Preapproval Information Exchange: Perspectives of U.S. Population Health Decision Makers on Preferences for Early Engagement with Investigational Therapies.

BACKGROUND: Preapproval information exchange (PIE) is the communication of clinical and health care economic information (HCEI) on therapies in development between U.S. population health decision makers (PHDMs) and drug manufacturers before regulatory approval. Early access to HCEI can help PHDMs plan budgets, inform formulary coverage decisions, and accelerate policy development to improve patient access to innovative health technologies. While recent FDA guidelines and proposed legislation aim to clarify definitions and execution of PIE, the level of U.S. PHDMs' awareness and preferences for early engagement with investigational therapies is unclear. OBJECTIVES: To (a) assess U.S. PHDMs' current knowledge and perceptions of PIE and (b) identify their preferences for PIE, in order to shape future development of related guidelines and policy. METHODS: An expert panel of 5 U.S. PHDMs representing national and regional payers from integrated health plans, pharmacy benefit management, and specialty pharmacy organizations participated in a 2-round modified Delphi process. A targeted literature review of PIE was used to develop a web-based survey administered to the panel. Survey responses were grouped by consensus, with ≥ 80% agreement or disagreement as the threshold in round 1. In round 2, content experts moderated an inperson meeting where panelists deliberated and then revoted on round 1 nonconsensus topics. RESULTS: In the round 1 survey, the panelists reached consensus on 35 of 54 (65%) multiple-choice questions. In the round 2 face-to-face discussion, 19 nonconsensus questions were debated. One question was removed due to duplication, and consensus was achieved on 16 additional questions, with 2 items of nonconsensus remaining. Overall, consensus was achieved on 51 of 53 topics (96%). There was full consensus by the panelists that PIE should encompass new molecular entities and new indications of marketed therapies. Panelists completely agreed on the need for a legislative "safe harbor" for PIE. Four of five panelists reported that the value of PIE was high to PHDMs, and they expressed a strong preference for peer-to-peer conversations with manufacturers' medical or outcomes liaisons for PIE. The main topic of nonconsensus was the optimal timing of PIE. CONCLUSIONS: This panel of U.S. PHDMs achieved consensus on the value of PIE to proactively budget, make informed formulary decisions, and develop pharmaceutical policy to facilitate patient access to new therapies. The PHDM panel's preferences for PIE should be considered in legislative discussions and planning for future PIE by PHDMs and manufacturers. The full contribution of PIE to improving the U.S. health system can best be realized under a safe harbor that allows U.S. PHDM and manufacturer experts to engage in robust scientific and economic discourse. Additional research and broad stakeholder engagement is needed to advance the development of formal U.S. PIE guidelines. DISCLOSURES: This study was funded by GlaxoSmithKline (GSK). Brixner, Oderda, and Biskupiak are principals of Millcreek Outcomes Group, a consultancy that received funding from GSK to conduct this study. Marciniak and Woodward are employees of GSK and own stock in GSK. Seifter was employed by GSK at the time of this study. Neumann served as external health policy advisor for this study and has consulted or served on advisory boards with Merck, Bayer, Pacira, Novo Nordisk, Amgen, Abbvie, Boston Health Economics, Vertex, Precision Health Economics, the Congressional Budget Office, CEA Registry Sponsors, Axovant, Veritech, Janssen, Parateck, Avexis, GSK, Celegene, Bluebird, Roche, Sage, Sarepta, Biogen, and Ipsen. Neumann also reports grants from Amgen, Lundbeck, Gates, NPC, Alzheimer's Association, and NIH.

Analysis of the psychological impact of cancer-related symptoms on patients with non-small cell lung cancer.

