Current and projected patient and insurer costs for the care of patients with non-small cell lung cancer in the United States through 2040.

AIMS: The objective of this study was to quantify the current and to project future patient and insurer costs for the care of patients with non-small cell lung cancer in the US. MATERIALS AND METHODS: An analysis of administrative claims data among patients diagnosed with non-small cell lung cancer from 2007-2015 was conducted. Future costs were projected through 2040 based on these data using autoregressive models. RESULTS: Analysis of claims data found the average total cost of care during first- and second-line therapy was $1,161.70 and $561.80 for patients, and $45,175.70 and $26,201.40 for insurers, respectively. By 2040, the average total patient out-of-pocket costs are projected to reach $3,047.67 for first-line and $2,211.33 for second-line therapy, and insurance will pay an average of $131,262.39 for first-line and $75,062.23 for second-line therapy. LIMITATIONS: Claims data are not collected for research purposes; therefore, there may be errors in entry and coding. Additionally, claims data do not contain important clinical factors, such as stage of disease at diagnosis, tumor histology, or data on disease progression, which may have important implications on the cost of care. CONCLUSIONS: The trajectory of the cost of lung cancer care is growing. This study estimates that the cost of care may double by 2040, with the greatest proportion of increase in patient out-of-pocket costs. Despite the average cost projections, these results suggest that a small sub-set of patients with very high costs could be at even greater risk in the future.

Relationship between major depressive disorder and associated painful physical symptoms: analysis of data from two pooled placebo-controlled, randomized studies of duloxetine.

The aim of this study was to evaluate the relationship between painful physical symptoms (PPS) and outcomes in major depressive disorder (MDD). Post-hoc analysis of two identically designed 8-week trials compared the efficacy of 60 mg/day duloxetine (N=523) with that of placebo (N=532) in treating PPS associated with MDD. The Montgomery-Åsberg Depression Rating Scale (MADRS) total score, the Brief Pain Inventory (BPI) average pain score, and the Sheehan Disability Scale global functional impairment score assessed depression symptoms, pain, and functioning, respectively. Remission was defined as a MADRS score of 10 or less, and the BPI response subgroup was defined as a 50% or greater reduction from baseline. Path analyses assessed relationships among variables. Duloxetine-treated patients who had a 50% or greater reduction in BPI score at endpoint had higher rates of remission. Path analysis indicated that 16% of likelihood of remission in depression symptoms was because of the direct effect of treatment, 41% because of pain reduction, and 43% because of functional improvement. Path analysis also indicated that 51% of improvement in functioning was attributed to pain improvement and 43% to mood improvement. Results demonstrate that improvement in pain and mood contributes to functional improvement, and pain reduction and functional improvement increase the likelihood of remission of depressive symptoms with duloxetine treatment in patients with both MDD and PPS at baseline.

Comparison of safety outcomes among Caucasian, Hispanic, Black, and Asian patients in duloxetine studies of chronic painful conditions.

OBJECTIVE: This post-hoc analysis was conducted to investigate if safety outcomes differed among race/ethnic subgroups of patients treated with duloxetine for chronic painful conditions. RESEARCH DESIGN AND METHODS: Pooled data from 15 placebo-controlled clinical trials were used to compare the safety outcomes of duloxetine among patients of Caucasian, Hispanic, Asian, and Black race/ethnic origins. Patients were randomized to receive placebo (n = 2199) or duloxetine (n = 3148) for treatment of diabetic peripheral neuropathic pain, fibromyalgia, osteoarthritis pain, or chronic low back pain. For categorical outcomes such as study discontinuation, adverse events leading to discontinuation, and treatment-emergent adverse events, incidence rates were summarized by race/ethnic subgroups. The Breslow-Day test was used to assess the homogeneity of treatment odds ratios across the four subgroups. For continuous outcomes such as changes in vital signs, body weight, and laboratory measures, an analysis of covariance or analysis of variance model was used and duloxetine effects were compared among race/ethnic subgroups based on the test of treatment-by-subgroup interaction. RESULTS: No significant differences were found among race/ethnic subgroups for discontinuation due to adverse events except for anxiety (p = 0.040). Rates of nausea and decreased appetite were significantly higher (p ≤ 0.05) in duloxetine-treated patients compared with placebo-treated patients within each race/ethnic subgroup. The Breslow-Day test was not significant for most safety outcomes, nor were treatment-by-race/ethnic subgroup interactions (p > 0.1), which suggested duloxetine effects were not significantly different among race/ethnic subgroups. CONCLUSION: Overall, these results detected only minimal differences among safety outcomes assessed in these race/ethnic subgroups in patients treated with duloxetine for chronic painful conditions. The unbalanced sample sizes among the race/ethnic subgroups may have limited the power to detect treatment by race subgroup interactions. These post-hoc subgroup analyses were of an exploratory nature and the results should be interpreted with appropriate caution.

