Medical cost,incidence rate,and treatment status of gastroesophageal reflux disease in Japan: analysis of claims data

Objectives: Published reports have shown the prevalence and incidence of gastroesophageal reflux disease (GERD) is increasing in Japan. The objective of this study is to examine change in GERD incidence, and to understand current patient demographics, medical costs, treatment status, and the suitability of current treatment based on analysis of an insurance claims database.

Methods: An insurance claims database with data on ～1.9 million company employees from January 2005 to May 2015 was used. Prevalence, demographics, and medical costs were analyzed by cross-sectional analysis, and incidence and treatment status were analyzed by longitudinal analysis among newly-diagnosed GERD patients.

Results: GERD prevalence in 2014 was 3.3% among 20–59 year-olds, accounting for 40,134 people in the database, and GERD incidence increased from 0.63% in 2009 to 0.98% in 2014. In 2014, mean medical cost per patient per month for GERD patients aged 20–59 was JPY 31,900 (USD 266 as of January 2016), which was ～2.4-times the mean national healthcare cost. The most frequently prescribed drugs for newly-diagnosed GERD patients were proton pump inhibitors (PPIs). Although PPIs were prescribed more often in patients with more doctor visit months, over 20% of patients that made frequent doctor visits (19 or more visits during a 24 calendar months period) were prescribed PPIs during only 1 calendar month or not at all.

Limitations: The database included only reimbursable claims data and, therefore, did not cover over-the-counter drugs. The database also consisted of employee-based claims data, so included little data on people aged 60 years and older.

Conclusions: Given the increasing incidence of GERD in Japan there is a need for up-to-date information on GERD incidence. This study suggests that some GERD patients may not be receiving appropriate treatment according to Japanese guidelines, which is needed to improve symptom control.     

Disease-specific cost savings of treating nighttime versus daytime gastroesophageal reflux disease in an employed population

Summary

Objective: The extent to which proton pump inhibitors (PPIs) can offset direct medical costs by reducing symptoms related to gastroesophageal reflux disease (GERD) in order to improve work productivity is not well understood. This study aimed to evaluate the economic impact of treating GERD with PPIs versus no treatment, from an employer's perspective.

Study design: An economic model was developed to simulate symptom reduction and breakthrough symptoms as well as associated costs over 1 year among a population of 100,000 with a 20% GERD prevalence rate. Medical costs, including GERD-related office visits, hospitalisations and procedures, were delineated by symptom severity. Indirect costs represented the monetised work productivity loss. PPI treatment costs $2/day (standard dose).

Results: The GERD burden was substantial ($62,500,000). Treatment yielded $32,600,000 in savings ($1,630 saved/patient/year), mostly from reducing indirect costs. Treatment produced greater savings among nighttime GERD patients throughout the PPI cost range ($1–$5/day). Savings dropped if the price of standard doses of PPI exceeded $3.92/day for the treatment of daytime GERD patients.     

Exenatide BID and liraglutide QD treatment patterns among type 2 diabetes patients in Germany

Abstract

Objectives:

This study evaluated patient and prescriber characteristics, treatment patterns, average daily dose (ADD), and glycemic control of patients initiating glucagon-like peptide 1 (GLP-1) receptor agonists in Germany.

Methods:

The LifeLink? EMR-EU database was searched to identify patients initiating exenatide twice daily (BID) or liraglutide once daily (QD) during the index period (January 1, 2009–April 4, 2010). Eligible patients had ≥180 days pre-index history, ≥90 days post-index follow-up, and a pre-index type 2 diabetes diagnosis. Univariate tests were conducted at α?=?0.05.

