S Balu

Health outcomes and economic impact of therapy conversion to a biphasic insulin analog pen among privately insured patients with type 2 diabetes mellitus.

Study Objective. To evaluate claims‐related treatment adherence, health care resource utilization, and associated costs of therapy conversion from an insulin vial and syringe to a premixed biphasic insulin analog pen device among privately insured patients with type 2 diabetes mellitus.

Differences in psychometric properties, cut-off scores, and outcomes between the Barthel Index and Modified Rankin Scale in pharmacotherapy-based stroke trials: systematic literature review

ABSTRACT Objective: Review published clinical trial studies on pharmacological treatment of stroke using both the Barthel Index (BI) and Modified Rankin Scale (MRS) as outcome measures, and to highlight the differences in psychometric properties and cut-off scores through a systematic review. Methods: A systematic literature search on stroke studies involving a pharmacological treatment was conducted between 1955–2008. Key words included Barthel index, Rankin, modified Rankin, pharmacotherapy, validity, reliability, responsiveness, sensitivity, specificity, outcomes, psychometrics, prediction, randomized clinical trials, analysis, and stroke. All search terms were limited to Medical Subjects Headings (MESH) terms, English-language abstracts, and human subjects. Results: Overall, 44 studies were identified, six studies comparing the psychometric properties of the BI and the MRS, 24 studies on use of both the BI and the MRS in clinical stroke trials involving a pharmacological treatment, and 14 studies reviewed the cut-off scores and statistical issues related to scale selection. Most studies measured outcomes at 90 days after initiating therapy although differences were observed in this lag time. There was inconsistency in cut-off points used for both scales in the studies. There was no apparent relation between time to initiation of stroke therapy and outcomes measured by the BI and the MRS. The time window ranged from 3 hours to 72 hours although most of the studies reported outcomes after therapy initiation within 3–6 hours of stroke onset. BI may not be an appropriate scale to measure treatment effects due to the inherent ceiling and floor effects. Use of total distribution scores on the scales rather that dichotomizing or trichotomizing the scales has been favored recently. In mild to moderate stroke patients, the MRS seems to detect small and significant treatment effect changes as compared to the BI. Since most stroke studies try to exhibit the effects of treatment within 3 hours after symptom onset, the MRS might be more relevant to clinicians and patients receiving early intervention. Key limitations of this review are absence of studies that might have been identified through databases other than PubMed and MEDLINE and exclusion of non-pharmacological stroke trials that used the BI and the MRS for outcome measurement. Conclusions: Despite the lack of uniformity in the cut-off points used in the trials, the follow-up time after administration of therapy, and the amount of time within which treatment is initiated after onset of stroke symptoms, the MRS seems to be more sensitive and responsive as compared to the BI in measuring stroke disability. However, more studies are required to differentiate the BI and the MRS that would help in selecting a scale that would appropriately capture outcomes among stroke patients.

Impact of fixed-dose and multi-pill combination dyslipidemia therapies on medication adherence and the economic burden of sub-optimal adherence