The effect of duloxetine treatment on cognition in patients with fibromyalgia.

OBJECTIVES: To determine the effect of duloxetine treatment on cognition in patients with fibromyalgia. METHODS: Cognitive testing was conducted in a subset of adult patients in a randomized, double-blind, placebo-controlled trial of duloxetine. Patients met the American College of Rheumatology criteria for fibromyalgia and had a score of 4 or higher on the Brief Pain Inventory 24-hour average pain severity item. Patients who consented to cognitive testing were randomized to duloxetine (n = 80) or placebo (n = 76). The primary end point was at Week 12. Speed of processing on tasks requiring visual attention, working memory, and executive function was assessed with a Symbol Digit Substitution Test and Trail-Making Test A and B. Episodic memory was tested using the Verbal Learning and Recall Test. The change from baseline to end point (last-observation-carried-forward analysis) was analyzed by an analysis of covariance model, which included baseline, treatment, investigator, and treatment-by-investigator interaction. RESULTS: Most of the patients were white (89%) women (92%), ranging in age from 21 to 88 years. Mean scores on the cognitive tests were within 2 SD of published scores for similar-aged participants in the general population, indicating no substantial impairment. Baseline-to-end point changes in cognitive scores did not differ significantly between duloxetine and placebo treatment groups. CONCLUSIONS: Although scores differed somewhat from norms for age, substantial cognitive impairment was not evident in patients with fibromyalgia as assessed by the Symbol Digit Substitution Test, Trail-Making Test, and Verbal Learning and Recall Test. Overall, duloxetine treatment had neither positive nor negative effects on cognition. TRIAL REGISTRATION: Clintrials.gov NCT00673452.

Duloxetine versus placebo in the treatment of major depressive disorder and associated painful physical symptoms: a replication study.

OBJECTIVE: Painful physical symptoms are common in patients with major depressive disorder (MDD) and can negatively affect patient outcomes. Duloxetine has demonstrated efficacy in treating MDD and other certain painful conditions; this study specifically evaluated patients with both MDD and MDD-associated pain. METHODS: This randomized, double-blind clinical trial enrolled adult outpatients with MDD (DSM-IV-TR criteria; Montgomery-Åsberg Depression Rating Scale [MADRS] total score ≥20) and at least moderate pain (Brief Pain Inventory, Short Form [BPI] average pain rating ≥3). Patients received placebo (N = 266) or duloxetine (N = 261) 60 mg once daily (QD) (after starting dose of 30 mg QD for 1 week). This study replicated another study evaluating MDD and MDD-associated pain. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov (NCT01070329). MAIN OUTCOME MEASURES: Co-primary outcomes were the MADRS total score (change from baseline at 8 week endpoint) and BPI average pain rating (overall main effect over 8 weeks of treatment). The Sheehan Disability Scale (SDS) global functional impairment score at week 8 assessed functioning as a secondary outcome. Changes were analyzed using mixed-effects model repeated measures (MMRM), and the MADRS remission rate (total score ≤12 at 8-week endpoint) was analyzed using the Cochran-Mantel-Haenszel test. RESULTS: Both co-primary objectives and the first two gated secondary objectives were achieved: compared with placebo, duloxetine significantly improved the mean MADRS total score, BPI average pain rating, SDS global functional impairment score, and remission of depression at 8-week endpoint (all p < 0.01). The third gated secondary objective, evaluating remission of depression at the last two non-missing visits, was not achieved. The within-group MADRS remission rate was greater for duloxetine-treated patients with ≥50% (versus <50%) improvement in BPI average pain (p < 0.001). Safety outcomes were similar to previous reports. This study did not address the effects of duloxetine on MDD and comorbid pain of a known origin. CONCLUSIONS: These results replicated findings supporting the efficacy and tolerability of duloxetine compared to placebo as treatment for depression and pain in patients with MDD and at least moderate pain associated with MDD.

