Darren Tayama

Cost-Effectiveness of Recombinant Tissue-Type Plasminogen Activator Within 3 Hours of Acute Ischemic Stroke Current Evidence

Background and Purpose— Despite the availability of results from multiple newer clinical trials and changing healthcare costs, the cost-effectiveness of recombinant tissue-type plasminogen activator (r-tPA) for treatment of acute ischemic stroke within 0 to 3 hours of symptom onset was last evaluated in 1998 for the United States Using current evidence, we evaluate the long-term cost-effectiveness of r-tPA administered 0 to 3 hours after acute ischemic stroke onset versus no r-tPA. Methods— A disease-based decision model to project lifetime outcomes of patients after acute ischemic stroke by r-tPA treatment status from the US payer perspective was developed. Model inputs were derived from a recent meta-analysis of r-tPA trials, cohort studies, and health state preference studies. Cost data, inflated to 2013 dollars, were based on drug wholesale acquisition cost and the literature. To compare r-tPA to no r-tPA, we calculated incremental total direct costs, incremental quality-adjusted life years, and incremental cost-effectiveness ratios. We performed 1-way and probabilistic sensitivity analyses to evaluate uncertainty in the results. Results— r-tPA resulted in a gain of 0.39 quality-adjusted life years (95% confidence range, 0.16–0.66) on average per patient and a lifetime cost-saving of

Effect of Intravenous Recombinant Tissue-Type Plasminogen Activator in Patients With Mild Stroke in the Third International Stroke Trial-3 Post Hoc Analysis

25 000 (95% confidence range, −

Comparison of hospital length of stay, costs, and readmissions of alteplase versus catheter replacement among patients with occluded central venous catheters.

42 500 to −

Atezolizumab in platinum-treated locally advanced or metastatic urothelial carcinoma: post-progression outcomes from the phase II IMvigor210 study

11 000) compared with no r-tPA. In probabilistic sensitivity analyses, r-tPA was dominant compared with no r-tPA in ≈100% of simulations. The model was sensitive to inputs for r-tPA efficacy, healthcare costs for disabled patients, mortality rates for disabled and nondisabled patients, and quality of life estimates. Conclusions— Our analysis supports earlier economic evaluations that r-tPA is a cost-effective method to treat stroke. Appropriate use of r-tPA should be prioritized nationally.

Regional disparities in the quality of stroke care

Background and Purpose— Randomized trial evidence on the risk/benefit ratio of thrombolysis for mild stroke is limited. We sought to determine the efficacy of intravenous recombinant tissue-type plasminogen activator (IV r-tPA) in a subset of patients with mild deficit in the third International Stroke Trial (IST-3). Methods— IST-3 compared IV r-tPA with control within 6 hours of onset in patients for whom IV r-tPA was considered promising but unproven. Analysis was restricted to subjects randomized within 3 hours of onset with a baseline National Institutes of Health Stroke Scale ⩽5, pretreatment blood pressure <185/110, and no other r-tPA exclusion criteria. We compared r-tPA and control arms for primary (Oxfordshire Handicap Score [OHS] 0–2) and secondary (ordinal OHS and OHS 0–1) outcomes at 6 months. Results— Among 3035 IST-3 subjects, 612 (20.2%) had an National Institutes of Health Stroke Scale ⩽5; of these 106 (17.6%) met the restricted criteria. Allocation to r-tPA was associated with an increase in OHS 0 to 2 (84% r-tPA versus 65% control; adjusted odds ratio, 3.31; 95% confidence interval, 1.24–8.79) and a favorable shift in OHS distribution (adjusted odds ratio, 2.38; 95% confidence interval, 1.17–4.85). There was no significant effect of r-tPA on OHS 0 to 1 (60% versus 51%; adjusted odds ratio, 1.92; 95% confidence interval, 0.83–4.43). Conclusions— This post hoc analysis in a highly selected sample of IST-3 supports the rationale of A Study of the Efficacy and Safety of Activase (Alteplase) in Patients With Mild Stroke (PRISMS) trial—a randomized, phase IIIb study to evaluate IV r-tPA in mild ischemic stroke.

Quality adjusted life year gains associated with administration of recombinant tissue-type plasminogen activator for treatment of acute ischemic stroke: 1998–2011

Background Central venous catheter (CVC) occlusion is common, affecting 30% of all CVCs. Objective To compare length of stay (LOS), costs, and readmissions associated with the use of alteplase to clear catheter blockage to outcomes associated with catheter replacement. Design Retrospective observational study utilizing a large hospital database. Participants Hospitalized patients treated for catheter occlusion from January 2006 to December 2011. Main Measures Univariate analyses of patient characteristics and treatment patterns and multivariable regression analyses of postocclusion hospital costs, LOS, and 30- and 90-day readmissions were conducted. Key Results We included 34,579 patients treated for a CVC occlusion by replacement (N = 1028) or by alteplase (2 mg) administration (N = 33,551). Patients receiving alteplase were somewhat younger than those having catheter replacement (60 ± 19 vs 62 ± 20 years old, P = 0.0002). After adjusting for patient and hospital factors via regression modeling, average daily postocclusion costs were

Comparison of statistical and operational properties of subject randomization procedures for large multicenter clinical trial treating medical emergencies.

