidney disease: myocardial infarction, 1.2 (95% confidence interval 1.1-1.4) and 3.1 (2.9-3.4); congestive heart failure, 1.7 (1.6-1.9) and 5.6 (5.3-5.8); stroke, 1.3 (1.2-1.5) and 2.3 (2.1-2.5); infection, 1.4 (1.3-1.5) and 2.9 (2.8-3.0). Among patients with stage 4-5 disease, 36-month cumulative incidence was nearly 22.8% for congestive heart failure, and 25.8% for infections. CONCLUSIONS: Diabetes-related kidney disease appears to be formally diagnosed at a more advanced stage than might be expected, given clinical practice guidelines. Risks of cardiovascular and non-cardiovascular outcomes are high.

Unmet need in major depressive disorder and acute suicidal ideation or behavior: findings from a longitudinal electronic health record data analysis.

AIMS: Using a national electronic health records (EHR) database, the current study describes treatments, depression severity, and health care resource utilization (HRU) among patients with major depressive disorder (MDD) and acute suicidal ideation or behavior (MDSI) prior to, during, and following a suicide-related event in the United States. MATERIALS AND METHODS: This retrospective matched cohort study used data collected from the Optum EHR de-identified database for patients with diagnosis codes for MDD and acute suicidal ideation or behavior and a propensity score-matched cohort of patients without MDD or a suicide-related event. The study period was 31 October 2015-30 September 2019. MDD-related treatments and 9-item Patient Health Questionnaire (PHQ-9) scores, when available, were assessed at the first health care encounter for a suicide-related event (index period), 12 months before (pre-period), and 6 months after (post-period). All-cause and MDD-related HRU were assessed during the post-period. RESULTS: The mean (standard deviation) age of patients with MDSI was 39 (16) years; 55.0% were female. Index events occurred as follows: inpatient stay, 38.9%; observation unit stay, 4.6%; emergency department (ED) visit, 46.5%; and outpatient visit, 10.1%. Antidepressants and psychotherapy were the most common pharmacologic and nonpharmacologic treatments, respectively, prescribed during the pre- (31.3%, 9.5%, respectively) and index (41.2%, 18.7%, respectively) periods. Post-period data (n = 40,261) revealed only 43.4% received an antidepressant and 20.5% had psychotherapy after the suicide-related event. Few patients had PHQ-9 scores recorded during the pre- (4.4%), index (1.3%), and post- (7.6%) periods. During the post-period, 11.8%, 5.0%, and 33.1% of patients had ≥1 all-cause inpatient stay, observation unit stay, and ED visit, respectively; 61.0% had ≥1 all-cause and 33.4% ≥1 MDD-related outpatient visit. Most patients with MDSI and an inpatient encounter or ED visit were discharged to home or self-care (65.4%). Odds of an all-cause hospital encounter during the post-period were higher for patients with versus without MDSI (by 30.1, 33.5, and 33.9 times for inpatient stay, ED visit, and observation unit stay, respectively). CONCLUSION: This analysis highlights an opportunity to improve outcomes for this vulnerable population. More complete data on patient outcomes is needed to inform strategies designed to optimize screening and treatment.

Clinical and economic burden of major depressive disorder with acute suicidal ideation or behavior in a US Veterans Health Affairs database.

OBJECTIVE: Although a high incidence of major depressive disorder (MDD) and an increased risk of suicide are observed among the veteran population, there are yet limited real-world data characterizing patients with MDD with acute suicidal ideation/behavior (MDSI) in the Veterans Health Administration (VHA) system. We assessed the clinical and economic burden, including comorbidities, treatment patterns, health care resource utilization, and health care costs, among veterans and their family members with MDSI within the VHA system. METHODS: This retrospective, longitudinal analysis of VHA datasets (10/1/2015-3/31/2018) evaluated the clinical and economic burden associated with MDSI and compared this population with matched MDD alone (i.e. MDD diagnosis without acute suicidal ideation/behavior) and non-MDD (i.e. neither MDD nor acute suicidal ideation/behavior) cohorts. RESULTS: Among 11,203 patients with MDSI, the proportions of patients who filled a prescription for ≥1 antidepressant during the 12-month pre- and 6-month post-periods were significantly higher compared with patients with MDD alone (53.7% vs 28.8%, p < .05; and 72.3% vs 44.1%, p < .05; respectively). During the 12-month pre-period, the MDSI cohort had the highest proportion of patients with ≥1 mental health-related inpatient visit compared with the MDD alone and non-MDD cohorts (13.2% vs 2.3% vs 1.4%, respectively; p < .05), and the highest mental health-related costs per patient ($8853 vs $1913 vs $1079, respectively). For the 6-month post-period, the MDSI cohort had the highest proportion of patients with ≥1 mental health-related inpatient visit compared with the MDD alone and non-MDD cohorts (60.4% vs 7.9% vs 0.8%, respectively; p < .05), and had the highest mental health-related costs per patient ($20,334 vs $4803 vs $545, respectively). CONCLUSIONS: Findings demonstrate significant clinical and economic burden for those in the VHA system diagnosed with MDSI and highlight unmet needs and opportunities for improving the care of this vulnerable group.