A randomized placebo-controlled trial of duloxetine in patients with major depressive disorder and associated painful physical symptoms.

OBJECTIVE: Painful physical symptoms are common in patients with major depressive disorder (MDD) and may predict poorer treatment outcomes. Duloxetine has demonstrated efficacy in treating both MDD and certain other painful conditions. This randomized, double-blind clinical trial assessed the effects of duloxetine in patients with both MDD and MDD-associated physical pain. METHODS: Participants were outpatient adults with current MDD (DSM-IV-TR criteria; Montgomery-Åsberg Depression Rating Scale [MADRS] total score ≥20) and at least moderate pain (Brief Pain Inventory Short Form [BPI] average pain rating ≥3) and with at least one prior episode of MDD. Patients received placebo (N = 266) or duloxetine (N = 262) 60 mg once daily. This trial is registered at clinicaltrials.gov (NCT01000805). MAIN OUTCOME MEASURES: Coprimary outcomes were MADRS total score (change from baseline at 8 weeks) and BPI average pain rating (overall main effect over 8 weeks). The Sheehan Disability Scale (SDS) global functional impairment score (change from baseline at 8 weeks) was used to assess functioning. Remission was defined as MADRS total score ≤12 at the 8-week endpoint. Changes were analyzed using mixed-effects model repeated measures (MMRM). RESULTS: Compared with placebo, duloxetine significantly improved the mean MADRS total score, BPI average pain rating, and SDS global functional impairment score (all p ≤ 0.05 for analyses described above). The remission rate was significantly greater with duloxetine compared with placebo (p = 0.001) and was greater for duloxetine-treated patients with ≥50% versus <50% improvement in BPI average pain score (p ≤ 0.001). Treatment emergent adverse events that occurred in at least 5% of duloxetine-treated patients and at twice the rate of placebo included nausea, somnolence, constipation, decreased appetite, and hyperhidrosis. Rates of discontinuation due to adverse events were greater for duloxetine than placebo (8.0% vs 3.4%, respectively; p = 0.024). This study did not address the effects of duloxetine on MDD and comorbid pain of a known origin. CONCLUSIONS: These results support the efficacy and tolerability of duloxetine in the treatment of depression and associated painful physical symptoms in patients with MDD and at least moderate MDD-associated pain.

Early improvement in pain predicts pain response at endpoint in patients with fibromyalgia.

UNLABELLED: An unanswered, but clinically important question is whether there are early indicators that a patient might respond to duloxetine treatment for fibromyalgia pain. To address this question, pooled data from 4 double-blind, placebo-controlled trials in duloxetine-treated patients (N = 797) with primary fibromyalgia as defined by the American College for Rheumatology were analyzed. Classification and Regression Tree (CART) analysis was used to determine what level of early pain improvement as measured by the 24-hour average pain severity question on the Brief Pain Inventory (BPI) best predicted later response. The predictor variables tested were 10, 15, 20, 25, and 30% decrease in BPI 24-hour average pain from baseline to Week 1 and Week 2. The results of the CART analysis showed that for patients with ≥15% improvement in pain at Week 1 and ≥30% improvement at Week 2, the probability of response at 3 months was 75%. For patients with <15% improvement at both Week 1 and Week 2, the probability of not responding at 3 months was 86%. Quantifiable early improvement in pain during the first 2 weeks of treatment with duloxetine was highly predictive of response or nonresponse after 3 months of treatment. PERSPECTIVE: This article presents early indicators that can highly predict later pain response or nonresponse in fibromyalgia patients treated with duloxetine. The results may aid clinicians to predict the likelihood of response at 3 months within the first 2 weeks of treatment.

Improvement in multiple dimensions of fatigue in patients with fibromyalgia treated with duloxetine: secondary analysis of a randomized, placebo-controlled trial.