317 lower for alteplase recipients than for catheter replacement patients (95% confidence interval [CI]: 238.22–392.24; P < 0.0001). Adjusted total postocclusion costs were

Atezolizumab in Platinum-treated Locally Advanced or Metastatic Urothelial Carcinoma: Clinical Experience from an Expanded Access Study in the United States

1419 lower for alteplase recipients versus patients receiving catheter replacement (95% CI: 307.27–2458.12; P = 0.0121). Postocclusion operating room/surgery, radiology, and supply costs were significantly lower for alteplase recipients (P < 0.001). Average adjusted postocclusion LOS was similar for both groups (P > 0.05). Odds of readmission were not significantly different at 30 or 90 days. Conclusions Among patients treated for an occluded CVC, alteplase-treated patients had lower daily and total postocclusion costs than patients receiving catheter replacement. Cost differences were mainly driven by lower operating room/surgery, radiology, and supplier costs. Journal of Hospital Medicine 2014;9:490–496.

What is the value of conducting a trial of r-tPA for the treatment of mild stroke patients?

Background Conventional criteria for tumor progression may not fully reflect the clinical benefit of immunotherapy or appropriately guide treatment decisions. The phase II IMvigor210 study demonstrated the efficacy and safety of atezolizumab, a programmed death-ligand 1-directed antibody, in patients with platinum-treated locally advanced or metastatic urothelial carcinoma. Patients could continue atezolizumab beyond Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 progression at the investigators discretion: this analysis assessed post-progression outcomes in these patients. Patients and methods Patients were treated with atezolizumab 1200 mg i.v. every 3 weeks until loss of clinical benefit. Efficacy and safety outcomes in patients who experienced RECIST v1.1 progression and did, or did not, continue atezolizumab were analyzed descriptively. Results In total, 220 patients who experienced progression from the overall cohort (n = 310) were analyzed: 137 continued atezolizumab for ≥ 1 dose after progression, 19 received other systemic therapy, and 64 received no further systemic therapy. Compared with those who discontinued, patients continuing atezolizumab beyond progression were more likely to have had a baseline Eastern Cooperative Oncology Group performance status of 0 (43.1% versus 31.3%), less likely to have had baseline liver metastases (27.0% versus 41.0%), and more likely to have had an initial response to atezolizumab (responses in 11.7% versus 1.2%). Five patients (3.6%) continuing atezolizumab after progression had subsequent responses compared with baseline measurements. Median post-progression overall survival was 8.6 months in patients continuing atezolizumab, 6.8 months in those receiving another treatment, and 1.2 months in those receiving no further treatment. Atezolizumab exposure-adjusted adverse event frequencies were generally similar before and following progression. Conclusion In this single-arm study, patients who continued atezolizumab beyond RECIST v1.1 progression derived prolonged clinical benefit without additional safety signals. Identification of patients most likely to benefit from atezolizumab beyond progression remains an important challenge in the management of metastatic urothelial carcinoma. ClinicalTrials.gov ID NCT02108652.

Pertuzumab plus trastuzumab for HER2-positive metastatic urothelial cancer (mUC): Preliminary data from MyPathway.

Background and purpose: There is widespread geographic variation in healthcare quality, but we often lack clear strategies for improving quality in underserved areas. This study characterized geographic disparities in stroke care quality to assess whether improved access to neurological services has the potential to bridge the care quality gap, particularly in terms of alteplase (rt‐PA) administration. Methods: This was a retrospective study using quality performance data from the 2015 Hospital Compare database linked to information on certification status from the Joint Commission and information on local access to neurological services from the Area Health Resources File. We used these data to compare stroke care quality according to geographic area, certification, and neurologist access. Results: Non‐metropolitan hospitals performed worse than metropolitan hospitals on all assessed stroke care quality measures. The most prevalent disparity occurred in the use of rt‐PA for eligible patients (52.2% versus 82.7%, respectively). Certified stroke centers in every geographic designation provided higher quality of care, whereas large variation was observed among non‐certified hospitals. Regression analyses suggested that improvements in hospital certification or access to neurologists were associated with absolute improvements of 44.9% and 21.3%, respectively, in the percentage of patients receiving rt‐PA. Conclusions: The large quality gap in stroke care between metropolitan and non‐metropolitan areas could be at least partly addressed through improved procedural efforts by stroke center certification increasing the supply of neurological services, (i.e. through training and hiring new neurologists) or by adopting decision support systems such as telemedicine.