Cost-Effectiveness of Pharmacomechanical Catheter-Directed Thrombolysis Versus Standard Anticoagulation in Patients With Proximal Deep Vein Thrombosis: Results From the ATTRACT Trial.

BACKGROUND: In patients with acute deep vein thrombosis (DVT), pharmacomechanical catheter-directed thrombolysis (PCDT) in conjunction with anticoagulation therapy is increasingly used with the goal of preventing postthrombotic syndrome. Long-term costs and cost-effectiveness of these 2 treatment strategies from the perspective of the US healthcare system have not been compared. METHODS AND RESULTS: Between 2009 and 2014, the ATTRACT trial (Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis) randomized 692 patients with acute proximal DVT to PCDT plus anticoagulation (n=337) or standard treatment with anticoagulation alone (n=355). Costs (2017 US dollars) were assessed over a 24-month follow-up period using a combination of resource-based costing, hospital bills, Medicare reimbursement rates, and the Drug Topics Red Book. Health state utilities were obtained from the Short Form-36. In-trial results and US life tables were used to develop a Markov cohort model to evaluate lifetime cost-effectiveness. For the PCDT group, mean costs of the initial procedure were $13 600; per-patient costs associated with the index hospitalization were $21 509 for PCDT and $3877 for standard care (difference=$17 632; 95% CI, $16 117-$19 243). The 24-month difference in costs was $20 045 (95% CI, $16 093-$24 120). Utility scores increased significantly between baseline and 6 months for both groups, with no significant differences between groups at any follow-up time point. Projected differences in lifetime costs of $16 740 and quality-adjusted life years (QALYs) of 0.08, yield an incremental cost-effectiveness ratio for PCDT of $222 041/QALY gained. In probabilistic sensitivity analysis, the probability that PCDT would achieve a lifetime incremental cost-effectiveness ratio <$50 000/QALY or <$150 000/QALY was 1% and 25%, respectively. For iliofemoral DVT, QALY gains with PCDT were greater, yielding an incremental cost-effectiveness ratio of $137 526/QALY; for femoral-popliteal DVT, standard therapy was an economically dominant strategy. CONCLUSIONS: With an incremental cost-effectiveness ratio >$200 000/QALY gained, PCDT is not an economically attractive treatment for proximal DVT. PCDT may be of intermediate value in patients with iliofemoral DVT. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT00790335.

Ambulatory Toxicity Management (AToM) in patients receiving adjuvant or neo-adjuvant chemotherapy for early stage breast cancer - a pragmatic cluster randomized trial protocol.

BACKGROUND: Population-based studies suggest that emergency department visits and hospitalizations are common among patients receiving chemotherapy and that rates in routine practice are higher than expected from clinical trials. Chemotherapy-related toxicities are often predictable and, consequently, acute care visits may be preventable with adequate treatment planning and support between visits to the cancer centre. We will evaluate the impact of proactive telephone-based toxicity management on emergency department visits and hospitalizations in women with early stage breast cancer receiving chemotherapy. METHODS: In this pragmatic covariate constraint-based cluster randomized trial, 20 centres in Ontario, Canada are randomly allocated to either proactive telephone toxicity management (intervention) or routine care (control). The primary outcome is the cluster-level mean number of ED + H visits per patient evaluated using Ontario administrative healthcare data. Participants are all patients with early stage (I-III) breast cancer commencing adjuvant or neo-adjuvant chemotherapy at participating institutions during the intervention period. At least 25 patients at each centre participate in a patient reported outcomes sub-study involving the collection of standardized questionnaires to measure: severity of treatment toxicities, self-care, self-efficacy, quality of life, and coordination of care. Patients participating in the patient reported outcomes (PRO) sub-study are asked to provide written consent to link their PRO data to administrative data. Unit costs will be applied to each per person resource utilized, and a total cost per population and patient will be generated. An incremental cost-effectiveness analysis will be undertaken to compare the incremental costs and outcomes between the intervention and control groups from the health system perspective. DISCUSSION: This study evaluates the effectiveness of a proactive toxicity management intervention in a routine care setting. The use of administrative healthcare data to evaluate the primary outcome enables an evaluation in a real world setting and at a much larger scale than previous studies. TRIAL REGISTRATION: Clinicaltrials.gov , NCT02485678. Registered 30 June 2015.

Population-Based Study to Determine the Health System Costs of Using the 21-Gene Assay.