INTRODUCTION: Fatigue is one of the most disabling symptoms associated with fibromyalgia that greatly impacts quality of life. Fatigue was assessed as a secondary objective in a 2-phase, 24-week study in outpatients with American College of Rheumatology-defined fibromyalgia. METHODS: Patients were randomized to duloxetine 60-120 mg/d (N = 263) or placebo (N = 267) for the 12-week acute phase. At Week 12, all placebo-treated patients were switched to double-blind treatment with duloxetine for the extension phase. Fatigue was assessed at baseline and every 4 weeks with the Multidimensional Fatigue Inventory (MFI) scales: General Fatigue, Physical Fatigue, Mental Fatigue, Reduced Activity, and Reduced Motivation. Other assessments that may be associated with fatigue included Brief Pain Inventory (BPI) average pain, numerical scales to rate anxiety, depressed mood, bothered by sleep difficulties, and musculoskeletal stiffness. Treatment-emergent fatigue-related events were also assessed. Changes from baseline to Week 12, and from Week 12 to Week 24, were analyzed by mixed-effects model repeated measures analysis. RESULTS: At Week 12, duloxetine versus placebo significantly (all p < .05) reduced ratings on each MFI scale, BPI pain, anxiety, depressed mood, and stiffness. Improvement in ratings of being bothered by sleep difficulties was significant only at Weeks 4 and 8. At Week 24, mean changes in all measures indicated improvement was maintained for patients who received duloxetine for all 24 weeks (n = 176). Placebo-treated patients switched to duloxetine (n = 187) had significant within-group improvement in Physical Fatigue (Weeks 16, 20, and 24); General Fatigue (Weeks 20 and 24); Mental Fatigue (Week 20); and Reduced Activity (Weeks 20 and 24). These patients also experienced significant within-group improvement in BPI pain, anxiety, depressed mood, bothered by sleep difficulties, and stiffness. Overall, the most common (> 5% incidence) fatigue-related treatment-emergent adverse events were fatigue, somnolence, and insomnia. CONCLUSIONS: Treatment with duloxetine significantly improved multiple dimensions of fatigue in patients with fibromyalgia, and improvement was maintained for up to 24 weeks. TRIAL REGISTRATION: ClinicalTrials.gov registry NCT00673452.

Flexible dosed duloxetine in the treatment of fibromyalgia: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To investigate the efficacy of flexible dose duloxetine 60-120 mg/day on changes in fibromyalgia (FM) symptoms assessed by the Patient Global Impression of Improvement (PGI-I) scale. METHODS: Outpatients ≥ 18 years of age who met American College of Rheumatology criteria for FM, and had ≥ 4 score on the Brief Pain Inventory (BPI) average pain item, were randomized to duloxetine (n = 263) or placebo (n = 267) for 24 week double-blind treatment (primary endpoint at Week 12). Key secondary measures included BPI average pain severity, patient-rated scales assessing mood, anxiety, pain, sleep, and stiffness, Clinical Global Impression of Severity (CGI-S), Multidimensional Fatigue Inventory, Cognitive and Physical Functioning Questionnaire, Beck Depression Inventory (BDI), Beck Anxiety Inventory, and Medical Outcome Study Short-Form Health Survey (SF-36). RESULTS: At Week 12, duloxetine-treated patients reported significantly greater global improvement with mean PGI-I scores of 2.8 compared to 3.4 in the placebo group (p < 0.001). Significantly more duloxetine- versus placebo-treated patients (57% vs 32%; p < 0.001) reported feeling "much" or "very much better" (PGI-I score ≤ 2). There was significantly greater improvement with duloxetine versus placebo treatment in BPI average pain severity, mood (including BDI total), anxiety (patient-rated only), stiffness, CGI-S, fatigue, all SF-36 domains (except role-physical and physical component summary), and being less bothered by pain or sleep difficulties. Treatment-emergent adverse events occurring significantly more frequently with duloxetine included: nausea, headache, constipation, dry mouth, dizziness, diarrhea, and hyperhidrosis. CONCLUSION: Treatment with duloxetine 60, 90, and 120 mg/day was associated with feeling much better, pain reduction, being less bothered by sleep difficulties, and improvement in mood, stiffness, fatigue and functioning. (Clinical trial registry NCT00673452).

Pain response profile of patients with fibromyalgia treated with duloxetine.