BACKGROUND: Patients with non-small cell lung cancer (NSCLC) experience adverse physical symptoms because of cancer, cancer treatment, and comorbidities. The relations among Cancer-Related Symptoms, Functional Impairment, and Psychological Symptoms in patients with NSCLC is not well understood. METHODS: Retrospective analysis of patient-reported symptoms with the 38-item Patient Care Monitor survey, collected in routine clinical care for 1138 patients with NSCLC at eight US community oncology practices. Study sample was randomly split, and structural equation models examined the direct and mediated effects of Cancer-Related Symptoms and Functional Impairment on symptoms of acute distress (Distress) and depression (Despair) in the training sample. The training model was cross validated in testing sample. Results are presented for the full model using the entire sample. RESULTS: Patients were 48.3% female, with mean age of 66.0 years. The most common comorbidities were anemia (60.8%) and respiratory disease (24.5%). Severity of Cancer-Related Symptoms was strongly and positively related to Functional Impairment and Psychological Symptoms in both training and testing models. The modeled effect of Functional Impairment on Distress and Despair was significant in the overall model using the total sample, and significant or near-significant in the training and testing models. The mediated effect of Cancer-Related Symptoms by Functional Impairment tended to be weaker than its direct modeled effect on Distress and Despair. CONCLUSIONS: Despite prior research suggesting that Functional Impairment plays a larger role than symptom burden in depression in NSCLC, the independent modeled effects of Functional Impairment were no greater than the direct modeled effects of Cancer-Related Symptoms. Copyright © 2016 John Wiley & Sons, Ltd.

Prospective observational comparison of clinical outcomes between african-american and caucasian patients receiving second-line treatment with pemetrexed for advanced non-small-cell lung cancer.

INTRODUCTION: This prospective observational study evaluated the effect of race on disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) in patients with NSCLC treated with second-line pemetrexed. PATIENTS AND METHODS: Eligibility criteria included stage IIIB or IV NSCLC patients receiving single-agent pemetrexed for second-line therapy in routine clinical practice. Noninferiority was evaluated using logistic regression analysis of DCR, controlling for predefined covariates. Noninferiority was considered if the upper 95% confidence bound on the adjusted odds ratio (OR) for Caucasian vs. African-American individuals was less than 1.78, corresponding to a difference in proportion of 14% assuming Caucasian individuals to have a DCR of approximately 50%. The bound was chosen to be half of the anticipated difference between treatment and no second-line treatment. PFS and OS were estimated using the Kaplan-Meier method. Tools were used to measure functional status and symptom burden. RESULTS: The unadjusted DCR was 43.7% (117/268) for Caucasian and 45.0% (27/60) for African-American individuals (unadjusted OR, 0.95; 95% confidence interval [CI], 0.54-1.66). The adjusted OR in the final logistic regression model was 0.82 (95% CI, 0.43-1.58). This upper 95% confidence bound was within the prespecified acceptable bound of 1.78. Median PFS times (months) were 2.7 (95% CI, 2.4-3.4) for Caucasian and 3.0 (95% CI, 2.3-4.7) for African-American individuals (P = .91). Median OS times (months) were 6.7 (95% CI, 5.7-7.9) for Caucasian and 6.9 (95% CI, 4.5-8.9) for African-American individuals (P = .92). Baseline and functional status after baseline assessment and mean symptom burden did not differ substantially among races. CONCLUSION: African-American race was not considered to be a significant predictor of disease control after second-line treatment with pemetrexed.

A randomized phase II study of paclitaxel and bevacizumab with and without gemcitabine as first-line treatment for metastatic breast cancer.

BACKGROUND: The addition of bevacizumab to paclitaxel improved progression-free survival (PFS) of patients with metastatic breast cancer (MBC). We examined the efficacy and safety of adding gemcitabine to paclitaxel/bevacizumab (PB). PATIENTS AND METHODS: In this multicenter, open-label, randomized phase II trial, women with locally advanced or MBC were randomly assigned to receive paclitaxel 90 mg/m(2) (days 1, 8, 15) and bevacizumab 10 mg/kg (days 1, 15) with or without gemcitabine 1500 mg/m(2) (days 1, 15) in 28-day cycles. Patients with prior cytotoxic therapy for MBC were ineligible. The primary endpoint was investigator-assessed overall response rate (ORR); secondary endpoints were PFS, overall survival (OS), safety, and quality of life. RESULTS: Ninety-four patients received PB, and 93 received paclitaxel/bevacizumab/gemcitabine (PB+G). The ORRs were 48.9% (95% confidence interval [CI], 38.5%-59.5%) and 58.7% (95% CI, 47.9%-68.9%; P = .117) with PB and PB+G, respectively. The median PFS was 8.8 months (95% CI, 8.1-10.4 months) and 11.3 months (95% CI, 9.7-12.7 months; P = .247; hazard ratio, 0.82); the median OS was 25.0 months (95% CI, 18.8-not assessable [N/A] months) and 24.3 months (95% CI, 20.3-N/A months; P = .475; hazard ratio, 0.84), with PB and PB+G, respectively. There was significantly more grade 3-4 neutropenia (P = .001) and dyspnea (P = .014) with PB+G. Patients treated with PB experienced more improvement in total FACT-B (Functional Assessment of Cancer Therapy-Breast) (P = .021), FACT-B Social/Family Well-being (P = .041), and Breast Cancer-Additional Concerns (P = .008) scores than patients treated with PB+G. CONCLUSION: The addition of gemcitabine to PB was not associated with a statistically significant improvement in ORR. Treatment with PB+G increased the incidence of severe neutropenia and dyspnea, although the regimen generally was well tolerated.