There are limited real-world data regarding patients diagnosed with major depressive disorder and having suicidal thoughts/behavior (MDSI) in the Veterans Health Administration (VHA) system. We examined data on 11,203 patients with MDSI from the VHA between October 1, 2015 and March 31, 2018. We compared patients with MDSI with patients with major depressive disorder alone (MDD) and patients with no depression (non-MDD). Our results showed that patients with MDSI were treated with more antidepressant therapy, had more hospital stays (inpatient visits), and incurred greater costs than the MDD and non-MDD patients. These results highlight the unmet need and potential opportunity to improve patient care among veterans and their families with MDSI.

Economic Burden of Commercially Insured Patients With Major Depressive Disorder and Acute Suicidal Ideation or Behavior in the United States.

Objective: Suicidal ideation or behavior (SIB) is a symptom of major depressive disorder (MDD). This study evaluated health care resource utilization (HRU) and costs of commercially insured adults who had diagnosed MDD with acute SIB (MDSI).Methods: Adults with MDSI (index date: first SIB claim) and controls without MDD or suicide-related claims (random index date) were identified using International Classification of Diseases, Clinical Modification, 10th Revision codes in the OptumHealth Care Solutions, Inc. database (October 2014 to March 2017). Adults with < 12 months of plan enrollment pre-index and/or selected psychiatric comorbidities were excluded. MDSI and control cohorts were matched 1:1 on demographics and comorbidities. HRU and costs were compared between matched cohorts during up to 1 and 12 months post-index (inclusive) using regressions adjusted for baseline costs.Results: Among patients with MDSI (n = 1,576, mean age = 34 years, 55.6% female), most index events occurred in emergency department (ED; 50.7%) and inpatient (45.2%) settings. The MDSI cohort, compared with the control cohort within 1 and 12 months post-index, respectively, had 157.7 and 28.0 times more inpatient admissions, 16.4 and 5.4 times more ED visits, and 4.9 and 3.2 times more outpatient visits (all P < .01). Incremental health care costs per patient per month in the MDSI compared with the control cohort within 1 and 12 months were $7,839 and $2,757, respectively (both P values < .01). Inpatient and ED costs constituted 70.6% and 16.5% of the total incremental costs, respectively, within the first month of follow-up.Conclusions: Among commercially insured adults, MDSI was associated with significant economic burden; inpatient and ED services drove incremental costs of the condition. Further assessment of treatment options for this vulnerable patient population is warranted.

Characteristics of hospital encounters and associated economic burden of patients with major depressive disorder and acute suicidal ideation or behavior.

OBJECTIVES: Relatively little is known about the hospital experience among patients with major depressive disorder (MDD) and acute suicidal ideation or behavior (MDSI). The objectives of this study were to examine hospital encounter characteristics, including the associated economic burden and risk of subsequent hospital encounters of patients with MDSI in the US. METHODS: In this retrospective analysis, patients ≥18 years of age with a hospital encounter (emergency department [ED] visit or inpatient admission) were selected from the de-identified Premier Hospital database between 1 January 2017 and 30 September 2018. Patients were required to have MDD as the primary and acute suicidal ideation or behavior as a secondary discharge diagnosis or vice versa. Patient demographics and characteristics of hospital encounters were examined. Rates and costs of subsequent all-cause and MDD-related hospital encounters 6 months following initial discharge were also evaluated. RESULTS: The study population consisted of 123,179 patients with a hospital encounter for MDSI (mean age: 38 years, 50.9% female, 74.6% White); 50.2% were treated in the ED only (mean ± standard deviation cost: $693±$630), while 49.8% were admitted as inpatients ($6,478±$7,001). Among those with ED visits, very few (7.0%) received an antidepressant (AD). Among those with an inpatient admission, 87.2% received ≥1 AD and 39.0% received AD augmentation. Overall rates and costs of subsequent all-cause and MDD-related hospital encounters were 22.3% ($5,136±$11,791) and 12.0% ($3,722±$9,621), respectively; nearly half of subsequent encounters (41.3% and 44.3%, respectively) occurred in the first month following initial discharge. CONCLUSIONS: This analysis of patients with MDSI presenting to US hospitals shows heterogeneity in treatment and a concentration of costly subsequent hospital encounters within 1-month post discharge, suggesting that healthcare systems may benefit from examination of current care pathways for this vulnerable patient population.