Abstract Objective: To compare medication adherence between patients initiating fixed-dose combination versus multi-pill combination dyslipidemia therapies and assess the association between optimal adherence (MPR ≥ 80%) and cardiovascular disease (CVD)-associated total healthcare resource utilization (THR) and costs (THC). Research design and methods: The HealthCore Integrated Research Database was used to identify patients ≥18 years newly initiating fixed-dose combination [niacin extended-release (NER) and lovastatin (NERL)] or multi-pill combination therapies [NER and simvastatin (NER/S) or lovastatin (NER/L)] between 1/1/2000 and 6/30/2006 (index date), with minimum 18 months of follow-up. Adherence was measured using medication possession ratio (MPR). Three multivariate models were developed controlling for demographic and clinical characteristics. A logistic model evaluated the association between study cohorts and optimal adherence, while negative binomial and gamma models estimated the association between optimal adherence and CVD-associated THR and THC, respectively. Results: In all, 6638 NERL, 1687 NER/S, and 663 NER/L patients were identified. Fixed-dose combination patients were younger [mean (SD) ages of 51.9 (10.5) vs. 56.0 (9.4) [NER/S] and 56.1 (10.6) [NER/L]; p < 0.01], had lower comorbidity (Deyo–Charlson Index 0.50 ± 0.9 vs. 0.7 ± 1.1 and 0.6 ± 1.1, p < 0.01 and p < 0.05) and comprised fewer males (73.1 vs. 83.0% and 77.7%; p < 0.01 and p = 0.1). Fixed-dose combination patients had higher average 1-year MPR versus NER/S and NER/L patients (0.54 ± 0.35 vs. 0.50 ± 0.35 and 0.47 ± 0.34, p < 0.01). NER/S and NER/L patients were 31.3% (95% CI: 22.9–39.5%) and 39.1% (95% CI: 26.7–49.4%) less likely to be optimally adherent than fixed-dose combination patients (p < 0.01). Additionally, optimally adherent patients had 8% and 40% decreases in annual CVD-attributable THR [0.920 (95% CI: 0.857–0.989); p = 0.023] and THC [0.601 (95% CI: 0.427–0.845); p = 0.003] versus sub-optimally adherent patients. Key limitations of the study include the limited ability of MPR to analyze the continuity of medication usage, inability to capture data on other key variables including race, income, and clinical characteristics such as smoking history, absence of laboratory values on all study patients, inability to capture over-the-counter fills of niacin, and inability to show causality of results obtained. Conclusions: Adherence was significantly higher among patients initiating fixed-dose combination versus multi-pill combination dyslipidemia therapies in this managed-care population. Additionally, patients with optimal adherence had a significantly lower CVD-associated THR and THC versus patients with sub-optimal adherence.

Clinical and economic burden of chemotherapy-induced nausea and vomiting among patients with cancer in a hospital outpatient setting in the United States

Abstract Objective: This study evaluated the overall burden of illness of chemotherapy-induced nausea and vomiting (CINV) and associated all-cause costs from a hospital’s perspective (costs to the hospital) in patients with cancer treated with chemotherapy (CT) in the US hospital outpatient setting. Methods: Patients with a cancer diagnosis aged ≥18 years initiating CT in a hospital outpatient setting for the first time between April 1 2007 and March 31 2009 were extracted from the Premier Perspective Database. Patients were followed through eight CT cycles or 6 months post-index date, whichever occurred first. Within each CT cycle, the follow-up time for CINV event estimation was from day 1 (except rescue medication use that was identified from day 2) to cycle end. A multivariate regression model was developed to predict the CINV event rate per CT cycle in the study follow-up period. Associated total all-cause costs of managing CINV from a hospital’s perspective were analyzed descriptively. Event rate and associated costs were estimated in the entire hospital setting (outpatient, inpatient, and emergency room). All-cause costs included inpatient, hospital outpatient, and ER visit costs (identified through a primary or secondary diagnosis code for nausea, vomiting, and/or volume depletion) and pharmacy cost (rescue medications for CINV treatment). All physician costs and non CINV-related treatment (pharmacy) costs were excluded from the analyses. Results: Among 11,495 study patients, 8,806 patients (76.6%) received prophylaxis for all cycles in the follow-up period. The overall base population had an average age of 63.3 years, was 51.0% female, and 72.7% White. The distribution of emetogenicity for cycle 1 CT cycle was 26.0% HEC, 46.1% MEC, and 26.4% LEC/MinEC combined. In the follow-up period, a total of 47,988 CINV events with an associated total all-cause treatment cost of

Likelihood of a subsequent chemotherapy-induced nausea and vomiting (CINV) event in patients receiving low, moderately or highly emetogenic chemotherapy (LEC/MEC/HEC)

89 million were observed. Average daily treatment cost for all care settings was

Impact of 5-HT3 receptor antagonists on chemotherapy-induced nausea and vomiting: a retrospective cohort study.