Out-of-pocket drug costs and drug utilization patterns of postmenopausal Medicare beneficiaries with osteoporosis.

BACKGROUND: The Medicare Part D coverage gap has been associated with lower adherence and drug utilization and higher discontinuation. Because osteoporosis has a relatively high prevalence among Medicare-eligible postmenopausal women, we examined changes in utilization of osteoporosis medications during this coverage gap. OBJECTIVES: The purpose of this study was to investigate changes in out-of-pocket (OOP) drug costs and utilization associated with the Medicare Part D coverage gap among postmenopausal beneficiaries with osteoporosis. METHODS: This retrospective analysis of 2007 pharmacy claims focuses on postmenopausal female Medicare beneficiaries enrolled in full-, partial-, or no-gap exposure standard or Medicare Advantage prescription drug plans (PDPs), retiree drug subsidy (RDS) plans, or the low-income subsidy program. We compared beneficiaries with osteoporosis who were taking teriparatide (Eli Lilly and Company, Indianapolis, Indiana) (n = 5657) with matched samples of beneficiaries who were taking nonteriparatide osteoporosis medications (NTO; n = 16,971) or who had other chronic conditions (OCC; n = 16,971). We measured average monthly prescription drug fills and OOP costs, medication discontinuation, and skipping. RESULTS: More than half the sample reached the coverage gap; OOP costs then rose for teriparatide users enrolled in partial- or full-gap exposure plans (increase of 121% and 186%; $300 and $349) but fell for those in no-gap exposure PDPs or RDS plans (decrease of 49% and 30%; $131 and $40). OOP costs for beneficiaries in partial- or full-gap exposure PDPs increased >120% (increase of $144 and $176) in the NTO group and nearly doubled for the OCC group (increase of $124 and $151); these OOP costs were substantially lower than those for teriparatide users. Both teriparatide users and NTO group members discontinued or skipped medications more often than persons in the OCC group, regardless of plan or benefit design. CONCLUSION: Medication discontinuation and OOP costs among beneficiaries with osteoporosis were highest for those enrolled in Part D plans with a coverage gap. Providers should be aware of potential cost-related nonadherence among Medicare beneficiaries taking osteoporosis medications.

Does Type of Tumor Histology Impact Survival among Patients with Stage IIIB/IV Non-Small Cell Lung Cancer Treated with First-Line Doublet Chemotherapy?

Chemotherapy regimens may have differential efficacy by histology in nonsmall cell lung cancer (NSCLC). We examined the impact of histology on survival of patients (N = 2,644) with stage IIIB/IV NSCLC who received first-line cisplatin/carboplatin plus gemcitabine (C/C+G) and cisplatin/carboplatin plus a taxane (C/C+T) identified retrospectively in the SEER cancer registry (1997-2002). Patients with squamous and nonsquamous cell carcinoma survived 8.5 months and 8.1 months, respectively (P = .018). No statistically significant difference was observed in survival between C/C+G and C/C+T in both histologies. Adjusting for clinical and demographic characteristics, the effect of treatment regimen on survival did not differ by histology (P for interaction = .257). There was no statistically significant difference in hazard of death by histology in both groups. These results contrast the predictive role of histology and improved survival outcomes observed for cisplatin-pemetrexed regimens in advanced nonsquamous NSCLC.

Neutropenia-related costs in patients treated with first-line chemotherapy for advanced non-small cell lung cancer.