Macrovascular Risk Equations Based on the CANVAS Program.

BACKGROUND: Widely used risk equations for cardiovascular outcomes for individuals with type 2 diabetes mellitus (T2DM) have been incapable of predicting cardioprotective effects observed in recent cardiovascular outcomes trials (CVOTs) involving individuals with T2DM at high risk for or with established cardiovascular disease (CVD). OBJECTIVE: We developed cardiovascular and mortality risk equations using patient-level data from the CANVAS (CANagliflozin cardioVascular Assessment Study) Program to address this shortcoming. METHODS: Data from 10,142 patients with T2DM at high risk for or with established CVD, randomized to canagliflozin + standard of care (SoC) or SoC alone and followed for a mean duration of 3.6 years in the CANVAS Program were used to derive parametric risk equations for myocardial infarction (MI), stroke, hospitalization for heart failure (HHF), and death. Accumulated knowledge from the widely used UKPDS-OM2 (United Kingdom Prospective Diabetes Study Outcomes Model 2) was leveraged, and any departures in parameterization were limited to those necessary to provide adequate goodness of fit. Candidate explanatory covariates were selected using only the placebo arm to minimize confounding effects. Internal validation was performed separately by study treatment arm. RESULTS: UKPDS-OM2 predicted CANVAS Program outcomes poorly. Recalibrating UKPDS-OM2 intercepts improved calibration in some cases. Refitting the coefficients but otherwise preserving the UKPDS-OM2 structure improved the fit substantially, which was sufficient for stroke and death. For MI, reselecting UKPDS-OM2 covariates and functional form proved sufficient. For HHF, selection from a broad set of candidate covariates and inclusion of a canagliflozin indicator was required. CONCLUSION: These risk equations address some of the limitations of widely used risk equations, such as the UKPDS-OM2, for modeling cardioprotective treatments for individuals with T2DM and high cardiovascular risk, including derivation from overly healthy patients treated with agents that lack cardioprotection and have been described as reflecting a different therapeutic era. Future work is needed to examine external validity.

Cluster Analysis of Care Pathways in Adults with Major Depressive Disorder with Acute Suicidal Ideation or Behavior in the USA.

BACKGROUND AND OBJECTIVE: Suicidal ideation or behavior are core symptoms of major depressive disorder (MDD). This study aimed to understand heterogeneity among patients with MDD and acute suicidal ideation or behavior. METHODS: Adults with a diagnosis of MDD on the same day or 6 months before a claim for suicidal ideation or behavior (index date) were identified in the MarketScan® Databases (10/01/2014-04/30/2019). A mathematical algorithm was used to cluster patients on characteristics of care measured pre-index. Patient care pathways were described by cluster during the 12-month pre-index period and up to 12 months post-index. RESULTS: Among 38,876 patients with MDD and acute suicidal ideation or behavior, three clusters were identified. Across clusters, pre-index exposure to mental healthcare was revealed as a key differentiator: Cluster 1 (N = 16,025) was least exposed, Cluster 2 (N = 5640) moderately exposed, and Cluster 3 (N = 17,211) most exposed. Patients whose MDD diagnosis was first observed during their index event comprised 86.0% and 72.8% of Clusters 1 and 2, respectively; in Cluster 3, all patients had an MDD diagnosis pre-index. Within 30 days post-index, in Clusters 1, 2, and 3, respectively, 79.3%, 85.2%, and 88.2% used mental health services, including outpatient visits for MDD. Within 12 months post-index, 61.5%, 91.5%, and 84.6% had one or more antidepressant claim, respectively. Per-patient index event costs averaged $5614, $6645, and $5853, respectively. CONCLUSIONS: Patients with MDD and acute suicidal ideation or behavior least exposed to the healthcare system pre-index similarly received the least care post-index. An opportunity exists to optimize treatment and follow-up with mental health services.

Development and Internal Validation of a Discrete Event Simulation Model of Diabetic Kidney Disease Using CREDENCE Trial Data.

