Cross-company evaluation of the human lymphocyte activation assay.

Nonclinical immunotoxicity evaluation is an important component of safety assessment for pharmaceuticals. One in vitro assay that can be applied in a weight of evidence assessment is the human lymphocyte activation (HuLA) assay, an antigen recall assay, similar in many respects to the in vivo T-cell-dependent antibody response (TDAR) in that cooperation of multiple immune cell types are needed to produce responses. This assay uses human cells and is more amenable than the TDAR to compound ranking and mechanistic studies. The HuLA assay requires less time and drug than TDAR assays, uses a relevant antigen (influenza), reflects a human immune response, and applies principles of the 3Rs to non-clinical safety assessment. Peripheral blood mononuclear cells (PBMC) from flu-immunized donors are re-stimulated with flu-vaccine in the presence of test articles, and proliferation is measured. Published data demonstrate the applicability of the HuLA assay, but it has not been evaluated for reproducibility across testing sites. To evaluate assay reproducibility, scientists from a consortium of institutions conducted the assay in parallel, using a common pool of donor PBMC, influenza vaccine, and known immunosuppressant compounds (cyclosporine A and mycophenolic acid). The HuLA assay was highly reproducible in identification of inhibition of antigen-specific responses, and there was significant agreement across testing sites in the half maximal inhibitory concentration (IC50) values. Intra-site variability was the largest contributor to the variability observed within the assay. The HuLA assay was demonstrated to be ideally suited to comparing multiple compounds (i.e. compound ranking or benchmarking) within the same assay. Overall, the data reported herein support the HuLA assay as a useful tool in mechanistic evaluations of antigen-specific immune responses.

The cost-effectiveness of health communication programs: what do we know?

While a considerable body of evidence has emerged supporting the effectiveness of communication programs in augmenting health, only a very small subset of studies has examined also whether these programs are cost-effective, that is, whether they achieve greater health gains for available financial resources than alternative interventions. In this article, we examine the available literature on the cost-effectiveness of health behavior change communication programs, focusing on communication interventions involving mass media, and, to a lesser extent, community mobilization and interpersonal communication or counseling. Our objective is to identify the state of past and current research efforts of the cost-effectiveness of behavior change communication programs. This review makes three principal conclusions. First, the analysis of the cost-effectiveness of health communication programs commonly has not been performed. Second, the studies reviewed here have utilized a considerable diversity of methods and have reflected varying levels of quality and adherence to standard cost-effectiveness methodologies. This leads to problems of transparency, comparability, and generalizability. Third, while the available studies generally are indicative of the cost-effectiveness of communication interventions relative to alternatives, the evidence base clearly needs to be expanded by additional rigorous cost-effectiveness analyses.

Traditional versus integrative behavioral couple therapy for significantly and chronically distressed married couples.

A randomized clinical trial compared the effects of traditional behavioral couple therapy (TBCT) and integrative behavioral couple therapy (IBCT) on 134 seriously and chronically distressed married couples, stratified into moderately and severely distressed groups. Couples in IBCT made steady improvements in satisfaction throughout the course of treatment, whereas TBCT couples improved more quickly than IBCT couples early in treatment but then, in contrast to the IBCT group, plateaued later in treatment. Both treatments produced similar levels of clinically significant improvement by the end of treatment (71% of IBCT couples and 59% of TBCT couples were reliably improved or recovered on the Dyadic Adjustment Scale; G. B. Spanier, 1976). Measures of communication also showed improvement for both groups. Measures of individual functioning improved as marital satisfaction improved.