BACKGROUND: Neutropenia is a major adverse event often associated with chemotherapy administration. Neutropenia-related complications often lead to increased use of costly health care including inpatient and outpatient services. Monitoring and treatment of neutropenia thus place an economic burden on the health care system. OBJECTIVES: To evaluate (a) costs and medical resource use for chemotherapy- related afebrile and febrile neutropenia in an elderly population with Stage IIIB or Stage IV non-small cell lung cancer (NSCLC), and (b) costs unrelated to neutropenia and total all-cause health care costs during first-line chemotherapy. METHODS: Study patients in this retrospective database analysis were aged 65 years or older with a diagnosis of Stage IIIB or Stage IV NSCLC in the Surveillance, Epidemiology and End Results (SEER) cancer registry from 1998 through 2002. Neutropenia was identified by the presence of a primary or secondary diagnosis code for diseases of white blood cells (ICD-9-CM = 288.xx) during a period of first-line chemotherapy treatment. Febrile neutropenia was defined by (a) an inpatient hospitalization with a primary or secondary diagnosis for neutropenia occurring at any time during first-line chemotherapy or (b) intravenous or intramuscular antibiotic administration occurring after the initial neutropenia diagnosis and during first-line chemotherapy. Patients with neutropenia without these events were considered to have afebrile neutropenia. Patients were followed in the SEER-Medicare database to evaluate costs (defined as all Medicare payments, primary insurer payments, and patient copayments and deductibles) and resource use associated with afebrile or febrile neutropenia while on first-line chemotherapy. If a patient switched to second-line chemotherapy, the day prior to the switch was defined as the end of first-line treatment. If a switch to second-line therapy did not occur, then first-line therapy was assumed to end 30 days following administration of the last first-line agent. Costs were summed for 2 main types of cost measures: neutropenia-related costs, defined as costs for claims with either a primary or secondary diagnosis of neutropenia, and costs unrelated to neutropenia. Costs were classified using ICD-9-CM diagnosis and procedure codes appearing on the claims, with confidence intervals [CIs] for cost measures estimated by using nonparametric bootstrapping methods. Group comparisons of patient characteristics, medical utilization, and cost study measures were made using 2-sided Pearson chi-square and t-test statistics for categorical and continuous measures, respectively. The no neutropenia group was used as the reference category for comparisons involving patient characteristic, medical utilization, and total all-cause health care cost study measures. For total neutropenia-related costs, afebrile and febrile neutropenia study groups were compared. RESULTS: Among elderly patients treated first-line for advanced NSCLC, 5,138 met inclusion criteria, of whom 1,228 (23.9%) developed afebrile (n = 740, 14.4%) or febrile neutropenia (n = 488, 9.5%) while on first-line chemotherapy. Mean per patient costs for treating neutropenia during first-line chemotherapy were $12,148 (standard deviation [SD] = $15,432, 95% confidence interval [CI] = $10,915-$13,607) for patients with febrile neutropenia and $3,099 (SD = $4,541, 95% CI = $2,796-$3,431) for patients with afebrile neutropenia (P<0.001), with mean (SD) length of follow-up (duration of first-line chemotherapy) of 4.5 (4.8) and 5.5 (7.0) months, respectively. Expressed as a percentage of total all-cause health care costs during first-line chemotherapy, neutropenia-related costs accounted for 32.2% of total costs for patients with febrile neutropenia (mean [SD] = $37,694 [$26,078]) and 9.1% of total costs for patients with afebrile neutropenia (mean [SD] = $34,204 [$26,317]). Mean neutropenia-related costs per patient per month (PPPM) during first-line chemotherapy were $2,700 for patients with febrile neutropenia and $563 for patients with afebrile neutropenia. PPPM costs unrelated to neutropenia for patients with afebrile neutropenia, febrile neutropenia, and no neutropenia, respectively, were $5,655, $5,677, and $6,146. In sensitivity analyses, results were highly sensitive to the definition of neutropenia (i.e., claims with primary diagnosis only vs. primary or secondary diagnosis) but insensitive to the type of chemotherapy regimen. CONCLUSION: Neutropenia is a major adverse event that places patients at an increased risk of infection and subsequent morbidity and mortality. For elderly patients undergoing first-line chemotherapy for NSCLC, neutropenia, particularly febrile neutropenia, is associated with substantially higher total all-cause health care costs.