Purpose The 21-gene assay Oncotype Dx (Genomic Health, Redwood City, CA) test is used to aid the decision about chemotherapy in patients with hormone receptor-positive breast cancer who received endocrine therapy. Economic studies to support test adoption used decision-analytic models with assumptions and data derived from disparate sources. The objective was to evaluate whether the 21-gene assay test resulted in an overall cost expense or saving to the health system. Patients and Methods One thousand participants enrolled in a field evaluation study, were linked to population-level health system administrative databases, and were observed for 20 months. The cost for the cohort, which included the cost of the test, subsequent treatments received, and health care encounters, was determined. The cost in the absence of the test was compared with the pretest recommendation about chemotherapy from the field study for a base case and under scenarios that reflected different adjuvant chemotherapy use. Overall health system costs and incremental costs were calculated. Results The 21-gene assay resulted in a net decrease in chemotherapy use of 23%. For the base case incremental analysis, the actual overall health system cost of this cohort, including the cost of 21-gene assay, was $29.2 million compared with $26.2 million in the absence of the test-an increase of $3.1 million. For three of the four scenario analyses, the actual overall cost to the health system exceeded the estimated cost in the absence of the test. Results showed that, when at least half of the population received adjuvant chemotherapy, the cost increased to $30.2 million. Conclusion The use of real-world administrative data showed that, despite lower rates of chemotherapy use, the 21-gene assay test results in an overall incremental cost to the health care system in the short-term under most assumptions.

Positron Emission Tomography-Computed Tomography (PET-CT) Versus No PET-CT in the Management of Potentially Resectable Colorectal Cancer Liver Metastases: Cost Implications of a Randomized Controlled Trial.

PURPOSE: To evaluate whether positron emission tomography (PET) combined with computed tomography (PET-CT) is cost saving, or cost neutral, compared with conventional imaging in management of patients with resectable colorectal cancer liver metastases. METHODS: Cost evaluation of a randomized trial that compared the effect of PET-CT on surgical management of patients with resectable colorectal cancer liver metastases. Health care use data ≤ 1 year after random assignment was obtained from administrative databases. Cost analysis was undertaken from the perspective of a third-party payer (ie, Ministry of Health). Mean costs with 95% credible intervals (CrI) were estimated by using a Bayesian approach. RESULTS: The estimated mean cost per patient in the 263 patients who underwent PET-CT was $45,454 CAD (range, $1,340 to $181,420) and in the 134 control patients, $40,859 CAD (range, $279 to $293,558), with a net difference of $4,327 CAD (95% CrI, -$2,207 to $10,614). The primary cost driver was hospitalization for liver surgery (difference of $2,997 CAD for PET-CT; 95% CrI, -$2,144 to $8,010), which was mainly a result of a longer length of hospital stay for the PET-CT arm (median, 7 v 6 days; P = .03) and a higher postoperative complication rate (20% v 10%; P = .01). Baseline characteristics were similar between groups, including the number of liver segments involved with cancer, number of segments resected, and type of liver resection performed. No difference in survival was detected between arms. CONCLUSION: PET-CT was associated with limited clinical benefit and a nonsignificant increased cost. Universal funding of PET-CT in the management of patients with resectable colorectal cancer liver metastases does not seem justified.

Cost effectiveness of a survivorship care plan for breast cancer survivors.

PURPOSE: Survivorship care plans (SCPs) are recommended for patients who have completed primary treatment and are transitioning to routine follow-up care. However, SCPs may be costly, and their effectiveness is unproven. The study objective was to assess the cost effectiveness of an SCP for breast cancer survivors transitioning to routine follow-up care with their own primary care physician (PCP) using data from a recent randomized controlled trial (RCT). METHODS: Resource use and utility data for 408 patients with breast cancer enrolled in the RCT comparing an SCP with standard care (no SCP) were used. The intervention group received a 30-minute educational session with a nurse and their SCP, and their PCPs received the SCP plus a full guideline on follow-up. Analysis assessed the societal costs and quality-adjusted life years (QALYs) for the intervention group and the control group over the 2-year follow-up of the RCT. Uncertainty concerning cost effectiveness was assessed through nonparametric bootstrapping and deterministic sensitivity analysis. RESULTS: The no-SCP group had better outcomes than the SCP group: total costs per patient were lower for standard care (Canadian $698 v $765), and total QALYs were almost equivalent (1.42 for standard care v 1.41 for the SCP). The probability that the SCP was cost effective was 0.26 at a threshold value of a QALY of $50,000. A variety of sensitivity analyses did not change the conclusions of the analysis. CONCLUSION: This SCP would be costly to introduce and would not be a cost effective use of scarce health care resources.