OBJECTIVES: This study examined the time course for minimal clinically significant improvement in pain severity during the initial 12 weeks of treatment in patients with fibromyalgia taking duloxetine. METHODS: Four double-blind, placebo-controlled trials of duloxetine were pooled. Patients received duloxetine 60 mg/d, 120 mg/d, or placebo. Clinically significant treatment response (>or=30% reduction in pain severity on the 24-hour average pain severity of the Brief Pain Inventory scale) was assessed over 12 weeks. RESULTS: At endpoint, 46.9% of duloxetine 60-mg-, 48.6% of duloxetine 120-mg-, and 32.1% of placebo-treated patients (P<0.001 for both doses) had >or=30% improvement on average pain from baseline. The probabilities of achieving >or=30% response at Weeks 1, 2, 4, 8, and 12 among duloxetine 60-mg-treated patients were 27%, 44%, 45%, 47%, and 49%, respectively, and among duloxetine 120-mg-treated patients were 35%, 43%, 53%, 53%, and 51%, respectively (P<0.01 vs. placebo at each week, for both doses). Among patients who did not respond by Weeks 1, 2, 4, and 8, the percentages of duloxetine 60-mg-treated patients who achieved a response by the endpoint of the study were 36.9%, 29.8%, 28.9%, and 26.9%, respectively. DISCUSSION: This article examines the time course for minimal clinically significant improvement in pain severity in duloxetine-treated patients with fibromyalgia. It provides information about continued treatment in patients who do not initially respond to duloxetine. This information could potentially help physicians facing clinical decisions about management of fibromyalgia with duloxetine.

Efficacy of duloxetine in patients with fibromyalgia: pooled analysis of 4 placebo-controlled clinical trials.

OBJECTIVE: To investigate the efficacy of duloxetine in the treatment of pain and improvement in functional impairment and quality of life in patients with fibromyalgia from a pooled analysis of 4 placebo-controlled, double-blind, randomized trials. METHOD: Patients were eligible for inclusion in the studies if they were at least 18 years of age, met criteria for fibromyalgia as defined by the American College of Rheumatology, and had specified minimum pain severity scores. Across all studies, 797 patients received duloxetine 60-120 mg/d and 535 patients received placebo. Pain was assessed by the Brief Pain Inventory (BPI) 24-hour average pain severity score; other efficacy measures included the Clinical Global Impressions-Severity of Illness scale (CGI-S), Patient Global Impressions-Improvement scale (PGI-I), 17-item Hamilton Depression Rating Scale (HDRS-17), Fibromyalgia Impact Questionnaire (FIQ) total score, BPI pain interference items, Sheehan Disability Scale (SDS), and Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) mental and physical components. Changes from baseline to endpoint (last observation carried forward) for most of the above efficacy measures were analyzed using an analysis-of-covariance model. RESULTS: After 12 weeks of treatment, pain was significantly reduced in patients treated with duloxetine (P < .001) compared with placebo. In addition, duloxetine was superior to placebo in improving CGI-S (P < .001); PGI-I (P < .001); FIQ total (P < .001); HDRS-17 total (P = .003); SDS global functioning (P < .001), work/school (P = .018), and family life (P < .001); SF-36 mental (P < .001) and physical (P = .026) component; and BPI pain interference (P < .001) scores. Treatment-by-subgroup interactions were not significant for sex (P = .320), age (P = .362), or race (P = .180). CONCLUSIONS: This pooled analysis provides evidence that 12 weeks of treatment with duloxetine 60-120 mg/d effectively improves fibromyalgia symptoms and may offer benefits beyond pain relief.

Early symptom change prediction of remission in depression treatment.

OBJECTIVES: This study investigated hypothesized early symptom changes as differential predictors of long-term remission for duloxetine and escitalopram. EXPERIMENTAL DESIGN: This was a post-hoc analysis from a placebo-controlled, randomized, double-blind study of patients with major depressive disorder treated for 8 weeks with duloxetine 60 mg/day (N = 273) or escitalopram 10 mg/day (N = 274), and for another 6 months with duloxetine up to 120 mg/day or escitalopram up to 20 mg/day. Odds ratios (ORs) for successful treatment (sustained remission), defined as a 17-item Hamilton Depression Rating Scale (HAMD-17) score 2.0. In a follow-up analysis, specific subscale items for psychological anxiety, motor retardation, and suicidality significantly predicted remission for duloxetine, and psychological and somatic anxiety for escitalopram. Notably, high NPVs on the Maier subscale indicated that a lack of 20% improvement on the "core" depression factor by Week 2 was highly predictive of unsuccessful treatment outcome over 8 months. CONCLUSIONS: In accord with hypotheses, early symptom changes were specific to treatment, with early response in the core depression factor (Maier subscale), anxiety, and motor activity for duloxetine, and core factor and anxiety for escitalopram. Lack of early response in depression symptom subscales was highly predictive of lack of sustained remission.