The cost of comorbid depression and pain for individuals diagnosed with generalized anxiety disorder.

Patients with generalized anxiety disorder (GAD) often have comorbid medical and psychiatric disorders and may incur higher costs. In this study, a total of 36,435 GAD patients aged 18 to 64 were identified from a claims database. Patient's total health care and component costs were compared between GAD patients with and without comorbid depression and pain using general linear models. The average total annual cost for all the GAD patients in the study was $7451. Compared with patients with GAD-only, the estimated total cost was $762 higher for GAD with depression (p < 0.001), $2989 higher for GAD with pain (p < 0.001), and $6073 higher for GAD with both depression and pain (p < 0.001). Comorbid depression and pain had significant impact on costs, especially those with pain or with both depression and pain. This suggests that an optimal strategy for GAD should take into account comorbid pain and depression.

Costs of first-line doublet chemotherapy and lifetime medical care in advanced non-small-cell lung cancer in the United States.

OBJECTIVES: The purpose of this study was to identify total lifetime medical-care costs and costs associated with first-line chemotherapy treatment among older patients with stage IIIB/IV non-small-cell lung cancer treated with commonly used two-drug chemotherapy ("doublet") regimens in the United States. METHODS: Study patients included individuals aged 65 years and older who received a diagnosis of stage IIIB/IV non-small-cell lung cancer in a Surveillance, Epidemiology and End Results cancer registry between 1997 and 2002 and who received first-line treatment with commonly used doublet regimens. Patients were followed retrospectively in the Surveillance, Epidemiology and End Results-Medicare database to evaluate lifetime medical-care costs and costs while on first-line chemotherapy treatment. Pairwise comparisons of treatment costs were estimated by using nonparametric bootstrap methods. RESULTS: Lifetime medical-care costs totaled approximately $70,000 and on-treatment costs for first-line chemotherapy totaled approximately $30,000 among study patients and were dominated by hospitalization and physician costs. Lifetime costs were significantly higher among patients treated with first-line cisplatin/carboplatin (platinum) plus a taxane compared with those who received platinum plus gemcitabine [difference: $4781 ($1558-$8039)] or other doublet therapy [difference: $5961 ($2333-$9614)]. Total on-treatment costs for first-line chemotherapy were significantly higher among patients treated with platinum plus a taxane compared with those who received platinum plus gemcitabine [difference: $5825 ($3872-$7770)], platinum plus another agent [difference: $5968 ($3995-$7975)], or another doublet therapy [difference: $3663 ($1620-$5740)]. CONCLUSIONS: There is a cost differential between first-line doublet regimens in terms of lifetime and on-treatment costs. Although doublet therapy with platinum and a taxane was the most frequently utilized regimen, it was associated with the highest lifetime and on-treatment costs.

Trends and predictors of first-line chemotherapy use among elderly patients with advanced non-small cell lung cancer in the United States.

PURPOSE: This study assessed first-line chemotherapy treatment patterns over time and identified predictors of chemotherapy use and treatment selection among elderly patients with newly diagnosed Stage IIIB/IV non-small cell lung cancer (NSCLC) in the United States. METHODS: Patients aged 65 years and older newly diagnosed with Stage IIIB/IV NSCLC between 1997 and 2002 were identified and followed through 2003 using the Surveillance, Epidemiology and End Results (SEER)-Medicare database to evaluate temporal trends in chemotherapy treatment. Multivariate logistic regression models were estimated to identify predictors of chemotherapy treatment and factors associated with use of cisplatin/carboplatin (platinum) and either a taxane or gemcitabine versus other treatments. RESULTS: Chemotherapy use increased from approximately 28% of Stage IIIB/IV NSCLC patients diagnosed in 1997 to 36% of patients diagnosed in 2002. Doublet therapy was most commonly used as first-line therapy, received by 74% of chemotherapy-treated patients across all study years. Use of doublet therapy with platinum and either a taxane or gemcitabine also increased over time (with the largest increase for gemcitabine combinations from 0.3% in 1997 to 11.8% in 2002). Males were more likely than females to be treated with chemotherapy (odds ratios [95% CI]: 1.14 [1.06-1.22]), as were patients in the Northeast and South relative to patients in the West (1.24 [1.13-1.36] and 1.33 [1.20-1.47], respectively). CONCLUSION: Use of first-line chemotherapy treatment among elderly Stage IIIB/IV NSCLC patients is low, but appears to be increasing, with potential regional and gender differences in treatment. These findings are likely to be of interest to clinicians and policymakers.