Results:

Six hundred and ninety-two patients were included (exenatide BID 292, liraglutide QD 400): mean (SD) age 59 (10) years, 59% male. Diabetologists prescribed liraglutide QD to a larger share of patients (65% vs 35% exenatide BID) than non-diabetologists (51% vs 49%). GLP-1 receptor agonist choice was not associated with age (p?=?0.282), gender (p?=?0.960), number of pre-index glucose-lowering medications (2.0 [0.9], p?=?0.159), pre-index HbA1c (8.2 [1.5%], p?=?0.231) or Charlson Comorbidity Index score (0.45 [0.78], p?=?0.547). Mean (SD) ADD was 16.7?mcg (9.2, label range 10–20?mcg) for exenatide BID and 1.4?mg (0.7, label range 0.6–1.8?mg) for liraglutide QD. Among patients with post-index HbA1c tests, mean unadjusted values did not differ between cohorts. Exenatide BID patients were more likely than liraglutide QD patients to continue pre-index glucose-lowering medications (67.1% vs 60.3%, p?=?0.027) or to start concomitant glucose-lowering medications at index (32.2% vs 25.0%, p?=?0.013); exenatide BID patients were less likely to augment treatment with another drug post-index (15.8% vs 22.5%, p?=?0.027).

Limitations:

Results may not be generalizable. Lab measures for clinical outcomes were available only for a sub-set of patients.

Conclusions:

Results suggested that some differences exist between patients initiating exenatide BID or liraglutide QD, with respect to prescribing physician specialty and pre- and post-index treatment patterns. Both GLP-1 receptor agonists showed comparable post-index HbA1c values in a sub-set of patients.     

Bayesian cost-effectiveness analysis for censored data: an application to antiplatelet therapy

Abstract

Objective:

Cost-effectiveness analysis (CEA) on trial-based data has played an important role in pharmacoeconomics. A regression model can be used to account for patient-level heterogeneity throughout covariates adjustment in CEA. However, the estimates from CEA could be biased if ignoring the censoring issue on effectiveness and costs. This study is to propose a regression model to account for both time-to-event effectiveness and cost.

Methods:

A bivariate regression model was proposed to analyze both effectiveness and cost simultaneously, while censored observations were also taken into account. The regression coefficients were estimated using a Bayesian approach by drawing a random sample from their posterior distribution derived from the Markov chain Monte Carlo (MCMC) method. The proposed method was illustrated using empirical data of anti-platelet therapies to the management of cardiovascular diseases for those patients with high risk of gastrointestinal (GI) bleeding, where cost-effectiveness between different therapies was analyzed under both censored and non-censored circumstances, where the effectiveness was defined as the time to re-hospitalization due to GI complications, and the cost was measured by the total drug expenditure.

Results:

Under censored circumstances, aspirin plus proton-pump inhibitors (PPIs) was considered more cost-effective than clopidogrel with/without PPIs, as shown in the cost-effectiveness acceptability curve, and clopidogrel was preferred to aspirin for a willingness-to-pay of 89 NTD for delaying 1 day to hospitalization due to GI complications.

Conclusions:

Ignoring censoring problems could possibly bias the results in CEA. This study has provided an appropriate method to conduct regression-based CEA to improve the estimation which serves its purpose for CEA concerns.

Limitations:

The normality assumption for the cost and effectiveness in the bivariate normal regression needs to be examined, and the conclusions may be biased if this assumption is violated. However, when sample size is sufficiently large, a slight deviation from normality would not be a serious problem.     

Medical and cost burden of atherosclerosis among patients treated in routine clinical practice

Abstract

Objective:

This investigation estimated medical costs attributable to treatment of patients diagnosed with atherosclerosis in routine US clinical practice.

Methods:

Using Medstat MarketScan claims data, direct costs of care and rates of cardiovascular (CV) events (i.e., myocardial infarction, stroke, revascularization) were examined for patients ≥18?years of age with and without a diagnostic code for atherosclerosis from 1/1/2002 through 12/31/2004. Patients with an atherosclerosis ICD-9 code who had no history of CV events in the preceding 12?months (n?=?75,469) were evaluated. A comparison cohort (n?=?238,702) was matched on age, gender, geographic region, enrollment time period, and Charlson comorbidity index to estimate incremental costs attributable to atherosclerosis. Differences between patient groups were tested for CV event rates per 1,000 patients and monthly costs for 6 and 12?months before and after diagnosis.