INTRODUCTION: The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study showed that compared with placebo, canagliflozin 100 mg significantly reduced the risk of major cardiovascular events and adverse renal outcomes in patients with diabetic kidney disease (DKD). We developed a simulation model that can be used to estimate the long-term health and economic consequences of DKD treatment interventions for patients matching the CREDENCE study population. METHODS: The CREDENCE Economic Model of DKD (CREDEM-DKD) was developed using patient-level data from CREDENCE (which recruited patients with estimated glomerular filtration rate 30 to < 90 mL/min/1.73 m2, urinary albumin to creatinine ratio > 300-5000 mg/g, and taking the maximum tolerated dose of a renin-angiotensin-aldosterone system inhibitor). Risk prediction equations were fit for start of maintenance dialysis, doubling of serum creatinine, hospitalization for heart failure, nonfatal myocardial infarction, nonfatal stroke, and all-cause mortality. A micro-simulation model was constructed using these risk equations combined with user-definable kidney transplant event risks. Internal validation was performed by loading the model to replicate the CREDENCE study and comparing predictions with trial Kaplan-Meier estimate curves. External validation was performed by loading the model to replicate a subgroup of the CANagliflozin cardioVascular Assessment Study (CANVAS) Program with patient characteristics that would have qualified for inclusion in CREDENCE. RESULTS: Risk prediction equations generally fit well and exhibited good concordance, especially for the placebo arm. In the canagliflozin arm, modest underprediction was observed for myocardial infarction, along with overprediction of dialysis, doubling of serum creatinine, and all-cause mortality. Discrimination was strong (0.85) for the renal outcomes, but weaker for the macrovascular outcomes and all-cause mortality (0.60-0.68). The model performed well in internal and external validation exercises. CONCLUSION: CREDEM-DKD is an important new tool in the evaluation of treatment interventions in the DKD population. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02065791.

Conducting and interpreting results of network meta-analyses in type 2 diabetes mellitus: A review of network meta-analyses that include sodium glucose co-transporter 2 inhibitors.

AIMS: Network meta-analyses (NMAs) are valuable ways to generate comparative effectiveness data for therapies available to treat type 2 diabetes mellitus (T2DM). This review assesses NMAs that evaluate sodium glucose co-transporter 2 (SGLT2) inhibitors for treatment of T2DM and discusses potential issues in conducting and interpreting NMAs. METHODS: A systematic literature search was conducted on September 13, 2018 using the search terms "network meta-analysis," "SGLT2," variations of these terms, and individual SGLT2 inhibitor names. Extracted data included NMA objectives, methods, target populations, treatments, study endpoints, length of follow-up, and funding. Differences between NMAs were investigated. RESULTS: Thirty-five full-length publications met criteria for inclusion. In most NMAs, the target population was defined by therapeutic regimen (e.g., combination with metformin). Follow-up intervals permitted in NMAs varied considerably (range, 4-208 weeks). Twenty-nine NMAs included dapagliflozin, 28 evaluated canagliflozin, and 27 evaluated empagliflozin. Nine NMAs used frequentist methods; 16 used Bayesian methods. Six NMAs were funded by pharmaceutical manufacturers. Heterogeneity across NMAs was seen in scope, time frame, and other aspects of analytic design. CONCLUSIONS: Although this review indicates that methodological guidelines for reporting NMAs were generally followed, it also emphasizes the need for T2DM-specific guidance requiring clear reporting of NMA scope and objectives to aid appropriate interpretation and use of NMA results.

Challenges and Opportunities Associated with Incorporating New Evidence of Drug-Mediated Cardioprotection in the Economic Modeling of Type 2 Diabetes: A Literature Review.