Prospective study of 2-[¹8F]fluorodeoxyglucose positron emission tomography in the assessment of regional nodal spread of disease in patients with breast cancer: an Ontario clinical oncology group study.

PURPOSE: 2-[(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) is potentially useful in assessing lymph nodes and detecting distant metastases in women with primary breast cancer. PATIENTS AND METHODS: Women diagnosed with operable breast cancer within 3 months underwent FDG-PET at one of five Ontario study centers followed by axillary lymph node assessment (ALNA) consisting of sentinel lymph node biopsy (SLNB) alone if sentinel lymph nodes (SLNs) were negative, SLNB with axillary lymph node dissection (ALND) if SLNB or PET was positive, or ALND alone if SLNs were not identified. RESULTS: Between January 2005 and March 2007, 325 analyzable women entered this study. Sentinel nodes were found for 312 (96%) of 325 women and were positive for tumor in 90 (29%) of 312. ALND was positive in seven additional women. Using ALNA as the gold standard, sensitivity for PET was 23.7% (95% CI, 15.9% to 33.6%), specificity was 99.6% (95% CI, 97.2% to 99.9%), positive predictive value was 95.8% (95% CI, 76.9% to 99.8%), negative predictive value was 75.4% (95% CI, 70.1% to 80.1%), and prevalence was 29.8% (95% CI, 25.0% to 35.2%). Using logistic regression, tumor size was predictive for prevalence of tumor in the axilla and for PET sensitivity. PET scan was suspicious for distant metastases in 13 patients; three (0.9%) were confirmed as metastatic disease and 10 (3.0%) were false positive. CONCLUSION: FDG-PET is not sufficiently sensitive to detect positive axillary lymph nodes, nor is it sufficiently specific to appropriately identify distant metastases. However, the very high positive predictive value (96%) suggests that PET when positive is indicative of disease in axillary nodes, which may influence surgical care.

Warfarin dose assessment every 4 weeks versus every 12 weeks in patients with stable international normalized ratios: a randomized trial.

BACKGROUND: Guidelines recommend that patients receiving warfarin undergo international normalized ratio (INR) monitoring every 4 weeks. OBJECTIVE: To investigate whether assessment of warfarin dosing every 12 weeks is as safe as assessment every 4 weeks. DESIGN: Noninferiority randomized trial. The randomization schedule (in a 1:1 ratio) was computer-generated, and allocation was concealed until the database was locked by using a centralized schedule. Patients, study and clinical personnel, adjudicators of clinical events, and the study statistician were blinded to treatment assignment. (ClinicalTrials.gov registration number: NCT00356759) SETTING: Single center in Hamilton, Ontario, Canada. PATIENTS: 250 patients receiving long-term warfarin therapy, whose dose was unchanged for at least 6 months; 226 completed the study. INTERVENTION: Dosing assessment every 12 weeks (n = 124) compared with every 4 weeks (n = 126) for 12 months. Patients in the 12-week group were tested every 4 weeks; sham INRs within the target range were reported for two of the three 4-week periods. MEASUREMENTS: Percentage of time in the therapeutic range (primary outcome) and number of extreme INRs, changes in maintenance dose, major bleeding events, objectively verified thromboembolism, and death (secondary outcomes). RESULTS: The percentage of time in the therapeutic range was 74.1% (SD, 18.8%) in the 4-week group compared with 71.6% (SD, 20.0%) in the 12-week group (absolute difference, 2.5 percentage points [1-sided 97.5% upper confidence bound, 7.3 percentage points]; noninferiority P = 0.020 for a 7.5-percentage point margin). Fewer patients in the 12-week group than in the 4-week group had any dose changes (37.1% vs. 55.6%; absolute difference, 18.5 percentage points [95% CI, 6.1 to 30.0 percentage points]; P = 0.004). Secondary outcomes did not differ between groups. LIMITATIONS: Patients in the 12-week group had testing and contact with clinic staff every 4 weeks. The study was conducted at a single center and used surrogate outcomes. CONCLUSION: Assessment of warfarin dosing every 12 weeks seems to be safe and noninferior to assessment every 4 weeks. A comparison of INR testing, patient contact, and warfarin dose assessment every 12 weeks versus every 4 weeks is necessary before INR testing every 12 weeks can be routinely recommended for practice. PRIMARY FUNDING SOURCE: Physicians' Services Incorporated Foundation.