Results:

Patients had a mean age of 58?years, 52% men, and a comorbidity index of 0.49. Patients diagnosed with atherosclerosis had significantly higher (p?<?0.001) rates of CV events (240/1000) after diagnosis, compared with patients without atherosclerosis (32/1000). Mean direct cost of care for patients diagnosed with atherosclerosis was $579/month for 12?months before and $1,074/month for 12?months after diagnosis, an 85% increase. Change in mean annual costs pre/post-index date was $5,232 ($436/month) higher among patients with than those without atherosclerosis (p?<?0.001).

Limitations:

The study population was restricted to patients with diagnosed clinical atherosclerosis based on specific ICD-9 codes. Matching of the patient cohorts was based on observed characteristics and other unobserved differences may exist.

Conclusions:

Patients with diagnosed atherosclerosis incur significant clinical and economic burden, indicating a need for earlier diagnosis and treatment of atherosclerosis to help in reducing this burden.     

Palonosetron versus other 5-HT3 receptor antagonists for prevention of chemotherapy-induced nausea and vomiting in patients with hematologic malignancies treated with emetogenic chemotherapy in a hospital outpatient setting in the United States

Abstract

Objective:

This study evaluated the rate of uncontrolled chemotherapy-induced nausea and vomiting (CINV) after initiating antiemetic prophylaxis with palonosetron versus other 5-HT₃ receptor antagonists (RAs) in patients diagnosed with hematologic malignancies (lymphoma and leukemia) and receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC) in a hospital outpatient setting.

Methods:

Patients aged?≥?18 years and diagnosed with hematologic malignancies initiating HEC or MEC and antiemetic prophylaxis with palonosetron (Group 1) and other 5-HT₃ RAs (Group 2) for the first time in a hospital outpatient setting between 4/1/2007 and 3/31/2009 were identified from the Premier Perspective Database. Within each cycle, CINV events were identified (in the hospital outpatient, inpatient, and emergency room settings) through ICD-9 codes for nausea, vomiting, and/or volume depletion (from each CT administration day 1 until the end of the CT cycle), or use of rescue medications (day 2 until the end of the CT cycle). Negative binomial distribution generalized linear multivariate regression model estimating the CINV event rate on CT, specific CT cycles, and cancer diagnosis (leukemia/lymphoma)-matched groups in the follow-up period (first of 8 cycles or 6 months) was developed.

Results:

Of 971 identified patients, 211 initiated palonosetron (Group 1). Group 1 patients comprised of more females [50.2 vs. 41.4%; p?=?0.0226], Whites [74.4 vs. 70.4%, and Hispanics [7.6 vs. 6.3%; all races p?=?0.0105], received more HEC treatments [89.6 vs. 84.2%; all CT types p?=?0.0129], and had more lymphoma diagnosed patients [89.6 vs. 76.3%; all cancer types p?=?0.0033] at baseline. After controlling for differences in several demographic and clinical variables, the regression model predicted a 20.4% decrease in CINV event rate per CT cycle for Group 1 versus Group 2 patients. Study limitations include potential lack of generalizability, absence of data on certain confounders including alcohol consumption and prior history of motion sickness, potential underestimation of incidence of uncontrolled CINV, and inability to draw conclusions pertaining to cause and effect relationship.

Conclusion:

In this retrospective hospital study, patients with hematologic malignancies treated with HEC or MEC and initiated on antiemetic prophylaxis with palonosetron in the hospital outpatient setting were more likely to experience significantly lower CINV event rates (in the hospital outpatient, inpatient, and emergency room settings) versus patients initiated on other 5-HT₃ RAs.     

