A total of 1,409 patients with NSCLC were identified who met the eligibility criteria for this study. Of these, 1,095 (78%) were treated on Pathway, and 314 (22%) were treated off Pathway. During the 12-month follow-up period, 735 patients (52%) died. Of those who lived, 494 (73%) had a full 12 months of follow-up time. Median follow-up time was similar for patients on pathway (median, 8.8 months) and off Pathway (median, 9.0 months).
shows the patient characteristics overall and by Pathway status. The overall median age of patients was 67 years (range, 30 to 94 years), and 54% (n = 766) were male. A majority of patients (n = 931; 72%) were diagnosed with advanced disease (stage IIIB to IV). Approximately two thirds of patients were initially treated with first-line regimens, 14% (n = 200) were treated in the adjuvant/neoadjuvant setting, 13% (n = 184) were treated with second-line care, and 7% (n = 105) were treated with third-line care or greater. Patients treated on versus off Pathway were similar with respect to age, sex, stage at diagnosis, and Eastern Cooperative Oncology Group performance status; however, they differed by line of therapy. Of patients treated on Pathway, 87% (n = 951) received adjuvant/neoadjuvant or first-line care, compared with 54% (n = 169) of off Pathway patients. By definition, patients treated with chemotherapy beyond third line were considered off Pathway (n = 47).
Patient Demographic and Clinical Characteristics
presents the 12-month cumulative costs of patients treated on Pathway versus patients treated off Pathway. Outpatient costs were 35% lower for on-Pathway (average 12-month cost, $18,041.62) versus off-Pathway patients (average 12-month cost, $27,736.51; on/off cost ratio, 0.65; 95% CI, 0.58 to 0.76). Applying estimated total hospitalization costs (on/off cost ratio for hospitalizations, 0.98; 95% CI, 0.83 to 1.17) to patients identified as having inpatient admissions did not have a significant effect on the observed difference in total cost by Pathway status (on/off cost ratio, 0.71; 95% CI, 0.64 to 80).
12-month cumulative cost by Pathway status.
We categorized costs to identify possible drivers of the observed cost differences and found that the majority of cost differences could be attributed to lower costs of chemotherapy and other infused medications among the on-Pathway cohort (). Chemotherapy costs were 37% lower (cost ratio, 0.63; 95% CI 0.55 to 0.76) for on-Pathway patients versus off-Pathway patients, and nonchemotherapy medications were 39% lower (cost ratio, 0.61; 95% CI, 0.52 to 0.74). For nonchemotherapy medications, we found that use of both erythropoietin stimulating agents (ESAs; cost ratio, 0.54; 95% CI, 0.42 to 0.69) and WBC growth factors (CSFs; cost ratio, 0.42; 95% CI, 0.32 to 0.63) was significantly lower in the on-Pathway cohort than in the off-Pathway cohort.
12-Month Average Cost by Pathway Status
Because of the significant difference in line of therapy for patients on Pathway versus off Pathway, we stratified the cost analysis by line of therapy. shows 12-month total costs by Pathway status for patients receiving adjuvant, first-line, and second-line care. We found that costs remained significantly lower for patients treated on Pathway versus off Pathway in the adjuvant and first-line settings, whereas no difference in overall cost was observed in patients receiving second-line care. Among patients in the adjuvant setting, we found that those treated on Pathway had a reduced cost of 39% compared with patients treated off Pathway (cost ratio, 0.61; 95% CI, 0.44 to 0.88); a 29% decreased overall cost was associated with on-Pathway patients receiving first-line care compared with off-Pathway patients receiving first-line care (cost ratio, 0.71; 95% CI, 0.59 to 0.87). Use of ESAs and CSFs was significantly less frequent among on-Pathway patients in adjuvant, first-line, and second-line settings. Because of the insufficient number of on-Pathway patients, we were unable to evaluate differences in cost by Pathway status among patients receiving third-line care.
12-month cumulative cost by Pathway status and line of therapy for patients receiving (A) adjuvant, (B) first-line, and (C) second-line care.
No difference in 12-month overall survival was observed by Pathway status (; 12-month survival probability, 0.45 v 0.46 for on v off Pathway; log-rank P = .867). In a multivariable Cox regression model (), we found that Pathway status was not associated with 12-month risk of mortality after adjusting for age, sex, stage, performance status, and line of therapy (multivariable hazard ratio [HR], 0.95; 95% CI, 0.77 to 1.16). Significant independent predictors of overall survival included stage at diagnosis (HR, 1.41; 95% CI, 1.10 to 1.80), lower performance status (HR, 1.78; 95% CI, 1.50 to 2.11 for performance status of 1; HR, 3.46; 95% CI, 2.63 to 4.57 for performance status of 2 to 3; P trend < .0001), and current treatment for metastatic disease (HR, 2.78; 95% CI, 1.83 to 4.23).
Cox Regression Analysis: Overall Survival
Again, because of differences in line of therapy by Pathway status, we evaluated the association between overall survival and Pathway status by line of therapy. No significant differences were observed in survival for patients on and off Pathway in adjuvant, first-line, and second-line settings. Furthermore, because patients receiving therapy beyond third line were considered to be off Pathway, and because there were few patients treated on Pathway in the third-line setting, we compared survival among patients receiving adjuvant and second line care combined and found no difference in survival by Pathway status (data not shown).
Finally, to estimate the overall cost effectiveness of Level I Pathways, we modeled the joint density of cost and effect (as measured by overall survival) by calculating the net monetary benefit approach of Pathways across a range of willingness to pay ceiling ratios (, online only). We found that treating patients on Pathway remained cost effective across the plausible range of society's (or payers') willingness to pay, even after adjusting for potential confounders (age, stage, line of therapy, and performance status).
Net monetary benefit (NMB) and cost-effectiveness acceptability curves.