1854.7. The regression model predicted a 20% CINV event rate per CT cycle in the follow-up period. Study limitations include potential lack of generalizibility, absence of data on certain confounders including alcohol consumption and prior history of motion sickness, lack of a control analysis group to estimate incremental use of resource utilization and associated costs, and a potential for cost under-estimation. Conclusion: In the current study analysis, a 20% CINV event rate per CT cycle per patient was predicted with an associated all-cause average daily total cost of approximately

Impact of 5-HT 3 RA selection within triple antiemetic regimens on uncontrolled highly emetogenic chemotherapy-induced nausea/vomiting

1850. Further studies on early and appropriate antiemetic prophylaxis on CINV rates and economic outcomes are warranted.

Development of a refractory gastro‐oesophageal reflux score using an administrative claims database

Abstract Objective: To assess the likelihood of subsequent chemotherapy-induced nausea and vomiting (CINV) events following a first chemotherapy administration CINV event in patients receiving single-day low, moderately, or highly emetogenic chemotherapy (LEC, MEC, or HEC). Methods: A retrospective analysis was conducted utilizing Georgia Cancer Specialists, Florida Cancer Specialists, and ACORN electronic medical records databases (April 2006 through July 2009). Patients were included who received more than one single-day LEC, MEC, or HEC administration (oral or intravenous) with no chemotherapy 3 months prior to the first LEC, MEC, or HEC administration. Two cohorts, patients with a first administration CINV and no first administration CINV, were created and followed for 6 months. A multivariate logistic regression assessed the likelihood of subsequent CINV, controlling for age, gender, Charlson comorbidity index, cancer type, number of chemotherapy administrations, gap between LEC, MEC, or HEC administrations, and number of different LEC, MEC, or HEC agents administered. Results: A total of 10,586 patients met the inclusion criteria (LEC = 3099; MEC = 5172; HEC = 2315). Of those patients, 4.4% (n = 136), 7.8% (n = 402), and 13.8% (n = 320) experienced a CINV event with their initial single-day LEC, MEC, or HEC administration, respectively. The unadjusted subsequent CINV rate was higher in the cohorts with first LEC, MEC, or HEC administration CINV for all groups receiving LEC (33.1% vs. 16.0%; p < 0.0001), MEC (46.5% vs. 18.9%; p < 0.0001), or HEC (59.1% vs. 26.9%; p < 0.0001). After controlling for covariates, patients with first LEC, MEC, or HEC administration CINV were 3.1, 3.8, and 3.7 times more likely to have a subsequent CINV compared to patients without a first LEC, MEC, or HEC administration CINV (Odds Ratio: 3.05 [95% CI: 2.08–4.48, p < 0.0001]; 3.77 [95% CI: 3.04–4.68, p < 0.0001]; and 3.70 [95% CI: 2.88–4.74, p < 0.0001], respectively). Conclusion: In this retrospective analysis, patients receiving single-day LEC, MEC, or HEC who had a prior CINV were at increased risk of subsequent CINV. Further studies assessing increased risk of a subsequent CINV events are warranted given this study represents an assessment of electronic medical record data within select community-based populations under usual care.