Burden of illness associated with sinusoidal obstruction syndrome/veno-occlusive disease in patients with hematopoietic stem cell transplantation

Aims: Sinusoidal obstruction syndrome (SOS) is a life-threatening complication of hematopoietic stem cell transplantation (HSCT) associated with significant morbidity and mortality. Healthcare utilization, costs, and mortality were assessed in HSCT patients diagnosed with SOS, with and without multi-organ dysfunction (MOD).

Materials and methods: This retrospective observational study identified real-world patients undergoing HSCT between January 1, 2009 and May 31, 2014 using the Premier Healthcare Database. In absence of a formal ICD-9-CM diagnostic code, SOS patients were identified using a pre-specified definition adapted from Baltimore and Seattle criteria and clinical practice. Severe SOS (SOS/MOD) and non-severe SOS (SOS/no-MOD) were classified according to clinical evidence for MOD in the database.

Results: Of the 5,418 patients with a discharge diagnosis of HSCT, 291 had SOS, with 134 categorized as SOS/MOD and 157 as SOS/no-MOD. The remaining 5,127 patients had HSCT without SOS. Overall SOS incidence was 5.4%, with 46% having evidence of MOD. Distribution of age, gender, and race were similar between the SOS cohorts and non-SOS patients. After controlling for hospital profile and admission characteristics, demographics, and clinical characteristics, the adjusted mean LOS was 31.0 days in SOS/MOD compared to 23.9 days in the non-SOS cohort (medians?=?26.9 days vs 20.8 days, p?p?Limitations: Limitations of retrospective observational studies apply, since the study was not randomized. Definition for SOS was based on ICD-9 diagnosis codes from a hospital administrative database and reliant on completeness and accuracy of coding.

Conclusions: Analysis of real-world data shows that SOS/MOD is associated with significant increases in healthcare utilization, costs, and inpatient mortality.     

Impact of upper and lower gastrointestinal blood loss on healthcare utilization and costs: a systematic review

Abstract

Objectives:

Gastrointestinal (GI) blood loss is a common medical condition which can have serious morbidity and mortality consequences and may pose an enormous burden on healthcare utilization. The purpose of this study was to conduct a systematic review to evaluate the impact of upper and lower GI blood loss on healthcare utilization and costs.

Methods:

We performed a systematic search of peer-reviewed English articles from MEDLINE published between 1990 and 2010. Articles were limited to studies with patients ≥18 years of age, non-pregnant women, and individuals without anemia of chronic disease, renal disease, cancer, congestive heart failure, HIV, iron-deficiency anemia or blood loss due to trauma or surgery. Two reviewers independently assessed abstract and article relevance.

Results:

Eight retrospective articles were included which used medical records or claims data. Studies analyzed resource utilization related to medical care although none of the studies assessed indirect resource use or costs. All but one study limited assessment of healthcare utilization to hospital use. The mean cost/hospital admission for upper GI blood loss was reported to be in the range $3180–8990 in the US, $2500–3000 in Canada and, in the Netherlands, the mean hospital cost/per blood loss event was €11,900 for a bleeding ulcer and €26,000 for a bleeding and perforated ulcer. Mean cost/ hospital admission for lower GI blood loss was $4800 in Canada, and $40,456 for small bowel bleeding in the US.

Conclusions:

Our findings suggest that the impact of GI blood loss on healthcare costs is substantial but studies are limited. Additional investigations are needed which examine both direct and indirect costs as well as healthcare costs by source of GI blood loss focusing on specific populations in order to target treatment pathways for patients with GI blood loss.     

Treatment patterns and economic burden of metastatic and recurrent locally-advanced head and neck cancer patients

Abstract

Objective:

To characterize treatment patterns and measure the economic burden associated with metastatic (mHNC) and recurrent, locally-advanced head and neck cancer (rHNC).