INTRODUCTION: Cardiovascular disease is a leading cause of mortality in people with type 2 diabetes mellitus (T2DM). Beginning in 2015, long-term cardiovascular outcomes trials (CVOTs) have reported cardioprotective benefits for two classes of diabetes drugs. In addition to improving the lives of patients, these health benefits affect relative value (i.e., cost-effectiveness) of these agents compared with each other and especially compared with other agents. While long-term CVOT data on hard outcomes are a great asset, economic modeling of the value of this cardioprotection faces many new empirical challenges. The aim of this study was to identify different approaches used to incorporate drug-mediated cardioprotection into T2DM economic models, to identify pros and cons of these approaches, and to highlight additional considerations. METHODS: A review of T2DM modeling applications (manuscript or conference abstracts) that included direct cardioprotective effects was conducted from January 2015 to September 2018. Model applications were classified on the basis of the mechanism used to model cardioprotection [i.e., directly via hazard ratios (HRs) for cardiovascular outcomes or indirectly via biomarker mediation]. Details were extracted and the studies were evaluated. RESULTS: Five full-length articles and 16 conference abstracts (of which 11 posters were found) qualified for study inclusion. While the approaches used were diverse, the five full-length publications and all but two of the abstracts modeled cardioprotection used direct HRs from the relevant CVOT. The remaining two posters modeled cardioprotection using CVOT HRs in combination with treatment effects mediated through known risk factors. CONCLUSION: The classification of empirical methods in cardioprotection was intended to facilitate a better understanding of the pros and cons of different methodologies. A substantial diversity was observed, though most used trial HRs directly. Given the differences observed, we believe that diabetes modelers and other stakeholders can benefit from a formal discussion and evolving consensus. FUNDING: Janssen Global Services, LLC (Raritan, NJ, USA).

Long-Term Clinical Benefits of Canagliflozin 100 mg Versus Sulfonylurea in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin in India.

OBJECTIVES: To simulate the long-term health outcomes of canagliflozin 100 mg versus glimepiride over 20 years in patients with type 2 diabetes mellitus (T2DM) inadequately controlled on metformin from the perspective of the Indian health care system. METHODS: Health outcomes were simulated using the validated Economic and Health Outcomes Model of T2DM. Patient demographic characteristics, biomarker values, and treatment effects were sourced from a subgroup of Indian patients enrolled in a 52-week, head-to-head study of canagliflozin versus glimepiride (mean maximum dose of 5.6 mg/d) in patients with T2DM inadequately controlled with metformin. Outcomes were discounted at 5%. Sensitivity analyses were conducted using alternative values for key model inputs. RESULTS: Relative to glimepiride, treatment with canagliflozin 100 mg was associated with approximately 14 more patients surviving at year 20 per 1,000 patients treated and 0.43 quality-adjusted life-years gained, largely because of improved body weight and reduced risk of macrovascular and microvascular morbidity over 20 years. Risk reductions were the largest for microvascular complications (e.g., chronic kidney disease and albuminuria). Improved health outcomes were driven by better glycated hemoglobin control associated with canagliflozin versus glimepiride, which also delayed the need for rescue therapy. Key components of quality-adjusted life-year gains included the avoidance of hypoglycemic episodes, chronic kidney disease, and weight gain, as well as increased survival with canagliflozin compared with glimepiride. CONCLUSIONS: Simulation results suggest that canagliflozin 100 mg may provide better long-term health outcomes compared with glimepiride in Indian patients with T2DM inadequately controlled with metformin.

Lifetime benefits of early detection and treatment of diabetic kidney disease.

OBJECTIVES: Diabetic kidney disease (DKD) is a frequent complication of diabetes with potentially devastating consequences that may be prevented or delayed. This study aimed to estimate the health and economic benefit of earlier diagnosis and treatment of DKD. METHODS: Life expectancy and medical spending for people with diabetes were modeled using The Health Economics Medical Innovation Simulation (THEMIS). THEMIS uses data from the Health and Retirement Study to model cohorts of individuals over age 50 to project population-level lifetime health and economic outcomes. DKD status was imputed based on diagnoses and laboratory values in the National Health and Nutrition Examination Survey. We simulated the implementation of a new biomarker identifying people with diabetes at an elevated risk of DKD and DKD patients at risk of rapid progression. RESULTS: Compared to baseline, the prevalence of DKD declined 5.1% with a novel prognostic biomarker test, while the prevalence of diabetes with stage 5 chronic kidney disease declined 3.0%. Consequently, people with diabetes gained 0.2 years in life expectancy, while per-capita annual medical spending fell by 0.3%. The estimated cost was $12,796 per life-year gained and $25,842 per quality-adjusted life-year. CONCLUSIONS: A biomarker test that allows earlier treatment reduces DKD prevalence and slows DKD progression, thereby increasing life expectancy among people with diabetes while raising healthcare spending by less than one percent.

Cost-Effectiveness Analysis of Canagliflozin 300 mg Versus Dapagliflozin 10 mg Added to Metformin in Patients with Type 2 Diabetes in the United States.

