The effect of medication nonadherence on progression-free survival among patients with renal cell carcinoma.

OBJECTIVE: To examine how observed medication nonadherence to 2 second-line, oral anticancer medications (axitinib and everolimus) affects progression-free survival (PFS) among patients with renal cell carcinoma. METHODS: We used an adherence-exposure-outcome model to simulate the impact of adherence on PFS. Using a pharmacokinetic/pharmacodynamic (PK/PD) population model, we simulated drug exposure measured by area under the plasma concentration-time curve (AUC) and minimum blood or trough concentration (Cmin) under 2 scenarios: 1) optimal adherence and 2) real-world adherence. Real-world adherence was measured using the medication possession ratios as calculated from health insurance claims data. A population PK/PD model was simulated on individuals drawn from the Medical Expenditure Panel Survey (MEPS), a large survey broadly representative of the US population. Finally, we used previously published PK/PD models to estimate the effect of drug exposure (i.e., Cmin and AUC) on PFS outcomes under optimal and real-world adherence scenarios. RESULTS: Average adherence measured using medication possession ratios was 76%. After applying our simulation model to 2164 individuals in MEPS, drug exposure was significantly higher among adherent patients compared with nonadherent patients for axitinib (AUC: 249.5 vs. 159.8 ng×h/mL, P<0.001) and everolimus (AUC: 185.4 vs. 118.0 µg×h/L, P<0.001). Patient nonadherence in the real world decreased the expected PFS from an optimally adherent population by 29% for axitinib (8.4 months with optimal adherence vs. 6.0 months using real-world adherence, P<0.001) and by 5% (5.5 vs. 5.2 months, P<0.001) for everolimus. CONCLUSION: Nonadherence by renal cell carcinoma patients to second-line oral therapies significantly decreased the expected PFS.

Infused therapy and survival in older patients diagnosed with metastatic breast cancer who received trastuzumab.

We used Surveillance, Epidemiology, and End Results-Medicare data (2000-2006) to describe treatment and survival in women diagnosed with metastatic breast cancer (MBC) who received trastuzumab. There were 610 patients with a mean age of 74 years. Overall, 32% received trastuzumab alone and 47% received trastuzumab plus a taxane. In multivariate analysis, trastuzumab plus chemotherapy was associated with a lower adjusted cancer mortality rate (Hazard Ratio [HR] 0.54; 95% Confidence Interval [CI] 0.39-0.74; p < .001) than trastuzumab alone among patients who received trastuzumab as part of first-line therapy. Adding chemotherapy to first-line trastuzumab for metastatic breast cancer is associated with improved cancer survival.

Insomnia medication use and the probability of an accidental event in an older adult population.

OBJECTIVE: This study examined the risk of accidental events in older adults prescribed a sedating antidepressant, long-acting benzodiazepine, short-acting benzodiazepine, and nonbenzodiazepine, relative to a reference group (selective melatonin receptor agonist). METHODS: This was a retrospective cohort analysis of older adults (≥65 years) with newly initiated pharmacological treatment of insomnia. Data were collected from the Thomson MarketScan(®) Medicare Supplemental and Coordination of Benefits databases (January 1, 2000, through June 30, 2006). Probit models were used to evaluate the probability of an accidental event. RESULTS: Data were analyzed for 445,329 patients. Patients taking a long-acting benzodiazepine (1.21 odds ratio [OR]), short-acting benzodiazepine (1.16 OR), or nonbenzodiazepine (1.12 OR) had a significantly higher probability of experiencing an accidental event during the first month following treatment initiation compared with patients taking the reference medication (P < 0.05 for all). A significantly higher probability of experiencing an accidental event was also observed during the 3-month period following the initiation of treatment (1.62 long-acting benzodiazepine, 1.60 short-acting benzodiazepine, 1.48 nonbenzodiazepine, and 1.56 sedating antidepressant; P < 0.05). CONCLUSIONS: Older adults taking an SAD or any of the benzodiazepine receptor agonists appear to have a greater risk of an accidental event compared with a reference group taking an MR.

Health benefit costs and absenteeism due to insomnia from the employer's perspective: a retrospective, case-control, database study.

OBJECTIVE: To objectively assess the economic impact of insomnia on direct medical and prescription costs and indirect absence-related salary replacement costs and on absences and to compare the prevalence and costs of comorbidities in employees with and without insomnia. METHOD: A retrospective analysis was performed on employee data from the Human Capital Management Services Research Reference Database (January 2001-September 2007). Employees were identified as having insomnia (ICD-9 criteria) based on history of receiving medications used to treat insomnia or physician's diagnosis of insomnia. Control employees had no history of medications used to treat insomnia and no insomnia diagnosis. Annual costs and number of absences were compared using 2-part regression models, controlling for demographics, job information, geographic region, comorbid disorders, and the Charlson Comorbidity Index score. Comorbidity prevalence, costs, and services were compared. RESULTS: Data were collected for 299,188 employees (17,230 employees with insomnia and 281,958 control employees). Annual mean incremental costs were $2,053 greater (in total) for employees with insomnia compared with controls (specific increments: medical $751, drug $735, sick leave $208, short-term disability $179, long-term disability $10, and workers' compensation $170). Employees with insomnia missed a mean of 3.10 more workdays annually than those without insomnia. Nearly all comorbid conditions were more prevalent, were more costly, and resulted in a greater utilization of services in employees with insomnia compared to those without. All of the above comparisons were significant (P < .05). CONCLUSION: Insomnia was associated with increased costs, greater absenteeism, and an increased number of comorbid conditions in an employed population. Consistent with other analyses based on these data, the study estimated the annual cost of insomnia in the US civilian labor force to be approximately $15.0-17.7 billion (US dollars).

Association of insomnia with quality of life, work productivity, and activity impairment.

PURPOSE: To assess the association of insomnia with health-related quality of life (HRQOL), work productivity, and activity impairment. METHODS: Data were obtained from the 2005 US National Health and Wellness Survey. Subjects were assigned to the insomnia group (diagnosed insomnia experienced at least a few times a month) or the noninsomnia group (no insomnia or sleep symptoms). HRQOL was assessed using the short form 8 (SF-8) (mental and physical scores). The work productivity and activity impairment questionnaire (WPAI) assessed absenteeism (work time missed), presenteeism (impairment at work), work productivity loss (overall work impairment), and activity impairment. Linear regression models were used to control for potential confounders. RESULTS: A total of 19,711 adults were evaluated (5,161 insomnia, 14,550 noninsomnia). Subjects in the insomnia group had significantly lower SF-8 physical (-5.40) and mental (-4.39) scores and greater activity impairment scores (+18.04) than subjects in the noninsomnia group (P < 0.01 for all). Employed subjects in the insomnia group had greater absenteeism (+6.27), presenteeism (+13.20), and work productivity loss (+10.33) scores than those in the noninsomnia group (P < 0.01 for all). CONCLUSIONS: Insomnia is significantly associated with poorer physical and mental quality of life and work productivity loss and activity impairment.