Methods:

Administrative claims from Medicare- and privately-insured individuals during 2004–2008 were used in this retrospective database study of patients with advanced HNC. Patients diagnosed with HNC were matched 1:1 to cancer-free controls to measure the incremental economic burden of HNC. Outcomes of interest were measured during the 6 months following the date of a secondary tumor diagnosis for metastatic patients or the date of a diagnosis indicating rHNC. To assess treatment patterns, HNC patients were evaluated for the use frequency of treatments (radiotherapy, chemotherapy and surgery). Costs were reported in 2008 US$ from a third-party payer perspective and were analyzed using generalized linear models and two-part regression models adjusting for differences in age and baseline Charlson Comorbidity Index (excluding cancer diagnoses) between the HNC and control cohorts. Components of cost included inpatient, outpatient and other medical services as well as pharmacy costs.

Results:

The mHNC cohort consisted of 1042 patients and the rHNC cohort included 324 patients. The most common treatments for mHNC patients were supportive care (90.2%), radiation therapy (48.5%), surgery (41.9%) and chemotherapy (38.3%). Patients with rHNC frequently received HNC-related supportive care (71.0%), radiation therapy (67.9%) and chemotherapy (27.2%); HNC-related surgery was infrequent (12.7%) during the study period. The 6-month incremental adjusted total costs were $60,414 per patient for mHNC and $21,141 per patient for rHNC (p?<?0.0001). Approximately 46–58% of the incremental cost was attributable to outpatient visits, 27–37% to inpatient costs and 11–13% to pharmacy, depending on the HNC cohort.

Limitations:

The identification of mHNC/rHNC was based on diagnosis codes and treatment patterns with the limitation of the claims database.

Conclusions:

Metastatic and recurrent, locally-advanced HNC patients frequently receive cancer-related treatments and incur substantial economic burden.     

Economic impact of using inhaled corticosteroids without prior exacerbation among elderly patients with chronic obstructive pulmonary disorder

Abstract

Objective:

To assess the economic impact of initiating inhaled corticosteroids (ICS) without evidence of prior exacerbation among elderly patients with chronic obstructive pulmonary disease (COPD) in the US.

Methods:

This retrospective study used administrative claims to identify newly diagnosed COPD patients between 1/1/2005 and 6/30/2006 who were dispensed ICS. The dispense date of the first ICS was set as the index date. Patients with prior diagnoses for asthma, cystic fibrosis, or lung cancer were excluded. Cohorts were constructed based on whether ICS therapy was concordant with recommended guidelines of having prior COPD exacerbation. Each COPD patient with prior exacerbation was matched to four patients without exacerbation based on age, gender, Charlson Comorbidity Index, and whether COPD diagnosis code was not elsewhere specified (i.e., 496). Multivariate regressions were estimated to assess the association between use of ICS therapy without prior exacerbation and total healthcare costs, controlling for demographics and clinical characteristics.

Results:

The study included 3650 patients: 730 with prior exacerbation and 2920 without prior exacerbation. Patients were 76 years of age and 54% were male. Those with prior exacerbation were more likely to have inpatient stays both prior to (74.4 vs. 44.1%, p?<?0.05) and following (37.0 vs. 33.1%, p?<?0.05) the index date. Controlling for patient characteristics, patients who were dispensed ICS without prior exacerbation had $1859 higher in total costs (p?<?0.05) compared to patients with prior exacerbation during the 12 months following ICS initiation.

Limitations:

The retrospective design of this study limits the interpretation of findings as association and not causality. This study is subject to selection bias due to unobservable confounders.

Conclusions:

Among COPD patients, initiation of ICS without prior exacerbation appears to be associated with increased healthcare costs. These findings suggest that ICS initiation without evidence of exacerbation as consistent with guidelines is associated with adverse economic consequences.     

Cost-utility of celecoxib use in different treatment strategies for osteoarthritis and rheumatoid arthritis from the Quebec healthcare system perspective

Abstract

Objective: To assess the cost-utility of celecoxib in three treatment strategies for arthritis in Quebec, considering both upper gastrointestinal (GI) and cardiovascular (CV) events.