INTRODUCTION: Agents that inhibit sodium glucose co-transporter 2 (SGLT2), including canagliflozin and dapagliflozin, are approved in the United States for the treatment of adults with type 2 diabetes mellitus (T2DM). SGLT2 inhibition lowers blood glucose by increasing urinary glucose excretion, which leads to a mild osmotic diuresis and a net loss of calories that are associated with reductions in body weight and blood pressure. This analysis evaluated the cost-effectiveness of canagliflozin 300 mg versus dapagliflozin 10 mg in patients with T2DM inadequately controlled with metformin in the United States. METHODS: A 30-year cost-effectiveness analysis was performed using the validated Economic and Health Outcomes Model of T2DM (ECHO-T2DM) from the perspective of the third-party health care system in the United States. Patient demographics, biomarker values, and treatment effects for the ECHO-T2DM model were sourced primarily from a network meta-analysis (NMA) that included studies of canagliflozin and dapagliflozin in patients with T2DM on background metformin. Costs were derived from sources specific to the United States. Outcomes and costs were discounted at 3%. Sensitivity analyses that varied key model parameters were conducted. RESULTS: Canagliflozin 300 mg dominated dapagliflozin 10 mg as an add-on to metformin over 30 years, with an estimated cost offset of $13,991 and a quality-adjusted life-year gain of 0.08 versus dapagliflozin 10 mg. Results were driven by the better HbA1c lowering achieved with canagliflozin, which translated to less need for insulin rescue therapy. Findings from sensitivity analyses were consistent with the base case. CONCLUSION: These results suggest that canagliflozin 300 mg is likely to provide better health outcomes at a lower overall cost than dapagliflozin 10 mg in patients with T2DM inadequately controlled with metformin from the perspective of the United States health care system. FUNDING: Janssen Scientific Affairs, LLC and Janssen Global Services, LLC.

Cost of Glycemic Target Achievement with Sodium Glucose Co-transporter 2 Inhibitors in Patients with Type 2 Diabetes in the UK.

INTRODUCTION: Diabetes-related costs make up a large portion of healthcare expenditures in the UK. Many of these costs are related to treatment of diabetes-related complications. Reducing HbA1c to <7.0% (53 mmol/mol) reduces the incidence of complications and comorbidities. Metformin plus sulfonylurea is the most common dual oral combination therapy in the UK. The costs of achieving HbA1c <7.0% in patients inadequately controlled on metformin plus sulfonylurea were analyzed for the sodium glucose co-transporter 2 (SGLT2) inhibitors canagliflozin, dapagliflozin, and empagliflozin from the perspective of the UK National Health System. METHODS: A Bayesian network meta-analysis (NMA) was used to compare the proportion of patients with type 2 diabetes mellitus inadequately controlled on metformin plus sulfonylurea that achieved HbA1c <7.0% after 26 weeks with canagliflozin 100 and 300 mg, dapagliflozin 10 mg, and empagliflozin 10 and 25 mg; odds ratios (ORs) and pairwise probabilities (P) for canagliflozin versus dapagliflozin and empagliflozin were calculated. The costs associated with achieving HbA1c <7.0% were estimated on the basis of medication costs and the proportion of patients achieving the HbA1c goal. RESULTS: NMA results showed that a higher proportion of patients treated with canagliflozin 300 mg achieved HbA1c <7.0% (41%) compared with those treated with dapagliflozin 10 mg (25%), empagliflozin 10 mg (23%), empagliflozin 25 mg (28%), or canagliflozin 100 mg (27%). The odds of achieving HbA1c <7.0% were greater with canagliflozin 300 mg than with dapagliflozin 10 mg (OR 2.03 [P = 94%]), empagliflozin 10 mg (OR 2.29 [P = 99%]), or empagliflozin 25 mg (OR 1.71 [P = 93%]). The per patient costs of achieving HbA1c <7.0% at 26 weeks were £881, £580, £951, £1034, and £849 with canagliflozin 100 and 300 mg, dapagliflozin 10 mg, and empagliflozin 10 and 25 mg. CONCLUSIONS: This analysis suggests that, in the UK, canagliflozin 300 mg provides the best value for money among all SGLT2 inhibitors in terms of achieving HbA1c <7.0% when used as part of triple therapy with metformin plus sulfonylurea. FUNDING: Janssen Global Services, LLC, Raritan, NJ, USA.

Cost-effectiveness of Canagliflozin versus Sitagliptin When Added to Metformin and Sulfonylurea in Type 2 Diabetes in Canada.