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

Background1st generation 5-hydroxytryptamine receptor antagonists (5-HT3 RAs), and palonosetron, a 2nd generation 5-HT3 RA, are indicated for the prevention of chemotherapy (CT)-induced nausea and vomiting (CINV) associated with moderately (MEC) and highly emetogenic CT agents (HEC). This study explores the impact of step therapy policies requiring use of an older 5-HT3 RA before palonosetron on risk of CINV associated with hospital or emergency department (ED) admissions.MethodsPatients who received cyclophosphamide post breast cancer (BC) surgery or who were diagnosed with lung cancer on carboplatin (LC-carboplatin) or cisplatin (LC-cisplatin) were selected from PharMetrics’ (IMS LifeLink) claims dataset (2005-2008). Patients were followed for 6 months from initial CT administration for CINV events identified through ICD-9-CM codes. Patients were grouped into those initiated with older, generic 5-HT3 RAs (ondansetron, granisetron, and dolasetron) and those initiated and maintained on palonosetron throughout study follow-up. CINV events and CINV days were analyzed using multivariate regressions controlling for demographic and clinical variables.ResultsEligible patients numbered 3,606 in BC, 4,497 in LC-carboplatin and 1,154 in LC-cisplatin cohorts, with 52%, 40%, and 34% in the palonosetron group, respectively. There was no significant difference between the two 5-HT3 RA groups in age or Charlson Comorbidity Index among the two MEC cohorts (BC and LC-carboplatin). Among the LC-cisplatin cohort, palonosetron users were older with more males than the older 5-HT3 RA group (age: 60.1 vs. 61.3; males, 66.9% vs. 56.9%). Compared to the older 5-HT3 RAs, the palonosetron groups incurred 22%-51% fewer 5-HT3 RA pharmacy claims, had fewer patients with CINV events (3.5% vs. 5.5% in BC, 9.5% vs. 12.8% in LC-carboplatin, 16.4% vs. 21.7% in LC-cisplatin), and had lower risk for CINV events (odds ratios 0.62, 0.71, or 0.71, respectively; p < 0.05). The BC and LC-carboplatin palonosetron groups experienced 50% and 30% fewer CINV days than the generic 5-HT3 RA group (p < 0.05).ConclusionsPatients with breast or lung cancer initiated and maintained on palonosetron were at significantly lower risk for potentially costly CINV versus those on older 5-HT3 RAs. Further studies on impact of step therapy policy are warranted in order to minimize the clinical and economic burden of CINV.

Chemotherapy-induced nausea and vomiting and antiemetic prophylaxis with palonosetron versus other 5-HT3 receptor antagonists in patients with cancer treated with low emetogenic chemotherapy in a hospital outpatient setting in the United States

Background: It is recommended that patients initiate triple antiemetic therapy with one of the 5-hydroxytryptamine receptor antagonists (5-HT3 RAs), aprepitant (or its intravenous prodrug fosaprepitant) and dexamethasone prior to the start of highly emetogenic chemotherapy (HEC). However, the impact of 5-HT3 RA selection within triple antiemetic regimens on the risk of uncontrolled chemotherapy-induced nausea and vomiting (CINV) with HEC has not been well studied. Aim: To assess the likelihood of an uncontrolled CINV event following antiemetic prophylaxis with the 5-HT3 RA palonosetron + aprepitant/fosaprepitant + dexamethasone (palonosetron cohort) versus any of the other 5-HT3 RAs + aprepitant/fosaprepitant + dexamethasone (other 5-HT3 RA cohort) among single-day HEC cycles. Methods: Single-day HEC cycles (a gap of at least 5 days between two administrations) among patients with a cancer diagnosis and receiving antiemetic prophylaxis with the aforementioned regimens between 1/1/2006 and 6/30/2010 were identified from the IMS LifeLink claims database. Uncontrolled CINV events were identified through ICD-9-CM codes (nausea and vomiting), Current Procedural Terminology codes (hydration), rescue medications and/or use of antiemetic therapy from days 2–5 following HEC administration. Risks for an uncontrolled CINV event among all patients, and within breast cancer and multiple cancer subpopulations, were analyzed at cycle level using logistic multivariate regression models. Results: A total of 8018 cycles for the palonosetron cohort and 1926 cycles for the other 5-HT3 RA cohort (3574 and 978 patients, respectively) were analyzed. Single-day HEC cycles received by the palonosetron cohort had a significantly lower unadjusted risk of an uncontrolled CINV event (17.5 vs 20.7% for the other 5-HT3 RA cohort; p = 0.0010), with a 17% lower adjusted risk for palonosetron-administered cycles (odds ratio: 0.83; 95% CI: 0.73–0.94; p = 0.0042). Results in the breast cancer and multiple cancer subgroups were consistent with those for the overall population. Conclusion: In this retrospective claims data analysis, single-day HEC cycles administered with palonosetron + aprepitant/fosaprepitant + dexamethasone had a lower risk for an uncontrolled CINV event versus other 5-HT3 RAs + aprepitant/fosaprepitant + dexamethasone.