Mean overall survival gain with aflibercept plus FOLFIRI vs placebo plus FOLFIRI in patients with previously treated metastatic colorectal cancer.

BACKGROUND: Mean survival in cancer trials can be estimated with statistical techniques to extrapolate study survival curves. This methodology was applied to data from the VELOUR trial, where use of the novel biologic aflibercept (ziv-aflibercept in the United States) in combination with fluorouracil+leucovorin+irinotecan (FOLFIRI), had significantly increased median overall survival (OS) by 1.44 months, vs placebo plus FOLFIRI in patients with metastatic colorectal cancer (mCRC) resistant to, or that had progressed following, an oxaliplatin-containing regimen. METHODS: Parametric survival analyses were used to identify distributions with the best fit to the empirical VELOUR data. Mean OS for the two treatment groups (and pre-defined subgroups) was calculated from the fitted curves over a 15-year survival period. RESULTS: Overall, the log-logistic distribution was the best-fitting for both treatment arms and, with it, the estimated difference in mean OS over 15 years between aflibercept+FOLFIRI and placebo+FOLFIRI was 4.7 months. In addition, the survival advantage with aflibercept was at least 3 months for the ITT population, whichever distribution was used to extrapolate survival. CONCLUSION: Extrapolation of survival curves suggests the mean OS difference for aflibercept in the VELOUR trial is at least 3 months in the ITT population and selected subgroups.

Persistence with hepatitis C therapy in the Department of Veterans Affairs.

BACKGROUND: Persistence with Hepatitis C therapy has been identified as a key variable for predicting treatment success. The primary purpose of this study was to assess the persistence with therapy for patients undergoing hepatitis C treatment in the VA healthcare system with two forms of combination therapies: peginterferon alfa-2a with Ribavirin (peg-IFN alpha-2a/Rib) and peginterferon alpha-2b with Ribavirin (peg-IFN alpha-2b/Rib). METHODS: A retrospective cohort study design was used to analyse persistence in VA patients undergoing hepatitis C therapy during FY 2003-2004 using a large national VA data set. Stringent inclusion and exclusion criteria along with various defining variables were used to identify the inception cohort. Persistence rates were calculated for each of the two treatment groups at 3, 6, 9 and 11 months using the Kaplan-Meier method. Likelihood ratio test of equality between the two treatment groups was performed to detect any differences in persistence rates. RESULTS: A total of 5816 hepatitis C patients formed the inception cohort. Persistence rates for the overall duration showed significantly higher rates for patients on peg-IFN alpha-2a/Rib than peg-IFN alpha-2b/Rib. Cox regression analysis also showed favourable hazard ratio of persistence (0.88) for peg-IFN alpha-2a/Rib over peg-IFN alpha-2b/Rib. CONCLUSION: Peg alfa-2A/Rib showed slightly higher persistence rates for the overall duration of treatment as compared to Peg alfa-2B/Rib. However the differences, even though statistically significant, are small and not likely to translate into any substantial clinical advantage. Further research involving other approaches is required to confirm these findings.

Physician perception of patient adherence compared to patient adherence of osteoporosis medications from pharmacy claims.

OBJECTIVE: This study explored physicians' perceptions of patient adherence to medications compared with patient adherence derived by administrative data in the treatment of osteoporosis. RESEARCH DESIGN AND METHODS: A study involving written questionnaires from prescribers treating patients with postmenopausal osteoporosis (PMO) compared the questionnaire responses to pharmacy claims of these prescribers' patients' refill patterns. Approximately 2000 physicians from a large US health plan were faxed or mailed a survey. Data from the physician survey were merged with administrative claims data of the participating physicians' patients. RESULTS: A total of 412 physicians (21.8%) responded. Although a low response rate, there were no significant demographic differences between participating and non-participating physicians. Surveyed physicians reported that 66% of their patients had private/commercial coverage and over 60% reported seeing their PMO patients annually. Overall, physicians estimated that 69.2% of patients were adherent 80% of the time after 12 months of therapy. Yet, pharmacy claims data for those physicians' patients indicated 48.7% of patients were adherent (defined as having an MPR of >or=80%) after 12 months of therapy. Physicians overestimated their patients' adherence regardless of medication class and across physician specialties. Regression modeling revealed that physicians who have been in practice longer estimated fewer patients as adherent, whereas those who prescribe more PMO treatments estimate a greater number of patients as adherent. Providers cited side effects and affordability of medication as the most frequent reasons for non-adherence. CONCLUSIONS: Physicians overestimate patient adherence to PMO therapies. Improving physician awareness of medication non-adherence to PMO therapies may facilitate physician-patient dialogue, with the aim of identifying patient-centered reasons for non-adherence. These discussions are important because patients with poorer adherence have a higher risk of fracture. Future research should focus on reasons for patient non-adherence to osteoporosis regimens and intervention strategies that improve communication between the provider and patient. Findings must be considered within the limitations of this claims database analysis. Some degree of incomplete or incorrect coding may exist, and the presence of a claim for a filled prescription does not indicate that the medication was consumed or taken as prescribed. Patients included in the study are not necessarily representative of all patients being treated for osteoporosis.

Divalproex sodium vs. valproic acid: drug utilization patterns, persistence rates and predictors of hospitalization among VA patients diagnosed with bipolar disorder.

OBJECTIVES: To compare divalproex sodium and valproic acid for therapeutic patterns, persistence rates and predictors of hospitalization among bipolar patients on monotherapy in the Veterans Affairs (VA) healthcare system. METHODS: Using VA administrative data bases, we conducted a retrospective inception cohort study of VA patients'>or= 18 years of age who had at least one outpatient diagnoses of bipolar disorder and two continuous prescription records for the study drugs in the VA PBM pharmacy database during the study period of 1st April 2001 to 30th September 2003. Persistence for the comparative drugs was reported as continuous variable and compared using t-tests. Logistic regression models were used to examine the risk of hospitalization whereas Cox proportional hazard regression models were used to evaluate the time to hospitalization and time to interruption of therapy for the two drug groups. RESULTS: We identified 4624 bipolar patients on monotherapy with valproic acid (n = 4036) and divalproex sodium (n = 588) during the study period. The descriptive statistics included sociodemographics, disability and comorbidity status and were similar for the two groups. For the crude persistence rates there were no statistically significant differences between divalproex sodium (120 days) and valproic acid (110 days). The logistic regression model for risk of hospitalization showed no statistically significant difference between the two comparators [odds ratio = 1.06, 95% confidence interval (CI) = 0.787-1.444]. The Cox model for time to interruption of therapy showed an insignificant hazard ratio (HR) for divalproex sodium vs. valproic acid (HR = 0.928, 95% CI = 0.844-1.020) and for time to hospitalization also no statistically significant difference in the HR for the two drugs (HR = 0.984, 95% CI = 0.784-1.295). CONCLUSION: The study showed a comparable profile of generic valproic acid with divalproex sodium for persistence and predictors of hospitalization for bipolar patients on monotherapy in the VA. Results have important healthcare implications for treatment and costs.