Methods: A Markov analytic framework was used to model patients with osteoarthritis and rheumatoid arthritis at low/average and high risk of GI and CV toxicity over 5 years with monthly cycles. Treatment strategies were modelled in line with Canadian clinical practice. In first-line treatment, patients started on celecoxib; second-line, patients started on a non-selective non-steroidal anti-inflammatory drug (NSAID) and switched to celecoxib after a first GI event; third-line, patients started on a non-selective NSAID, added a proton pump inhibitor (PPI) after a first GI event, and switched to celecoxib after a second GI event (while maintaining the PPI). Model inputs were determined through comprehensive literature searches (MEDLINE and EMBASE) from 1995 to 2006. Included studies evaluated GI (dyspepsia, uncomplicated and complicated ulcers, death) and CV (myocardial infarction, stroke, death) events. Drug and procedure costs were derived from Canadian published sources (Can$2005).

Results: Total costs per patient for celecoxib first-, second-, and third-line treatment were Can$4,790, $3,390, and $3,466, and total quality-adjusted life-years (QALY) were 3.251, 3.231, and 3.230, respectively. In all risk categories, celecoxib second-line was less costly and as effective as celecoxib third-line, producing savings to the healthcare system. Although celecoxib first-line generated incremental expenditures versus celecoxib second-line, it was also more effective. The resulting cost-utility ratio for the high-risk population was Can$54,696/QALY. Based on this analytical approach, a treatment strategy where celecoxib is used before the combination of a non-selective NSAID plus a PPI possesses cost advantages for the Quebec provincial drug programme. One-way sensitivity analysis (varying GI and CV event rates, utilities, and cost) generally showed second-line treatment with celecoxib as the dominant strategy compared with third-line treatment with celecoxib.

Conclusion: Although effectiveness of second- and third-line celecoxib use is similar, total cost is lower for second-line. These results suggest that the use of celecoxib before the combination of a non-selective NSAID plus a PPI is relatively cost-effective in the treatment of arthritis pain and support the full benefit listing of celecoxib in Quebec's drug programme.     

Healthcare costs of urinary tract infections and genital mycotic infections among patients with type 2 diabetes mellitus initiated on canagliflozin: a retrospective cohort study

Objective: To assess the economic impact of urinary tract infections (UTIs) and genital mycotic infections (GMIs) among patients with type 2 diabetes mellitus (T2DM) initiated on canagliflozin.

Methods: Administrative claims data from April 2013 through June 2014 MarketScan^® databases were extracted. Adults with ≥1 claim for canagliflozin, T2DM diagnosis, and ≥90 days enrollment before and after canagliflozin initiation were propensity score matched to controls with T2DM initiated on other anti-hyperglycemic agents (AHAs). UTI and GMI healthcare costs were evaluated 90-days post-index and reported as cohort means.

Results: Rates of UTI claims 90 days post-index were similar in patients receiving canagliflozin for T2DM (n?=?31,257) and matched controls (2.7% vs 2.8%, p?=?.677). More canagliflozin than control patients had GMI claims (1.2% vs 0.6%, p?p?p?=?.150). GMI treatment costs were higher for the canagliflozin cohort ($3.68 vs $2.44, p?=?.041). Combined costs to treat either UTI and/or GMI averaged $31.29 per patient for the canagliflozin cohort v $39.77 for controls (p?=?.211). Rates and costs of UTIs and GMIs were higher for females than males, but the canagliflozin vs control trends observed for the overall sample were similar for both sexes. There were no significant cost differences between the canagliflozin and control cohorts among patients aged 18–64. Among patients aged 65 and above, GMI treatment costs were not significantly different, but costs to treat UTIs and either UTI and/or GMI were significantly lower for canagliflozin patients vs controls.

Conclusions: In a real-world setting, the costs to payers of treating UTIs and GMIs are generally similar for patients with T2DM initiated on canagliflozin vs other AHAs.