Phase III study of immediate compared with delayed docetaxel after front-line therapy with gemcitabine plus carboplatin in advanced non-small-cell lung cancer.

PURPOSE: Gemcitabine plus carboplatin (GC) is active as front-line treatment for advanced non-small-cell lung cancer (NSCLC). For patients without progression, timing of second-line chemotherapy for optimum clinical benefit remains uncertain. This phase III, randomized trial assessed the efficacy and safety of docetaxel administered either immediately after GC or at disease progression. PATIENTS AND METHODS: The chemotherapy-naïve patients enrolled had either stage IIIB NSCLC with pleural effusion or stage IV NSCLC. Gemcitabine (1,000 mg/m(2)) was administered on days 1 and 8 followed by carboplatin (area under the curve = 5) on day 1. After four 21-day cycles, patients who did not have progression were randomly assigned either to an immediate docetaxel group (docetaxel 75 mg/m(2) on day 1 every 21 days, with maximum of six cycles) or to a delayed docetaxel group. The primary end point was overall survival (OS) measured from random assignment. Additional analyses included tumor response, toxicity, progression-free survival (PFS), and quality of life (QOL). RESULTS: Enrollment totaled 566 patients; 398 patients completed GC; 309 patients were randomly assigned equally to the two docetaxel treatment groups. Toxicity profiles were generally comparable for the docetaxel groups. Median PFS for immediate docetaxel (5.7 months) was significantly greater (P = .0001) than for delayed docetaxel (2.7 months). Median OS for immediate docetaxel (12.3 months) was greater than for delayed docetaxel (9.7 months), but the difference was not statistically significant (P = .0853). QOL results were not statistically different (P = .76) between docetaxel groups. CONCLUSION: We observed a statistically significant improvement in PFS and a nonstatistically significant increase in OS when docetaxel was administered immediately after front-line GC, without increasing toxicity or decreasing QOL.

Duloxetine treatment for role functioning improvement in generalized anxiety disorder: three independent studies.

OBJECTIVE: Generalized anxiety disorder (GAD) is associated with impaired role functioning and diminished well-being. The present work examined the efficacy of duloxetine treatment for improving functional outcomes for patients with GAD in 3 independent clinical studies. METHOD: Studies were randomized, double-blind, placebo-controlled multicenter trials conducted in adult outpatients with DSM-IV-defined GAD. One study compared 9-week fixed-dose treatment with duloxetine 60 or 120 mg (N = 168 and N = 170, respectively) with placebo (N = 175). The other 2 studies compared 10-week flexible-dose treatment with duloxetine 60-120 mg (study 2, N = 168; study 3, N = 162) with placebo (study 2, N = 159; study 3, N = 161). The main functional outcome measure for each study was the Sheehan Disability Scale (SDS). Additional measures were the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form and the European Quality of Life 5 Dimensions. The 3 studies were conducted in the time period from June 2004 to November 2005. RESULTS: Duloxetine-treated patients improved significantly more than placebo-treated patients on SDS global functioning (study 1, p

Use of effect size to determine optimal dose of duloxetine in major depressive disorder.

OBJECTIVE: At effective doses, patients with major depressive disorder (MDD) treated with duloxetine have been found to experience significant symptom improvement as measured by HAMD(17) total score. In addition, duloxetine-treated patients have significantly higher remission and response rates compared with placebo. The objective of this analysis is to determine the optimal dose of duloxetine in MDD. MATERIALS AND METHODS: Effect size for duloxetine 40mg, 60mg, 80mg, and 120mg per day were estimated using all 6 acute phase III clinical trials in patients with MDD. The tolerability of duloxetine 40mg, 60mg, 80mg, and 120mg were evaluated using pooled data from the 6 studies. The primary efficacy measure in all trials was the HAMD(17) total score, from which were determined the effect size for HAMD(17) change scores, response rates (50% reduction from baseline to endpoint), and remission rates (HAMD(17) total score < or =7). RESULTS: A total of 1619 randomized patients were included in these studies, of which 632 were treated with placebo; 177 with duloxetine 40mg/day; 251 with 60mg/day; 363 with 80mg/day; and 196 with 120mg/day. An evaluation of increments in effect size between doses consistently showed that the most notable gain in effect size for efficacy was the 40-60mg/day dosage range. All dosages from 60 to 120mg were effective. The tolerability assessment indicated duloxetine at 40-120mg/day is well tolerated. Furthermore, the initial doses of 40-80mg/day were found to have comparable tolerability. CONCLUSIONS: The effect size analyses demonstrate that duloxetine 40mg has minimum efficacy, and that duloxetine 60-120mg/day is effective in the treatment of patients with MDD. An initial dose less than 60mg/day might provide better tolerability for some patients diagnosed with MDD.