BackgroundCanagliflozin, an agent that inhibits sodium glucose co-transporter 2, is approved as add-on to metformin plus sulfonylurea for the treatment of type 2 diabetes in Canada. Canagliflozin offers greater glycemic control, as well as important additional benefits such as weight loss and blood pressure reductions, versus dipeptidyl peptidase-4 inhibitors such as sitagliptin.  ObjectiveThis analysis evaluated the cost-effectiveness of canagliflozin 300 mg and canagliflozin 100 mg versus sitagliptin 100 mg in patients with type 2 diabetes inadequately controlled on metformin plus sulfonylurea from the perspective of the Canadian Agency for Drugs and Technologies in Health. MethodsA 40-year cost-effectiveness analysis was performed using the validated Economic and Health Outcomes Model of Type 2 Diabetes Mellitus (ECHO-T2DM). Patient characteristics, treatment effects, and rates of hypoglycemia and adverse events were sourced from the canagliflozin clinical program. Canada-specific costs and utilities were applied. Sensitivity analyses were conducted using alternative values for key model inputs. ResultsBoth canagliflozin 300 and 100 mg dominated sitagliptin 100 mg over 40 years, providing quality-adjusted life-year gains of 0.31 and 0.28, and cost offsets of $2,217 and $2,560, respectively. Both canagliflozin doses dominated sitagliptin in each of the sensitivity analyses. ConclusionsSimulation results suggested that canagliflozin 300 and 100 mg provided better health outcomes and lower costs than sitagliptin 100 mg as a third-line therapy added-on to metformin and sulfonylurea in patients with type 2 diabetes in Canada.

Recent antihyperglycemic prescribing trends for US privately insured patients with type 2 diabetes.

OBJECTIVE: The mid-1990s witnessed the introduction of new classes of medications to treat hyperglycemia of type 2 diabetes. There is evidence that these newer classes have found a place in the therapeutic armamentarium, but details of their use patterns are not known. We sought to determine whether antihyperglycemic prescribing patterns changed concurrently with new drug introductions, and whether such changes were related to changes in the underlying patient population. RESEARCH DESIGN AND METHODS: A sample of U.S. privately insured patients with suspected type 2 diabetes was identified from the MarketScan Research Database over the period of 1997-2000. Patients with type 2 diabetes were identified among those continuously enrolled in the database for at least 1 year. Drug therapy episodes were defined by sequential fulfillment of prescriptions implying a continuous supply of a particular drug (or combination) of at least 30 days duration. Univariate analyses were used to explore trends over time in drug prescriptions and patient characteristics. Multivariate logistic regressions were used to isolate the impact of year from other variables on the likelihood of receiving prescriptions for a specific therapy. RESULTS: A total of 232,020 unique diabetic patients had an average of 1.91 diabetes drug therapy episodes between 1997 and 2000. Monotherapy with sulfonylureas decreased, but monotherapy with thiazolidinedione, metformin, and other oral antihyperglycemics increased over time. Combinations of sulfonylureas and metformin; sulfonylureas and thiazolidinedione; metformin and thiazolidinedione; and sulfonylureas, metformin, and thiazolidinedione each increased over the time interval. Insulin monotherapy decreased, as did insulin combination therapy with sulfonylureas. The combination of insulin and metformin increased, whereas insulin and thiazolidinedione was stable. The influence of year on prescribing patterns remained highly significant (P < 0.001) after adjusting for patient characteristics. CONCLUSIONS: Antihyperglycemic prescription patterns in the U.S. have changed in recent years in parallel with, and probably as a direct result of, the introduction of different classes of medications to the marketplace. Overall, the prescribing trend has been away from monotherapy with insulins and sulfonylureas and toward combination therapies, presumably in attempts to reduce hypoglycemic symptoms and to achieve better glucose control.

Cost-Effectiveness of Canagliflozin versus Sitagliptin as Add-on to Metformin in Patients with Type 2 Diabetes Mellitus in Mexico.

