(18) F-FDG PET-CT and trephine biopsy assessment of bone marrow involvement in lymphoma.

The ability of positron emission tomography-computerized tomography (PET-CT) to accurately detect bone marrow involvement (BMI) has been suggested in Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL), but its abilities in other histologies is less established. The aim of this retrospective study was to confirm the role of PET-CT in detecting BMI in DLBCL and HL, and to explore its usefulness in other subtypes. Of the 149 newly diagnosed patients, common subtypes included DLBCL, follicular lymphoma (FL) and HL. In DLBCL, the sensitivity and specificity of PET-CT at diagnosis were 75% and 92%. In FL, the sensitivity and specificity of PET-CT were 67% and 85% at diagnosis, and 73% and 89% at relapse. In HL, the sensitivity and specificity were 100% and 74%. PET-CT was able to detect BMI in patients with negative biopsies. Most of the patients in which PET-CT failed to identify BMI were already advanced stage by imaging. In this analysis, PET-CT was highly accurate for detecting BMI at diagnosis in DLBCL and HL and highly specific in FL at diagnosis and relapse. Results also suggested the diagnostic advantage of PET-CT over bone marrow biopsy in detecting BMI. Prospective evaluation is necessary and may eliminate biopsies in future patients.

A study on confidence intervals for incremental cost-effectiveness ratios.

In health policy and economics studies, the incremental cost-effectiveness ratio (ICER) has long been used to compare the economic consequences relative to the health benefits of therapies. Due to the skewed distributions of the costs and ICERs, much research has been done on how to obtain confidence intervals of ICERs, using either parametric or nonparametric methods, with or without the presence of censoring. In this paper, we will examine and compare the finite sample performance of many approaches via simulation studies. For the special situation when the health effect of the treatment is not statistically significant, we will propose a new bootstrapping approach to improve upon the bootstrap percentile method that is currently available. The most efficient way of constructing confidence intervals will be identified and extended to the censored data case. Finally, a data example from a cardiovascular clinical trial is used to demonstrate the application of these methods.

On the equivalence of some medical cost estimators with censored data.

In clinical trials comparing different treatments and in health economics and outcomes research, medical costs are frequently analysed to evaluate the economical impacts of new treatment options and economic values of health-care utilization. Since Lin et al.'s first finding in the problem of applying the survival analysis techniques to the cost data, many new methods have been proposed. In this report, we establish analytic relationships among several widely adopted medical cost estimators that are seemingly different. Specifically, we report the equivalence among various estimators that were introduced by Lin et al., Bang and Tsiatis, and Zhao and Tian. Lin's estimators are formerly known to be asymptotically unbiased in some discrete censoring situations and biased otherwise, whereas all other estimators discussed here are consistent for the expected medical cost. Thus, we identify conditions under which these estimators become identical and, consequently, the biased estimators achieve consistency. We illustrate these relationships using an example from a clinical trial examining the effectiveness of implantable cardiac defibrillators in preventing death among people who had prior myocardial infarctions.

Estimating incremental cost-effectiveness ratios and their confidence intervals with differentially censored data.

With medical costs escalating over recent years, cost analysis is being conducted more and more to assess economic impact of new treatment options. An incremental cost-effectiveness ratio (ICER) is a measure that assesses the additional cost for a new treatment for each additional unit of effectiveness, such as saving 1 year of life. In this article, we consider cost-effectiveness analysis for new treatments evaluated in a randomized clinical trial setting with staggered entries. In particular, the censoring times are different for cost and survival data. We propose a method for estimating the ICER and obtaining its confidence interval when differential censoring exists. Simulation experiments are conducted to evaluate our proposed method. We also apply our methods to a clinical trial example comparing the cost-effectiveness of implanted defibrillators with conventional therapy for individuals with reduced left ventricular function after myocardial infarction.

The cost effectiveness of implantable cardioverter-defibrillators: results from the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II.

OBJECTIVES: We sought to evaluate the cost implications of the implantable cardioverter-defibrillator (ICD), using utilization, cost, and survival data from the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II. BACKGROUND: This trial showed that prophylactic implantation of a defibrillator reduces the rate of mortality in patients who experienced a previous myocardial infarction and low left ventricular ejection fraction. Given the size of the eligible population, the cost effectiveness of the ICD has substantial implications. METHODS: Our research comprises the cost-effectiveness component of the randomized controlled trial, MADIT-II, based on utilization, cost, and survival information from 1,095 U.S. patients who were assigned randomly to receive an ICD or conventional medical care. Utilization data were converted to costs using a variety of national and hospital-specific data. The incremental cost-effectiveness ratio (iCER) was calculated as the difference in discounted costs divided by the difference in discounted life expectancy within 3.5 years. Secondary analyses included projections of survival (using three alternative assumptions), corresponding cost assumptions, and the resulting cost-effectiveness ratios until 12 years after randomization. RESULTS: During the 3.5-year period of the study, the average survival gain for the defibrillator arm was 0.167 years (2 months), the additional costs were 39,200 dollars, and the iCER was 235,000 dollars per year-of-life saved. In three alternative projections to 12 years, this ratio ranged from 78,600 dollars to 114,000 dollars. CONCLUSIONS: The estimated cost per life-year saved by the ICD in the MADIT-II study is relatively high at 3.5 years but is projected to be substantially lower over the course of longer time horizons.