The cost of treating anxiety: the medical and demographic correlates that impact total medical costs.

The purpose of this retrospective, multivariate analysis is to examine how medical conditions and demographic characteristics affect the costs of treating individuals diagnosed with anxiety. Data from MarketScan Databases [The MEDSTAT Group, 2000] were used to identify individuals with new episodes of anxiety. Multivariate analysis was used, with the dependent variable being the log of total medical costs. This analysis controlled for demographic characteristics, medical comorbidities, anxiety diagnosis, and prior resource utilization. A smearing estimate is used to calculate the total medical costs for patients with any anxiety disorder. The mean estimated total medical cost for individuals diagnosed with any anxiety disorder was $6,475. The multivariate model indicates that controlling for demographics and other disease states, generalized anxiety disorder (GAD), panic disorders, and posttraumatic stress disorder (PTSD) are associated with a $2,138, $1,603, and $3,940 increase, respectively, in the total medical cost (P < .0001). The incremental impact of depression, other anxiety disorders, and prior mental health diagnoses on the total medical costs were $1,945, $1,900, and $1,515, respectively (P < .0001). Individuals with the highest costs, and therefore the greatest need for intervention, are anxious patients with depression, individuals diagnosed with PTSD or GAD, and individuals diagnosed with both anxiety and a comorbid medical condition such as an acute myocardial infarction or diabetes.

Medical and productivity costs of anxiety disorders: case control study.

This retrospective case-control study examines the medical and productivity costs associated with a diagnosis of anxiety. The study used a data set from a large employer database that collected medical, pharmaceutical, absenteeism, short-term disability, and worker compensation records during 2000 from 6 major employers. Patients diagnosed with anxiety disorders (n= 1917) were matched at a 1:1 ratio to patients not diagnosed with anxiety disorders (n= 1917) based on age, sex, metropolitan statistical area, and type of insurance coverage. Paired-difference t tests, McNemer's test, and analyses of covariance were used to compare the anxiety population with the control group. Employees diagnosed with anxiety disorders were significantly more likely to have additional diagnoses, use more services, require hospitalization, or visit the emergency room compared with the control group. Furthermore, after controlling for differences in comorbidities, employees diagnosed with anxiety disorders had significantly higher medical costs [$1555; 95% confidence interval (CI) $1066-2043], productivity costs ($1366; 95% CI $708-2023), and total costs ($2920; 95% CI $2035-3805) compared with the control group. Results indicate that anxiety disorders are associated with significant medical and productivity costs.

The benefits of switching smoking cessation drugs to over-the-counter status.

This paper provides an analysis of the benefits to society from the conversion of nicotine replacement drugs (nicotine patches and gum) in 1996 from sale by prescription only in the United States to over-the-counter (OTC) sales. To estimate these benefits, we first estimate statistical demand functions for nicotine patches and gum. Second, we calculate the effects of OTC conversion on sales of each type of nicotine replacement drug. Third, we survey the literature on the effects of nicotine replacement drugs on total quits of cigarette smoking. Fourth, we survey the literature on the effects of quits achieved on expected lifespan, and on the estimated monetary value of longer lives from smoking cessation. Finally, we use all this evidence to calculate the value of the social benefits of the OTC conversion to the US. As a result of the OTC conversion, consumption of nicotine replacement drugs has increased substantially, by 78-92% for nicotine patches and 180% for nicotine gum. We estimate that the resulting increase in smoking cessation generated annual net social benefits of the order of magnitude of 1.8-2 billion dollars, based on conservative estimates both of the number of quits achieved and the value of added quality-adjusted life years from the reduced smoking.