OBJECTIVE: To assess the cost-effectiveness of canagliflozin versus sitagliptin for the treatment of type 2 diabetes mellitus (T2DM) as an add-on to metformin in Mexico. METHODS: A validated model (Economic and Health Outcomes [ECHO]-T2DM) was used to estimate the cost-effectiveness of canagliflozin 300 or 100 mg versus sitagliptin 100 mg in patients with T2DM inadequately controlled on metformin monotherapy. Data from a head-to-head, phase III clinical trial, including patients' baseline demographic characteristics, biomarker values, and treatment effects, were used to simulate outcomes and resource use over 20 years from the perspective of the Mexican health care system. Costs of complications and adverse events were tailored to the Mexican setting and discounted at 5%. Cost-effectiveness was assessed using willingness-to-pay thresholds equivalent to 1 times the gross domestic product per capita (locally perceived to be "very cost-effective") and 3 times the gross domestic product per capita (locally perceived to be "cost-effective") on the basis of recommendations of the Mexican government and the World Health Organization. RESULTS: Owing primarily to better glycated hemoglobin (HbA1c), body weight, and systolic blood pressure values, canagliflozin 300 and 100 mg were associated with an incremental benefit of 0.16 and 0.06 quality-adjusted life-years (QALYs) versus sitagliptin 100 mg, respectively, over 20 years. The mean differences in cost for canagliflozin 300 and 100 mg versus sitagliptin 100 mg were Mexican pesos (MXP) 1797 (US $134) and MXP 7262 (US $540), respectively, resulting in a cost per QALY gained of MXP 11,210 (US $834) and MXP 128,883 (US $9590), respectively. Both of these cost-effectiveness ratios are below the very cost-effective willingness-to-pay threshold in Mexico. The general finding that canagliflozin is cost-effective versus sitagliptin in Mexico was supported by sensitivity analyses. CONCLUSION: In Mexico, both doses of canagliflozin are likely to be cost-effective versus sitagliptin in patients with T2DM who have inadequate glucose control on metformin, primarily because of better biomarker control and higher QALYs.

Treating allergic rhinitis in patients with comorbid asthma: the risk of asthma-related hospitalizations and emergency department visits.

BACKGROUND: Although asthma and allergic rhinitis commonly occur together, the nature of the association has yet to be determined. Treatments for one condition could potentially alleviate the coexisting condition. OBJECTIVE: Patients with both allergic rhinitis and asthma were studied to test the hypothesis that treating allergic rhinitis reduces health care utilization for co-morbid asthma. METHODS: A retrospective cohort study was carried out with 1994-1995 MarketScan claims data. The cohort was limited to patients with both allergic rhinitis and asthma, aged 12 to 60 years, who were continuously enrolled and had no evidence of chronic obstructive pulmonary disease. Allergic rhinitis treatment and asthma-related events (hospitalizations and emergency department visits) were identified. An incidence density ratio (IDR) associated with exposure to allergic rhinitis treatment was calculated. A multivariate Poisson regression was estimated, and the parameter estimates were transformed into IDRs for each explanatory variable. An allergic rhinitis treatment indicator was included in all regressions. RESULTS: The study sample population consisted of 4944 patients with allergic asthma, approximately 73% of whom were treated for their allergic rhinitis. Asthma-related events occurred more often for the untreated group compared with the treated group, 6.6% compared with 1.3%. An IDR of 0.49 for the treatment group (P =.001) indicates that the risk of an asthma-related event for the treated group was about half that for the untreated group. CONCLUSION: In summary, those who were treated for allergic rhinitis have a significantly lower risk of subsequent asthma-related events (emergency department visits or hospitalizations) than those who were not treated.

Health care costs of allergic rhinitis-associated conditions vary with allergy season.

BACKGROUND: Studies have documented how allergic respiratory symptoms vary with allergen levels, but the impact of allergen levels on health care expenditures for allergy-related conditions has never been shown using actual data on outdoor allergen levels. Evidence linking respiratory allergy to comorbid conditions has also been scanty. OBJECTIVE: To investigate the link between respiratory allergy and presumably associated conditions by documenting seasonal patterns in their severity and co-occurrence, and to suggest a plan for future research. METHODS: A retrospective, cross-sectional analysis of medical claims data from 1995 to 1996 were linked to monthly data from federal counting stations on outdoor allergen levels. Participants were employed persons and their dependents, living within 15 miles of an allergen-counting station, continuously enrolled in a health plan for 1995 and 1996, and identified through medical claims data as having asthma, allergic rhinitis (AR), migraines, sinusitis, tonsillitis, otitis media, depression, or anxiety disorder. RESULTS: All conditions studied were more likely to occur during allergy season than during nonallergy season. For persons with health care claims for a condition of interest in both seasons, total health care costs during allergy season were significantly higher than during nonallergy season. Predicted condition-related expenditures were higher in allergy season for every condition even after controlling for the effect of AR. CONCLUSION: Allergy effects appear to extend beyond AR symptoms. Other conditions may be affected by outdoor allergen levels even in the absence of AR symptoms, implying that these conditions may be etiologically related to allergy, irrespective of their co-existence with allergic rhinitis, further implying that allergic sensitization can independently affect different parts of the respiratory tract as well as the brain.